FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Manchikanti, L Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Hirsch, Joshua A. TI REGARDING: UDEH BL, ET AL. THE 2-YEAR COST-EFFECTIVENESS OF 3 OPTIONS TO TREAT LUMBAR SPINAL STENOSIS PATIENTS. PAIN PRACT 2014 JAN 3 [EPUB AHEAD OF PRINT] SO PAIN PRACTICE LA English DT Letter ID CAUDAL EPIDURAL INJECTIONS; LOW-BACK-PAIN; DOUBLE-BLIND; CONTROLLED-TRIAL; DISC-HERNIATION; OUTCOMES; UTILITY C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ, Sch Med, Dept PM & R, Philadelphia, PA 19122 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 12 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1530-7085 EI 1533-2500 J9 PAIN PRACT JI Pain Pract. PD SEP PY 2014 VL 14 IS 7 BP E161 EP E162 DI 10.1111/papr.12236 PG 2 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AO9YK UT WOS:000341716500001 PM 25113809 ER PT J AU Ghogare, AA Rizvi, I Hasan, T Greer, A AF Ghogare, Ashwini A. Rizvi, Imran Hasan, Tayyaba Greer, Alexander TI "Pointsource" Delivery of a Photosensitizer Drug and Singlet Oxygen: Eradication of Glioma Cells In Vitro SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PHOTODYNAMIC THERAPY; AQUEOUS-SOLUTION; CHEMISTRY; SILICA; PHOSPHORESCENCE; PHOTOCHEMISTRY; NANOPARTICLES; ENHANCEMENT; GENERATION; EFFICIENCY AB We describe a pointsource sensitizer-tipped microoptic device for the eradication of glioma U87 cells. The device has a mesoporous fluorinated silica tip which emits singlet oxygen molecules and small quantities of pheophorbide sensitizer for additional production of singlet oxygen in the immediate vicinity. The results show that the device surges in sensitizer release and photokilling with higher rates about midway through the reaction. This was attributed to a self-amplified autocatalytic reaction where released sensitizer in the extracellular matrix provides positive feedback to assist in the release of additional sensitizer. The photokilling of the glioma cells was analyzed by global toxicity and live/dead assays, where a killing radius around the tip with similar to 0.3mm precision was achieved. The implication of these results for a new PDT tool of hard-to-resect tumors, e.g. in the brain, is discussed. C1 [Ghogare, Ashwini A.; Greer, Alexander] CUNY Brooklyn Coll, Dept Chem, Grad Ctr, Brooklyn, NY 11210 USA. [Rizvi, Imran; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Rizvi, Imran; Hasan, Tayyaba] Harvard Univ, Sch Med, Boston, MA USA. RP Greer, A (reprint author), CUNY Brooklyn Coll, Dept Chem, Grad Ctr, Brooklyn, NY 11210 USA. EM thasan@partners.org; agreer@brooklyn.cuny.edu FU NIH-National Institute of General Medical Sciences [SC1GM093830]; NIH-National Cancer Institute [5R01CA160998] FX A.A.G and A.G acknowledge support from the NIH-National Institute of General Medical Sciences (SC1GM093830). Grant support to I. R. and T. H. was provided by the NIH-National Cancer Institute (5R01CA160998). We thank Bryan Spring, Aki Palanisami, Huang-Chiao (Joe) Huang and Girgis Obaid for comments, and Leda Lee for the graphic arts work. NR 45 TC 6 Z9 6 U1 4 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2014 VL 90 IS 5 BP 1119 EP 1125 DI 10.1111/php.12274 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AP2AB UT WOS:000341873400020 PM 24673689 ER PT J AU Bibas, L Levi, M Bendayan, M Mullie, L Forman, DE Afilalo, J AF Bibas, Lior Levi, Michael Bendayan, Melissa Mullie, Louis Forman, Daniel E. Afilalo, Jonathan TI Therapeutic Interventions for Frail Elderly Patients: Part I. Published Randomized Trials SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Frailty; Sarcopenia; Randomized clinical trials ID PHYSICAL-ACTIVITY INTERVENTION; JAPANESE SARCOPENIC WOMEN; PLACEBO-CONTROLLED TRIAL; DWELLING OLDER-ADULTS; FUNCTIONAL DECLINE; BODY-COMPOSITION; CLINICAL-TRIAL; DOUBLE-BLIND; MUSCLE MASS; HEART-FAILURE AB The body of literature for frailty as a prognostic marker continues to grow, yet the evidence for frailty as a therapeutic target is less well defined. In the setting of cardiovascular disease, the prevalence of frailty is elevated and its impact on mortality and major morbidity is substantial. Therapeutic interventions aimed at improving frailty may impart gains in functional status and survival. Randomized clinical trials that tested one or more therapeutic interventions in a population of frail older adults were reviewed. The interventions studied were exercise training in 13 trials, nutritional supplementation in 4 trials, combined exercise plus nutritional supplementation in 7 trials, pharmaceutical agents in 8 trials, multi-dimensional programs in 5 trials, and home-based services in 1 trial. The main findings of these trials are explored along with a discussion of their relative merits and limitations. (c) 2014 Elsevier Inc. All rights reserved. C1 [Bibas, Lior; Levi, Michael; Mullie, Louis] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Afilalo, Jonathan] McGill Univ, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Bendayan, Melissa; Afilalo, Jonathan] McGill Univ, Dept Physiol, Montreal, PQ H3T 1E2, Canada. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Geratr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada. RP Afilalo, J (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, 3755 Cote Ste Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada. EM jonathan.afilalo@mcgill.ca NR 48 TC 30 Z9 30 U1 3 U2 28 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2014 VL 57 IS 2 BP 134 EP 143 DI 10.1016/j.pcad.2014.07.004 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP1AN UT WOS:000341798900003 PM 25216612 ER PT J AU Bendayan, M Bibas, L Levi, M Mullie, L Forman, DE Afilalo, J AF Bendayan, Melissa Bibas, Lior Levi, Michael Mullie, Louie Forman, Daniel E. Afilalo, Jonathan TI Therapeutic Interventions for Frail Elderly Patients: Part II. Ongoing and Unpublished Randomized Trials SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Frailty; Sarcopenia; Randomized clinical trials ID MUSCLE STRENGTH; OLDER-ADULTS; SARCOPENIA; MEN; SUPPLEMENTATION; METAANALYSIS; EXERCISE; HEALTH; PEOPLE AB There is increasing momentum to measure frailty in clinical practice given its proven value as a predictor of outcomes, particularly in elderly patients with cardiovascular disease. The number of randomized clinical trials targeting frail older adults has been modest to date. Therefore, we systematically searched the ClinicalTrials.gov registry in order to review the frailty intervention trials that had been actively initiated or completed but not yet published. The interventions studied were exercise training in 2 trials, nutritional supplementation in 3 trials, combined exercise plus nutritional supplementation in 5 trials, pharmaceutical agents in 5 trials, multidimensional programs in 2 trials, and home-based services in 3 trials. Their respective study designs, populations, interventions, and planned outcomes are presented in this article. (c) 2014 Elsevier Inc. All rights reserved. C1 [Bendayan, Melissa] McGill Univ, Dept Physiol, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Mullie, Louie; Afilalo, Jonathan] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Afilalo, Jonathan] McGill Univ, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Geratr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada. RP Afilalo, J (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, 3755 Cote Ste Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada. EM jonathan.afilalo@mcgill.ca NR 16 TC 13 Z9 13 U1 1 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2014 VL 57 IS 2 BP 144 EP 151 DI 10.1016/j.pcad.2014.07.005 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP1AN UT WOS:000341798900004 PM 25216613 ER PT J AU Menezes, AR Lavie, CJ Forman, DE Arena, R Milani, RV Franklin, BA AF Menezes, Arthur R. Lavie, Carl J. Forman, Daniel E. Arena, Ross Milani, Richard V. Franklin, Barry A. TI Cardiac Rehabilitation in the Elderly SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Coronary heart disease; Cardiac rehabilitation; Exercise therapy; Cardiorespiratory fitness; Elderly ID CORONARY-HEART-DISEASE; RANDOMIZED-CONTROLLED-TRIAL; PSYCHOLOGICAL RISK-FACTORS; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; SECONDARY PREVENTION; PHYSICAL-ACTIVITY; OLDER-ADULTS; EXERCISE AB Coronary heart disease (CHD) is the leading cause of death worldwide. Advanced age is associated with a higher prevalence of CHD as well as increased morbidity and mortality. One key vulnerability relates to the fact that older individuals are generally among the least fit, least active cohort and at increased risk of complications after an acute cardiac event and/or major surgery. There is ample evidence to demonstrate the beneficial effects of exercised-based cardiac rehabilitation (CR) programs on improving functional capacity and other indices of cardiovascular (CV) health. Although the predominant number of studies is in middle-aged patients, there is an escalating amount of new information that establishes the cardioprotective role of CR and, in particular, structured exercise therapy (ET) among the elderly. The present review summarizes the current data available regarding CR and ET and its salutary impact on today's growing population of older adults with CHD. (c) 2014 Elsevier Inc. All rights reserved. C1 [Menezes, Arthur R.; Lavie, Carl J.; Milani, Richard V.] Univ Queensland, Sch Med, Ochsner Clin Sch, Dept Cardiovasc Dis,John Ochsner Heart & Vasc Ins, New Orleans, LA 70121 USA. [Lavie, Carl J.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Dept Prevent Cardiol, Baton Rouge, LA USA. [Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Forman, Daniel E.] VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Arena, Ross] Univ Illinois, Coll Appl Hlth Sci, Dept Phys Therapy, Chicago, IL USA. [Arena, Ross] Univ Illinois, Coll Appl Hlth Sci, Integrat Physiol Lab, Chicago, IL USA. [Franklin, Barry A.] William Beaumont Hosp, Dept Prevent Cardiol & Rehabil, Royal Oak, MI 48072 USA. RP Lavie, CJ (reprint author), Univ Queensland, Sch Med, Ochsner Clin Sch, Exercise Labs,John Ochsner Heart & Vasc Inst, 1514 Jefferson Highway, New Orleans, LA 70121 USA. EM clavie@ochsner.org RI Arena, Ross/A-3141-2008; Lavie, Carl/A-6014-2011; Milani, Richard/A-6045-2011 OI Arena, Ross/0000-0002-6675-1996; NR 64 TC 16 Z9 16 U1 2 U2 20 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2014 VL 57 IS 2 BP 152 EP 159 DI 10.1016/j.pcad.2014.01.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP1AN UT WOS:000341798900005 PM 25216614 ER PT J AU Lahoti, S Gokhale, S Caplan, L Michel, P Samson, Y Rosso, C Limaye, K Hinduja, A Singhal, A Ali, S Pettigrew, LC Kryscio, R Dedhia, N Hastak, S Liebeskind, DS AF Lahoti, Sourabh Gokhale, Sankalp Caplan, Louis Michel, Patrik Samson, Yves Rosso, Charlotte Limaye, Kaustubh Hinduja, Archana Singhal, Aneesh Ali, Syed Pettigrew, Luther Creed Kryscio, Richard Dedhia, Nikita Hastak, Shirish Liebeskind, David S. TI Thrombolysis in Ischemic Stroke Without Arterial Occlusion at Presentation SO STROKE LA English DT Article DE magnetic resonance imaging; stroke, lacunar; thrombolytic therapy; tissue-type plasminogen activator ID TISSUE-PLASMINOGEN ACTIVATOR; LACUNAR STROKE; TRIAL; CLASSIFICATION; ANGIOGRAPHY; ALTEPLASE; SUBTYPES AB Background and Purpose-None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative. Methods-We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6). Results-A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in nonlacunar group with odds ratio 8.25 (P<0.01). Conclusions-This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis. C1 [Lahoti, Sourabh; Pettigrew, Luther Creed] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Kryscio, Richard] Univ Kentucky, Dept Biostat, Lexington, KY 40536 USA. [Gokhale, Sankalp] Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA. [Caplan, Louis] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Michel, Patrik] CHU Vaudois, Dept Neurol, CH-1011 Lausanne, Switzerland. [Samson, Yves; Rosso, Charlotte] Univ Paris 06, Pitie Salpetriere Hosp, APHP, Dept Neurol, Paris, France. [Limaye, Kaustubh; Hinduja, Archana] Univ Arkansas, Dept Neurol, Little Rock, AR 72204 USA. [Singhal, Aneesh; Ali, Syed] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dedhia, Nikita; Hastak, Shirish] Kokilaben Dhirubhai Ambani Hosp, Ctr Brain & Nervous Syst, Bombay, Maharashtra, India. [Liebeskind, David S.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Lahoti, S (reprint author), Univ Kentucky, 740 S Limestone Rd,L445, Lexington, KY 40536 USA. EM dr.s.lahoti@gmail.com RI Michel, Patrik/Q-2275-2016; samson, yves/C-5647-2013; OI Michel, Patrik/0000-0003-4954-7579; samson, yves/0000-0002-8080-1427; Limaye, Kaustubh/0000-0002-7280-7407 FU National Center for Research Resources [UL1RR033173]; National Center for Advancing Translational Sciences [UL1TR000117] FX This project was supported by grants awarded to the University of Kentucky by the National Center for Research Resources (UL1RR033173) and the National Center for Advancing Translational Sciences (UL1TR000117). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 23 TC 11 Z9 11 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2014 VL 45 IS 9 BP 2722 EP 2727 DI 10.1161/STROKEAHA.114.005757 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AO6VX UT WOS:000341491500047 PM 25074517 ER PT J AU Cronin, CA Sheth, KN Zhao, X Messe, SR Olson, DM Hernandez, AF Bhatt, DL Schwamm, LH Smith, EE AF Cronin, Carolyn A. Sheth, Kevin N. Zhao, Xin Messe, Steven R. Olson, DaiWai M. Hernandez, Adrian F. Bhatt, Deepak L. Schwamm, Lee H. Smith, Eric E. TI Adherence to Third European Cooperative Acute Stroke Study 3- to 4.5-Hour Exclusions and Association With Outcome Data From Get With The Guidelines-Stroke SO STROKE LA English DT Article DE stroke; thrombolytic therapy ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; THROMBOLYSIS; ALTEPLASE; ATTACK; TRIAL; OLDER; TIME AB Background and Purpose-The American Heart Association/American Stroke Association guidelines recommend intravenous tissue-type plasminogen activator (tPA) treatment 3 to 4.5 hours from symptom onset according to criteria used in the Third European Cooperative Acute Stroke Study (ECASS III). However, ECASS III excluded certain patient groups in addition to the standard exclusions used for 0 to 3 hours in the United States: age > 80 years, history of stroke and diabetes mellitus, oral anticoagulant treatment, and National Institutes of Health Stroke Scale > 25. We investigated adherence to these additional exclusion criteria for patients treated 3 to 4.5 hours from onset and their association with outcome. Methods-We analyzed data from Get With The Guidelines-Stroke on 32 019 patients with ischemic stroke from 1464 hospitals who were treated with tPA <= 4.5 hours from onset from January 2009 to January 2012, excluding patients transferred from another hospital. The percent of patients meeting versus not meeting each exclusion criterion were compared between treatment time windows. Results-Overall, 1544 of 4910 (31.5%) patients treated with tPA > 3 to 4.5 hours had at least 1 of the additional exclusions, the most common was age > 80 years. With the exception of prior stroke and diabetes mellitus, the percent of tPA-treated patients with each exclusion criterion was significantly lower at > 3 to 4.5 hours compared with 0 to 3 hours. For each additional exclusion criterion, there was no increased risk of symptomatic intracranial hemorrhage or worse hospital outcome for patients treated > 3 to 4.5 hours compared with 0 to 3 hours, after adjusting for baseline differences. Conclusions-Patients with ECASS III-specific exclusion criteria for the > 3 to 4.5 hours window are frequently treated with tPA. The presence of the additional exclusion criteria was not associated with worse outcomes in the > 3 to 4.5 hours window compared with the 0 to 3 hours window. C1 [Cronin, Carolyn A.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Zhao, Xin; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Messe, Steven R.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Olson, DaiWai M.] Univ Texas Southwestern, Dept Neurol, Dallas, TX USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Bhatt, Deepak L.; Schwamm, Lee H.] Harvard Univ, Sch Med, Boston, MA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. RP Cronin, CA (reprint author), Univ Maryland, Sch Med, Div Neurol, 110 S Paca St,Third Floor, Baltimore, MD 21201 USA. EM ccronin@som.umaryland.edu RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU American Heart Association (AHA)/American Stroke Association (ASA); Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; Janseen Pharmaceutical Companies of Johnson and Johnson; AHA Pharmaceutical Roundtable FX This project was supported by a Young Investigator Database Research Seed Grant from the American Heart Association (AHA)/American Stroke Association (ASA). The Get With The Guidelines (GWTG)-Stroke program is provided by the AHA/ASA. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, Janseen Pharmaceutical Companies of Johnson and Johnson, and the AHA Pharmaceutical Roundtable. NR 19 TC 13 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2014 VL 45 IS 9 BP 2745 EP + DI 10.1161/STROKEAHA.114.005443 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AO6VX UT WOS:000341491500051 PM 25104846 ER PT J AU Shoamanesh, A Masoud, H Furey, K Duerfeldt, K Lau, H Romero, JR Pikula, A Teal, P Nguyen, TN Kase, CS Babikian, VL AF Shoamanesh, Ashkan Masoud, Hesham Furey, Katrina Duerfeldt, Kaylyn Lau, Helena Romero, Jose R. Pikula, Aleksandra Teal, Philip Nguyen, Thanh N. Kase, Carlos S. Babikian, Viken L. TI Larger A1/M1 Diameter Ratio Predicts Embolic Anterior Cerebral Artery Territorial Stroke SO STROKE LA English DT Article DE cerebral infarction; cerebrovascular circulation; embolism; hemodynamics ID INFARCTION; PATTERNS; REGISTRY; MODEL AB Background and Purpose-In contrast to middle cerebral artery territory strokes, anterior cerebral artery strokes (ACAS) occur rarely. The low frequency of ACAS, in relation to middle cerebral artery territory strokes, may be explained by differences in ACA and middle cerebral artery anatomy influencing their respective flow-directed embolism rates. We aimed to determine whether variability in ACA anatomy, and in particular A1 segment diameter, is associated with embolic ACAS. Methods-Consecutive patients admitted to Boston Medical Center with embolic ACAS were reviewed. Ipsilateral and contralateral A1 diameters, M1 diameters, and terminal internal carotid artery bifurcation angles were measured from computed tomographic angiography and MRI angiography images. We compared these measurements between cases of ACAS and consecutive cases of embolic middle cerebral artery territory strokes. Results-The study comprised 55 individuals (27 ACAS, 28 middle cerebral artery territory strokes) with mean age of 69 years. In multivariate regression analysis, larger ipsilateral A1 diameters (odds ratio per 1 mm increment: 8.5; 95% confidence interval, 1.4-53.3) and ipsilateral A1/M1 diameter ratio (odds ratio per 10% increment: 1.8; 95% confidence interval, 1.2-2.9) were associated with ACAS, whereas larger ipsilateral M1 diameters was protective for ACAS (odds ratio per 1 mm increment: 0.8; 95% confidence interval, 0.0-0.9). Conclusions-Larger ipsilateral A1 diameters and A1/M1 diameter ratio are associated with embolic ACAS. These findings suggest that A1 diameters and M1 diameters are important in determining the path of emboli that reach the terminal internal carotid artery. C1 [Shoamanesh, Ashkan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Masoud, Hesham; Furey, Katrina; Duerfeldt, Kaylyn; Lau, Helena; Romero, Jose R.; Pikula, Aleksandra; Nguyen, Thanh N.; Kase, Carlos S.; Babikian, Viken L.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02215 USA. [Teal, Philip] Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. RP Shoamanesh, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, JP Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM ashkan.sho@gmail.com NR 10 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2014 VL 45 IS 9 BP 2798 EP 2800 DI 10.1161/STROKEAHA.114.005672 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AO6VX UT WOS:000341491500061 PM 25082805 ER PT J AU Bambakidis, NC Cockroft, KM Hirsch, JA Connolly, ES Amin-Hanjani, S Meyers, PM Friedlander, RM AF Bambakidis, Nicholas C. Cockroft, Kevin M. Hirsch, Joshua A. Connolly, E. Sander Amin-Hanjani, Sepideh Meyers, Philip M. Friedlander, Robert M. TI The Case Against A Randomized Trial of Unruptured Brain Arteriovenous Malformations Misinterpretation of a Flawed Study SO STROKE LA English DT Article DE arteriovenous malformation; vascular malformation ID STENOSIS; ENDARTERECTOMY; THERAPY C1 [Bambakidis, Nicholas C.] Univ Hosp Case Med Ctr, Dept Neurol Surg, Cleveland, OH 44106 USA. [Cockroft, Kevin M.] Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Connolly, E. Sander; Meyers, Philip M.] Columbia Univ, Med Ctr, Dept Neurosurg, New York, NY USA. [Amin-Hanjani, Sepideh] Univ Illinois, Dept Neurosurg, Chicago, IL USA. [Friedlander, Robert M.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. RP Bambakidis, NC (reprint author), Univ Hosp Case Med Ctr, Dept Neurol Surg, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM nicholas.bambakidis2@uhhospitals.org RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 10 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2014 VL 45 IS 9 BP 2808 EP 2810 DI 10.1161/STROKEAHA.114.006519 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AO6VX UT WOS:000341491500064 PM 25082809 ER PT J AU Gartrell, BA Ying, J Sivendran, S Boucher, KM Choueiri, TK Sonpavde, G Oh, WK Agarwal, N Galsky, MD AF Gartrell, Benjamin A. Ying, Jian Sivendran, Shanthi Boucher, Kenneth M. Choueiri, Toni K. Sonpavde, Guru Oh, William K. Agarwal, Neeraj Galsky, Matthew D. TI Pulmonary complications with the use of mTOR inhibitors in targeted cancer therapy: a systematic review and meta-analysis SO TARGETED ONCOLOGY LA English DT Article DE Systematic review; Meta-analysis; mTOR inhibitor; Adverse event; Solid tumor; Pneumonitis ID RENAL-CELL CARCINOMA; PHASE-II TRIAL; MAMMALIAN TARGET; CLINICAL-TRIALS; TEMSIROLIMUS CCI-779; RAPAMYCIN INHIBITOR; EVEROLIMUS RAD001; ONCOLOGY-GROUP; BREAST-CANCER; LUNG-CANCER AB Mammalian target of rapamycin (mTOR) inhibitors have gained regulatory approval for use in several cancer types. Pulmonary adverse events associated with mTOR inhibitors are well recognized but their frequency has varied considerably among trials. PubMed and ASCO abstracts were searched to identify clinical trials of mTOR inhibitors in solid tumors. Twenty-two eligible trials on which 4,242 patients were treated met the criteria for inclusion in this systematic review and meta-analysis. Adverse event data were extracted and used to determine the incidence rate and incidence rate ratio for pneumonitis, dyspnea, and cough. The incidence rate of any grade pneumonitis in patients with solid tumors treated with mTOR inhibitors was 0.11 (95 % confidence interval (CI), 0.06-0.17) per patient, while the incidence of grade 3-4 pneumonitis was 0.03 (95 % CI, 0.01-0.04) per patient. The incidence rate ratio (IRR) of any grade pneumonitis with mTOR inhibitors relative to controls was 19.0 (95 % CI, 6.5-55.4), and for grade 3-4 pneumonitis was 8.0 (95 % CI, 2.6-24.1). The incidence rate for any grade and grade 3-4 cough was 0.23 (95 % CI, 0.20-0.27) per patient and 0.01 (95 % CI, 0.00-0.01) per patient, respectively. The incidence rate for any grade and grade 3-4 dyspnea was 0.15 (95 % CI, 0.10-0.21) per patient and 0.03 (95 % CI, 0.02-0.04) per patient, respectively. Compared to control, treatment with mTOR inhibitors were associated with a significant increase in any grade cough [IRR = 1.9 (95 % CI, 1.6-2.4)] and grade 3-4 dyspnea [IRR = 2.0 (95 % CI, 1.2-3.3)]. This study provides an estimation of the risk of pulmonary adverse events in solid tumor patients treated with mTOR inhibitors. While pulmonary adverse events are relatively common with mTOR inhibitors, most are low grade and asymptomatic. C1 [Gartrell, Benjamin A.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med Oncol, Bronx, NY 10467 USA. [Ying, Jian; Boucher, Kenneth M.] Univ Utah, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT USA. [Sivendran, Shanthi] Lancaster Gen Hlth, Hematol Oncol Med Specialists, Lancaster, PA USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sonpavde, Guru] Univ Alabama Birmingham Comprehens Canc Ctr, Birmingham, AL USA. [Oh, William K.; Galsky, Matthew D.] Mt Sinai Sch Med, Div Hematol Oncol, Tisch Canc Inst, New York, NY USA. [Agarwal, Neeraj] Univ Utah, Dept Internal Med, Div Med Oncol, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Gartrell, BA (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med Oncol, Bronx, NY 10467 USA. EM bgartrel@montefiore.org OI Boucher, Kenneth/0000-0003-2833-0127 FU NCI NIH HHS [R21 CA176551] NR 35 TC 4 Z9 4 U1 2 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 EI 1776-260X J9 TARGET ONCOL JI Target. Oncol. PD SEP PY 2014 VL 9 IS 3 BP 195 EP 204 DI 10.1007/s11523-013-0289-2 PG 10 WC Oncology SC Oncology GA AP1LU UT WOS:000341832300002 PM 23852656 ER PT J AU Lee, GQ Bangsberg, DR Muzoora, C Boum, Y Oyugi, JH Emenyonu, N Bennett, J Hunt, PW Knapp, D Brumme, CJ Harrigan, PR Martin, JN AF Lee, Guinevere Q. Bangsberg, David R. Muzoora, Conrad Boum, Yap Oyugi, Jessica H. Emenyonu, Nneka Bennett, John Hunt, Peter W. Knapp, David Brumme, Chanson J. Harrigan, P. Richard Martin, Jeffrey N. TI Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE; DISEASE PROGRESSION; INHIBITOR THERAPY; 2009 UPDATE; INFECTION; MUTATIONS; SUBTYPE; TRANSMISSION AB Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n = 81 and n = 491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcomes (UARTO) pilot study in Kampala (AMU 2002-2004) and main cohort in Mbarara (MBA 2005-2010). TDR-associated mutations were defined by the WHO 2009 surveillance mutation list. Posttreatment viral load data were available for both populations. Overall TDR prevalence was 7% (Kampala) and 3% (Mbarara) with no significant time trend. There was a slight but statistically nonsignificant trend indicating that the presence of TDR was associated with a worse treatment outcome. Virologic suppression (<= 400 copies/ml within 6 months posttherapy initiation) was achieved in 87% and 96% of participants with wildtype viruses versus 67% and 83% of participants with TDR (AMU, MBA p = 0.2 and 0.1); time to suppression (log-rank p = 0.3 and p = 0.05). Overall, 85% and 96% of study participants achieved suppression regardless of TDR status. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. The majority of patients benefited from the local HIV care system even without resistance monitoring. Overall, TDR prevalence was relatively low and its presence did not always imply treatment failure. C1 [Lee, Guinevere Q.; Knapp, David; Brumme, Chanson J.; Harrigan, P. Richard] BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada. [Bangsberg, David R.; Muzoora, Conrad; Boum, Yap; Emenyonu, Nneka] Mbarara Univ Sci Technol, Mbarara, Uganda. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Oyugi, Jessica H.; Bennett, John; Hunt, Peter W.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Harrigan, PR (reprint author), BC Ctr Excellence HIV AIDS, 603-1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. EM prharrigan@cfenet.ubc.ca RI Lee, Guinevere/D-4436-2017; OI Lee, Guinevere/0000-0002-9412-886X; Knapp, David/0000-0002-2161-9959; Brumme, Chanson/0000-0003-2722-5288 FU Canadian Institutes of Health Research (CIHR); National Institutes of Health (NIH) Centers for AIDS Research (CFAR) Program; National Institute of Mental Health [RO-1 54907, P30 AI27763, U01 CA066529]; National Institute on Alcohol Abuse and Alcoholism [R-21 014784] FX This work was funded by the Canadian Institutes of Health Research (CIHR), National Institutes of Health (NIH) Centers for AIDS Research (CFAR) Program, National Institute of Mental Health RO-1 54907, P30 AI27763, and U01 CA066529, and National Institute on Alcohol Abuse and Alcoholism R-21 014784. NR 55 TC 8 Z9 8 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2014 VL 30 IS 9 BP 896 EP 906 DI 10.1089/aid.2014.0043 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AO7IO UT WOS:000341526800012 PM 24960249 ER PT J AU Hess, PL Mirro, MJ Diener, HC Eikelboom, JW Al-Khatib, SM Hylek, EM Bosworth, HB Gersh, BJ Singer, DE Flaker, G Mega, JL Peterson, ED Rumsfeld, JS Steinberg, BA Kakkar, AK Califf, RM Granger, CB AF Hess, Paul L. Mirro, Michael J. Diener, Hans-Christoph Eikelboom, John W. Al-Khatib, Sana M. Hylek, Elaine M. Bosworth, Hayden B. Gersh, Bernard J. Singer, Daniel E. Flaker, Greg Mega, Jessica L. Peterson, Eric D. Rumsfeld, John S. Steinberg, Benjamin A. Kakkar, Ajay K. Califf, Robert M. Granger, Christopher B. CA Atrial Fibrillation Think-Tank Par TI Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012 SO AMERICAN HEART JOURNAL LA English DT Article ID INTERNATIONAL NORMALIZED RATIO; AMERICAN-HEART-ASSOCIATION; VITAMIN-K ANTAGONISTS; RANDOMIZED EVALUATION; ANTIPLATELET THERAPY; RISK STRATIFICATION; STROKE PREVENTION; SYSTEMIC EMBOLISM; PREDICTING STROKE; ACTIVE-W AB Approximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives. C1 [Hess, Paul L.; Al-Khatib, Sana M.; Bosworth, Hayden B.; Peterson, Eric D.; Steinberg, Benjamin A.; Califf, Robert M.; Granger, Christopher B.] Duke Clin Res Inst, Durham, NC 27705 USA. [Mirro, Michael J.] Parkview Hlth Syst, Ft Wayne, IN USA. [Diener, Hans-Christoph] Univ Hosp Essen, Essen, Germany. [Eikelboom, John W.] Populat Hlth Res Inst, Hamilton, ON, Canada. [Hylek, Elaine M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bosworth, Hayden B.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Gersh, Bernard J.] Mayo Clin, Coll Med, Rochester, MN USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Flaker, Greg] Univ Missouri, Columbia, MO USA. [Mega, Jessica L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Kakkar, Ajay K.] Thrombosis Res Inst, London, England. [Kakkar, Ajay K.] UCL, London, England. RP Hess, PL (reprint author), Duke Clin Res Inst, Durham, NC 27705 USA. EM p.hess@duke.edu RI Kaynar, Leylagul/F-6991-2013 OI Kaynar, Leylagul/0000-0002-2035-9462 FU AHRQ HHS [U19 HS021092]; NHLBI NIH HHS [T32 HL069749] NR 66 TC 10 Z9 10 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD SEP PY 2014 VL 168 IS 3 BP 239 EP U27 DI 10.1016/j.ahj.2014.04.007 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4QY UT WOS:000341327200002 PM 25173533 ER PT J AU Byrd, JB Maddox, TM O'Donnell, CI Grunwald, GK Bhatt, DL Tsai, TT Rumsfeld, JS Ho, PM AF Byrd, James B. Maddox, Thomas M. O'Donnell, Colin I. Grunwald, Gary K. Bhatt, Deepak L. Tsai, Thomas T. Rumsfeld, John S. Ho, P. Michael TI Clopidogrel prescription filling delays and cardiovascular outcomes in a pharmacy system integrating inpatient and outpatient care: Insights from the Veterans Affairs CART Program SO AMERICAN HEART JOURNAL LA English DT Article ID STENT AB Background Delays in filling clopidogrel prescriptions after percutaneous coronary intervention (PCI) have been demonstrated previously and associated with adverse outcomes. Methods This was a retrospective cohort study of 11,418 patients undergoing PCI with stent placement in Veterans Affairs (VA) hospitals between January 1, 2005, and September 30, 2010. Data were obtained from the national VA Clinical Assessment, Reporting, and Tracking Program, including post-PCI clopidogrel prescription fill date and outcomes of myocardial infarction and death within 90 days of discharge. Patients who did not fill a clopidogrel prescription on the day of discharge were considered to have a delay. Multivariable models assessed the association between clopidogrel delay and myocardial infarction/death using clopidogrel delay as a time-varying covariate. Results Of the patients, 7.2% had a delay in filling their clopidogrel prescription. Delay in filling clopidogrel was associated with increased risk of major adverse events (hazard ratio 2.34, 95% CI 1.66-3.29, P < .001). The percentage of patients who delayed filling varied by hospital, ranging from 0 to 43.5% with a median of 6.2% (P < .001, X-2 for difference across hospitals) and a median odds ratio of 2.13 (95% CI 1.85-2.68) suggesting large site variation in clopidogrel delay across hospitals. Conclusions In a health care system with integrated inpatient and outpatient pharmacy services, 1 in 14 patients delays filling a clopidogrel prescription. The large site variation suggests a need to identify best practices that allow hospitals to optimize prescription filling at discharge to potentially improve patient outcomes. C1 [Byrd, James B.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Maddox, Thomas M.; O'Donnell, Colin I.; Grunwald, Gary K.; Tsai, Thomas T.; Rumsfeld, John S.; Ho, P. Michael] VA Eastern Colorado Hlth Care Syst, Cardiol Sect, Denver, CO USA. [Maddox, Thomas M.; Tsai, Thomas T.; Rumsfeld, John S.; Ho, P. Michael] Univ Colorado, Dept Med, Denver, CO USA. [Maddox, Thomas M.; Tsai, Thomas T.; Rumsfeld, John S.; Ho, P. Michael] Colorado Cardiovasc Outcomes Res Grp, Denver, CO USA. [Grunwald, Gary K.] Univ Colorado Denver, Dept Biostat & Informat, Aurora, CO USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Cardiol Sect, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Ho, PM (reprint author), 1055 Clermont St,Cardiol 111B, Denver, CO 80220 USA. EM michael.ho@va.gov OI Byrd, J. Brian/0000-0002-0509-3520 FU Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company FX Dr Byrd, investigator: Medtronic clinical trial. Dr Bhatt, advisory board: Medscape Cardiology; board of directors: Boston VA Research Institute and Society of Chest Pain Centers; chair: AHA Get With The Guidelines Science Subcommittee; honoraria: ACC (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), and WebMD (CME steering committees); other: Senior Associate Editor, Journal of Invasive Cardiology; research grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; and unfunded research: FlowCo, PLx Pharma, and Takeda. NR 13 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD SEP PY 2014 VL 168 IS 3 BP 340 EP 345 DI 10.1016/j.ahj.2014.05.012 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4QY UT WOS:000341327200015 PM 25173546 ER PT J AU Bradley, SM Stanislawski, MA Bekelman, DB Monteith, LL Cohen, BE Schilling, JH Hunt, SC Milek, D Maddox, TM Ho, PM Shore, S Varosy, PD Matthieu, MM Rumsfeld, JS AF Bradley, Steven M. Stanislawski, Maggie A. Bekelman, David B. Monteith, Lindsey L. Cohen, Beth E. Schilling, John H. Hunt, Stephen C. Milek, Debra Maddox, Thomas M. Ho, P. Michael Shore, Supriya Varosy, Paul D. Matthieu, Monica M. Rumsfeld, John S. TI Invasive coronary procedure use and outcomes among veterans with posttraumatic stress disorder: Insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program SO AMERICAN HEART JOURNAL LA English DT Article ID GENERALIZED ANXIETY DISORDER; MAJOR DEPRESSIVE DISORDER; HEART-DISEASE; CART PROGRAM; MYOCARDIAL-INFARCTION; PSYCHIATRIC-DISORDERS; CARDIOVASCULAR EVENTS; HEALTH BEHAVIORS; ARTERY-DISEASE; RISK-FACTOR AB Background Posttraumatic stress disorder (PTSD) is prevalent in the general population and US veterans in particular and is associated with an increased risk of developing coronary artery disease (CAD). We compared the patient characteristics and postprocedural outcomes of veterans with and without PTSD undergoing coronary angiography. Methods This is a multicenter observational study of patients who underwent coronary angiography in Veterans Affairs hospitals nationally from October 2007 to September 2011. We described patient characteristics at angiography, angiographic results, and after coronary angiography, we compared risk-adjusted 1-year rates of all-cause mortality, myocardial infarction (MI), and revascularization by the presence or absence of PTSD. Results Overall, of 116,488 patients undergoing angiography, 14,918 (12.8%) had PTSD. Compared with those without PTSD, patients with PTSD were younger (median age 61.9 vs 63.7; P < .001), had higher rates of cardiovascular risk factors, and were more likely to have had a prior MI (26.4% vs 24.7%; P < .001). Patients with PTSD were more likely to present for stable angina (22.4% vs 17.0%) or atypical chest pain (58.5% vs 48.6%) and less likely to have obstructive CAD identified at angiography (55.9% vs 62.2%; P < .001). After coronary angiography, PTSD was associated with lower unadjusted 1-year rates of MI (hazard ratio (HR), 0.86; 95% CI [0.75-1.00]; P = 0.04), revascularization (HR, 0.88; 95% CI [0.83-0.93]; P < .001), and all-cause mortality (HR, 0.66; 95% CI [0.60-0.71]; P < .001). After adjustment for cardiovascular risk, PTSD was no longer associated with 1-year rates of MI or revascularization but remained associated with lower 1-year all-cause mortality (HR, 0.91; 95% CI [0.84-0.99]; P = .03). Findings were similar after further adjustment for depression, anxiety, alcohol or substance use disorders, and frequency of outpatient follow-up. Conclusions Among veterans undergoing coronary angiography in the Veterans Affairs, those with PTSD were more likely to present with elective indications and less likely to have obstructive CAD. After coronary angiography, PTSD was not associated with adverse 1-year outcomes of MI, revascularization, or all-cause mortality. C1 [Bradley, Steven M.; Stanislawski, Maggie A.; Bekelman, David B.; Monteith, Lindsey L.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Denver, CO 80220 USA. [Bradley, Steven M.; Bekelman, David B.; Schilling, John H.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] Univ Colorado, Sch Med, Aurora, CO USA. [Bradley, Steven M.; Stanislawski, Maggie A.; Bekelman, David B.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] Colorado Cardiovasc Outcomes Res Consortium, Denver, CO USA. [Cohen, Beth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hunt, Stephen C.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Hunt, Stephen C.; Milek, Debra] Univ Washington, Seattle, WA 98195 USA. [Matthieu, Monica M.] St Louis VA Med Ctr, St Louis, MO USA. [Matthieu, Monica M.] St Louis Univ, St Louis, MO 63103 USA. RP Bradley, SM (reprint author), VA Eastern Colorado Hlth Care Syst, Dept Vet Affairs, 1055 Clermont St,111B, Denver, CO 80220 USA. EM Steven.Bradley@va.gov FU VA Health Services Research Development [HSRD-CDA2 10-199] FX Dr Bradley is supported by a Career Development Award (HSR&D-CDA2 10-199) from VA Health Services Research & Development. The authors report no relevant relationships with industry or other disclosures. NR 47 TC 1 Z9 1 U1 2 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD SEP PY 2014 VL 168 IS 3 BP 381 EP U200 DI 10.1016/j.ahj.2014.05.015 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4QY UT WOS:000341327200020 PM 25173551 ER PT J AU Abtahian, F Yonetsu, T Kato, K Jia, HB Vergallo, R Tian, JW Hu, SN McNulty, I Lee, H Yu, B Jang, IK AF Abtahian, Farhad Yonetsu, Taishi Kato, Koji Jia, Haibo Vergallo, Rocco Tian, Jinwei Hu, Sining McNulty, Iris Lee, Hang Yu, Bo Jang, Ik-Kyung TI Comparison by Optical Coherence Tomography of the Frequency of Lipid Coronary Plaques in Current Smokers, Former Smokers, and Nonsmokers SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ARTERY-DISEASE; CIGARETTE-SMOKING; MYOCARDIAL-INFARCTION; RISK-FACTORS; ATHEROSCLEROSIS; REVASCULARIZATION; ACQUISITION; PREDICTORS; REGISTRY AB Smoking is associated with high incidence of cardiovascular events including acute coronary syndrome. We sought to characterize coronary plaques in patients with ongoing smoking using optical coherence tomography (OCT) compared with former smokers and nonsmokers. We identified 465 coronary plaques from 182 subjects who underwent OCT imaging for all 3 coronary arteries. Subjects were divided into 3 groups: current smokers (n = 41), former smokers (n = 67), and nonsmokers (n = 74). OCT analysis included the presence of lipid-rich plaque, thin-cap fibroatheroma (TCFA), calcification, maximum lipid arc, lipid core length, lipid index, and fibrous cap thickness. Lipid index was defined by mean lipid arc multiplied by lipid core length. Compared with former smokers and nonsmokers, the incidence of lipid plaques and TCFA was significantly higher in current smokers (lipid plaques: 68.0% vs 45.9% and 52.6%, p = 0.002; TCFA: 18.4% vs 7.6% and 9.9%, p = 0.018). There was a trend for higher plaque disruption in current smokers. Former smokers were more likely to have calcified plaques than current and nonsmokers (52.9% vs 32.0% and 38.0%, p = 0.001). In a multivariate analysis, current smoking, low-density lipoprotein, and presentation with acute coronary syndrome were independently associated with the presence of TCFAs. In conclusion, current smokers are more likely to have lipid plaques and OCT-defined vulnerable plaques (TCFAs). Former smokers have increased number of calcified plaques. These results may explain the increased risk of acute cardiac events among smokers. (C) 2014 Elsevier Inc. All rights reserved. C1 [Abtahian, Farhad; Jia, Haibo; Vergallo, Rocco; Tian, Jinwei; Hu, Sining; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02163 USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Yonetsu, Taishi; Jia, Haibo] Kameda Med Ctr, Dept Cardiol, Chiba, Japan. [Kato, Koji] Nippon Med Sch, Dept Cardiovasc Med, Tokyo 113, Japan. [Tian, Jinwei; Hu, Sining; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Minist Myocardial Ischemia Mechanism & Treatment, Dept Cardiol,Key Labs Educ, Harbin, Peoples R China. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02163 USA. EM ijang@partners.org FU Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad; Mitsukoshi Health and Welfare Foundation; "Enrico ed Enrica Sovena" Foundation, Rome, Italy; National Natural Science Foundation of China [30871064/C140401, 81200076, 81300201]; China Postdoctoral Science Foundation [2013M531074]; Heilongjiang Postdoctoral Science Foundation [LBH-Z12180]; LightLab Imaging/St. Jude Medical; St. Jude Medical; Cardiology Division of Massachusetts General Hospital FX Dr. Kato is supported by the Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad and the Mitsukoshi Health and Welfare Foundation. Dr. Vergallo is supported by the "Enrico ed Enrica Sovena" Foundation, Rome, Italy. Dr. Yu has received grant support from the National Natural Science Foundation of China (30871064/C140401). Dr. Jia is supported by the National Natural Science Foundation of China (81200076). Dr. Tian received grant support from the National Natural Science Foundation of China (81300201), from China Postdoctoral Science Foundation (2013M531074), and from Heilongjiang Postdoctoral Science Foundation (LBH-Z12180). Dr. Jang received a research grant and consulting fee from LightLab Imaging/St. Jude Medical. This study was supported by research grants from St. Jude Medical and the Cardiology Division of Massachusetts General Hospital. NR 26 TC 5 Z9 6 U1 0 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2014 VL 114 IS 5 BP 674 EP 680 DI 10.1016/j.amjcard.2014.05.056 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4TF UT WOS:000341333600003 PM 25048344 ER PT J AU Vaduganathan, M Dei Cas, A Mentz, RJ Greene, SJ Khan, S Subacius, HP Chioncel, O Maggioni, AP Konstam, MA Senni, M Fonarow, GC Butler, J Gheorghiade, M AF Vaduganathan, Muthiah Dei Cas, Alessandra Mentz, Robert J. Greene, Stephen J. Khan, Sadiya Subacius, Haris P. Chioncel, Ovidiu Maggioni, Aldo P. Konstam, Marvin A. Senni, Michele Fonarow, Gregg C. Butler, Javed Gheorghiade, Mihai CA EVEREST Trial Investigators TI Mineralocorticoid Receptor Antagonist Use in Hospitalized Patients With Heart Failure, Reduced Ejection Fraction, and Diabetes Mellitus (from the EVEREST Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; POSTDISCHARGE OUTCOMES; CLINICAL-OUTCOMES; DOUBLE-BLIND; ALDOSTERONE; EPLERENONE; MORTALITY; SPIRONOLACTONE; HYPERKALEMIA; TOLVAPTAN AB Despite the well-established benefits of mineralocorticoid receptor agonists (MRAs) in heart failure with reduced ejection fraction, safety concerns remain in patients with concomitant diabetes mellitus (DM) because of common renal and electrolyte abnormalities in this population. We analyzed all-cause mortality and composite cardiovascular mortality and HF hospitalization over a median 9.9 months among 1,998 patients in the placebo arm of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial by DM status and discharge MRA use. Of the 750 patients with DM, 59.2% were receiving MRAs compared with 62.5% in the non-DM patients. DM patients not receiving MRAs were older, more likely to be men, with an ischemic heart failure etiology and slightly worse renal function compared with those receiving MRAs. After adjustment for baseline risk factors, among DM patients, MRA use was not associated with either mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.75 to 1.15) or the composite end point (HR 0.94; 95% CI 0.80 to 1.10). Similar findings were seen in non-DM patients (mortality [RR 1.01; 95% CI 0.84 to 1.22] or the composite end point [RR 0.98; 95% CI 0.85 to 1.13] [p > 0.43 for DM interaction]). In conclusion, in-hospital initiation of MRA therapy was low (15% to 20%), and overall discharge MRA use was only 60% (with regional variation), regardless of DM status. There does not appear to be clear, clinically significant in-hospital hemodynamic or even renal differences between those on and off MRA. Discharge MRA use was not associated with postdischarge end points in patients hospitalized for worsening heart failure with reduced ejection fraction and co-morbid DM. DM does not appear to influence the effectiveness of MRA therapy. (C) 2014 Elsevier Inc. All rights reserved. C1 [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Dei Cas, Alessandra] Univ Parma, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy. [Mentz, Robert J.] Duke Univ, Med Ctr, Dept Cardiol, Durham, NC USA. [Greene, Stephen J.; Khan, Sadiya; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Subacius, Haris P.] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. [Chioncel, Ovidiu] Inst Emergency Cardiovasc Dis Prof CC Iliescu, Bucharest, Romania. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Konstam, Marvin A.] Tufts Med Ctr, Dept Med, Boston, MA USA. [Senni, Michele] Azienda Osped Papa Giovannni XXIII, Dipartimento Cardiovasc, Bergamo, Italy. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI chioncel, ovidiu/0000-0002-3197-3628; Dei Cas, Alessandra/0000-0002-8666-4849; Vaduganathan, Muthiah/0000-0003-0885-1953; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka Inc. (Rockville, MD) FX Otsuka Inc. (Rockville, MD) provided financial and material support for the EVEREST trial. Database management was performed by the sponsor. NR 30 TC 4 Z9 4 U1 0 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 SEP 1 PY 2014 VL 114 IS 5 BP 743 EP 750 DI 10.1016/j.amjcard.2014.05.064 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4TF UT WOS:000341333600014 PM 25060414 ER PT J AU Hoang, MP Reuter, J Papalas, JA Edwards, L Selim, MA AF Hoang, Mai P. Reuter, Jason Papalas, John A. Edwards, Libby Selim, Maria A. TI Vulvar Inflammatory Dermatoses: An Update and Review SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Review DE vulva; inflammatory dermatoses; ISSVD ID HAILEY-HAILEY-DISEASE; SQUAMOUS-CELL CARCINOMA; EROSIVE LICHEN-PLANUS; LOCALIZED EPIDERMOLYTIC HYPERKERATOSIS; PAPULAR ACANTHOLYTIC DYSKERATOSIS; NEONATAL BEHCETS-DISEASE; FEMALE GENITAL-TRACT; LINEAR IGA DISEASE; CROHNS-DISEASE; AMICROBIAL PUSTULOSIS AB Currently, urogenital complaints are among the most common problems encountered by family practitioners, gynecologists, and dermatologists. In response to the intricacy of vulvar disorders, the International Society for the Study of Vulvovaginal Disease was created to facilitate the exchange between clinicians and pathologists involved in the care of these patients. Recent classifications for inflammatory disorders and intraepithelial neoplasm have been proposed. In addition, vulvar skin biopsies are the most common source of intradepartmental consultation during dermatopathology sign-out. The purpose of this article is to review the various inflammatory dermatoses of the vulva and to update readers with new advances regarding these entities. C1 [Hoang, Mai P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Hoang, Mai P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reuter, Jason] Piedmont Pathol Associates, Hickory, NC USA. [Papalas, John A.] Eastern Dermatol & Pathol, Pathol Sect, Greenville, NC USA. [Edwards, Libby] Carolinas Med Ctr, Dept Dermatol, Charlotte, NC 28203 USA. [Selim, Maria A.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Selim, MA (reprint author), Duke Univ, Med Ctr, Dept Pathol, DUMC 3712, Durham, NC 27710 USA. EM angelica.selim@duke.edu NR 134 TC 2 Z9 2 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 EI 1533-0311 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD SEP PY 2014 VL 36 IS 9 BP 689 EP + PG 16 WC Dermatology SC Dermatology GA AO5WX UT WOS:000341418400003 PM 25147985 ER PT J AU Koyner, JL Cerda, J Goldstein, SL Jaber, BL Liu, KD Shea, JA Faubel, S AF Koyner, Jay L. Cerda, Jorge Goldstein, Stuart L. Jaber, Bertrand L. Liu, Kathleen D. Shea, Judy A. Faubel, Sarah CA Amer Soc Nephrology TI The Daily Burden of Acute Kidney Injury: A Survey of US Nephrologists on World Kidney Day SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Acute kidney injury (AKI); survey; nephrology; dialysis; dialysis dosing; World Kidney Day; epidemiology; workload; public health ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; REPLACEMENT THERAPY; AKI; DISEASE; OUTCOMES; DIALYSIS; RISK; CKD; HEMODIALYSIS AB Background: World Kidney Day 2013 focused on raising awareness of the impact and consequences of acute kidney injury (AKI). Although many studies have examined rates of AKI in hospitalized patients, we were interested in the impact of AKI on the workload of nephrologists. Study Design: Cross-sectional forced-choice internet-based survey. Setting & Participants: 598 survey respondents who were US-based nephrologist members of the American Society of Nephrology. Outcomes: Numbers of inpatients and outpatients seen on World Kidney Day 2013 for the management of AKI or other conditions (and specifically in-hospital renal replacement therapies [RRTs]), based on self-report of number/percentage of patients seen on World Kidney Day and in the prior year. Results: Of 598 physician respondents (response rate, 12%), 310 saw patients in the hospital on World Kidney Day. Of 3,285 patients seen by respondents, 1,500 were seen for AKI (46%); 1,233, for end-stage renal disease (37%); and 552, for non-AKI/end-stage renal disease-related problems (17%). Of patients with AKI, 688 (46%) were in the intensive care unit and 415 (28%) received RRT. Intermittent hemodialysis was performed in 315 patients (76%) who received RRT. Delivered dialysis dose was quantified in only 48 (15%) of those receiving intermittent hemodialysis. 260 respondents saw 2,380 patients in the ambulatory setting, of whom 207 (9%) were seen for follow-up of AKI. Limitations: There was a low response rate to the survey. Numbers of patients were self-reported. Conclusions: This is the first physician survey examining the care of patients and impact of AKI on current in-hospital and ambulatory nephrology practices. In our sample, AKI was the most common reason for in-hospital nephrology consultation. Furthermore, our findings point to significant areas in which improvement is needed, including inadequate quantification of dialysis delivered dose. Finally, our survey highlights that AKI is a major public health issue. (C) 2014 by the National Kidney Foundation, Inc. C1 [Koyner, Jay L.] Univ Chicago, Nephrol Sect, Chicago, IL 60637 USA. [Cerda, Jorge] Albany Med Coll, Albany, NY 12208 USA. [Goldstein, Stuart L.] Cincinnati Childrens Hosp Med Ctr, Ctr Acute Care Nephrol, Cincinnati, OH 45229 USA. [Jaber, Bertrand L.] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Med,Div Nephrol, Boston, MA 02111 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shea, Judy A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Faubel, Sarah] Univ Colorado, Denver Vet Affairs Med Ctr, Div Nephrol, Aurora, CO 80045 USA. RP Faubel, S (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, Div Nephrol, 12700 19th Ave,Box C281, Aurora, CO 80045 USA. EM sarah.faubel@ucdenver.edu FU ASN FX Support: The study was supported by the ASN, which had no role in the development of the survey, analysis and interpretation of data, writing the report, or the decision to submit the report for publication. NR 38 TC 10 Z9 10 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2014 VL 64 IS 3 BP 394 EP 401 DI 10.1053/j.ajkd.2014.03.018 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AO5BV UT WOS:000341357100016 PM 24815216 ER PT J AU Dean, JH Woznicki, EM O'Gara, P Montgomery, DG Trimarchi, S Myrmel, T Pyeritz, RE Harris, KM Suzuki, T Braverman, AC Hughes, GC Kline-Rogers, E Nienaber, CA Isselbacher, EM Eagle, KA Bossone, E AF Dean, Joshua H. Woznicki, Elise M. O'Gara, Patrick Montgomery, Daniel G. Trimarchi, Santi Myrmel, Truls Pyeritz, Reed E. Harris, Kevin M. Suzuki, Toru Braverman, Alan C. Hughes, G. Chad Kline-Rogers, Eva Nienaber, Christoph A. Isselbacher, Eric M. Eagle, Kim A. Bossone, Eduardo TI Cocaine-related Aortic Dissection: Lessons from the International Registry of Acute Aortic Dissection SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Acute aortic dissection; Cocaine; Outcomes ID OUTCOMES; INSIGHTS AB BACKGROUND: Acute aortic dissection associated with cocaine use is rare and has been reported predominantly as single cases or in small patient cohorts. METHODS: Our study analyzed 3584 patients enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2012. We divided the population on the basis of documented cocaine use (C+) versus noncocaine use (C-) and further stratified the cohorts into type A (33 C+/2332, 1.4%) and type B (30 C+/1252, 2.4%) dissection. RESULTS: C+ patients presented at a younger age and were more likely to be male and black. Type B dissections were more common among C+ patients than in C-patients. Cocaine-related acute aortic dissection was reported more often at US sites than at European sites (86.4%, 51/63 vs 13.6%, 8/63; P < .001). Tobacco use was more prevalent in the C+ cohort. No differences were seen in history of hypertension, known atherosclerosis, or time from symptom onset to presentation. Type B C+ patients were more likely to be hypertensive at presentation. C+ patients had significantly smaller ascending aortic diameters at presentation. Acute renal failure was more common in type A C+ patients; however, mortality was significantly lower in type A C+ patients. CONCLUSIONS: Cocaine use is implicated in 1.8% of patients with acute aortic dissection. The typical patient is relatively young and has the additional risk factors of hypertension and tobacco use. In-hospital mortality for those with cocaine-related type A dissection is lower than for those with noncocaine-related dissection, likely due to the younger age at presentation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Dean, Joshua H.; Woznicki, Elise M.; Montgomery, Daniel G.; Kline-Rogers, Eva; Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [O'Gara, Patrick] Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy. [Myrmel, Truls] Univ Tromso Hosp, Dept Thorac & Cardiovasc Surg, N-9012 Tromso, Norway. [Pyeritz, Reed E.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Pyeritz, Reed E.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Harris, Kevin M.] Minneapolis Heart Inst, Div Cardiovasc, Minneapolis, MN USA. [Suzuki, Toru] Univ Tokyo, Tokyo, Japan. [Braverman, Alan C.] Washington Univ, Sch Med, Div Cardiovasc, St Louis, MO 63110 USA. [Hughes, G. Chad] Duke Univ, Med Ctr, Div Cardiovasc Thorac Surg, Durham, NC USA. [Nienaber, Christoph A.] Univ Rostock, Div Cardiol & Vasc Med, D-18055 Rostock, Germany. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Bossone, Eduardo] Univ Salerno, Div Cardiol, I-84100 Salerno, Italy. RP Bossone, E (reprint author), Univ Salerno Italy, Div Cardiol, Cava de Tirreni & Amalfi Coast Hosp, Heart Dept, Via Pr Amedeo 36, I-83023 Lauro, AV, Italy. EM ebossone@hotmail.com RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU WL Gore & Associates, Inc; Medtronic, Inc; Varbedian Aortic Research Fund; Hewlett Foundation; Mardigian Foundation; UM Faculty Group Practice; Terumo; Robert and Anne Aikens FX The International Registry of Acute Aortic Dissection receives funding from WL Gore & Associates, Inc, Medtronic, Inc, Varbedian Aortic Research Fund, the Hewlett Foundation, the Mardigian Foundation, UM Faculty Group Practice, Terumo, and Robert and Anne Aikens. NR 15 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD SEP PY 2014 VL 127 IS 9 BP 878 EP 885 DI 10.1016/j.amjmed.2014.05.005 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AO6AW UT WOS:000341431000041 PM 24835037 ER PT J AU Backus, LI Belperio, PS Loomis, TP Mole, LA AF Backus, Lisa I. Belperio, Pamela S. Loomis, Timothy P. Mole, Larry A. TI Impact of Race/Ethnicity and Gender on HCV Screening and Prevalence Among US Veterans in Department of Veterans Affairs Care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEPATITIS-C VIRUS; UNITED-STATES; AFRICAN-AMERICANS; INFECTION; EPIDEMIOLOGY; MORTALITY AB Objectives. We assessed HCV screening and prevalence among veterans and estimated the potential impact of complete birth cohort screening, accounting for the disparate HCV disease burden by race/ethnicity and gender. Methods. We used the Department of Veterans Affairs (VA) Corporate Data Warehouse to identify birth dates, gender, race/ethnicity, and laboratory tests for veterans with at least 1 VA outpatient visit in 2012. We calculated HCV screening rates, prevalence, and HCV infection incident diagnosis. Results. Among 5 499 743 veterans, 54.7% had HCV screening through the VA. In more than 2.9 million veterans screened, HCV prevalence was 6.1% overall and highest among Blacks (11.8%), particularly Black men born in 1945 to 1965 (17.7%). HCV infection incident diagnosis in 2012 was 5.9% for men and 2.3% for women. An estimated additional 48 928 male veterans, including 12 291 Black men, and 1484 female veterans would potentially be identified as HCV infected with full birth cohort screening. Conclusions. HCV prevalence was markedly elevated among veterans born in 1945 to 1965, with substantial variation by race/ethnicity and gender. Full adoption of birth cohort screening may reveal substantial numbers of veterans with previously unknown HCV infection. C1 [Backus, Lisa I.; Belperio, Pamela S.; Loomis, Timothy P.; Mole, Larry A.] Off Publ Health Populat Hlth, Dept Vet Affairs, Washington, DC USA. [Backus, Lisa I.] VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA. [Belperio, Pamela S.] VA Greater Los Angeles Hlth Care Syst, Dept Pharm, Los Angeles, CA USA. RP Backus, LI (reprint author), 3801 Miranda Ave,Mail Code 132, Palo Alto, CA 94304 USA. EM Lisa.Backus@va.gov NR 22 TC 13 Z9 13 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S555 EP S561 DI 10.2105/AJPH.2014.302090 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000014 PM 25100421 ER PT J AU Blosnich, JR Mays, VM Cochran, SD AF Blosnich, John R. Mays, Vickie M. Cochran, Susan D. TI Suicidality Among Veterans: Implications of Sexual Minority Status SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OF-LIFE SURVEY; HEALTH; INDIVIDUALS; GAY; ORIENTATION; MILITARY; DISORDER; IDEATION; RISK AB Using the California Quality of Life surveys, we examined suicidal ideation and attempts in 129 lesbian, gay, and bisexual (LGB) veterans and in 315 heterosexual veterans in 2008-2009 and 2012-2013. Although there were no significant differences in the past 12-month suicidal ideation and lifetime attempts, LGB veterans had higher odds of lifetime suicidal ideation than heterosexual veterans (adjusted odds ratio = 3.00; 95% confidence interval = 1.38, 6.53). Suicide assessment and prevention efforts in LGB veterans could benefit from a life-course perspective regarding suicide risk. C1 [Blosnich, John R.] Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Pittsburgh, PA USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15260 USA. [Mays, Vickie M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Mays, Vickie M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cochran, Susan D.] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Cochran, Susan D.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM John.blosnich@va.gov FU Office of Academic Affiliations in the Department of Veterans Affairs; Center for Health Equity Research and Promotion in the VA Pittsburgh Healthcare System; National Center for Minority Health and Health Disparities [MD006923]; National Institute on Drug Abuse [DA20826] FX This work was supported by a postdoctoral fellowship to J. R. B. from the Office of Academic Affiliations in the Department of Veterans Affairs and the Center for Health Equity Research and Promotion in the VA Pittsburgh Healthcare System. This work was supported by a grant from the National Center for Minority Health and Health Disparities (MD006923) to V. M. M. and a grant from the National Institute on Drug Abuse (DA20826) to S. D. C. NR 19 TC 5 Z9 5 U1 0 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S535 EP S537 DI 10.2105/AJPH.2014.302100 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000011 PM 25100418 ER PT J AU Blosnich, JR Gordon, AJ Bossarte, RM AF Blosnich, John R. Gordon, Adam J. Bossarte, Robert M. TI Suicidal Ideation and Mental Distress Among Adults With Military Service History: Results From 5 US States, 2010 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; OEF/OIF VETERANS; HEALTH SYSTEM; WAR VETERANS; RISK-FACTORS; FOLLOW-UP; MORTALITY; SAMPLE; BEHAVIOR AB Objectives. We examined the association of military service history with past-year suicidal ideation and past-30-days mental distress in a probability-based sample of adults. Methods. We gathered 2010 Behavioral Risk Factor Surveillance System data from 5 states that asked about past-year suicidal ideation. Military service was defined as current or former active-duty service or National Guard or Reserves service. We stratified analyses into 18 to 39 years, 40 to 64 years, and 65 years and older age groups and used multiple logistic regression analyses, adjusted for demographic confounders, to discern the association of military service history with past-year suicidal ideation and past-30-days mental distress. Results. Among the 26 736 respondents, 13.1% indicated military service history. After adjusting for several confounders, we found military history status among those aged 40 to 64 years was associated with both past-year suicidal ideation and past-30-days mental distress. We found no significant associations among the younger or older age groups. Conclusions. Differences in suicidal ideation between military and nonmilitary individuals may occur in midlife. Future research should examine the possibility of cohort effects, service era effects, or both. C1 [Blosnich, John R.; Gordon, Adam J.] US Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Blosnich, John R.; Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY 14627 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Bossarte, Robert M.] VISN 2 Ctr Excellence Suicide Prevent, Canandaigua, NY USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM John.blosnich@va.gov FU VISN 2 Center of Excellence for Suicide Prevention; US Department of Veterans Affairs Office of Academic Affiliations; Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System FX This work was partially supported by the VISN 2 Center of Excellence for Suicide Prevention and a postdoctoral fellowship to J. R. Blosnich through the US Department of Veterans Affairs Office of Academic Affiliations and the Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System. NR 56 TC 5 Z9 5 U1 5 U2 11 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S595 EP S602 DI 10.2105/AJPH.2014.302064 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000019 PM 25100426 ER PT J AU Copeland, LA McIntyre, RT Stock, EM Zeber, JE MacCarthy, DJ Pugh, MJ AF Copeland, Laurel A. McIntyre, Raphael T. Stock, Eileen M. Zeber, John E. MacCarthy, Daniel J. Pugh, Mary Jo TI Prevalence of Suicidality Among Hispanic and African American Veterans Following Surgery SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID QUALITY-OF-LIFE; OLDER-ADULTS; PAIN; MECHANISMS; ETHNICITY; IMPACT; RISK AB Objectives. We evaluated factors associated with suicidal behavior and ideation (SBI) during 3 years of follow-up among 89 995 Veterans Health Administration (VHA) patients who underwent major surgery from October 2005 to September 2006. Methods. We analyzed administrative data using Cox proportional hazards models. SBI was ascertained by International Classification of Disease, 9th Revision codes. Results. African Americans (18% of sample; 16 252) were at an increased risk for SBI (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 1.10, 1.32), whereas Hispanics were not (HR = 1.10; 95% CI = 0.95, 1.28). Other risk factors included schizophrenia, bipolar disorder, depression, posttraumatic stress disorder, pain disorders, postoperative new-onset depression, and postoperative complications; female gender and married status were protective against SBI. Conclusions. The postoperative period might be a time of heightened risk for SBI among minority patients in the VHA. Tailored monitoring and postoperative management by minority status might be required to achieve care equity. C1 [Copeland, Laurel A.; McIntyre, Raphael T.; Stock, Eileen M.; Zeber, John E.] Cent Texas Vet Hlth Care Syst Scott & White Healt, Ctr Appl Hlth Res, Temple, TX USA. [MacCarthy, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Copeland, LA (reprint author), Ctr Appl Hlth Res, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM LaurelACopeland@gmail.com OI Pugh, Mary Jo/0000-0003-4196-7763; Copeland, Laurel/0000-0002-9478-0209 FU Veterans Health Administration, Health Services Research Development [IIR-09-335]; Center for Applied Health Research - Central Texas Veterans Health Care System; Center for Applied Health Research - Scott & White Healthcare, in Temple, Texas, Scott & White Minority Health Research Predoctoral Fellowship FX This work was supported by a research award from Veterans Health Administration, Health Services Research & Development #IIR-09-335 to Central Texas Veterans Health Care System to partially support the salaries of L. A. Copeland, J. E. Zeber, M. J. Pugh, and D. J. MacCarthy. Additional support was provided by the Center for Applied Health Research, a center jointly sponsored by Central Texas Veterans Health Care System and Scott & White Healthcare, in Temple, Texas, including the Scott & White Minority Health Research Predoctoral Fellowship awarded to R. T. McIntyre. NR 39 TC 2 Z9 2 U1 1 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S603 EP S608 DI 10.2105/AJPH.2014.301938 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000020 PM 25100427 ER PT J AU Ibrahim, SA Egede, LE Uchendu, US Fine, MJ AF Ibrahim, Said A. Egede, Leonard E. Uchendu, Uchenna S. Fine, Michael J. TI The Struggle for Health Equity: The Sustained Effort by the VA Healthcare System SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID QUALITY-OF-CARE C1 [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Ctr Hlth Equ Res & Promot, Dept Vet Affairs VA, Philadelphia, PA USA. [Egede, Leonard E.] Med Univ S Carolina, Charleston, SC USA. [Egede, Leonard E.] Charleston Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Uchendu, Uchenna S.] VA Cent Off, Vet Hlth Adm Off Hlth Equ, Washington, DC USA. [Fine, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Fine, Michael J.] Ctr Hlth Equ Res & Promot, VA, Pittsburgh, PA USA. RP Ibrahim, SA (reprint author), Philadelphia VA Med Ctr ANNEX, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM said.ibrahim2@va.gov FU NIAMS NIH HHS [K24 AR055259]; NIDDK NIH HHS [K24 DK093699] NR 16 TC 0 Z9 0 U1 2 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S514 EP S516 DI 10.2105/AJPH.2014.302199 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000003 PM 25100410 ER PT J AU Kauth, MR Shipherd, JC Lindsay, J Blosnich, JR Brown, GR Jones, KT AF Kauth, Michael R. Shipherd, Jillian C. Lindsay, Jan Blosnich, John R. Brown, George R. Jones, Kenneth T. TI Access to Care for Transgender Veterans in the Veterans Health Administration: 2006-2013 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB A 2011 Veterans Health Administration directive mandated medically necessary care for transgender veterans. Internal education efforts informed staff of the directive and promoted greater access to care. For fiscal years 2006 through 2013, we identified 2662 unique individuals with International Classification of Diseases, Ninth Revision diagnoses related to transgender status in Veterans Health Administration medical records, with 40% of new cases in the 2 years following the directive. A bottom-up push for services by veterans and top-down education likely worked synergistically to speed implementation of the new policy and increase access to care. C1 [Kauth, Michael R.] Michael E DeBakey VA Med Ctr, VA South Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Boston, MA USA. [Blosnich, John R.] Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Brown, George R.; Jones, Kenneth T.] Off Hlth Equ, Dept Vet Affairs, Washington, DC USA. RP Kauth, MR (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,ATTN 152 VA, Houston, TX 77030 USA. EM michael.kauth@va.gov FU VA South Central Mental Illness Research Education and Clinical Center; Health Services Research and Development Service Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX This material is based upon work supported in part by the VA South Central Mental Illness Research Education and Clinical Center and the Health Services Research and Development Service Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). NR 19 TC 18 Z9 18 U1 0 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S532 EP S534 DI 10.2105/AJPH.2014.302086 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000010 PM 25100417 ER PT J AU Lynch, J Whatley, A Uchendu, US Ibrahim, SA AF Lynch, Julie Whatley, Angela Uchendu, Uchenna S. Ibrahim, Said A. TI Race and Genomics in the Veterans Health Administration SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID GROWTH-FACTOR RECEPTOR; WIDE ASSOCIATION; PROSTATE-CANCER; UNITED-STATES; ANCESTRY; MEN C1 [Lynch, Julie] CHOIR, Vet Hlth Adm, Bedford, MA 01730 USA. [Lynch, Julie] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Whatley, Angela] Vet Hlth Adm, Washington, DC USA. [Uchendu, Uchenna S.] Off Hlth Equ, Dept Vet Affairs, Washington, DC USA. [Ibrahim, Said A.] Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Lynch, J (reprint author), CHOIR, Vet Hlth Adm, 200 Springs Ave, Bedford, MA 01730 USA. EM julie.lynch@va.gov FU NIAMS NIH HHS [K24 AR055259] NR 10 TC 3 Z9 3 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S522 EP S524 DI 10.2105/AJPH.2014.302202 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000006 PM 25100413 ER PT J AU Feemster, LC Au, DH AF Feemster, Laura C. Au, David H. TI Chronic Obstructive Pulmonary Disease Readmissions and Medicare Reimbursement Reply SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 [Feemster, Laura C.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Feemster, LC (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. FU NHLBI NIH HHS [K23 HL111116, K23HL111116] NR 2 TC 1 Z9 1 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2014 VL 190 IS 5 BP 591 EP 592 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AO7TB UT WOS:000341554400018 PM 25171313 ER PT J AU Madenci, AL Michailidou, M Chiou, G Thabet, A Fernandez-del Castillo, C Fagenholz, PJ AF Madenci, Arin L. Michailidou, Maria Chiou, Grace Thabet, Ashraf Fernandez-del Castillo, Carlos Fagenholz, Peter J. TI A contemporary series of patients undergoing open debridement for necrotizing pancreatitis SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Pancreatic diseases; Acute necrotizing pancreatitis; Debridement; Minimally invasive surgical procedures; Sensitivity and specificity ID STEP-UP APPROACH; SURGICAL-TREATMENT; INVASIVE-APPROACH; NECROSECTOMY; NECROSIS; MULTICENTER; MORTALITY; STERILE; SAFETY AB BACKGROUND: For patients with acute pancreatitis complicated by infected necrosis, minimally invasive techniques have taken hold without substantial comparison with open surgery. We present a contemporary series of open necrosectomies as a benchmark for newer techniques. METHODS: Using a prospective database, we retrospectively identified consecutive patients undergoing debridement for necrotizing pancreatitis (2006 to 2009). The primary endpoint was in-hospital mortality. RESULTS: Sixty-eight patients underwent debridement for pancreatic/peripancreatic necrosis. In-hospital mortality was 8.8% (n = 6). Infection (n = 43, 63%) and failure-to-thrive (n = 13, 19%) comprised the most common indications for necrosectomy. The false negative rate (FNR) for infection of percutaneous aspirate was 20.0%. Older age (P = .02), Acute Physiology and Chronic Health Evaluation II score upon admission(P = .03) or preoperatively (P < .01), preoperative intensive care unit admission (P = .01), and postoperative organ failure (P = .03) were associated with mortality. CONCLUSIONS: Open debridement for necrotizing pancreatitis results in a low mortality, providing a useful comparator for other interventions. Given the high FNR of percutaneous aspirate, debridement should not be predicated on proven infection. (C) 2014 Elsevier Inc. All rights reserved. C1 [Madenci, Arin L.; Michailidou, Maria; Chiou, Grace; Fernandez-del Castillo, Carlos; Fagenholz, Peter J.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Crit Care, Dept Surg, Boston, MA 02114 USA. [Thabet, Ashraf] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Crit Care, Dept Surg, 165 Cambridge St, Boston, MA 02114 USA. EM pfagenholz@partners.org OI Madenci, Arin/0000-0003-1258-7278 NR 30 TC 6 Z9 8 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 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2014 VL 208 IS 3 BP 324 EP 331 DI 10.1016/j.amjsurg.2013.11.004 PG 8 WC Surgery SC Surgery GA AO2KG UT WOS:000341149900002 PM 24767969 ER PT J AU Busch, RA Heneghan, AF Pierre, JF Wang, XY Kudsk, KA AF Busch, Rebecca A. Heneghan, Aaron F. Pierre, Joseph F. Wang, Xinying Kudsk, Kenneth A. TI The Enteric Nervous System Neuropeptide, Bombesin, Reverses Innate Immune Impairments During Parenteral Nutrition SO ANNALS OF SURGERY LA English DT Article DE antimicrobial peptides; bombesin; enteric nervous system; parenteral nutrition; Paneth cells ID RESPIRATORY-TRACT IMMUNITY; POLYMERIC IMMUNOGLOBULIN RECEPTOR; INTESTINAL PANETH CELLS; MAJOR ABDOMINAL-TRAUMA; LECTIN REGIII-GAMMA; MUCOSAL IMMUNITY; LYMPHOID-TISSUE; PHOSPHOLIPASE A(2); BARRIER FUNCTION; FED MICE AB Background: Lack of enteral stimulation during parenteral nutrition (PN) impairs mucosal immunity. Bombesin (BBS), a gastrin-releasing peptide analogue, reverses PN-induced defects in acquired immunity. Paneth cells produce antimicrobial peptides (AMPs) of innate immunity for release after cholinergic stimulation. Objective: Determine if BBS restores AMPs and bactericidal function during PN. Methods: Intravenously cannulated male ICR mice were randomized to Chow, PN, or PN+BBS (15 mu g 3 times daily, n = 7 per group) for 5 days. Ileum was analyzed for AMPs (Protein: sPLA2 by fluorescence, lysozyme and RegIII-gamma by western andcryptdin-4 by ELISA; mRNA: all by RT-PCR). Cholinergic stimulated (100 mu M bethanechol) ileal specimens assessed Pseudomonas bactericidal activity. Ileum (Chow: n = 7; PN: n = 9; PN+BBS: n = 8) was assessed for Escherichia coli invasion in ex-vivo culture. Results: PN significantly decreased most AMPs versus Chow while BBS maintained Chow levels (sPLA(2):Chow: 107 + 14*, PN: 44.6 + 7.2, PN+BBS: 78.7 + 13.4* Fl/min/mu L/total protein; Lysozyme: Chow: 63.9 + 11.9*, PN: 26.8 + 6.2; PN+BBS: 64.9 + 13.8* lysozyme/total protein; RegIII-gamma: Chow: 51.5 + 10.0*, PN: 20.4 + 4.3, PN+BBS: 31.0 + 8.4 RegIII-gamma/total protein; Cryptdin-4: Chow: 18.4 + 1.5*, PN: 12.7 + 1.6, PN+BBS: 26.1 + 2.4*dagger pg/mg [all *P < 0.05 vs PN and dagger P < 0.05 vs Chow]). Functionally, BBS prevented PN loss of bactericidal activity after cholinergic stimulation (Chow: 25.3 + 3.6*, PN: 13.0 + 3.2; PN+BBS: 27.0 + 4.7* percent bacterial killing, *P < 0.05 vs PN). BBS reduced bacterial invasion in unstimulated tissue barely missing significance (P = 0.06). Conclusions: The enteric nervous system (ENS) controls AMP levels in Paneth cells during PN but mucosal protection by innate immunity requires both ENS and parasympathetic stimulation. C1 [Busch, Rebecca A.; Heneghan, Aaron F.; Pierre, Joseph F.; Wang, Xinying; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Wang, Xinying] Nanjing Univ, Dept Surg, Jinling Hosp, Sch Med, Nanjing, Peoples R China. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [I01BX001672]; National Institute of Health [T32 CA090217-13] FX Supported by award No. I01BX001672 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development. Also based upon work supported in part by National Institute of Health grant T32 CA090217-13. The contents of this article do not represent the views of the Department of Veterans Affairs or the US government. The authors have no conflicts of interest to declare. NR 100 TC 8 Z9 8 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2014 VL 260 IS 3 BP 432 EP 444 DI 10.1097/SLA.0000000000000871 PG 13 WC Surgery SC Surgery GA AO2SJ UT WOS:000341175600004 PM 25115419 ER PT J AU Adler, JT Sethi, RKV Yeh, H Markmann, JF Nguyen, LL AF Adler, Joel T. Sethi, Rosh K. V. Yeh, Heidi Markmann, James F. Nguyen, Louis L. TI Market Competition Influences Renal Transplantation Risk and Outcomes SO ANNALS OF SURGERY LA English DT Article DE disparities; market competition; renal transplantation ID KIDNEY-TRANSPLANTATION; UNITED-STATES; ACCESS AB Objective: To evaluate the impact of market competition on patient mortality and graft failure after kidney transplantation. Background: Kidneys are initially allocated within 58 donation service areas (DSAs), which have varying numbers of transplant centers. Market competition is generally considered beneficial. Methods: The Scientific Registry of Transplant Recipients database was queried and the Herfindahl-Hirschman index (HHI), a measure of market competition, was calculated for each DSA from 2003 to 2012. Receipt of low-quality kidneys (Kidney Donor Profile Index >= 85) was modeled with multivariable logistic regression, and Cox proportional hazards models were created for graft failure and patient mortality. Results: A total of 127,355 adult renal transplants were performed. DSAs were categorized as 7 no (HHI = 1), 17 low (HHI = 0.52-0.97), 17 medium (HHI = 0.33-0.51), or 17 high (HHI = 0.09-0.32) competition. For deceased donor kidney transplantation, increasing market competition was significantly associated with mortality [hazard ratio (HR): 1.11, P = 0.01], graft failure (HR: 1.18, P = 0.0001), and greater use of low-quality kidneys (odds ratio = 1.39, P < 0.0001). This was not true for living donor kidney transplantation (mortality HR: 0.94, P = 0.48; graft failure HR: 0.99, P = 0.89). Competition was associated with longer waitlists (P = 0.04) but not with the number of transplants per capita in a DSA (P = 0.21). Conclusions: Increasing market competition is associated with increased patient mortality and graft failure and the use of riskier kidneys. These results may represent more aggressive transplantation and tolerance of greater risk for patients who otherwise have poor alternatives. Market competition should be better studied to ensure optimal outcomes. C1 [Adler, Joel T.; Nguyen, Louis L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Adler, Joel T.; Sethi, Rosh K. V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Yeh, Heidi; Markmann, James F.; Nguyen, Louis L.] Harvard Univ, Sch Med, Boston, MA USA. [Nguyen, Louis L.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. RP Nguyen, LL (reprint author), Brigham & Womens Hosp, Div Vasc & Endovasc Surg, 75 Francis St, Boston, MA 02115 USA. EM llnguyen@partners.org RI gholamnezhad, reza/D-5731-2015; OI gholamnezhad, reza/0000-0003-0326-7061; Adler, Joel/0000-0001-8190-3444 FU Center for Surgery and Public Health at Brigham; Women's Hospital; Arthur Tracy Cabot Fellowship; Claude E. Welch Fellowship FX The authors declare there are no conflicts of interest. The study was supported by Center for Surgery and Public Health at Brigham and Women's Hospital. J.T.A. is funded by the Arthur Tracy Cabot Fellowship and the Claude E. Welch Fellowship. The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the SRTR or the US Government. NR 14 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2014 VL 260 IS 3 BP 550 EP 557 DI 10.1097/SLA.0000000000000896 PG 8 WC Surgery SC Surgery GA AO2SJ UT WOS:000341175600016 PM 25115431 ER PT J AU Ju, MH Chung, JW Kinnier, CV Bentrem, DJ Mahvi, DM Ko, CY Bilimoria, KY AF Ju, Mila H. Chung, Jeanette W. Kinnier, Christine V. Bentrem, David J. Mahvi, David M. Ko, Clifford Y. Bilimoria, Karl Y. TI Association Between Hospital Imaging Use and Venous Thromboembolism Events Rates Based on Clinical Data SO ANNALS OF SURGERY LA English DT Article DE ACS NSQIP; clinical registry data; hospital quality performance; surveillance bias; venous thromboembolism (VTE) ID DEEP-VEIN THROMBOSIS; QUALITY IMPROVEMENT PROGRAM; TRAUMA DATA-BANK; PATIENT SAFETY INDICATORS; FACTORS-AN ANALYSIS; REPORTED DVT RATES; SURVEILLANCE BIAS; SURGICAL QUALITY; OF-CARE; TEACHING STATUS AB Objective: The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance bias using high-quality clinical data. Background: Hospital VTE rates are publicly reported and used in pay-for-performance programs. Prior work suggested surveillance bias: hospitals that look more for VTE with imaging studies find more VTE, thereby incorrectly seem to have worse performance. However, these results have been questioned as the risk adjustment and VTE measurement relied on administrative data. Methods: Data (2009-2010) from 208 hospitals were available for analysis. Hospitals were divided into quartiles according to VTE imaging use rates (Medicare claims). Observed and risk-adjusted postoperative VTE event rates (regression models using American College of Surgeons National Surgical Quality Improvement Project data) were examined across VTE imaging use rate quartiles. Multivariable linear regression models were developed to assess the impact of hospital characteristics (American Hospital Association) and hospital imaging use rates on VTE event rates. Results: The mean risk-adjusted VTE event rates at 30 days after surgery increased across VTE imaging use rate quartiles: 1.13% in the lowest quartile to 1.92% in the highest quartile (P < 0.001). This statistically significant trend remained when examining only the inpatient period. Hospital VTE imaging use rate was the dominant driver of hospital VTE event rates (P < 0.001), as no other hospital characteristics had significant associations. Conclusions: Even when examined with clinically ascertained outcomes and detailed risk adjustment, VTE rates reflect hospital imaging use and perhaps signify vigilant, high-quality care. The VTE outcome measure may not be an accurate quality indicator and should likely not be used in public reporting or pay-for-performance programs. C1 [Ju, Mila H.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Ju, Mila H.; Chung, Jeanette W.; Kinnier, Christine V.; Bentrem, David J.; Mahvi, David M.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org FU AHRQ [R21HS021857]; National Institutes of Health [5T32HL094293]; American College of Surgeons Clinical Scholar in Residence program FX Dr Bilimoria is partially supported by AHRQ R21HS021857. Dr Ju is supported by National Institutes of Health #5T32HL094293 and American College of Surgeons Clinical Scholar in Residence program. No conflict of interest related to this work. NR 40 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2014 VL 260 IS 3 BP 558 EP 566 DI 10.1097/SLA.0000000000000897 PG 9 WC Surgery SC Surgery GA AO2SJ UT WOS:000341175600017 PM 25115432 ER PT J AU Li, J Echevarria, KL Hughes, DW Cadena, JA Bowling, JE Lewis, JS AF Li, Julius Echevarria, Kelly L. Hughes, Darrel W. Cadena, Jose A. Bowling, Jason E. Lewis, James S., II TI Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIMICROBIAL THERAPY; RISK-FACTORS; ENDOCARDITIS; NAFCILLIN; OUTCOMES AB Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and antistaphylococcal penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P = 0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P = 0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P = 0.05) and to have an osteoarticular source (57% versus 33%; P = 0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P = 0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P = 0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P = 0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation. C1 [Li, Julius; Echevarria, Kelly L.; Cadena, Jose A.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Li, Julius; Echevarria, Kelly L.; Hughes, Darrel W.; Lewis, James S., II] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Li, Julius; Echevarria, Kelly L.; Hughes, Darrel W.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Echevarria, Kelly L.; Cadena, Jose A.; Bowling, Jason E.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Hughes, Darrel W.; Lewis, James S., II] Univ Hlth Syst, Dept Pharm, San Antonio, TX USA. RP Li, J (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM juli@ochsner.org NR 30 TC 16 Z9 16 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2014 VL 58 IS 9 BP 5117 EP 5124 DI 10.1128/AAC.02800-14 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AO3UV UT WOS:000341262700015 PM 24936596 ER PT J AU Pape, TLB Mallinson, T Guernon, A AF Pape, Theresa Louise-Bender Mallinson, Trudy Guernon, Ann TI Psychometric Properties of the Disorders of Consciousness Scale SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Consciousness disorders; Outcome measures; Rehabilitation ID PERSISTENT VEGETATIVE STATE; COMA; PRECISION; ATTENTION; VALIDITY; INJURY AB Objective: To provide evidence for psychometric properties of the Disorders of Consciousness Scale (DOCS). Design: Prospective observational cohort. Settings: Seven rehabilitation facilities. Participants: Patients (N=174) with severe brain injury. Interventions: Not applicable. Main Outcome Measure: DOCS. Results: Initial analyses suggested eliminating 6 items to maximize psychometrics, resulting in the DOCS-25. The 25 items form a unidimensional hierarchy, rating scale categories are ordered, there are no misfitting items, and differential item functioning was not found according to sex, type of brain injury, veteran status, and days from onset. Person separation reliability (.91) indicates that the DOCS-25 is appropriate for individual patient measurement. Items are well targeted to the sample, with the difference between mean person and item calibrations less than 1 logit. DOCS-25 Rasch measures result in a 62% gain in relative precision over total raw scores. Internal consistency is very good (Cronbach alpha=.86); interrater agreement is excellent (intracIass correlation coefficient =.90) for both the DOCS-25 and the sensory subscales. The DOCS-25 total measure, but not subscale measures, correlates with the Glasgow Coma Scale and the Coma/Near-Coma Scales and distinguishes significantly between vegetative and minimally conscious states, indicating concurrent validity. Conclusions: The DOCS-25 is psychometrically strong. It has excellent measurement precision and captures a broad range of patient function, which is critical for capturing recovery of consciousness. The sensory subscales are clinically informative but should not be reported as separate measures. The Keyform synthesizes clinical observations to visualize response patterns with potential for informing clinical decision-making Future studies should determine sensitivity to change, examine issues of rater severity, and explore the usefulness of the Keyform in clinical practice. (c) 2014 by the American Congress of Rehabilitation Medicine C1 [Pape, Theresa Louise-Bender] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Pape, Theresa Louise-Bender] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Dept Vet Affairs, Hines, IL 60141 USA. [Pape, Theresa Louise-Bender] Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. [Mallinson, Trudy] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Guernon, Ann] Marianjoy Rehabil Hosp, Wheaton, IL USA. RP Pape, TLB (reprint author), Edward Hines Jr Vet Hosp, Res & Dev Serv, POB 5000,MC 151H, Hines, IL 60141 USA. EM Theresa.Pape@va.gov OI Pape, Theresa/0000-0001-7738-5963 FU United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development [CCN 07-133-1]; Rehabilitation Research and Development Career Development Transition Award [B4949N] FX Supported by the United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development (merit grant no. CCN 07-133-1) and Rehabilitation Research and Development Career Development Transition Award (no. B4949N). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the United States Department of Veterans Affairs or the United States Government. NR 55 TC 2 Z9 2 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2014 VL 95 IS 9 BP 1672 EP 1684 DI 10.1016/j.apmr.2014.04.015 PG 13 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AO4TU UT WOS:000341335100010 PM 24814459 ER PT J AU Bartels, CM Johnson, H Voelker, K Thorpe, C McBride, P Jacobs, EA Pandhi, N Smith, M AF Bartels, Christie M. Johnson, Heather Voelker, Katya Thorpe, Carolyn McBride, Patrick Jacobs, Elizabeth A. Pandhi, Nancy Smith, Maureen TI Impact of Rheumatoid Arthritis on Receiving a Diagnosis of Hypertension Among Patients With Regular Primary Care SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CARDIOVASCULAR RISK-FACTORS; QUALITY-OF-CARE; EULAR RECOMMENDATIONS; ADMINISTRATIVE DATA; DISEASE; MEDICARE; COMORBIDITIES; POPULATION; MORTALITY AB Objective. Despite numerous studies reporting increased cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA), the impact of RA on managing modifiable CVD risk factors remains understudied. We tested the hypothesis that RA is a risk factor for not receiving a hypertension diagnosis. Methods. Using a cohort design, we studied adult patients with and without RA/inflammatory arthritis from a large academic multispecialty practice. All were seen regularly in primary care and met clinical guideline hypertension criteria, but lacked prior hypertension diagnosis/treatment. The primary outcome was time to International Classification of Diseases, Ninth Revision code for hypertension or elevated blood pressure, or antihypertensive medication prescription. Kaplan-Meier survival curve analysis and Cox proportional hazards modeling were used to examine the impact of RA on diagnosis of hypertension. Results. Among 14,974 patients with undiagnosed hypertension, 201 patients had RA codes. RA patients had equivalent primary care visits and more total visits compared to patients without RA. At the end of the study, the likelihood of hypertension diagnosis was 36% in RA patients compared to 51% in patients without RA. In adjusted Cox models, RA patients had a 29% lower hypertension diagnosis hazard (hazard ratio 0.71, 95% confidence interval 0.55-0.93), reflecting more undiagnosed hypertension than with other comorbidities. Conclusion. Among patients meeting guideline-based hypertension criteria, RA patients were less likely to be diagnosed despite more visits than those without RA. Given heightened CVD risks in RA and the importance of hypertension diagnosis as a first step toward controlling risk, rheumatologists should collaborate to improve rates of diagnosis for this modifiable CVD risk factor. C1 [Bartels, Christie M.; Johnson, Heather; Voelker, Katya; McBride, Patrick; Jacobs, Elizabeth A.; Pandhi, Nancy; Smith, Maureen] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Voelker, Katya] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, Carolyn] Univ Pittsburgh, Pittsburgh, PA USA. RP Bartels, CM (reprint author), 1685 Highland Ave,Room 4132, Madison, WI 53705 USA. EM cb4@medicine.wisc.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [K23-AR062381]; NIH/National Heart, Lung, and Blood Institute [1-K23-HL112907]; National Center for Advancing Translational Sciences, NIH [9U54TR000021]; Health Innovation Program/Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research/Clinical and Translational Science Award; Shapiro Student Research Program FX Dr. Bartels's work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH (award K23-AR062381). Dr. Johnson's work was supported by the NIH/National Heart, Lung, and Blood Institute (grant 1-K23-HL112907). Additional project support was provided through the National Center for Advancing Translational Sciences, NIH (grant 9U54TR000021) and the Health Innovation Program/Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research/Clinical and Translational Science Award and the Shapiro Student Research Program. NR 48 TC 9 Z9 9 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2014 VL 66 IS 9 BP 1281 EP 1288 DI 10.1002/acr.22302 PG 8 WC Rheumatology SC Rheumatology GA AO3OK UT WOS:000341241200002 PM 24585741 ER PT J AU Li, J Hsu, HC Ding, YN Li, H Wu, Q Yang, PA Luo, B Rowse, AL Spalding, DM Bridges, SL Mountz, JD AF Li, Jun Hsu, Hui-Chen Ding, Yana Li, Hao Wu, Qi Yang, PingAr Luo, Bao Rowse, Amber L. Spalding, David M. Bridges, S. Louis, Jr. Mountz, John D. TI Inhibition of Fucosylation Reshapes Inflammatory Macrophages and Suppresses Type II Collagen-Induced Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; T-CELLS; SYNOVIAL FIBROBLASTS; ANTIGEN PRESENTATION; LYMPH-NODES; E-SELECTIN; FUCT-VII; ACTIVATION; FUCOSE; IL-10 AB Objective. Fucosylation catalyzed by fucosyltransferases (FUTs) is an important posttranslational modification involved in a variety of biologic processes. This study was undertaken to determine the roles of fucosylation in rheumatoid arthritis (RA) and to assess the efficacy of reestablishing immune homeostasis with the use of 2-deoxy-D-galactose (2-D-gal), a fucosylation inhibitor. Methods. Quantitative polymerase chain reaction was performed to determine the expression of FUT genes in synovial tissue from RA and osteoarthritis (OA) patients and in fluorescence-activated cell-sorted cells from RA synovial fluid. The in vivo inhibitory effect of 2-D-gal was evaluated in a murine collagen-induced arthritis (CIA) model. The in vitro effects of 2-D-gal on differentiation of inflammatory macrophages, production of cytokines, and antigen uptake, processing, and presentation functions were analyzed. Results. FUTs that are involved in terminal or subterminal fucosylation, but not those involved in core fucosylation or O-fucosylation, were up-regulated in RA compared to OA synovial tissue. The expression of terminal FUTs was highly positively correlated with the expression of TNF (encoding for tumor necrosis factor alpha). Terminal FUTs were predominantly expressed in M1 macrophages. In vivo, 2-D-gal treatment of mice precluded the development of CIA by reducing inflammatory macrophages and Th17 cells in the draining lymph nodes and decreasing the levels of TNF alpha, interleukin-6 (IL-6), and antibodies to type II collagen in the serum. In vitro, treatment with 2-D-gal skewed the differentiation of M1 macrophages to IL-10-producing M2 macrophages. Furthermore, 2-D-gal significantly inhibited the antigen-presenting function of M1 macrophages. Conclusion. Terminal fucosylation is a novel hallmark of inflammatory macrophages. Inhibition of terminal FUTs reshapes the differentiation and functions of M1 macrophages, leading to resolution of inflammation in arthritis. C1 [Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Dept Med, SHEL Bldg,Suite 307,1825 Univ Blvd, Birmingham, AL 35294 USA. EM jdmountz@uab.edu RI Li, Hao/N-7406-2015 OI Li, Hao/0000-0002-2171-8826 FU Arthritis Foundation; Lupus Research Institute; Daiichi Sankyo Co., Ltd; NIH [1R01-AI-083705, 1R01-AI-071110, P30-AR-048311, P30-AI-027767, P30-AR-46031]; Rheumatology Research Foundation; Department of Veterans Affairs [1I01BX000600] FX Supported by the Arthritis Foundation (grant to Dr. J. Li), the Lupus Research Institute (grant to Dr. Hsu), and Daiichi Sankyo Co., Ltd (grant to Dr. Mountz), the NIH (grants 1R01-AI-083705 to Dr. Hsu and 1R01-AI-071110 and P30-AR-048311 to Dr. Mountz), a Rheumatology Research Foundation grant to Dr. Mountz, and the Department of Veterans Affairs (Merit Review grant 1I01BX000600 to Dr. Mountz). Portions of the study were performed at the University of Alabama at Birmingham Rheumatic Diseases Core Center (Analytical Genomics and Transgenics Core, Comprehensive Flow Cytometry Core, and Analytic Imaging and Immunoreagents Core), supported by NIH grant P30-AR-048311, the Center for AIDS Research flow cytometry facility, supported by NIH grant P30-AI-027767, and the Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core Laboratory, supported by NIH grant P30-AR-46031. NR 46 TC 6 Z9 6 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2014 VL 66 IS 9 BP 2368 EP 2379 DI 10.1002/art.38711 PG 12 WC Rheumatology SC Rheumatology GA AO3RD UT WOS:000341251100009 PM 24838610 ER PT J AU Ding, YN Li, J Yang, PA Luo, B Wu, Q Zajac, AJ Wildner, O Hsu, HC Mountz, JD AF Ding, Yanna Li, Jun Yang, PingAr Luo, Bao Wu, Qi Zajac, Allan J. Wildner, Oliver Hsu, Hui-Chen Mountz, John D. TI Interleukin-21 Promotes Germinal Center Reaction by Skewing the Follicular Regulatory T Cell to Follicular Helper T Cell Balance in Autoimmune BXD2 Mice SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FOXP3 EXPRESSION; B-CELLS; GENERATION; IL-21; DIFFERENTIATION; RECEPTOR; SUBSET; MTOR; TH17 AB Objective. Follicular regulatory T (Tfr) cells act as the regulatory counterpart of follicular helper T (Tfh) cells to suppress germinal center (GC) B cell differentiation. We recently showed that interleukin-21 (IL-21) promoted Tfh cell differentiation in autoimmune BXD2 mice that develop spontaneous GCs. This study was undertaken to determine the modulatory effects of IL-21 on Tfr cells and the Tfr cell to Tfh cell balance in BXD2 mice. Methods. The percentage and phenotype of Tfr cells were determined in BXD2 and BXD2-IL21(-/-) mice. The effects of IL-21 on Tfr cells and the Tfr cell:Tfh cell ratio were evaluated. Sorted Tfr cells from BXD2-IL21(-/-) mice were cocultured with Tfh cells and B cells, or transferred into BXD2 mice to determine their function. Results. The percentages and numbers of GC B cells and Tfh cells were significantly reduced, but the percentage of Tfr cells was 2-fold higher in BXD2-IL21(-/-) mice than in wild-type BXD2 mice. Administration of AdIL-21 to BXD2-IL21(-/-) mice decreased the percentages and numbers of Tfr cells and the Tfr cell:Tfh cell ratio but increased the number of GC B cells in the spleen. Recombinant murine IL-21 suppressed FoxP3 and significantly reduced Tgfb1, Il2, and Gitr but enhanced Il21, Il6, Pd1, Cxcr5, and Icos expression in Tfr cells. IL-21 also counteracted Tfr cell-mediated inhibition of antibody secretion in the Tfh cell-B cell coculture system. Transfer of Tfr cells into young BXD2 mice reduced GC size and decreased the numbers of autoantibody-producing B cells. Conclusion. Our findings indicate that high levels of IL-21 selectively enhance Tfh cell differentiation but inhibit Tfr cell commitment and the suppressive function of Tfr cells on Tfh cells and B cells, suggesting that IL-21 skews the balance from Tfr cells to Tfh cells to promote autoreactive GC reactions in BXD2 mice. C1 [Ding, Yanna; Li, Jun; Yang, PingAr; Luo, Bao; Wu, Qi; Zajac, Allan J.; Hsu, Hui-Chen; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Wildner, Oliver] Swissmedic, Swiss Agcy Therapeut Prod, Bern, Switzerland. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Hsu, HC (reprint author), Univ Alabama Birmingham, Dept Med, 1825 Univ Blvd, Birmingham, AL 35294 USA. EM rheu078@uab.edu; jdmountz@uab.edu FU Arthritis Foundation; NIH (National Institute of Allergy and Infectious Diseases) [U01-AI-082966, 1R01-AI-0837051, R01-AI-071110]; Lupus Research Institute; Rheumatology Research Foundation; Department of Veterans Affairs [1I01BX000600]; NIH [P30-AR-048311, P30-A-I027767] FX Supported by the Arthritis Foundation (grant to Dr. Li), the NIH (National Institute of Allergy and Infectious Diseases grants U01-AI-082966 to Dr. Zajac, 1R01-AI-083705 to Dr. Hsu, and 1R01-AI-071110 to Dr. Mountz), the Lupus Research Institute (grant to Dr. Hsu), a Disease Targeted Research Grant from the Rheumatology Research Foundation (to Dr. Mountz), and the Department of Veterans Affairs (Merit Review grant 1I01BX000600 to Dr. Mountz). Flow cytometry and confocal imaging data acquisition were performed at the University of Alabama at Birmingham Comprehensive Flow Cytometry Core (supported by NIH grants P30-AR-048311 and P30-A-I027767) and Analytic Imaging and Immunoreagents Core (supported by NIH grant P30-AR-048311). NR 40 TC 21 Z9 24 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2014 VL 66 IS 9 BP 2601 EP 2612 DI 10.1002/art.38735 PG 12 WC Rheumatology SC Rheumatology GA AO3RD UT WOS:000341251100031 PM 24909430 ER PT J AU Yang, A Kimmelman, AC AF Yang, Annan Kimmelman, Alec C. TI Inhibition of autophagy attenuates pancreatic cancer growth independent of TP53/TRP53 status SO AUTOPHAGY LA English DT Editorial Material DE PDAC; Trp53; TP53; Atg5; autophagy; chloroquine; pancreatic cancer C1 [Yang, Annan; Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. RP Kimmelman, AC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. EM Alec_Kimmelman@dfci.harvard.edu FU NCI NIH HHS [R01CA157490, R01 CA157490] NR 0 TC 15 Z9 15 U1 0 U2 7 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD SEP PY 2014 VL 10 IS 9 BP 1683 EP 1684 DI 10.4161/auto.29961 PG 2 WC Cell Biology SC Cell Biology GA AO9AH UT WOS:000341647200017 PM 25046107 ER PT J AU LeBaron, V Beck, SL Black, F Palat, G AF LeBaron, Virginia Beck, Susan L. Black, Fraser Palat, Gayatri TI Nurse Moral Distress and Cancer Pain Management An Ethnography of Oncology Nurses in India SO CANCER NURSING LA English DT Article DE Developing countries; Ethnography; Global health; India; Low- and middle-income countries; Moral distress; Morphine; Nurses; Oncology; Opioids; Palliative care ID CRITICAL-CARE NURSES; FUTILE CARE; HEALTH-CARE; PERCEPTIONS; BANGLADESH AB Background: The majority of cancer patients in low-and middle-income countries (LMICs) present with late-stage, incurable disease, and basic tools to alleviate patient suffering-such as morphine-are often absent. Oncology nurses must cope with many challenges and may experience moral distress (MD), yet little research has examined this experience in LMICs. Objective: This ethnographic study explored the experience of MD with oncology nurses (n = 37) and other providers (n = 22) in India and its potential relationship to opioid availability. Methods: Data (semistructured interviews and field observations) were collected at a 300-bed government cancer hospital in urban South India over 9 months. Dedoose v.4.5.91 supported analysis of transcripts using a coding schema that mapped to an Integrated Model of Nurse Moral Distress and concepts that emerged from field notes. Results: Primary themes included "We feel bad,'' "We are alone and afraid,'' "We are helpless,'' and "We leave it.'' A weak link between MD and opioid availability was found. Conclusions: Participants described significant work-related distress, but the moral dimension to this distress was less clear as some key aspects of the Integrated Model of Nurse Moral Distress were not supported. The concept of MD may have limited applicability in settings where alternative courses of action are unknown, or not feasible, and where differing social and cultural norms influence moral sensitivity. Implications for Practice: Improving job-related conditions is prerequisite to creating an environment where MD can manifest. Educational initiatives in LMICs must account for the role of the oncology nurse and their contextual moral and professional obligations. C1 [LeBaron, Virginia] Univ Massachusetts, Dana Farber Canc Inst, Boston, MA 02125 USA. [Beck, Susan L.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Black, Fraser] Victoria Hospice, Victoria, BC, Canada. [Palat, Gayatri] Int Network Canc Treatment & Res, Pallium, India. RP LeBaron, V (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW517, Boston, MA 02215 USA. EM virginia_lebaron@dfci.harvard.edu FU American Cancer Society [117214-DSCN-09-141-01-SCN, 121673-DSCNR-09-141-03-SCN]; Fulbright Program; University of Utah Graduate School FX Dr LeBaron received grant support from the American Cancer Society (grant 117214-DSCN-09-141-01-SCN; grant 121673-DSCNR-09-141-03-SCN), the Fulbright Program, and the University of Utah Graduate School to complete this research. NR 53 TC 5 Z9 5 U1 2 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X EI 1538-9804 J9 CANCER NURS JI Cancer Nurs. PD SEP-OCT PY 2014 VL 37 IS 5 BP 331 EP 344 DI 10.1097/NCC.0000000000000136 PG 14 WC Oncology; Nursing SC Oncology; Nursing GA AO6XZ UT WOS:000341497500011 PM 24918627 ER PT J AU Mallick, EM Garber, JJ Vanguri, VK Balasubramanian, S Blood, T Clark, S Vingadassalom, D Louissaint, C McCormick, B Snapper, SB Leong, JM AF Mallick, Emily M. Garber, John J. Vanguri, Vijay K. Balasubramanian, Sowmya Blood, Timothy Clark, Stacie Vingadassalom, Didier Louissaint, Christopher McCormick, Beth Snapper, Scott B. Leong, John M. TI The ability of an attaching and effacing pathogen to trigger localized actin assembly contributes to virulence by promoting mucosal attachment SO CELLULAR MICROBIOLOGY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; HEMOLYTIC-UREMIC SYNDROME; CITROBACTER-RODENTIUM INFECTION; MURINE COLONIC HYPERPLASIA; HUMAN INTESTINAL-MUCOSA; ADAPTER PROTEIN NCK; SHIGA-TOXIN; HOST-CELLS; IN-VIVO; N-WASP AB Enterohaemorrhagic Escherichia coli (EHEC) colonizes the intestine and causes bloody diarrhoea and kidney failure by producing Shiga toxin. Upon binding intestinal cells, EHEC triggers a change in host cell shape, generating actin 'pedestals' beneath bound bacteria. To investigate the importance of pedestal formation to disease, we infected genetically engineered mice incapable of supporting pedestal formation by an EHEC-like mouse pathogen, or wild type mice with a mutant of that pathogen incapable of generating pedestals. We found that pedestal formation promotes attachment of bacteria to the intestinal mucosa and vastly increases the severity of Shiga toxin-mediated disease. C1 [Mallick, Emily M.; Blood, Timothy; Vingadassalom, Didier; Louissaint, Christopher; McCormick, Beth; Leong, John M.] Univ Massachusetts, Dept Microbiol & Physiol Syst, Sch Med, Worcester, MA 01655 USA. [Garber, John J.; Snapper, Scott B.] Childrens Hosp, Div Gastroenterol Nutr, Boston, MA 02114 USA. [Garber, John J.; Snapper, Scott B.] Childrens Hosp, Ctr Inflammatory Bowel Dis Treatment & Res, Boston, MA 02114 USA. [Garber, John J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Garber, John J.; Snapper, Scott B.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. [Vanguri, Vijay K.; Balasubramanian, Sowmya] Univ Massachusetts, Dept Pathol, Sch Med, Worcester, MA 01655 USA. [Clark, Stacie; Leong, John M.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Snapper, Scott B.] Brigham & Womens Hosp, Div Gastroenterol & Hepatol, Boston, MA 02115 USA. RP Leong, JM (reprint author), Univ Massachusetts, Dept Microbiol & Physiol Syst, Sch Med, 55 Lake Ave North, Worcester, MA 01655 USA. EM Scott.Snapper@childrens.harvard.edu; john.leong@tufts.edu FU Inflammatory Bowel Disease Grant [DK43351]; Boston Area Diabetes and Endocrinology Research Center (BADERC) [DK57521]; NIH [R21 AI092009, R01 AI46454, P01 HL059561, R01 AI052354, 5P30DK034854, K08 DK094966, DK56754, DK33506]; Crohn's and Colitis Foundation of America; National Center for Research Resources [UL1 RR025752]; National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR000073] FX We thank Z. Demma for invaluable assistance with Salmonella infection of mice. We thank the UMMS DERC for processing tissue for histology, L. Strittamatter and G. Hendricks of the UMMS EM Core for processing EM samples, L. Sonenshein and M. Osburne for thoughtful comments on the manuscript, Stephen Baker of UMMS for help with statistical analyses, Marc Kirshner for the N-WASP antibody, and the Tufts University CTSI consultative services. Electron microscopy on littermate control and iNWKO mice was performed in the Microscopy Core of the Center for Systems Biology/Program in Membrane Biology, which is partially supported by an Inflammatory Bowel Disease Grant DK43351 and a Boston Area Diabetes and Endocrinology Research Center (BADERC) Award DK57521. The work in this manuscript was supported by NIH Grants R21 AI092009 and R01 AI46454 to JML, NIH Grants P01 HL059561, R01 AI052354, 5P30DK034854 to SBS, NIH Grant K08 DK094966 to JJG, a Career Development Award from the Crohn's and Colitis Foundation of America to JJG, a Senior Research Award from the Crohn's and Colitis Foundation of America to JML and SBS, NIH Grants DK56754 and DK33506 to BAM, and by the National Center for Research Resources Grant No. UL1 RR025752 and the National Center for Advancing Translational Sciences, National Institutes of Health, Grant No. UL1 TR000073 to Tufts University CTSI consultative services. NR 95 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD SEP PY 2014 VL 16 IS 9 BP 1405 EP 1424 DI 10.1111/cmi.12302 PG 20 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA AO3PP UT WOS:000341245700011 PM 24780054 ER PT J AU Swenson, ER AF Swenson, Erik R. TI New Insights into Carbonic Anhydrase Inhibition, Vasodilation, and Treatment of Hypertensive-Related Diseases SO CURRENT HYPERTENSION REPORTS LA English DT Article DE Sulfonamide; Acetazolamide; Hypoxic pulmonary vasoconstriction; Arterial hypertension; Thiazide; Loop diuretic ID INTRACELLULAR PH REGULATION; CHRONIC KIDNEY-DISEASE; CEREBRAL-BLOOD-FLOW; THIAZIDE DIURETICS; SMOOTH-MUSCLE; NITRIC-OXIDE; IN-VITRO; IMMUNOHISTOCHEMICAL LOCALIZATION; CARDIOMYOCYTE HYPERTROPHY; PULMONARY VASODILATION AB Carbonic anhydrase (CA) and its inhibitors are relevant to many physiological processes and diseases. The enzyme is differentially expressed throughout the body, in concentration and subcellular location, and as 13 catalytically active isoforms. Blood vessels contain small amounts of CA, but the enzyme's role in vascular physiology and blood pressure regulation is uncertain. However, considerable recent evidence points to vasodilation by CA inhibitors. CA inhibition in vascular smooth muscle, endothelium, heart, blood cells, and nervous system could all contribute. It is equally plausible that other targets besides CA for all known CA inhibitors may account for their vascular effects. I will review this knowledge and important remaining gaps relating to treatment of hypertensive-related diseases with potent sulfonamide inhibitors, such as acetazolamide; but also the possibility that CA inhibition by thiazides and loop diuretics, although generally weaker, may have antihypertensive effects beyond their inhibition of renal sodium transporters. C1 Univ Washington, Dept Vet Affairs Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Swenson, ER (reprint author), Univ Washington, Dept Vet Affairs Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98195 USA. EM eswenson@u.washington.edu NR 108 TC 9 Z9 9 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1522-6417 EI 1534-3111 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD SEP PY 2014 VL 16 IS 9 AR 467 DI 10.1007/s11906-014-0467-3 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AO6AE UT WOS:000341428700002 PM 25079851 ER PT J AU Chan, J Kulke, M AF Chan, Jennifer Kulke, Matthew TI Targeting the mTOR Signaling Pathway in Neuroendocrine Tumors SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Article DE Neuroendocrine tumor; Carcinoid; Pancreatic neuroendocrine tumor; mTOR inhibitor; Everolimus ID ENDOTHELIAL GROWTH-FACTOR; PANCREATIC ENDOCRINE CARCINOMAS; PHASE-II; LOW-GRADE; EXPRESSION; EVEROLIMUS; OCTREOTIDE; AKT; RAPAMYCIN; STREPTOZOCIN AB Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies characterized by variable but most often indolent biologic behavior. Well-differentiated NETs can be broadly classified as either carcinoid or pancreatic NET. Although they have similar characteristics on routine histologic evaluation, the 2 tumor subtypes have different biology and respond differently to treatment, with most therapeutic agents demonstrating higher response rates in pancreatic NETs compared with carcinoid. Until recently, systemic treatment options for patients with advanced NETs were limited. However, improvements in our understanding of signaling pathways involved in the pathogenesis, growth, and spread of NETs have translated into an expansion of treatment options. Aberrant signaling through the mechanistic pathway of rapamycin (mTOR) pathway has been implicated in neuroendocrine tumorigenesis. Additionally, altered expression of mTOR pathway components has been observed in NETs and has been associated with clinical outcomes. Targeting the mTOR pathway has emerged as an effective treatment strategy in the management of advanced NETs. In a randomized, placebo-controlled study of patients with advanced pancreatic NET, treatment with the mTOR inhibitor everolimus was associated with improved progression-free survival (PFS). Largely based upon these data, everolimus has been approved in the United States and Europe for the treatment of patients with advanced pancreatic NET. The activity of everolimus remains under investigation in patients with carcinoid tumors. In a randomized study of patients with advanced carcinoid tumors associated with carcinoid syndrome, the addition of everolimus to octreotide was associated with improved PFS compared with octreotide. However, the results did not meet the prespecified level of statistical significance based on central review of radiographic imaging. Results from a randomized study examining the efficacy of everolimus in patients with nonfunctional gastrointestinal and lung NETs are awaited. In addition, further investigation is needed to determine whether primary tumor site or other clinical and molecular factors can impact response to mTOR inhibition. Although everolimus can slow tumor progression, significant tumor reduction is rarely obtained. Targeting multiple signaling pathways is a treatment strategy that may provide better tumor control and overcome resistance mechanisms involved with targeting a single pathway. Results of ongoing and future studies will provide important information regarding the added benefit of combining mTOR inhibitors with other targeted agents, such as VEGF pathway inhibitors, and cytotoxic chemotherapy in the treatment of advanced NETs. C1 [Chan, Jennifer; Kulke, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Chan, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM jang@partners.org; matthew_kulke@dfci.harvard.edu FU Novartis; Merck; Bayer FX Jennifer Chan reports grants from Novartis, Merck, and Bayer. Matthew Kulke reports grants from Novartis and has served as a consultant to Pfizer, Ipsen, Lexicon, and Novartis. NR 66 TC 20 Z9 20 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2729 EI 1534-6277 J9 CURR TREAT OPTION ON JI Curr. Treat. Options Oncol. PD SEP PY 2014 VL 15 IS 3 BP 365 EP 379 DI 10.1007/s11864-014-0294-4 PG 15 WC Oncology SC Oncology GA AO6AK UT WOS:000341429500002 PM 25092520 ER PT J AU Marder, TJ Flores, VL Bolo, NR Hoogenboom, WS Simonson, DC Jacobson, AM Foote, SE Shenton, ME Sperling, RA Musen, G AF Marder, Thomas J. Flores, Veronica L. Bolo, Nicolas R. Hoogenboom, Wouter S. Simonson, Donald C. Jacobson, Alan M. Foote, Sarah E. Shenton, Martha E. Sperling, Reisa A. Musen, Gail TI Task-Induced Brain Activity Patterns in Type 2 Diabetes: A Potential Biomarker for Cognitive Decline SO DIABETES LA English DT Article ID ALZHEIMERS-DISEASE; FUNCTIONAL CONNECTIVITY; MEMORY; RISK; INSULIN; HIPPOCAMPAL; DEMENTIA; HUMANS; ADULTS; MRI AB Patients with type 2 diabetes demonstrate reduced functional connectivity within the resting state default mode network (DMN), which may signal heightened risk for cognitive decline. In other populations at risk for cognitive decline, additional magnetic resonance imaging abnormalities are evident during task performance, including impaired deactivation of the DMN and reduced activation of task-relevant regions. We investigated whether middle-aged type 2 diabetic patients show these brain activity patterns during encoding and recognition tasks. Compared with control participants, we observed both reduced 1) activation of the dorsolateral prefrontal cortex during encoding and 2) deactivation of the DMN during recognition in type 2 diabetic patients, despite normal cognition. During recognition, activation in several task-relevant regions, including the dorsolateral prefrontal cortex and DMN regions, was positively correlated with HbA(1c) and insulin resistance, suggesting that these important markers of glucose metabolism impact the brain's response to a cognitive challenge. Plasma glucose 11 mmol/L was associated with impaired deactivation of the DMN, suggesting that acute hyperglycemia contributes to brain abnormalities. Since elderly type 2 diabetic patients often demonstrate cognitive impairments, it is possible that these task-induced brain activity patterns observed in middle age may signal impending cognitive decline. C1 [Marder, Thomas J.; Flores, Veronica L.; Hoogenboom, Wouter S.; Jacobson, Alan M.; Foote, Sarah E.; Musen, Gail] Joslin Diabet Ctr, Boston, MA 02215 USA. [Flores, Veronica L.] Brandeis Univ, Dept Psychol, Waltham, MA 02254 USA. [Bolo, Nicolas R.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Bolo, Nicolas R.; Simonson, Donald C.; Jacobson, Alan M.; Shenton, Martha E.; Sperling, Reisa A.; Musen, Gail] Harvard Univ, Sch Med, Boston, MA USA. [Hoogenboom, Wouter S.; Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Hoogenboom, Wouter S.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. [Simonson, Donald C.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Jacobson, Alan M.] Winthrop Univ Hosp, Res Inst, Mineola, NY 11501 USA. [Foote, Sarah E.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Shenton, Martha E.] Vet Affairs Boston Healthcare Syst, Clin Neurosci Div, Lab Neurosci, Brockton Div,Dept Psychiat, Brockton, MA USA. [Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Sperling, Reisa A.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Musen, G (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM gail.musen@joslin.harvard.edu FU National Institutes of Health [5R01-AG-034165-A2, P30-DK-036836]; Herbert Graetz Fund FX This study was supported in part by National Institutes of Health grants 5R01-AG-034165-A2 (G.M.) and P30-DK-036836 (to the Joslin Diabetes Research Center, Genetics Core) and by the Herbert Graetz Fund. NR 25 TC 13 Z9 14 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2014 VL 63 IS 9 BP 3112 EP 3119 DI 10.2337/db13-1783 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AO7AV UT WOS:000341505300028 PM 24705405 ER PT J AU Beam, CA Gitelman, SE Palmer, JP AF Beam, Craig A. Gitelman, Stephen E. Palmer, Jerry P. CA Type 1 Diabet TrialNet Study Grp TI Recommendations for the Definition of Clinical Responder in Insulin Preservation Studies SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; C-PEPTIDE; COMPLICATIONS TRIAL; MEASUREMENT ERROR; DIABETES CONTROL; TEPLIZUMAB; MISCLASSIFICATION; IMPACT AB Clinical responder studies should contribute to the translation of effective treatments and interventions to the clinic. Since ultimately this translation will involve regulatory approval, we recommend that clinical trials prespecify a responder definition that can be assessed against the requirements and suggestions of regulatory agencies. In this article, we propose a clinical responder definition to specifically assist researchers and regulatory agencies in interpreting the clinical importance of statistically significant findings for studies of interventions intended to preserve -cell function in newly diagnosed type 1 diabetes. We focus on studies of 6-month -cell preservation in type 1 diabetes as measured by 2-h-stimulated C-peptide. We introduce criteria (bias, reliability, and external validity) for the assessment of responder definitions to ensure they meet U.S. Food and Drug Administration and European Medicines Agency guidelines. Using data from several published TrialNet studies, we evaluate our definition (no decrease in C-peptide) against published alternatives and determine that our definition has minimum bias with external validity. We observe that reliability could be improved by using changes in C-peptide later than 6 months beyond baseline. In sum, to support efficacy claims of -cell preservation therapies in type 1 diabetes submitted to U.S. and European regulatory agencies, we recommend use of our definition. C1 [Beam, Craig A.] Univ S Florida, Dept Pediat, Div Epidemiol & Biostat, Tampa, FL 33620 USA. [Gitelman, Stephen E.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Palmer, Jerry P.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Palmer, Jerry P.] Univ Washington, Seattle, WA 98195 USA. RP Beam, CA (reprint author), Western Michigan Univ, Homer Stryker MD Sch Med, Dept Biomed Sci, Div Epidemiol & Biostat, Kalamazoo, MI 49008 USA. EM craig.beam@med.wmich.edu FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, U01-DK-085509, HHSN267200800019C]; National Center for Research Resources [UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986, M01-RR-00400]; Juvenile Diabetes Research Foundation International; American Diabetes Association FX Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Allergy and Infectious Diseases; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, and U01-DK-085509 and contract HHSN267200800019C; the National Center for Research Resources, through Clinical and Translational Science Awards UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, and UL1-RR-031986 and General Clinical Research Center Award M01-RR-00400; the Juvenile Diabetes Research Foundation International; and the American Diabetes Association. NR 25 TC 5 Z9 5 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2014 VL 63 IS 9 BP 3120 EP 3127 DI 10.2337/db14-0095 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AO7AV UT WOS:000341505300029 PM 24722251 ER PT J AU Spiegelman, BM Wrann, C AF Spiegelman, Bruce M. Wrann, Christiane TI RESPONSE TO COMMENT ON WU AND SPIEGELMAN Irisin ERKs the Fat. Diabetes 2014;63:381-383 SO DIABETES LA English DT Letter C1 [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wrann, Christiane] Harvard Univ, Sch Med, Dana Farber Canc Inst, Spiegelman Lab,Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu NR 1 TC 1 Z9 1 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2014 VL 63 IS 9 BP E17 EP E17 DI 10.2337/db14-0898 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AO7AV UT WOS:000341505300002 PM 25146478 ER PT J AU Grossbard, JR Malte, CA Saxon, AJ Hawkins, EJ AF Grossbard, Joel R. Malte, Carol A. Saxon, Andrew J. Hawkins, Eric J. TI Clinical monitoring and high-risk conditions among patients with SUD newly prescribed opioids and benzodiazepines SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Opioid therapy; Substance use disorders; Clinical monitoring; Veterans; Benzodiazepines ID SUBSTANCE USE DISORDER; CHRONIC NONCANCER PAIN; PRESCRIPTION OPIOIDS; ELDERLY PERSONS; UNITED-STATES; VETERANS; THERAPY; CARE; PREVALENCE; ALCOHOL AB Background: Opioid therapy alone or in combination with benzodiazepines poses safety concerns among patients with substance use disorders (SUD). Guidelines for opioid therapy recommend SUD treatment and enhanced monitoring, especially in patients with additional risk factors, but information on monitoring practices is sparse. This study estimated high-risk conditions - psychiatric comorbidity, suicide risk, and age <35 and >= 65 - and described clinical monitoring among patients with SUD who were newly prescribed opioids alone and concurrent with benzodiazepines long-term. Methods: This study included VA Northwest Veterans Network patients with SUD who started opioids only (n = 980) or benzodiazepines and opioids concurrently (n = 353) long-term (>= 90 days) in 2009-2010. Clinical characteristics, outpatient visits and urine drug screens (UDS) documented within 7-months after starting medications were extracted from VA data. Results: Approximately 67% (95% CI: 64-70) of opioids only and 94% (92-97) of concurrent medications groups had >= 1 psychiatric diagnoses. Prevalences of suicide risk and age <35 and >= 65 were 7% (5-8), 6% (5-8) and 18% (15-20) among the opioids only group, and 20% (16-24), 8% (5-11) and 13% (9-16) among the concurrent medications group. Among patients prescribed opioids only and medications concurrently, 87% and 91% attended primary care, whereas 28% and 26% attended SUD specialty-care. Overall, 30% and 48% of opioids only and concurrent medications groups engaged in mental health or SUD care, and 35% and 39% completed UDS. Conclusions: Improvements in clinical monitoring are needed as many VA patients with SUD and comorbid risks who initiate opioid therapy do not receive sufficient mental health/SUD care or UDS monitoring. Published by Elsevier Ireland Ltd. C1 [Grossbard, Joel R.; Malte, Carol A.; Hawkins, Eric J.] VA Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Malte, Carol A.; Saxon, Andrew J.; Hawkins, Eric J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Saxon, Andrew J.; Hawkins, Eric J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Grossbard, JR (reprint author), VA Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM joel.grossbard@va.gov FU VA Puget Sound Health Services Research and Development Service (PhD Postdoctoral Fellowship Program) [TPP 61-025]; Department of Veterans Affairs, Veterans Health Administration, Center of Excellence in Substance Abuse Treatment Education FX The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or University of Washington. The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Center of Excellence in Substance Abuse Treatment & Education, and VA Puget Sound Health Services Research and Development Service (PhD Postdoctoral Fellowship Program, TPP 61-025) and these organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. We certify that we have no affiliation with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript (e.g., employment, consultancies, stock, ownership, honoraria). NR 40 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 24 EP 32 DI 10.1016/j.drugalcdep.2014.03.020 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700003 PM 24969956 ER PT J AU Lapham, GT Rubinsky, AD Williams, EC Hawkins, EJ Grossbard, J Chavez, LJ Kivlahan, DR Bradley, KA AF Lapham, Gwen T. Rubinsky, Anna D. Williams, Emily C. Hawkins, Eric J. Grossbard, Joel Chavez, Laura J. Kivlahan, Daniel R. Bradley, Katharine A. TI Decreasing sensitivity of clinical alcohol screening with the AUDIT-C after repeated negative screens in VA clinics SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Unhealthy alcohol use; Alcohol screening; Validation; AUDIT-C ID DISORDERS IDENTIFICATION TEST; US GENERAL-POPULATION; PRIMARY-CARE PATIENTS; RISK DRINKING; VETERANS-AFFAIRS; COUNSELING INTERVENTIONS; CONSUMPTION QUESTIONS; DIAGNOSTIC-TESTS; MISUSE; PROBABILITY AB Background: Routine screening for unhealthy alcohol use is widely recommended in primary care settings. However, the validity of repeat screening among patients who have previously screened negative remains unknown. This study aims to evaluate the performance of a clinical alcohol screen compared to a confidential comparison alcohol screen among patients with previous negative alcohol screens. Methods: This study included four nested samples of Veteran Health Administration (VA) outpatients with at least one (N=18,493) and up to four (N=714) prior negative annual clinical AUDIT-C screens who completed the AUDIT-C the following year, both in a VA clinic (clinical screen) and on a confidential mailed survey (comparison screen). AUDIT-C screens were categorized as either negative (0-3 points men; 0-2 women) or positive (>= 4 men; >= 3 women). For each sample, the performance of the clinical screen was compared to the comparison screen, the reference measure for unhealthy alcohol use. Results: The sensitivity of clinical screens decreased as the number of prior negative screens in a sample increased (40.0-17.4%) for patients with 1-4 negative screens. The positive predictive value also decreased as the number of prior negative screens in a sample increased (67.7-33.3%) while specificity was consistently high for all samples (>= 97.8%). Conclusions: Repeat clinical alcohol screens became progressively less sensitive for identifying unhealthy alcohol use among patients who repeatedly screened negative over several years. Alternative approaches for assessing unhealthy alcohol use may be needed for these patients. Published by Elsevier Ireland Ltd. C1 [Lapham, Gwen T.; Rubinsky, Anna D.; Williams, Emily C.; Hawkins, Eric J.; Grossbard, Joel; Chavez, Laura J.; Kivlahan, Daniel R.; Bradley, Katharine A.] Denver Seattle Ctr Innovat Vet Ctr & Value Driven, Vet Hlth Adm VA, Seattle, WA 98101 USA. [Lapham, Gwen T.; Rubinsky, Anna D.; Williams, Emily C.; Hawkins, Eric J.; Grossbard, Joel; Chavez, Laura J.; Kivlahan, Daniel R.; Bradley, Katharine A.] VA Puget Sound Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Rubinsky, Anna D.; Hawkins, Eric J.; Grossbard, Joel; Kivlahan, Daniel R.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Williams, Emily C.; Chavez, Laura J.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.; Bradley, Katharine A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Rubinsky, Anna D.] VA Palo Alto Hlth Care Syst, HSR&D Ctr Innovat Implementat Ci2i, Menlo Pk, CA 94304 USA. RP Lapham, GT (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM lapham.g@ghc.org FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSRD) [RRP 11-021]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, HSRD QUERI; Agency for Healthcare Research and Quality (AHRQ) [NIH 1R36HS022800-01] FX The research reported here was funded by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSR&D) Substance Use Disorders Quality Enhancement Research Initiative (QUERI) RRP 11-021. A preliminary version of this work was presented at both the 36th Annual Research Society for Alcoholism Scientific Meeting in Orlando, FL, June 25, 2013 and the Addiction Health Services Conference in Portland, OR, October 24, 2013. Dr. Williams is supported by a Career Development Award from the VA Health Services Research & Development (CDA 12-276) and a fellowship from the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work at Washington University. IRI is supported through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, HSR&D QUERI. Ms. Chavez is supported by an Agency for Healthcare Research and Quality (AHRQ) dissertation grant (NIH 1R36HS022800-01). These funding sources had no influence on the study's design, data collection, analyses or interpretation and reporting of results. NR 53 TC 2 Z9 2 U1 3 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 209 EP 215 DI 10.1016/j.drugalcdep.2014.06.017 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700029 PM 25034900 ER PT J AU Baumeister, SE Gelberg, L Leake, BD Yacenda-Murphy, J Vahidi, M Andersen, RM AF Baumeister, Sebastian E. Gelberg, Lillian Leake, Barbara D. Yacenda-Murphy, Julia Vahidi, Mani Andersen, Ronald M. TI Effect of a primary care based brief intervention trial among risky drug users on health-related quality of life SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Primary care clinics; Illicit drug use; Screening; Brief intervention; Quality of life ID OPIATE-DEPENDENT INDIVIDUALS; SCREENING-TEST ASSIST; CLINICALLY IMPORTANT DIFFERENCE; STARTING METHADONE TREATMENT; RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE-ABUSE TREATMENT; ALCOHOL; SETTINGS; OUTCOMES; SMOKING AB Background: Improvement in quality of life (QOL) is a long term goal of drug treatment. Although some brief interventions have been found to reduce illicit drug use, no trial among adult risky (moderate non-dependent) drug users has tested effects on health-related quality of life. Methods: A single-blind randomized controlled trial of patients enrolled from February 2011 to November 2012 was conducted in waiting rooms of five federally qualified health centers. 413 adult primary care patients were identified as risky drug users using the WHO-ASSIST and 334 (81% response; 171 intervention, 163 control) consented to participate in the trial. Three-month follow-ups were completed by 261 patients (78%). Intervention patients received the QUIT intervention of brief clinician advice and up to two drug-use health telephone sessions. The control group received usual care and information on cancer screening. Outcomes were three-month changes in the Short Form Health Survey (SF-12) mental health component summary score (MCS) and physical health component summary score (PCS). Results: The average treatment effect (ATE) was non-significant for MCS (0.2 points, p-value = 0.87) and marginally significant for PCS (1.7 points, p-value = 0.08). The average treatment effect on the treated (ATT) was 0.1 (p-value = 0.93) for MCS and 1.9 (p-value = 0.056) for PCS. The effect on PCS was stronger at higher (above median) baseline number of drug use days: ATE = 2.7, p-value = 0.04; ATT = 3.21, p-value = 0.02. Conclusions: The trial found a marginally significant effect on improvement in PCS, and significant and stronger effect on the SF-12 physical component among patients with greater frequency of initial drug use. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Baumeister, Sebastian E.] Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany. [Gelberg, Lillian; Leake, Barbara D.; Yacenda-Murphy, Julia; Vahidi, Mani] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90095 USA. [Gelberg, Lillian; Andersen, Ronald M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. [Gelberg, Lillian] VA Greater Angeles Healthcare Syst, Off Healthcare Transformat & Innovat, Los Angeles, CA 90073 USA. RP Baumeister, SE (reprint author), Univ Med Greifswald, Inst Community Med, Walther Rathenau Str 48, D-17489 Greifswald, Germany. EM sebastian.baumeister@uni-greifswald.de FU NIDA ("Preventing Drug Use in Low Income Clinic Populations") [R01 DA022445-01]; UCLA/DREW Project EXPORT, National Center on Minority Health and Health Disparities [P20MD000148/P20MD000182] FX This research was funded primarily by a grant from NIDA ("Preventing Drug Use in Low Income Clinic Populations." R01 DA022445-01). Ronald Andersen received additional support from the UCLA/DREW Project EXPORT, National Center on Minority Health and Health Disparities, P20MD000148/P20MD000182. Sebastian E. Baumeister received travel expenses for short stays at UCLA from the International Office at the University of Greifswald. NR 56 TC 6 Z9 6 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 254 EP 261 DI 10.1016/j.drugalcdep.2014.06.034 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700035 PM 25042213 ER PT J AU Durazzo, TC Mattsson, N Weiner, MW Korecka, M Trojanowski, JQ Shaw, LM AF Durazzo, Timothy C. Mattsson, Niklas Weiner, Michael W. Korecka, Magdalena Trojanowski, John Q. Shaw, Leslie M. CA Alzheimer's Dis Neuroimaging Initi TI History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cigarette smoking; Oxidative stress; Isoprostanes; Hippocampus; Cerebrospinal fluid; Elder adults ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; TOBACCO-SMOKE; CARDIOVASCULAR-DISEASE; LIPID-PEROXIDATION; UNITED-STATES; HUMAN URINE; RISK-FACTOR; BACOSIDE-A AB Background: Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F-2-isoprostane biomarkers of OxS. Methods: Elders with a lifetime history of smoking (smokers; n = 50; 75 +/- 5 years of age; 34 +/- 28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n = 61; 76 +/- 6 years of age) on CSF iPF(2 alpha)-III and 8,12, iso-iPF(2 alpha)-VI F-2-isoprostanes levels. F-2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F-2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated. Results: Smokers showed higher iPF(2 alpha)-III level than never-smokers. An age x smoking status interaction was observed for 8,12, iso-iPF(2 alpha)-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF(2 alpha)-VI concentration was associated with smaller hippocampal volume, and greater iPF(2 alpha)-III level was related to greater pack years. Conclusions: This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F-2-isoprostane levels and greater age-related increases in F-2-isoprostanes, and that higher F-2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Korecka, Magdalena; Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Korecka, Magdalena; Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Ctr Neurodegenerat Dis Res, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438 FU National Institutes of Health [NIH DA24136]; ADNI; National Institute on Aging [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co.,Inc.; Novartis AG; Pfizer Inc; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; Wyeth; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; U.S. Food and Drug Administration; Northern California Institute for Research and Education; NIH [P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435]; Dana Foundation FX This work was supported by the National Institutes of Health (NIH DA24136 to TCD) and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. All data collection and sharing for this project was supported by ADNI. ADNI is funded by the National Institute on Aging (U01 AG024904; PI MWW), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co.,Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org; http://www.fnih.org; http://www.fnih.org; http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University Southern California. This research was also supported by NIH grants P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435, and The Dana Foundation and by resources. The above funding agencies had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript. Original data used in preparation of this article were obtained from the ADNI database (www.loni.usc.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNLAuthorship_ List.pdf. NR 83 TC 4 Z9 4 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 262 EP 268 DI 10.1016/j.drugalcdep.2014.06.030 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700036 PM 25037769 ER PT J AU McCauley, JL Mercer, MA Barth, KS Brady, KT Back, SE AF McCauley, Jenna L. Mercer, Mary Ashley Barth, Kelly S. Brady, Kathleen T. Back, Sudie E. TI Pain management perceptions among prescription opioid dependent individuals SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Prescription opioid; Pain management; Addictive behaviors; Substance abuse ID MOTIVES; ABUSE AB Background: Nearly two-thirds of prescription opioid dependent individuals report chronic pain conditions as both an initial and current motivation for prescription opioid use. However, to date, limited information exists regarding perceptions of the adequacy of pain management and pain management behaviors among prescription opioid dependent individuals with a history of treatment for chronic pain. Methods: The current study examined perceptions of the medical management of chronic pain among community-recruited individuals (N = 39) who met DSM-IV-TR criteria for current prescription opioid dependence and reported a history of treatment for chronic pain. Prescription opioid dependence, symptoms of depression, and pain management perceptions were assessed using the Structured Clinical Interview for DSM disorders, Beck Depression Inventory, and the Pain Management Questionnaire, respectively. Results: Reports of insufficient pain management were common (46.2%), as was utilization of emergency room services for pain management (56.4%). Nearly half reported a physician as their initial source (46.2%) and pain management as their primary initial reason for prescription opioid use (53.8%), whereas 35.9% reported pain relief as their primary reason for current prescription opioid use. Symptoms of depression were common (51.3%), as was comorbid abuse of other substances and history of treatment for substance abuse. Conclusions: Results highlight the complicated clinical presentation and prevalent perception of the under-treatment of pain among this population. Findings underscore the importance of interdisciplinary approaches to managing the complex presentation of chronic pain patients with comorbid prescription opioid dependence. Implications for future research are discussed. Published by Elsevier Ireland Ltd. C1 [McCauley, Jenna L.; Mercer, Mary Ashley; Barth, Kelly S.; Brady, Kathleen T.; Back, Sudie E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Brady, Kathleen T.; Back, Sudie E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP McCauley, JL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St MSC 861, Charleston, SC 29425 USA. EM mccaule@musc.edu OI Mercer, Mary/0000-0001-9538-5019 FU NIDA [K23 DA021228, K12 DA031794]; MUSC Clinical & Translational Research Center (CTRC) NIH/NCRR [UL1 RR029880] FX Funding for this study was provided by NIDA grant K23 DA021228 (PI: Back), NIDA grant K12 DA031794 (PI: Brady; Sub-Award PI: McCauley), and the MUSC Clinical & Translational Research Center (CTRC) NIH/NCRR Grant number UL1 RR029880 (PI: Brady). The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 28 TC 1 Z9 1 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 354 EP 358 DI 10.1016/j.drugalcdep.2014.06.024 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700050 PM 25034899 ER PT J AU McMillan, GP AF McMillan, Garnett P. TI On Reliability SO EAR AND HEARING LA English DT Editorial Material ID SPEECH; THRESHOLD; CHILDREN; NOISE C1 Natl Ctr Rehabil Auditory Res, Portland VA Med Ctr, Portland, OR 97239 USA. RP McMillan, GP (reprint author), Natl Ctr Rehabil Auditory Res, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 12 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD SEP-OCT PY 2014 VL 35 IS 5 BP 589 EP 590 PG 2 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AO7BI UT WOS:000341506600018 PM 24722511 ER PT J AU Garshick, E AF Garshick, Eric TI Effects of short- and long-term exposures to ambient air pollution on COPD SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; PARTICULATE AIR; LUNG-FUNCTION; SYSTEMIC INFLAMMATION; CASE-CROSSOVER; HOSPITAL ADMISSIONS; POLLUTANTS; ASTHMA; COHORT; ASSOCIATIONS C1 [Garshick, Eric] Harvard Univ, Brigham & Womens Hosp, VA Boston Healthcare Syst,Med Sch,Med Serv, Channing Div Network Med,Pulm & Crit Care Med Sec, Boston, MA 02115 USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM eric.garshick@va.gov FU NIEHS NIH HHS [R01ES019853, R01 ES019853] NR 42 TC 3 Z9 3 U1 1 U2 10 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD SEP PY 2014 VL 44 IS 3 BP 558 EP 561 DI 10.1183/09031936.00108814 PG 4 WC Respiratory System SC Respiratory System GA AO4VH UT WOS:000341339000002 PM 25176946 ER PT J AU Thomas, JC Odonkor, C Griffith, L Holt, N Percac-Lima, S Leveille, S Ni, PS Latham, NK Jette, AM Bean, JF AF Thomas, Julia C. Odonkor, Charles Griffith, Laura Holt, Nicole Percac-Lima, Sanja Leveille, Suzanne Ni, Pensheng Latham, Nancy K. Jette, Alan M. Bean, Jonathan F. TI Reconceptualizing balance: attributes associated with balance performance SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Balance; Body systems; Activity; FICSIT; Boston Rehabilitative Impairment Study of the Elderly ID DWELLING OLDER-ADULTS; CONFIDENCE ABC SCALE; PERIPHERAL NEUROPATHY; PHYSICAL PERFORMANCE; MOBILITY PROBLEMS; UNIPEDAL BALANCE; RISK-ASSESSMENT; HEALTH ABC; REHABILITATION; STANCE AB Balance tests are commonly used to screen for impairments that put older adults at risk for falls. The purpose of this study was to determine the attributes that were associated with balance performance as measured by the Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) balance test. This study was a cross-sectional secondary analysis of baseline data from a longitudinal cohort study, the Boston Rehabilitative Impairment Study of the Elderly (Boston RISE). Boston RISE was performed in an outpatient rehabilitation research center and evaluated Boston area primary care patients aged 65 to 96 (N = 364) with self-reported difficulty or task-modification climbing a flight of stairs or walking 1/2 of a mile. The outcome measure was standing balance as measured by the FICSIT-4 balance assessment. Other measures included: self-efficacy, pain, depression, executive function, vision, sensory loss, reaction time, kyphosis, leg range of motion, trunk extensor muscle endurance, leg strength and leg velocity at peak power. Participants were 67% female, had an average age of 76.5 (+/- 7.0) years, an average of 4.1 (+/- 2.0) chronic conditions, and an average FICSIT-4 score of 6.7 (+/- 2.2) out of 9. After adjusting for age and gender, attributes significantly associated with balance performance were falls self-efficacy, trunk extensor muscle endurance, sensory loss, and leg velocity at peak power. FICSIT-4 balance performance is associated with a number of behavioral and physiologic attributes, many of which are amenable to rehabilitative treatment. Our findings support a consideration of balance as multidimensional activity as proposed by the current International Classification of Functioning, Disability, and Health (ICF) model. (C) 2014 Elsevier Inc. All rights reserved. C1 [Thomas, Julia C.] Wake Forest Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. [Odonkor, Charles] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Griffith, Laura; Holt, Nicole; Bean, Jonathan F.] Spaulding Cambridge Outpatient Ctr, Cambridge, MA 02138 USA. [Percac-Lima, Sanja] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Leveille, Suzanne] UMass Boston, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Ni, Pensheng; Latham, Nancy K.; Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA. [Bean, Jonathan F.] Harvard Univ, Sch Med, Dept PM&R, Boston, MA 02129 USA. RP Bean, JF (reprint author), Spaulding Cambridge Outpatient Ctr, 1575 Cambridge St, Cambridge, MA 02138 USA. EM juthomas@wakehealth.edu; charles.odonkor@yale.edu; lagriffith@partners.org; nholt1@partners.org; spercaclima@partners.org; suzanne.leveille@umb.edu; psni@bu.edu; nlatham@bu.edu; ajette@bu.edu; jfbean@partners.org RI Bean, Jonathan/F-5798-2017; OI Bean, Jonathan/0000-0001-8385-8210; Odonkor, Charles Amoatey/0000-0002-8280-4015 FU Medical Student Training in Aging Research [1T35AG038027-02]; American Federation for Aging Research [T35AG038027-01]; NIH [R01 AG032052, K24HD070966]; National Center for Research Resource [1 UL1 RR025758-01] FX The authors acknowledge support from the Medical Student Training in Aging Research 1T35AG038027-02; the American Federation for Aging Research (T35AG038027-01); NIH grants R01 AG032052 and K24HD070966 (PI-Jonathan F. Bean): and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resource. NR 48 TC 2 Z9 2 U1 7 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP PY 2014 VL 57 BP 218 EP 223 DI 10.1016/j.exger.2014.06.012 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AO5HI UT WOS:000341374300029 PM 24952097 ER PT J AU Urashima, M Mezawa, H Noya, M Camargo, CA AF Urashima, Mitsuyoshi Mezawa, Hidetoshi Noya, Miki Camargo, Carlos A., Jr. TI Effects of vitamin D supplements on influenza A illness during the 2009 H1N1 pandemic: a randomized controlled trial SO FOOD & FUNCTION LA English DT Article ID INFECTION; PNEUMONIA; CHILDREN; KABUL AB In a prior randomized trial, we found that the incidence of influenza A was less in the vitamin D3 group than among those on placebo, but the total incidence of either influenza A or B did not differ between groups. In this trial, the incidence of influenza A or B was less in the vitamin D3 group than in the placebo group only during the first half of the study. To elucidate whether vitamin D3 has preventive actions against influenza A, we conducted another trial during the 2009 pandemic of the H1N1 subtype of influenza A. Students (n = 247) of a Japanese high school were randomly assigned to receive vitamin D3 supplements (n = 148; 2000 IU per day) or a placebo (n = 99) in a double-blind study for 2 months. The primary outcome was incidence of influenza A diagnosed by a rapid influenza diagnostic test by medical doctors. Influenza A was equally likely in the vitamin D3 group (20/148: 13.5%) compared with the placebo group (12/99: 12.1%). By post hoc analysis, influenza A occurred significantly less in the vitamin D3 group (2/148: 1.4%) compared with the placebo group (8/99: 8.1%) (risk ratio, 0.17; 95% confidence interval, 0.04 to 0.77; P = 0.009) in the first month. However, during the second month, the vitamin D3 group experienced more events and effectively caught up with the placebo group. Vitamin D3 supplementation did not lower the overall incidence of influenza A during the 2009 H1N1 pandemic. A post hoc analysis suggests that the initial benefit during the first month of treatment was lost during the second month. C1 [Urashima, Mitsuyoshi; Mezawa, Hidetoshi; Noya, Miki] Jikei Univ, Sch Med, Div Mol Epidemiol, Minato Ku, Tokyo 1058461, Japan. [Urashima, Mitsuyoshi; Mezawa, Hidetoshi] Jikei Univ, Sch Med, Dept Pediat, Tokyo 1058461, Japan. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Urashima, M (reprint author), Jikei Univ, Sch Med, Div Mol Epidemiol, Minato Ku, Nishi Shimbashi 3-25-8, Tokyo 1058461, Japan. EM urashima@jikei.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology in the Japan; Jikei University School of Medicine FX We sincerely appreciate the assistance of the principal, Michio Nagahara, and teachers of Seisoku High School. We also thank the students (and their parents) for their participation. This study was supported by the Ministry of Education, Culture, Sports, Science and Technology in the Japan-Supported Program for the Strategic Research Foundation at Private Universities and the Jikei University School of Medicine. Funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 14 TC 9 Z9 9 U1 0 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2042-6496 EI 2042-650X J9 FOOD FUNCT JI Food Funct. PD SEP PY 2014 VL 5 IS 9 BP 2365 EP 2370 DI 10.1039/c4fo00371c PG 6 WC Biochemistry & Molecular Biology; Food Science & Technology SC Biochemistry & Molecular Biology; Food Science & Technology GA AO0QQ UT WOS:000341016500042 PM 25088394 ER PT J AU Shiovitz, S Bertagnolli, MM Renfro, LA Nam, E Foster, NR Dzieciatkowski, S Luo, YX Lao, VV Monnat, RJ Emond, MJ Maizels, N Niedzwiecki, D Goldberg, RM Saltz, LB Venook, A Warren, RS Grady, WM AF Shiovitz, Stacey Bertagnolli, Monica M. Renfro, Lindsay A. Nam, Eunmi Foster, Nathan R. Dzieciatkowski, Slavomir Luo, Yanxin Lao, Victoria Valinluck Monnat, Raymond J., Jr. Emond, Mary J. Maizels, Nancy Niedzwiecki, Donna Goldberg, Richard M. Saltz, Leonard B. Venook, Alan Warren, Robert S. Grady, William M. CA Alliance Clinical Trials Oncology TI CpG Island Methylator Phenotype Is Associated With Response to Adjuvant Irinotecan-Based Therapy for Stage III Colon Cancer SO GASTROENTEROLOGY LA English DT Article DE CALGB (Alliance) 89803; CRC; Epigenetic Factors; Chemotherapy ID TRIAL CALGB 89803; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; CLINICAL-PRACTICE; SURVIVAL BENEFIT; DNA METHYLATION; RECQ HELICASES; BRAF MUTATION; FLUOROURACIL; CHEMOTHERAPY AB BACKGROUND & AIMS: The CpG island methylator phenotype (CIMP), defined by a high frequency of aberrantly methylated genes, is a characteristic of a subclass of colon tumors with distinct clinical and molecular features. Cohort studies have produced conflicting results on responses of CIMP-positive tumors to chemotherapy. We assessed the association between tumor CIMP status and survival of patients receiving adjuvant fluorouracil and leucovorin alone or with irinotecan (IFL). METHODS: We analyzed data from patients with stage III colon adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or IFL after surgery, from April 1999 through April 2001. The primary end point of the trial was overall survival and the secondary end point was disease-free survival. DNA isolated from available tumor samples (n = 615) was used to determine CIMP status based on methylation patterns at the CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1 loci. The effects of CIMP on survival were modeled using Kaplan-Meier and Cox proportional hazards; interactions with treatment and BRAF, KRAS, and mismatch repair (MMR) status were also investigated. RESULTS: Of the tumor samples characterized for CIMP status, 145 were CIMP positive (23%). Patients with CIMP-positive tumors had shorter overall survival times than patients with CIMP-negative tumors (hazard ratio - 1.36; 95% confidence interval: 1.01-1.84). Treatment with IFL showed a trend toward increased overall survival for patients with CIMP-positive tumors, compared with treatment with fluorouracil and leucovorin (hazard ratio 0.62; 95% CI: 0.37-1.05; P = .07), but not for patients with CIMP-negative tumors (hazard ratio = 1.38; 95% CI: 1.00-1.89; P = .049). In a 3-way interaction analysis, patients with CIMP-positive, MMR-intact tumors benefited most from the addition of irinotecan to fluorouracil and leucovorin therapy (for the interaction, P = .01). CIMP was more strongly associated with response to IFL than MMR status. Results for disease-free survival times were comparable among all analyses. CONCLUSIONS: Patients with stage III, CIMP-positive, MMR-intact colon tumors have longer survival times when irinotecan is added to combination therapy with fluorouracil and leucovorin. C1 [Shiovitz, Stacey; Grady, William M.] Univ Washington, Dept Med, Seattle, WA USA. [Shiovitz, Stacey; Dzieciatkowski, Slavomir; Luo, Yanxin; Lao, Victoria Valinluck; Grady, William M.] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98109 USA. [Bertagnolli, Monica M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bertagnolli, Monica M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Renfro, Lindsay A.; Foster, Nathan R.] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA. [Nam, Eunmi] Ewha Womans Univ, Sch Med, Div Hematol Oncol, Seoul, South Korea. [Luo, Yanxin] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou, Guangdong, Peoples R China. [Lao, Victoria Valinluck] Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. [Monnat, Raymond J., Jr.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Monnat, Raymond J., Jr.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Emond, Mary J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Maizels, Nancy] Univ Washington, Dept Immunol, Seattle, WA 98195 USA. [Maizels, Nancy] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Niedzwiecki, Donna] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [Goldberg, Richard M.] Ohio State Univ, Columbus, OH 43210 USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Venook, Alan; Warren, Robert S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Venook, Alan; Warren, Robert S.] Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. RP Grady, WM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D4-100, Seattle, WA 98109 USA. EM wgrady@fhcrc.org OI Cohen, Stacey/0000-0002-6207-9856; Saltz, Leonard/0000-0001-8353-4670 FU National Institutes of Health (NIH) National Cancer Institute (NCI) Program [P01CA77852]; NIH [5T32-CA009515-28/29, RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, P01CA077852, 2T32DK007742-16]; Burroughs Wellcome Fund Translational Research Award for Clinician Scientist; ACS fellowship [PF-11-086-01-TBG]; ASCRS GSRRIG; NIH NCI [F32CA1591555-01, CA32291, CA77658, CA77651, CA60138]; NCI [CA31946, CA33601] FX The research reported in this article was supported by National Institutes of Health (NIH) National Cancer Institute (NCI) Program award P01CA77852 (RJM); NIH awards 5T32-CA009515-28/29 (SS), RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, and P01CA077852 (WMG); Burroughs Wellcome Fund Translational Research Award for Clinician Scientist (WMG); ACS fellowship PF-11-086-01-TBG, NIH 2T32DK007742-16, ASCRS GSRRIG, and NIH NCI F32CA1591555-01 (VVL); CA32291 (MMB); CA77658 (RMG); CA77651 (LBS); CA60138 (AV, RSW). CALGB 89803 (Alliance) was supported partly by grants from the NCI (CA31946) to the Alliance for Clinical Trials in Oncology (MMB, Chair) and to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD, CA33601) (LAR, NRF, DN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 34 TC 30 Z9 30 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2014 VL 147 IS 3 BP 637 EP 645 DI 10.1053/j.gastro.2014.05.009 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO5RK UT WOS:000341402700025 PM 24859205 ER PT J AU Feng, R Aihara, E Kenny, S Yang, L Li, J Varro, A Montrose, MH Shroyer, NF Wang, TC Shivdasani, RA Zavros, Y AF Feng, Rui Aihara, Eitaro Kenny, Susan Yang, Li Li, Jing Varro, Andrea Montrose, Marshall H. Shroyer, Noah F. Wang, Timothy C. Shivdasani, Ramesh A. Zavros, Yana TI Indian Hedgehog Mediates Gastrin-Induced Proliferation in Stomach of Adult Mice SO GASTROENTEROLOGY LA English DT Article DE Development; Gastric Epithelium; Signal Transduction; Tissue Regeneration ID SONIC HEDGEHOG; HELICOBACTER-PYLORI; GENE-EXPRESSION; PARIETAL-CELLS; ACID-SECRETION; PIT CELL; HYPERGASTRINEMIA; MORPHOGENESIS; INFLAMMATION; ACTIVATION AB BACKGROUND & AIMS: Loss of expression of Sonic Hedgehog (Shh) from parietal cells results in hypergastrinemia in mice, accompanied by increased expression of Indian Hedgehog (Ihh) and hyperproliferation of surface mucous cells. We investigated whether hypergastrinemia induces gastric epithelial proliferation by activating Ihh signaling in mice. METHODS: We studied mice with parietal cell-specific deletion of Shh (PC-ShhKO) and hypergastrinemia, crossed with gastrin-deficient (GKO) mice (PC-ShhKO/GKO). When mice were 3-4 months old, gastric tissues were collected and analyzed by histology, for incorporation of bromodeoxyuridine, and for expression of the surface mucous cell marker Ulex europaeus. PC-ShhKO/GKO mice were given gastrin infusions for 7 days; gastric surface epithelium was collected and expression of Ihh was quantified by laser capture microdissection followed by quantitative reverse transcriptase polymerase chain reaction. Mouse stomach-derived organoids were incubated with or without inhibitors of WNT (DKK1) or Smoothened (vismodegib) and then cocultured with immortalized stomach mesenchymal cells, to assess proliferative responses to gastrin. RESULTS: Gastric tissues from PC-ShhKO/GKO mice with hypergastrinemia had an expanded surface pit epithelium, indicated by a significant increase in numbers of bromodeoxyuridine-and Ulex europaeus-positive cells, but there was no evidence for hyperproliferation. Gastrin infusion of PC PC-ShhKO/GKO mice increased expression of Ihh and proliferation within the surface epithelium compared with mice given infusions of saline. In gastric organoids cocultured with immortalized stomach mesenchymal cells, antagonists of WNT and Smoothened inhibited gastrin-induced proliferation and WNT activity. Activity of WNT in media collected from immortalized stomach mesenchymal cells correlated with increased expression of glioma-associated oncogene homolog 1, and was inhibited by DKK1 or vismodegib. CONCLUSIONS: Ihh signaling mediates gastrin-induced proliferation of epithelial cells in stomachs of adult mice. C1 [Feng, Rui; Aihara, Eitaro; Yang, Li; Li, Jing; Montrose, Marshall H.; Zavros, Yana] Univ Cincinnati, Coll Med, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA. [Kenny, Susan; Varro, Andrea] Univ Liverpool, Physiol Lab, Sch Biomed Sci, Liverpool L69 3BX, Merseyside, England. [Shroyer, Noah F.] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA. [Wang, Timothy C.] Columbia Univ, Dept Med, Div Digest & Liver Dis, Coll Phys & Surg, New York, NY 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 RI Varro, Andras/M-2647-2016; OI Varro, Andras/0000-0003-0745-3603; Shroyer, Noah/0000-0002-5934-2852 FU National Institutes of Health [1R01DK083402]; Digestive Health Center Cincinnati Children's Medical Health Center (DHC: Bench to Bedside Research in Pediatric Digestive Disease) CHTF/SUB [DK078392] FX This work was supported by National Institutes of Health grant 1R01DK083402 (to Y. Zavros). Work was also supported in part by the Digestive Health Center Cincinnati Children's Medical Health Center (DHC: Bench to Bedside Research in Pediatric Digestive Disease) CHTF/SUB DK078392. NR 29 TC 11 Z9 11 U1 0 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2014 VL 147 IS 3 BP 655 EP + DI 10.1053/j.gastro.2014.05.006 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO5RK UT WOS:000341402700027 PM 24859162 ER PT J AU Abdel-Motal, UM Harbison, C Han, T Pudney, J Anderson, DJ Zhu, Q Westmoreland, S Marasco, WA AF Abdel-Motal, U. M. Harbison, C. Han, T. Pudney, J. Anderson, D. J. Zhu, Q. Westmoreland, S. Marasco, W. A. TI Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer SO GENE THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE PROTEASE INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; ADENOASSOCIATED VIRUS; HIV-INFECTION; HUMANIZED MICE; VAGINAL GEL; STEM-CELLS; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY AB Topical microbicides are a leading strategy for prevention of HIV. Mucosal infection to women; however, numerous pharmacokinetic limitations associated with coitally related dosing strategy have contributed to their limited success. Here we test the hypothesis that adeno-associated virus (AAV) mediated delivery of the b12 human anti-HIV-1 gp120 minibody gene to the lower genital tract of female rhesus macaques (Rh) can provide prolonged expression of b12 minibodies in the cervical vaginal secretions. Gene transfer studies demonstrated that, of various green fluorescent protein (GFP)-expressing AAV serotypes, AAV-6 most efficiently transduced freshly immortalized and primary genital epithelial cells (PGECs) of female Rh in vitro. In addition, AAV-6-b12 minibody transduction of Rh PGECs led to inhibition of SHIV162p4 transmigration and virus infectivity in vitro. AAV-6-GFP could also successfully transduce vaginal epithelial cells of Rh when applied intravaginally, including p63+ epithelial stem cells. Moreover, intravaginal application of AAV-6-b12 to female Rh resulted in prolonged minibody detection in their vaginal secretions throughout the 79-day study period. These data provide proof of principle that AAV-6-mediated delivery of anti-HIV broadly neutralizing antibody (BnAb) genes to the lower genital tract of female Rh results in persistent minibody detection for several months. This strategy offers promise that an anti-HIV-1 genetic microbicide strategy may be possible in which topical application of AAV vector, with periodic reapplication as needed, may provide sustained local BnAb expression and protection. C1 [Abdel-Motal, U. M.; Han, T.; Zhu, Q.; Marasco, W. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Harbison, C.; Westmoreland, S.] Harvard Univ, New England Primate Res Ctr, Sch Med, Div Comparat Pathol, Southborough, MA 01772 USA. [Pudney, J.; Anderson, D. J.] Boston Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02118 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave JF 824, Boston, MA 02215 USA. EM wayne_marasco@dfci.harvard.edu FU NIH [R21/R33 AI079767]; New England Primate Research Center Base Grant (NEPRC) [P51OD011103-51]; T32 Training Grant [T32OD011064] FX We thank Dennis Burton (The Scripps Research Institute, La Jolla, CA, USA) for providing the scFv b12DNA plasmid, and Leonidas Stamatatos for providing the SHIV162p4 virus. We thank clinical staff Joshua Kramer, Amber Hoggatt and Matt Beck for veterinary services and Karen Boisvert for microscopy and immunofluorescence assistance. This work was supported by NIH R21/R33 AI079767 (to WAM), by the New England Primate Research Center Base Grant P51OD011103-51 (NEPRC) and the T32 Training Grant T32OD011064 (to SW). NR 79 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 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD SEP PY 2014 VL 21 IS 9 BP 802 EP 810 DI 10.1038/gt.2014.56 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AO4BG UT WOS:000341280600003 PM 24965083 ER PT J AU James, P Arcaya, MC Parker, DM Tucker-Seeley, RD Subramanian, SV AF James, Peter Arcaya, Mariana C. Parker, Devin M. Tucker-Seeley, Reginald D. Subramanian, S. V. TI Do minority and poor neighborhoods have higher access to fast-food restaurants in the United States? SO HEALTH & PLACE LA English DT Article DE Food access; Poverty; Race ID LONGITUDINAL-ASSOCIATIONS; OUTLET DATABASES; HEALTHY FOODS; FULL-SERVICE; CONSUMPTION; ENVIRONMENT; DEPRIVATION; OBESITY; VALIDATION; ADULTS AB Background: Disproportionate access to unhealthy foods in poor or minority neighborhoods may be a primary determinant of obesity disparities. We investigated whether fast-food access varies by Census block group (CBG) percent black and poverty. Methods: We measured the average driving distance from each CBG population weighted ceramid to the five closest Lop Len fast-food chains and CBG percent black and percent below poverty. Results: Among 209,091 CBGs analyzed (95.1% of all US CBGs), CBG percent black was positively associated with fast-food access controlling for population density and percent poverty (average distance to Fast-food was 3.56 miles closer (95% Cl: -3.64, -3.48) in CBGs with the highest versus lowest quartile of percentage of black residents). Poverty was not independently associated with fast-food access. The relationship between fast-food access and race was stronger in CBGs with higher levels of poverty (p for interaction <0.0001), Conclusions: Predominantly black neighborhoods had higher access to Fast-food while poverty was not an independent predictor of fast-food access. (C) 2014 Elsevier Ltd. All rights reserved C1 [James, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Arcaya, Mariana C.] Harvard Ctr Populat & Dev Studies, Cambridge, MA 02138 USA. [Parker, Devin M.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH 03755 USA. [Tucker-Seeley, Reginald D.] Dana Farber Canc Inst, Dept Social & Behav Sci, Ctr Community Based Res, Boston, MA 02115 USA. [Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Subramanian, SV (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 665 Huntington Ave,Kresge Bldg 7th Floor,716, Boston, MA 02115 USA. EM pjames@hsph.harvard.edu; mca767@mail.harvard.edu; devinmarisaparker@gmail.com; retucker@hsph.harvard.edu; svsubram@hsph.harvard.edu OI James, Peter/0000-0002-2858-1973 FU Harvard NHLBI Cardiovascular Epidemiology Training Grant [T32 HL 098048]; Robert Wood Johnson Investigator Award in Health Policy Research; NCI K01 Career Development Grant [1K01CA169041] FX The research conducted for this manuscript was supported by the Harvard NHLBI Cardiovascular Epidemiology Training Grant T32 HL 098048 and the Robert Wood Johnson Investigator Award in Health Policy Research (PI Subramanian). Dr. Reginald Tucker-Seeley is supported by an NCI K01 Career Development Grant (1K01CA169041). NR 41 TC 5 Z9 5 U1 5 U2 30 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8292 EI 1873-2054 J9 HEALTH PLACE JI Health Place PD SEP PY 2014 VL 29 BP 10 EP 17 DI 10.1016/j.healthplace.2014.05.011 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5MI UT WOS:000341388500002 PM 24945103 ER PT J AU Cai, CC Huang, H Whelan, S Liu, L Kautza, B Luciano, J Wang, GL Chen, GQ Stratimirovic, S Tsung, A Billiar, TR Zuckerbraun, BS AF Cai, Changchun Huang, Hai Whelan, Sean Liu, Li Kautza, Benjamin Luciano, Jason Wang, Guoliang Chen, Guoqiang Stratimirovic, Sladjana Tsung, Allan Billiar, Timothy R. Zuckerbraun, Brian S. TI Benzyl Alcohol Attenuates Acetaminophen-Induced Acute Liver Injury in a Toll-Like Receptor-4-Dependent Pattern in Mice SO HEPATOLOGY LA English DT Article ID GROUP BOX-1 PROTEIN; INDUCED HEPATOTOXICITY; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; ISCHEMIA-REPERFUSION; STERILE INFLAMMATION; HEPATIC-INJURY; UNITED-STATES; RECEPTOR 4; HMGB1 AB Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in industrialized countries. Understanding the mechanisms of APAP-induced liver injury as well as other forms of sterile liver injury is critical to improve the care of patients. Recent studies demonstrate that danger signaling and inflammasome activation play a role in APAP-induced injury. The aim of these investigations was to test the hypothesis that benzyl alcohol (BA) is a therapeutic agent that protects against APAP-induced liver injury by modulation of danger signaling. APAP-induced liver injury was dependent, in part, on Toll-like receptor (TLR) 9 and receptor for advanced glycation endproducts (RAGE) signaling. BA limited liver injury over a dose range of 135-540 mu g/g body weight or when delivered as a pre-, concurrent, or post-APAP therapeutic. Furthermore, BA abrogated APAP-induced cytokines and chemokines as well as high-mobility group box 1 release. Moreover, BA prevented APAP-induced inflammasome signaling as determined by interleukin (IL)-1 beta, IL-18, and caspase-1 cleavage in liver tissues. Interestingly, the protective effects of BA on limiting liver injury and inflammasome activation were dependent on TLR4 signaling, but not TLR2 or CD14. Cell-type-specific knockouts of TLR4 were utilized to further determine the protective mechanisms of BA. These studies found that TLR4 expression specifically in myeloid cells (LyzCre-tlr4(-/-)) were necessary for the protective effects of BA. Conclusion: BA protects against APAP-induced acute liver injury and reduced inflammasome activation in a TLR4-dependent manner. BA may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury. C1 [Cai, Changchun; Chen, Guoqiang] Cent Hosp Wuhan, Wuhan, Peoples R China. [Cai, Changchun; Huang, Hai; Whelan, Sean; Liu, Li; Kautza, Benjamin; Luciano, Jason; Wang, Guoliang; Chen, Guoqiang; Stratimirovic, Sladjana; Tsung, Allan; Billiar, Timothy R.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Stratimirovic, Sladjana; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Surg, F1271 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu RI Huang, Hai/F-4286-2012 OI Huang, Hai/0000-0001-7430-0119 FU NIGMS NIH HHS [R01 GM082830] NR 39 TC 11 Z9 11 U1 0 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2014 VL 60 IS 3 BP 990 EP 1002 DI 10.1002/hep.27201 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO3NV UT WOS:000341239200025 PM 24798499 ER PT J AU Trinh, QD Schrag, D AF Quoc-Dien Trinh Schrag, Deborah TI Measuring the Effectiveness of Androgen-Deprivation Therapy for Prostate Cancer in the Medicare Population Adequate Data Are Neither the Same as Nor the Enemy of Perfect Data SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID HORMONE-THERAPY; REIMBURSEMENT; RISK C1 [Quoc-Dien Trinh; Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Quoc-Dien Trinh] Dana Farber Canc Inst, Div Urol Surg, Boston, MA 02215 USA. RP Schrag, D (reprint author), Dana Farber Canc Inst, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. EM deb_schrag@dfci.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP PY 2014 VL 174 IS 9 BP 1468 EP 1469 DI 10.1001/jamainternmed.2014.1107 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AO8AL UT WOS:000341574400013 PM 25023522 ER PT J AU Long, A Rahmaoui, A Rothman, KJ Guinan, E Eisner, M Bradley, MS Iribarren, C Chen, H Carrigan, G Rosen, K Szefler, SJ AF Long, Aidan Rahmaoui, Abdelkader Rothman, Kenneth J. Guinan, Eva Eisner, Mark Bradley, Mary S. Iribarren, Carlos Chen, Hubert Carrigan, Gillis Rosen, Karin Szefler, Stanley J. TI Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Cancer; safety; anti-IgE; EXCELS; allergic asthma ID SEVERE ALLERGIC-ASTHMA; SEVERE PERSISTENT ASTHMA; ANTI-IGE ANTIBODY; CANCER INCIDENCE; RISK; THERAPY; EXACERBATIONS; COHORT AB Background: The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma (EXCELS) assessed the long-term safety of omalizumab in a clinical practice setting as part of a phase IV US Food and Drug Administration postmarketing commitment. Objective: We sought to evaluate long-term safety in omalizumab-treated and nonomalizumab-treated patients. Primary outcome measures focused on assessment of malignancies. Methods: EXCELS was a prospective observational cohort study in patients (>= 12 years of age) with moderate-to-severe allergic asthma. There were 2 cohorts: omalizumab (taking omalizumab at baseline) and nonomalizumab (no history of omalizumab treatment). Primary outcomes included all confirmed, incident, study-emergent primary malignancies (malignancies), including and excluding nonmelanoma skin cancer (NMSC); all malignancies were externally adjudicated. Results: The omalizumab cohort had a higher proportion of patients with severe asthma compared with the nonomalizumab cohort (50.0% vs 23.0%). Median follow-up was approximately 5 years for both cohorts. Crude malignancy rates were similar in the omalizumab and nonomalizumab cohorts, with a rate ratio of 0.84 (95% CI, 0.62-1.13) for all malignancies and 0.98 (95% CI, 0.71-1.36) for all malignancies excluding NMSC. Kaplan-Meier plots of time to first confirmed study-emergent primary malignancy were similar for the 2 treatment cohorts. Cox proportional hazards modeling, adjusting for confounders and risk factors, resulted in a hazard ratio (omalizumab vs nonomalizumab) of 1.09 (95% CI, 0.87-1.38) for all malignancies and 1.15 (95% CI, 0.83-1.59) for all malignancies excluding NMSC. Conclusion: Results from EXCELS suggest that omalizumab therapy is not associated with an increased risk of malignancy. C1 [Long, Aidan] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Long, Aidan] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rahmaoui, Abdelkader; Eisner, Mark; Bradley, Mary S.; Chen, Hubert; Carrigan, Gillis; Rosen, Karin] Genentech Inc, South San Francisco, CA USA. [Rothman, Kenneth J.] RTI Hlth Solut, Res Triangle Pk, NC USA. [Guinan, Eva] Dana Farber Canc Inst, Boston, MA USA. [Iribarren, Carlos] Kaiser Permanente Med Care Program, Div Res, Oakland, CA USA. [Szefler, Stanley J.] Childrens Hosp, Denver, CO USA. [Szefler, Stanley J.] Univ Colorado, Sch Med, Denver, CO 80202 USA. RP Long, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cox 201,55 Fruit St, Boston, MA 02114 USA. EM aalong@mgh.harvard.edu FU Genentech, South San Francisco, California; Novartis Pharmaceuticals, East Hanover, New Jersey FX Supported by Genentech, South San Francisco, California, and Novartis Pharmaceuticals, East Hanover, New Jersey. NR 21 TC 41 Z9 42 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2014 VL 134 IS 3 BP 560 EP + DI 10.1016/j.jaci.2014.02.007 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA AO5GR UT WOS:000341372400007 PM 24679845 ER PT J AU Patil, SU Shreffler, WG AF Patil, Sarita U. Shreffler, Wayne G. TI BATting above average: Basophil activation testing for peanut allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material DE IgE-mediated peanut allergy; serum IgE testing; oral food challenge; basophil activation test; skin prick testing ID FOOD ALLERGY; DIAGNOSIS; IGE; CHILDREN C1 [Patil, Sarita U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA USA. [Shreffler, Wayne G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Food Allergy Ctr,Dept Pediat,Div Allergy & Immuno, Boston, MA USA. RP Shreffler, WG (reprint author), Massachusetts Gen Hosp, 55 Fruit St,CNY 149 8-405, Boston, MA 02114 USA. EM wshreffler@mgh.harvard.edu NR 15 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2014 VL 134 IS 3 BP 653 EP 654 DI 10.1016/j.jaci.2014.07.040 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA AO5GR UT WOS:000341372400018 PM 25171867 ER PT J AU Mattoo, H Mahajan, VS Della-Torre, E Sekigami, Y Carruthers, M Wallace, ZS Deshpande, V Stone, JH Pillai, S AF Mattoo, Hamid Mahajan, Vinay S. Della-Torre, Emanuel Sekigami, Yurie Carruthers, Mollie Wallace, Zachary S. Deshpande, Vikram Stone, John H. Pillai, Shiv TI De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG(4)-related disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE IgG(4)-related disease; autoreactivity; rituximab; next-generation sequencing; somatic hypermutation; plasmablasts; immunoglobulin heavy chain variable region repertoire; CDR3 ID IGG4-RELATED SYSTEMIC-DISEASE; AUTOIMMUNE PANCREATITIS; B-CELLS; SCLEROSING PANCREATITIS; MONOCLONAL-ANTIBODIES; RITUXIMAB; REPERTOIRE; CHOLANGITIS; EXPRESSION; GENERATION AB Background: IgG(4)-related disease (IgG(4)-RD) is a poorly understood, multiorgan, chronic inflammatory disease characterized by tumefactive lesions, storiform fibrosis, obliterative phlebitis, and accumulation of IgG(4)-expressing plasma cells at disease sites. Objective: The role of B cells and IgG(4) antibodies in IgG(4)-RD pathogenesis is not well defined. We evaluated patients with IgG(4)-RD for activated B cells in both disease lesions and peripheral blood and investigated their role in disease pathogenesis. Methods: B-cell populations from the peripheral blood of 84 patients with active IgG(4)-RD were analyzed by using flow cytometry. The repertoire of B-cell populations was analyzed in a subset of patients by using next-generation sequencing. Fourteen of these patients were longitudinally followed for 9 to 15 months after rituximab therapy. Results: Numbers of CD19(+)CD27(+)CD20(-)CD38(hi) plasmablasts, which are largely IgG(4)(+), are increased in patients with active IgG(4)-RD. These expanded plasmablasts are oligoclonal and exhibit extensive somatic hypermutation, and their numbers decrease after rituximab-mediated B-cell depletion therapy; this loss correlates with disease remission. A subset of patients relapse after rituximab therapy, and circulating plasmablasts that re-emerge in these subjects are clonally distinct and exhibit enhanced somatic hypermutation. Cloning and expression of immunoglobulin heavy and light chain genes from expanded plasmablasts at the peak of disease reveals that disease-associated IgG(4) antibodies are self-reactive. Conclusions: Clonally expanded CD19(+)CD27(+)CD20(-)CD38(hi) plasmablasts are a hallmark of active IgG(4)-RD. Enhanced somatic mutation in activated B cells and plasmablasts and emergence of distinct plasmablast clones on relapse indicate that the disease pathogenesis is linked to de novo recruitment of naive B cells into T cell-dependent responses by CD4(+) T cells, likely driving a self-reactive disease process. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Pillai, S (reprint author), Ctr Canc Res, 149 13th St Boston, Boston, MA 02129 USA. EM jhstone@partners.org; pillai@helix.mgh.harvard.edu OI Della Torre, Emanuel/0000-0002-9192-4270 FU National Institutes of Health [AI 064930, AI 076505]; Helmsley Charitable Trust FX Supported by grants AI 064930 and AI 076505 from the National Institutes of Health and a pilot grant from the Harvard Institute of Translational Immunology supported by the Helmsley Charitable Trust (to S.P.). NR 34 TC 64 Z9 67 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2014 VL 134 IS 3 BP 679 EP 687 DI 10.1016/j.jaci.2014.03.034 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA AO5GR UT WOS:000341372400022 PM 24815737 ER PT J AU Mandala, WL Ananworanich, J Apornpong, T Kerr, SJ MacLennan, JM Hanson, C Jaimulwong, T Gondwe, EN Rosenblatt, HM Bunupuradah, T Molyneux, ME Spector, SA Pancharoen, C Gelman, RS MacLennan, CA Shearer, WT AF Mandala, Wilson L. Ananworanich, Jintanat Apornpong, Tanakorn Kerr, Stephen J. MacLennan, Jenny M. Hanson, Celine Jaimulwong, Tanyathip Gondwe, Esther N. Rosenblatt, Howard M. Bunupuradah, Torsak Molyneux, Malcolm E. Spector, Stephen A. Pancharoen, Chitsanu Gelman, Rebecca S. MacLennan, Calman A. Shearer, William T. TI Control lymphocyte subsets: Can one country's values serve for another's? SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID HEALTHY; CHILDREN; MANAGEMENT; CYTOKINES; ADULTS; VIRUS; CELLS; CD4; AGE C1 [Mandala, Wilson L.; MacLennan, Jenny M.; Gondwe, Esther N.; Molyneux, Malcolm E.; MacLennan, Calman A.] Malawi Liverpool Wellcome Trust, Clin Res Programme, Blantyre, Malawi. [Mandala, Wilson L.] Coll Med, Dept Basic Med Sci, Blantyre, Malawi. [Mandala, Wilson L.; Gondwe, Esther N.; Molyneux, Malcolm E.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Ananworanich, Jintanat; Apornpong, Tanakorn; Kerr, Stephen J.; Jaimulwong, Tanyathip; Bunupuradah, Torsak] HIV Netherlands Australia Thailand Res Collaborat, Bangkok, Thailand. [Ananworanich, Jintanat] SEARCH, Thai Red Cross AIDS Res Ctr, Bangkok, Thailand. [Ananworanich, Jintanat] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand. [Kerr, Stephen J.] UNSW Australia, Kirby Inst, Sydney, NSW, Australia. [MacLennan, Jenny M.] Univ Oxford, Dept Zool, Oxford OX1 2JD, England. [Hanson, Celine] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Rosenblatt, Howard M.] Specialty Children, Austin, TX USA. [Spector, Stephen A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Gelman, Rebecca S.] Rady Childrens Hosp, San Diego, CA USA. [Gelman, Rebecca S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gelman, Rebecca S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [MacLennan, Calman A.] Univ Birmingham, Coll Med, MRC Ctr Immune Regulat & Clin Immunol Serv, Sch Immun & Infect, Birmingham, W Midlands, England. [MacLennan, Calman A.] Novartis Vaccines Inst Global Hlth, Siena, Italy. [Shearer, William T.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Mandala, WL (reprint author), Malawi Liverpool Wellcome Trust, Clin Res Programme, Blantyre, Malawi. EM wmandala2002@gmail.com RI MacLennan, Calman/L-9343-2014 OI MacLennan, Calman/0000-0001-9694-0846 FU NCRR NIH HHS [M01 RR-00188, M01 RR000188]; NIAID NIH HHS [P30 AI036211, P30 AI36211, R01 AI075408, R01 AI94029, R01AI075408-0, U01 AI027551, U01 AI041110, U01 AI068616, U01 AI068632, U01 AI41110, U01AI27551, UM1 AI069536]; Wellcome Trust [, 101113] NR 20 TC 2 Z9 2 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2014 VL 134 IS 3 BP 759 EP + DI 10.1016/j.jaci.2014.06.030 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA AO5GR UT WOS:000341372400041 PM 25171870 ER PT J AU Forman, DE LaFond, K Panch, T Allsup, K Manning, K Sattelmair, J AF Forman, Daniel E. LaFond, Karen Panch, Trishan Allsup, Kelly Manning, Kenneth Sattelmair, Jacob TI Utility and Efficacy of a Smartphone Application to Enhance the Learning and Behavior Goals of Traditional Cardiac Rehabilitation A FEASIBILITY STUDY SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION LA English DT Article DE cardiac rehabilitation; feasibility study; phone application ID AMERICAN-HEART-ASSOCIATION; SECONDARY PREVENTION; TASK-FORCE; SURGERY; COLLEGE; DISEASE AB PURPOSE: Most eligible patients do not participate in traditional clinic-based cardiac rehabilitation (CR) despite well-established benefits. Novel approaches to overcome logistic obstacles and increase efficiencies of learning, behavior modification, and exercise surveillance may increase CR participation. In an observational study, the feasibility and utility of a mobile smartphone application for CR, Heart Coach (HC), were assessed as part of standard care. Ultimately, innovative CR models incorporating HC may facilitate better CR usage and value. METHODS: Twenty-six patients enrolled in CR installed HC. Over the next 30 days, they were prompted by HC to complete a daily "task list" that included medications, walking, education (text and videos), and surveys. Cardiac rehabilitation providers monitored each patient's progress through a HC-based Web dashboard and also sent them personalized feedback and support. Completion of the tasks and feedback (qualitative and quantitative) from patients and clinicians were tracked. RESULTS: Patients engaged with HC 90% of days during the study period, with uniformly favorable impact on compliance and adherence. Eighty-three percent of patients reported a positive/very positive HC experience. Providers reported that HC enhanced their provision of therapy by improving communication, clinical insight, patient participation, and program efficiency. CONCLUSIONS: Integrating a mobile care delivery platform into CR was feasible, safe, and agreeable to patients and clinicians. It enhanced patient perceptions of CR care and physician perceptions of the CR caregiving process. Mobile-enabled technologies hold promise to extend the quality and reach of CR, and to better achieve contemporary accountable care goals. C1 [Forman, Daniel E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Forman, Daniel E.; Allsup, Kelly; Manning, Kenneth] VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [LaFond, Karen] South Shore Hosp, Dept Cardiac & Pulm Rehabil, South Weymouth, MA USA. [LaFond, Karen] Massachusetts Assoc Cardiovasc & Pulm Rehabil, Falmouth, MA USA. [Panch, Trishan; Sattelmair, Jacob] Wellframe Inc, Boston, MA USA. RP Forman, DE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM deforman@partners.org NR 13 TC 6 Z9 6 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-7501 EI 1932-751X J9 J CARDIOPULM REHABIL JI J. Cardiopulm. Rehabil. Prev. PD SEP-OCT PY 2014 VL 34 IS 5 BP 327 EP 334 DI 10.1097/HCR.0000000000000058 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO7WA UT WOS:000341562100004 PM 24866355 ER PT J AU Bejar, R Stevenson, KE Caughey, B Lindsley, RC Mar, BG Stojanov, P Getz, G Steensma, DP Ritz, J Soiffer, R Antin, JH Alyea, E Armand, P Ho, V Koreth, J Neuberg, D Cutler, CS Ebert, BL AF Bejar, Rafael Stevenson, Kristen E. Caughey, Bennett Lindsley, R. Coleman Mar, Brenton G. Stojanov, Petar Getz, Gad Steensma, David P. Ritz, Jerome Soiffer, Robert Antin, Joseph H. Alyea, Edwin Armand, Philippe Ho, Vincent Koreth, John Neuberg, Donna Cutler, Corey S. Ebert, Benjamin L. TI Somatic Mutations Predict Poor Outcome in Patients With Myelodysplastic Syndrome After Hematopoietic Stem-Cell Transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGNOSTIC SCORING SYSTEM; TP53 MUTATIONS; DECISION-ANALYSIS; DNMT3A MUTATIONS; POINT MUTATIONS; IMPACT; LEUKEMIA; MDS; CLASSIFICATION; U2AF1 AB Purpose Recurrently mutated genes in myelodysplastic syndrome (MDS) are pathogenic drivers and powerfully associated with clinical phenotype and prognosis. Whether these types of mutations predict outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with MDS is not known. Patients and Methods We used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes. Results Mutations were identified in 92% of patients, most frequently in the ASXL1 (29%), TP53 (21%), DNMT3A (18%), and RUNX1 (16%) genes. In univariable analyses, only TP53 mutations were associated with shorter overall (OS; hazard ratio [HR], 3.74; P < .001) and progression-free survival (HR, 3.97; P < .001). After adjustment for clinical variables associated with these end points, mutations in TP53 (HR, 2.30; P = .027), TET2 (HR, 2.40; P = .033), and DNMT3A (HR, 2.08; P = .049) were associated with decreased OS. In multivariable analysis including clinical variables, complex karyotype status, and candidate genes, mutations in TP53 (HR, 4.22; P <= .001) and TET2 (HR, 1.68; P = .037) were each independently associated with shorter OS. Nearly one half of patients (46%) carried a mutation in TP53, DNMT3A, or TET2 and accounted for 64% of deaths. Three-year OS in patients without these mutations was 59% (95% CI, 43% to 72%), versus 19% (95% CI, 9% to 33%) in patients with these mutations. Conclusion Mutations in TP53, TET2, or DNMT3A identify patients with MDS with shorter OS after HSCT. (C) 2014 by American Society of Clinical Oncology C1 [Bejar, Rafael; Caughey, Bennett] Univ Calif San Diego, La Jolla, CA 92093 USA. [Stevenson, Kristen E.; Lindsley, R. Coleman; Mar, Brenton G.; Steensma, David P.; Ritz, Jerome; Soiffer, Robert; Antin, Joseph H.; Alyea, Edwin; Armand, Philippe; Ho, Vincent; Koreth, John; Neuberg, Donna; Cutler, Corey S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lindsley, R. Coleman; Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Stojanov, Petar; Getz, Gad; Ebert, Benjamin L.] Broad Inst, Cambridge, MA USA. RP Ebert, BL (reprint author), Brigham & Womens Hosp, 1 Blackfan Circle,Karp CHRB 5-211, Boston, MA 02115 USA. EM benjamin_ebert@dfci.harvard.edu OI Lindsley, Coleman/0000-0001-9822-806X; Ritz, Jerome/0000-0001-5526-4669; Mar, Brenton/0000-0002-3857-9324 FU National Institute of Diabetes and Digestive and Kidney Diseases [5K08DK091360]; American Society of Hematology scholar award; National Heart, Lung, and Blood Institute [R01HL082945]; Leukemia and Lymphoma Society scholar award; Yellow Diamond Foundation Fund FX Supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant No. 5K08DK091360 and an American Society of Hematology scholar award (R.B.) and by National Heart, Lung, and Blood Institute Grant No. R01HL082945, a Leukemia and Lymphoma Society scholar award, and the Yellow Diamond Foundation Fund (B.L.E.). NR 33 TC 93 Z9 95 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2014 VL 32 IS 25 BP 2691 EP + DI 10.1200/JCO.2013.52.3381 PG 9 WC Oncology SC Oncology GA AO7WF UT WOS:000341562600006 PM 25092778 ER PT J AU Dieras, V Harbeck, N Budd, GT Greenson, JK Guardino, AE Samant, M Chernyukhin, N Smitt, MC Krop, IE AF Dieras, Veronique Harbeck, Nadia Budd, G. Thomas Greenson, Joel K. Guardino, Alice E. Samant, Meghna Chernyukhin, Nataliya Smitt, Melanie C. Krop, Ian E. TI Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: An Integrated Safety Analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NODULAR REGENERATIVE HYPERPLASIA; PHASE-II; MAYTANSINE AB Purpose The antibody-drug conjugate trastuzumab emtansine (T-DM1) combines the cytotoxic activity of DM1 with the human epidermal growth factor receptor 2 (HER2) -targeted, antitumor properties of trastuzumab. T-DM1 has shown activity in phase I and II single-arm studies in patients with pretreated HER2-positive metastatic breast cancer (MBC) and has demonstrated superior efficacy and improved tolerability versus standard MBC treatments in randomized phase II and III studies. This analysis, combining available data from all single-agent T-DM1 studies to date, was conducted to better define the T-DM1 safety profile. Patients and Methods Six studies in patients with HER2-positive MBC who received T-DM1 3.6 mg/kg every 3 weeks and follow-up data from patients in an extension study were analyzed. Analyses included adverse events (AEs) by grade; AEs leading to death, drug discontinuation, or dose reduction; and select AEs. Results Among 884 T-DM1-exposed patients, the most commonly reported all-grade AEs were fatigue (46.4%), nausea (43.0%), thrombocytopenia (32.2%), headache (29.4%), and constipation (26.5%). The most common grade 3 to 4 AEs were the laboratory abnormalities of thrombocytopenia (11.9%) and increased AST serum concentration (4.3%). These were manageable and not generally associated with clinical symptoms. There were 12 AE-related deaths. AEs resulted in dose reductions in 17.2% of patients and drug discontinuations in 7.0%. Conclusion In this analysis of 884 T-DM1-exposed patients, grade 3 or greater AEs were infrequent and typically asymptomatic and manageable. This favorable safety profile makes T-DM1 treatment suitable for exploration in other breast cancer settings. (C) 2014 by American Society of Clinical Oncology C1 [Dieras, Veronique] Inst Curie, F-75005 Paris, France. [Harbeck, Nadia] Univ Munich, Munich, Germany. [Budd, G. Thomas] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Greenson, Joel K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Guardino, Alice E.; Samant, Meghna; Chernyukhin, Nataliya; Smitt, Melanie C.] Genentech Inc, San Francisco, CA 94080 USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dieras, V (reprint author), Inst Curie, 26 Rue Ulm, F-75005 Paris, France. EM veronique.dieras@curie.fr FU Genentech/Roche; Genentech FX G. Thomas Budd, Genentech/Roche; Ian E. Krop, Genentech NR 19 TC 24 Z9 24 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2014 VL 32 IS 25 BP 2750 EP + DI 10.1200/JCO.2013.54.4999 PG 11 WC Oncology SC Oncology GA AO7WF UT WOS:000341562600014 PM 25024070 ER PT J AU Billmire, DF Krailo, M Rodriguez-Galindo, C Frazier, AL AF Billmire, Deborah F. Krailo, Mark Rodriguez-Galindo, Carlos Frazier, A. Lindsay TI Adjuvant Chemotherapy in Stage I Ovarian Germ Cell Tumors: Should Indications and Treatment Modalities Be Different in Young Girls and Adults? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID YOLK-SAC TUMOR; TESTICULAR-CANCER; ETOPOSIDE; BLEOMYCIN; CHILDREN; SURVEILLANCE; ADOLESCENTS; CISPLATIN; SURGERY C1 [Billmire, Deborah F.] Indiana Univ, Riley Hosp Children, Indianapolis, IN 46204 USA. [Krailo, Mark] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Boston Childrens Hosp, Boston, MA USA. RP Billmire, DF (reprint author), Indiana Univ, Riley Hosp Children, Indianapolis, IN 46204 USA. FU NCI NIH HHS [U10 CA098543] NR 14 TC 2 Z9 2 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 SEP 1 PY 2014 VL 32 IS 25 BP 2816 EP 2817 DI 10.1200/JCO.2014.56.3890 PG 2 WC Oncology SC Oncology GA AO7WF UT WOS:000341562600028 PM 25071123 ER PT J AU Tirumani, H Saddala, P Fasih, N AF Tirumani, Harika Saddala, Prashanth Fasih, Najla TI INCARCERATED MORGAGNI HERNIA: AN UNUSUAL CAUSE OF LARGE BOWEL OBSTRUCTION SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article C1 [Tirumani, Harika] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Saddala, Prashanth] Kurnool Med Coll & Hosp, Kurnool, India. [Fasih, Najla] Ottawa Hosp, Dept Diagnost Radiol, Ottawa, ON, Canada. RP Tirumani, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. NR 6 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 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2014 VL 47 IS 3 BP 320 EP 322 DI 10.1016/j.jemermed.2013.12.004 PG 3 WC Emergency Medicine SC Emergency Medicine GA AO6ET UT WOS:000341443300020 PM 24915742 ER PT J AU Siegelman, JN Marill, KA Adler, JN AF Siegelman, Jeffrey N. Marill, Keith A. Adler, Jonathan N. TI TACHYDYSRHYTHMIA TREATMENT AND ADVERSE EVENTS IN PATIENTS WITH WOLFF-PARKINSON-WHITE SYNDROME SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE WPW; Wolff-Parkinson-White syndrome; tachydysrhythmia; AV-nodal blockade; atrial fibrillation; cardiovascular emergencies ID ACUTE ATRIAL-FIBRILLATION; VENTRICULAR-FIBRILLATION; INTRAVENOUS AMIODARONE; PRECIPITATION; TACHYCARDIA; ADENOSINE; VERAPAMIL AB Background: Current guidelines recommend avoiding atrioventricular-nodal blocking agents (AVNB) when treating tachydysrhythmias in Wolff-Parkinson-White syndrome (WPW) patients. Study Objectives: We investigated medications selected and resulting outcomes for patients with tachydysrhythmias and WPW. Methods: In this single-center retrospective cohort study, we searched a hospital-wide database for the following inclusion criteria: WPW, tachycardia, and intravenous antidysrhythmics. The composite outcome of adverse events was acceleration of tachycardia, new hypotension, new malignant dysrhythmia, and cardioversion. The difference in binomial proportions of patients meeting the composite outcome after AVNB or non-AVNB (NAVNB) treatment was calculated after dividing the groups by QRS duration. A random-effects mixed linear analysis was performed to analyze the vital sign response. Results: The initial database search yielded 1158 patient visits, with 60 meeting inclusion criteria. Patients' median age was 52.5 years; 53% were male, 43% presented in wide complex tachycardia (WCT), with 75% in atrial fibrillation (AF) or flutter. AVNBs were administered in 42 (70%) patient visits. For those patients with WCT in AF, the difference in proportions of patients meeting the composite outcome after AVNBs vs. NAVNBs treatment was an increase of 3% (95% confidence interval [CI] -39%-49%), and for those with narrow complex AF it was a decrease of 13% (95% CI -37%-81%). No instances of malignant dysrhythmia occurred. Mixed linear analysis showed no statistically significant effects on heart rate, though suggested a trend toward increasing heart rate after AVNB in wide complex AF. Conclusion: In this sample of WPW-associated tachydysrhythmia patients, many were treated with AVNBs. The composite outcome was similarly met after use of either AVNB or NAVNB, and no malignant dysrhythmias were observed. (C) 2014 Elsevier Inc. C1 [Siegelman, Jeffrey N.] Emory Univ, Dept Emergency Med, Atlanta, GA 30322 USA. [Marill, Keith A.; Adler, Jonathan N.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Siegelman, JN (reprint author), Emory Univ, Dept Emergency Med, Atlanta, GA 30322 USA. FU Massachusetts College of Emergency Physicians Resident research grant FX This work was supported in part by a Massachusetts College of Emergency Physicians Resident research grant. We also greatly appreciate the efforts of Blair Parry, Laura Meloney, and the MGH Research Staff. NR 15 TC 0 Z9 0 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2014 VL 47 IS 3 BP 357 EP 366 DI 10.1016/j.jemermed.2013.11.127 PG 10 WC Emergency Medicine SC Emergency Medicine GA AO6ET UT WOS:000341443300028 PM 24880554 ER PT J AU Boland, GW Enzmann, DR Duszak, R AF Boland, Giles W. Enzmann, Dieter R. Duszak, Richard, Jr. TI Actionable Reporting SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Boland, Giles W.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Enzmann, Dieter R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. RP Boland, GW (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 4 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2014 VL 11 IS 9 BP 844 EP 845 DI 10.1016/j.jacr.2014.06.002 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO7NZ UT WOS:000341541200005 PM 25096482 ER PT J AU Durand, DJ Robertson, CT Agarwal, G Duszak, R Krupinski, EA Itri, JN Fotenos, A Savoie, B Ding, A Lewin, JS AF Durand, Daniel J. Robertson, Christopher T. Agarwal, Gautam Duszak, Richard, Jr. Krupinski, Elizabeth A. Itri, Jason N. Fotenos, Anthony Savoie, Brent Ding, Alexander Lewin, Jonathan S. TI Expert Witness Blinding Strategies to Mitigate Bias in Radiology Malpractice Cases: A Comprehensive Review of the Literature SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Review DE Observer performance; observer bias; medical malpractice; expert-witness blinding; blinded peer review ID HINDSIGHT BIAS; LITIGATION; NEGLIGENCE; CONTEXT; CANCER; ISSUES; IMAGES; ERRORS; CLAIMS; HEAD AB Like all physicians, radiologists in the United States are subject to frequent and costly medical malpractice claims. Legal scholars and physicians concur that the US civil justice system is neither precise nor accurate in determining whether malpractice has truly occurred in cases in which claims are made. Sometimes, this inaccuracy is driven by biases inherent in medical expert-witness opinions. For example, expert-witness testimony involving "missed" radiology findings can be negatively affected by several cognitive biases, such as contextual bias, hindsight bias, and outcome bias. Biases inherent in the US legal system, such as selection bias, compensation bias, and affiliation bias, also play important roles. Fortunately, many of these biases can be significantly mitigated or eliminated through the use of appropriate blinding techniques. This paper reviews the major works on expert-witness blinding in the legal scholarship and the radiology professional literature. Its purpose is to acquaint the reader with the evidence that unblinded expert-witness testimony is tainted by multiple sources of bias and to examine proposed strategies for addressing these biases through blinding. C1 [Durand, Daniel J.; Agarwal, Gautam; Fotenos, Anthony; Savoie, Brent; Lewin, Jonathan S.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Robertson, Christopher T.] Harvard Univ, Sch Law, Cambridge, MA 02138 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA USA. [Krupinski, Elizabeth A.] Univ Arizona, Dept Med Imaging, Tucson, AZ USA. [Itri, Jason N.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Ding, Alexander] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Durand, DJ (reprint author), Russell H Morgan Dept Radiol & Radiol Sci, Div Pediat Radiol, 1800 Orleans St,Zayed Tower,4th Floor,Rm 4174, Baltimore, MD 21287 USA. EM Daniel.J.Durand@gmail.com RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 38 TC 1 Z9 1 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2014 VL 11 IS 9 BP 868 EP 873 DI 10.1016/j.jacr.2014.05.001 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO7NZ UT WOS:000341541200011 PM 25041992 ER PT J AU Niel, BL Gavenonis, SC Motazedi, T Chubiz, JC Halpern, EP Rafferty, EA Lee, JM AF Niel, Bethany L. Gavenonis, Sara C. Motazedi, Tina Chubiz, Jessica Cott Halpern, Elkan P. Rafferty, Elizabeth A. Lee, Janie M. TI Auditing a Breast MRI Practice: Performance Measures for Screening and Diagnostic Breast MRI SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Audit; breast MRI; positive predictive value; cancer detection rate; abnormal interpretation rate ID POSITIVE PREDICTIVE-VALUE; PROBABLY BENIGN LESIONS; HIGH-RISK; MAMMOGRAPHY; CANCER; WOMEN; BENCHMARKS; MALIGNANCY; FREQUENCY AB Purpose: Breast MRI is increasingly used for both screening and diagnostic purposes. Although performance benchmarks for screening and diagnostic mammography have been published, performance benchmarks for breast MRI have yet to be established. The purpose of this study was to comprehensively evaluate breast MRI performance measures, stratified by screening and diagnostic indications, from a single academic institution. Methods: Institutional review board approval was acquired for this HIPAA-compliant study. Informed consent was not required. Retrospective review of the institutional database identified all breast MRI examinations performed from April 1, 2007, to March 31, 2008. After application of exclusion criteria, the following performance measures for screening and diagnostic indications were calculated: cancer detection rate, positive predictive value (PPV), and abnormal interpretation rates. Results: The study included 2,444 examinations, 1,313 for screening and 1,131 for diagnostic indications. The cancer detection rates were 14 per 1,000 screening breast MRI examinations and 47 per 1,000 diagnostic examinations (P < .00001). The abnormal interpretation rate was 12% (152 of 1,313) for screening and 17% (194 of 1,131) for diagnostic indications (P = .00008). The PPVs of MRI were lower for screening [PPV1 (abnormal findings) = 12%, PPV2 (biopsy recommended) = 24%, PPV3 (biopsy performed) = 27%] compared with diagnostic indications (PPV1 (abnormal findings) = 28%, PPV2 (biopsy recommended) = 36%, PPV3 (biopsy performed) = 38%]. Conclusions: Breast MRI performance measures differ significantly between screening and diagnostic MRI indications. Medical audits for breast MRI should calculate performance measures for screening and diagnostic breast MRI separately, as recommended for mammography. C1 [Niel, Bethany L.; Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Gavenonis, Sara C.] Christiana Care Hlth Syst, Dept Radiol, Newark, DE USA. [Motazedi, Tina] Univ Texas Hlth Sci Ctr San Antonio, San Antonio Sch Med, San Antonio, TX 78229 USA. [Chubiz, Jessica Cott; Halpern, Elkan P.; Lee, Janie M.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. RP Niel, BL (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Wang Bldg,Suite 240, Boston, MA 02114 USA. EM bniell@partners.org FU National Institutes of Health (Bethesda, Maryland) [K07 CA128816] FX Dr Lee's participation was supported in part by grant K07 CA128816 from the National Institutes of Health (Bethesda, Maryland). NR 30 TC 3 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2014 VL 11 IS 9 BP 883 EP 889 DI 10.1016/j.jacr.2014.02.003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO7NZ UT WOS:000341541200013 PM 24787571 ER PT J AU Abujudeh, H Pyatt, RS Bruno, MA Chetlen, AL Buck, D Hobbs, SK Roth, C Truwit, C Agarwal, R Kennedy, STO Glenn, L AF Abujudeh, Hani Pyatt, Robert S., Jr. Bruno, Michael A. Chetlen, Alison L. Buck, David Hobbs, Susan K. Roth, Christopher Truwit, Charles Agarwal, Rajan Kennedy, Scott T. O. Glenn, Lucille TI RADPEER Peer Review: Relevance, Use, Concerns, Challenges, and Direction Forward SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE RADPEER; peer review; OPPE; quality and safety; PQI AB RADPEER is a product developed by the ACR that aims to assist radiologists with quality assessment and improvement through peer review. The program opened in 2002, was initially offered to physician groups in 2003, developed an electronic version in 2005 (eRADPEER), revised the scoring system in 2009, and first surveyed the RADPEER membership in 2010. In 2012, a survey was sent to 16,000 ACR member radiologists, both users and nonusers of RADPEER, with the goal of understanding how to make RADPEER more relevant to its members. A total of 31 questions were used, some of which were repeated from the 2010 survey. The ACR's RADPEER committee has published 3 papers on the program since its inception. In this report, the authors summarize the survey results and suggest future opportunities for making RADPEER more useful to its membership. C1 [Abujudeh, Hani] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pyatt, Robert S., Jr.] Chambersburg Imaging Associates, Chambersburg, PA USA. [Bruno, Michael A.; Chetlen, Alison L.] Penn State Milton Hershey Med Ctr, Hershey, PA USA. [Buck, David] Indiana Reg Imaging, Indiana, PA USA. [Hobbs, Susan K.] Univ Rochester, Rochester, NY USA. [Roth, Christopher] Duke Univ, Durham, NC USA. [Truwit, Charles] Hennepin Hlth Syst, Minneapolis, MN USA. [Agarwal, Rajan] Lansdale Hosp, Abington Hlth, Lansdale, PA USA. [Kennedy, Scott T. O.] Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. [Glenn, Lucille] Virginia Mason Med Ctr, Seattle, WA 98101 USA. RP Abujudeh, H (reprint author), Massachusetts Gen Hosp, Founders Bldg 213 D,55 Fruit St, Boston, MA 02114 USA. EM habujudeh@partners.org RI Roth, Christopher/L-3395-2016; OI Roth, Christopher/0000-0002-9634-7126; Chetlen, Alison/0000-0001-5304-2392 NR 5 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2014 VL 11 IS 9 BP 899 EP 904 DI 10.1016/j.jacr.2014.02.004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO7NZ UT WOS:000341541200016 PM 24842585 ER PT J AU Hoagland, LF Alkasab, TK Freer, PE AF Hoagland, Luke F. Alkasab, Tank K. Freer, Phoebe E. TI Case Tracking and Sharing System to Foster Consistent Group Standards of Practice and Improve Radiologist Experience in DBT SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID BREAST TOMOSYNTHESIS; DIGITAL MAMMOGRAPHY C1 [Hoagland, Luke F.; Alkasab, Tank K.; Freer, Phoebe E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Freer, PE (reprint author), Massachusetts Gen Hosp, Div Breast Imaging, Dept Radiol, 55 Fruit St,WAC 219, Boston, MA 02114 USA. EM pfreer@mgh.harvard.edu OI Freer, Phoebe/0000-0001-6886-7100 NR 9 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2014 VL 11 IS 9 BP 910 EP 912 DI 10.1016/j.jacr.2014.05.006 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO7NZ UT WOS:000341541200019 PM 25037109 ER PT J AU Ju, MH Cohen, ME Bilimoria, KY Latus, MS Scholl, LM Schwab, BJ Byrd, CM Ko, CY Dellinger, EP Hall, BL AF Ju, Mila H. Cohen, Mark E. Bilimoria, Karl Y. Latus, Melissa S. Scholl, Lisa M. Schwab, Bradley J. Byrd, Claudia M. Ko, Clifford Y. Dellinger, E. Patchen Hall, Bruce L. TI Effect of Wound Classification on Risk Adjustment in American College of Surgeons NSQIP SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGICAL QUALITY; ACS-NSQIP; INFECTIONS AB BACKGROUND: Surgical wound classification has been used in risk-adjustment models. However, it can be subjective and could potentially improperly bias hospital quality comparisons. The objective is to examine the effect of wound classification on hospital performance risk-adjustment models. STUDY DESIGN: Retrospective review of the 2011 American College of Surgeons NSQIP database was conducted for the following wound classification categories: clean, clean-contaminated, contaminated, and dirty-infected. To assess the influence of wound classification on risk adjustment, 2 models were developed for all outcomes: 1 including and 1 excluding wound classification. For each model, hospital postoperative complications were estimated using hierarchical multivariable regression methods. Absolute changes in hospital rank, correlations of odds ratios, and outlier status agreement between models were examined. RESULTS: Of the 442,149 cases performed in 315 hospitals: 53.6% were classified as clean; 34.2% as clean-contaminated; 6.7% as contaminated; and 5.5% as dirty-infected. The surgical site infection rate was highest in dirty-infected (8.5%) and lowest in clean (1.8%) cases. For overall surgical site infection, the absolute change in risk-adjusted hospital performance rank between models, including vs excluding wound classification, was minimal (mean 4.5 of 315 positions). The correlations between odds ratios of the 2 performance models were nearly perfect (R 0.9976, p < 0.0001), and outlier status agreement was excellent (kappa = 0.95ss08, p < 0.0001). Similar findings were observed in models of subgroups of surgical site infections and other postoperative outcomes. CONCLUSIONS: In circumstances where alternate information is available for risk adjustment, there appear to be minimal differences in performance models that include vs exclude wound classification. Therefore, the American College of Surgeons NSQIP is critically evaluating the continued use of wound classification in hospital performance risk-adjustment models. (C) 2014 by the American College of Surgeons C1 [Ju, Mila H.; Cohen, Mark E.; Bilimoria, Karl Y.; Latus, Melissa S.; Scholl, Lisa M.; Schwab, Bradley J.; Byrd, Claudia M.; Ko, Clifford Y.; Hall, Bruce L.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Ju, Mila H.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Ju, Mila H.; Bilimoria, Karl Y.] NW Mem Hosp, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dellinger, E. Patchen] Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] BJC Healthcare, St Louis VA Med Ctr, St Louis, MO USA. RP Ju, MH (reprint author), Amer Coll Surg, 633 North St Clair St,22nd Fl, Chicago, IL 60611 USA. EM mju@facs.org FU NIH [5T32HL094293]; AHRQ; NCCN; ACS; ACoS; BCBS-IL; Tetraphrase; Applied Medical; Health and Human Services; Michigan Hospital Association; Louisiana Woman's Hospital FX Dr Ju is supported by NIH Grant #5T32HL094293, and is a Scholar in Residence at the ACS. Dr Bilimoria receives grants from NIH, AHRQ, NCCN, ACS, ACoS, and BCBS-IL; and lecture payments from hospitals and professional societies for grand rounds. Dr Dellinger is a paid consultant to Merck, Targanta, Astellas, Care Fusion, Durata, Pfizer, Rib-X, Affinium, and 3M; receives grants from Tetraphrase and lecture payments from Applied Medical; and other expenses paid by Health and Human Services, Michigan Hospital Association, and Louisiana Woman's Hospital. Dr Hall is a paid consultant to the ACS. This study received no outside funding. NR 20 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2014 VL 219 IS 3 BP 371 EP + DI 10.1016/j.jamcollsurg.2014.04.009 PG 16 WC Surgery SC Surgery GA AO5VW UT WOS:000341415100008 PM 25053222 ER PT J AU Dawes, AJ Sacks, GD Russell, MM Lin, AY Maggard-Gibbons, M Winograd, D Chung, HR Tillou, A Hiatt, JR Ko, C AF Dawes, Aaron J. Sacks, Greg D. Russell, Marcia M. Lin, Anne Y. Maggard-Gibbons, Melinda Winograd, Deborah Chung, Hallie R. Tillou, Areti Hiatt, Jonathan R. Ko, Clifford TI Preventable Readmissions to Surgical Services: Lessons Learned and Targets for Improvement SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; HOSPITAL READMISSION; RISK-FACTORS; MEDICARE BENEFICIARIES; UNPLANNED READMISSION; PATIENT READMISSION; 30-DAY READMISSIONS; COLORECTAL SURGERY; ILEOSTOMY CREATION; DEHYDRATION AB BACKGROUND: Hospital readmissions are under intense scrutiny as a measure of health care quality. The Center for Medicare and Medicaid Services (CMS) has proposed using readmission rates as a benchmark for improving care, including targeting them as nonreimbursable events. Our study aim was to describe potentially preventable readmissions after surgery and to identify targets for improvement. STUDY DESIGN: Patients discharged from a general surgery service over 8 consecutive quarters (Q4 2009 to Q3 2011) were selected. A working group of attending surgeons defined terms and created classification schemes. Thirty-day readmissions were identified and reviewed by a 2-physician team. Readmissions were categorized as preventable or unpreventable, and by target for future quality improvement intervention. RESULTS: Overall readmission rate was 8.3% (315 of 3,789). The most common indication for initial admission was elective general surgery. Among readmitted patients in our sample, 28% did not undergo an operation during their index admission. Only 21% (55 of 258) of readmissions were likely preventable based on medical record review. Of the preventable readmissions, 38% of patients were discharged within 24 hours and 60% within 48 hours. Dehydration occurred more frequently among preventable readmissions (p < 0.001). Infection accounted for more than one-third of all readmissions. Among preventable readmissions, targets for improvement included closer follow-up after discharge (49%), management in the outpatient setting (42%), and avoidance of premature discharge (9%). CONCLUSIONS: A minority of readmissions may potentially be preventable. Targets for reducing readmissions include addressing the clinical issues of infection and dehydration as well as improving discharge planning to limit both early and short readmissions. Policies aimed at penalizing reimbursements based on readmission rates should use clinical data to focus on inappropriate hospitalization in order to promote high quality patient care. (C) 2014 by the American College of Surgeons C1 [Dawes, Aaron J.; Sacks, Greg D.; Russell, Marcia M.; Lin, Anne Y.; Maggard-Gibbons, Melinda; Winograd, Deborah; Chung, Hallie R.; Tillou, Areti; Hiatt, Jonathan R.; Ko, Clifford] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Sacks, Greg D.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, Ronald Reagan UCLA Med Ctr, David Geffen Sch Med, Dept Surg, 757 Westwood Plaza B7-11, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program FX Dr Dawes was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. NR 33 TC 21 Z9 21 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2014 VL 219 IS 3 BP 382 EP 389 DI 10.1016/j.jamcollsurg.2014.03.046 PG 8 WC Surgery SC Surgery GA AO5VW UT WOS:000341415100009 PM 24891209 ER PT J AU Vagefi, PA Feng, S Dodge, JL Markmann, JF Roberts, JP AF Vagefi, Parsia A. Feng, Sandy Dodge, Jennifer L. Markmann, James F. Roberts, John P. TI Multiple Listings as a Reflection of Geographic Disparity in Liver Transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CADAVERIC KIDNEY; OUTCOMES; BENEFIT; PATIENT; ACCESS AB BACKGROUND: Geographic disparity in access to liver transplantation (LT) exists. This study sought to examine Model for End-Stage Liver Disease-era multiply listed (ML) LT candidate (ie, candidates who list at 2 or more LT centers to receive a liver transplant). STUDY DESIGN: Data on adult, primary, non-status 1 LT candidates (n = 59,557) listed from January 1, 2005 to December 31, 2011 were extracted from the United Network for Organ Sharing's Standard Transplant Analysis and Research files. Comparisons of ML vs singly listed LT candidates were performed, with additional analysis performed at the donor service area (DSA) and regional level, as well as assessment of the donor population used. RESULTS: There were 1,358 (2.3%) ML candidates during the 7-year study period. Multiply listed candidates compared with singly listed candidates were more often male, white, blood type O, nondiabetic, college educated, and privately insured. The odds of pursuing ML increased considerably as time on the waitlist increased. Of the ML candidates, 918 (67.6%) went on to receive a liver transplant (ML-LT), 767 (83.6%) at the secondary listing DSA, which was a median of 588 miles (range 229 to 1095 miles) from the primary listing DSA. When compared with the primary listing DSA, the secondary listing DSA had significantly lower match Model for End-Stage Liver Disease scores, as well as shorter wait times. Regional analysis demonstrated significantly higher odds for pursuing ML from LT candidates located within regions 1, 5, and 9. CONCLUSIONS: A small and distinctive cohort of LT candidates pursue ML, indicating willingness and means to travel to receive a liver transplant. Efforts toward equalizing LT access across regional disparities are warranted, and can help obviate the need for ML. (C) 2014 by the American College of Surgeons C1 [Vagefi, Parsia A.; Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. [Vagefi, Parsia A.; Markmann, James F.] Harvard Univ, Sch Med, Boston, MA USA. [Feng, Sandy; Dodge, Jennifer L.; Roberts, John P.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, 55 Fruit St,White 521c, Boston, MA 02114 USA. EM pvagefi@mgh.harvard.edu FU American Society of Transplant Surgeons/Novartis Fellowship in Transplantation Award FX Dr Vagefi is a recipient of the American Society of Transplant Surgeons/Novartis Fellowship in Transplantation Award. NR 13 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2014 VL 219 IS 3 BP 496 EP 504 DI 10.1016/j.jamcollsurg.2014.03.048 PG 9 WC Surgery SC Surgery GA AO5VW UT WOS:000341415100022 PM 25026876 ER PT J AU Friedlander, AH Bertolami, CN AF Friedlander, Arthur H. Bertolami, Charles N. TI The ethics of managing incidental findings Implications and challenges for the profession SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Bertolami, Charles N.] NYU, Coll Dent, New York, NY USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 4 TC 2 Z9 2 U1 0 U2 2 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2014 VL 145 IS 9 BP 910 EP 911 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AO5IV UT WOS:000341378700001 PM 25169990 ER PT J AU Keith, D AF Keith, David TI MORE INFORMATION, PLEASE SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter C1 [Keith, David] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Keith, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Keith, D (reprint author), Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2014 VL 145 IS 9 BP 914 EP 914 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AO5IV UT WOS:000341378700003 PM 25169992 ER PT J AU Plana, JC Galderisi, M Barac, A Ewer, MS Ky, B Scherrer-Crosbie, M Ganame, J Sebag, IA Agler, DA Badano, LP Banchs, J Cardinale, D Carver, J Cerqueira, M DeCara, JM Edvardsen, T Flamm, SD Force, T Griffin, BP Jerusalem, G Liu, JE Magalhaes, A Marwick, T Sanchez, LY Sicari, R Villarraga, HR Lancellotti, P AF Plana, Juan Carlos Galderisi, Maurizio Barac, Ana Ewer, Michael S. Ky, Bonnie Scherrer-Crosbie, Marielle Ganame, Javier Sebag, Igal A. Agler, Deborah A. Badano, Luigi P. Banchs, Jose Cardinale, Daniela Carver, Joseph Cerqueira, Manuel DeCara, Jeanne M. Edvardsen, Thor Flamm, Scott D. Force, Thomas Griffin, Brian P. Jerusalem, Guy Liu, Jennifer E. Magalhaes, Andreia Marwick, Thomas Sanchez, Liza Y. Sicari, Rosa Villarraga, Hector R. Lancellotti, Patrizio TI Expert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy: A Report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Chemotherapy; Doxorubicin; Trastuzumab; Left ventricular dysfunction; Three-dimensional echocardiography; Early detection; Strain; Biomarkers ID VENTRICULAR EJECTION FRACTION; CARDIAC MAGNETIC-RESONANCE; CONGESTIVE-HEART-FAILURE; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; DOBUTAMINE-STRESS ECHOCARDIOGRAPHY; TRASTUZUMAB-INDUCED CARDIOTOXICITY; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; HIGH-DOSE CHEMOTHERAPY; NATIVE VALVULAR REGURGITATION C1 [Agler, Deborah A.; Cerqueira, Manuel; Flamm, Scott D.; Griffin, Brian P.] Cleveland Clin, Cleveland, OH 44106 USA. [Galderisi, Maurizio] Federico II Univ Hosp, Naples, Italy. [Barac, Ana] Medstar Washington Hosp Ctr, Washington, DC USA. [Ewer, Michael S.; Banchs, Jose; Sanchez, Liza Y.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ky, Bonnie] Univ Penn, Philadelphia, PA 19104 USA. [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ganame, Javier] McMaster Univ, Hamilton, ON, Canada. [Sebag, Igal A.] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Sebag, Igal A.] McGill Univ, Montreal, PQ, Canada. [Badano, Luigi P.] Univ Padua, Padua, Italy. [Cardinale, Daniela] European Inst Oncol, Milan, Italy. [Carver, Joseph] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [DeCara, Jeanne M.] Univ Chicago Med, Chicago, IL USA. [Edvardsen, Thor] Oslo Univ Hosp, Oslo, Norway. [Edvardsen, Thor] Univ Oslo, Oslo, Norway. [Force, Thomas] Temple Univ, Philadelphia, PA 19122 USA. [Jerusalem, Guy; Lancellotti, Patrizio] Univ Liege, Liege, Belgium. [Liu, Jennifer E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Magalhaes, Andreia] Santa Marie Univ Hosp, Lisbon, Portugal. [Marwick, Thomas] Menzies Res Inst Tasmania, Hobart, Tas, Australia. [Sicari, Rosa] CNR, Inst Clin Physiol, I-56100 Pisa, Italy. [Villarraga, Hector R.] Mayo Clin, Rochester, MN USA. RP Plana, JC (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org RI Edvardsen, Thor/F-4079-2012; OI Edvardsen, Thor/0000-0002-3800-765X; Barac, Ana/0000-0002-9935-8904; Force, Thomas/0000-0002-0450-8659; Galderisi, Maurizio/0000-0003-0311-9069; Badano, Luigi/0000-0002-0379-3283 FU Cell Therapeutics; Genentech; Perceptive Informatics, Inc; GE Healthcare; FluoroPharma; Astellas; Siemens Healthcare; National Health and Medical Research Council in Australia; Royal Hobart Hospital Foundation; Philips Medical Systems; Siemens; GE Medical Systems FX The following authors reported relationships with one or more commercial interests: Ana Barac, MD, received research funding and lectures honoraria from Genentech and consultancy fees from Cell Therapeutics. Manuel Cerqueira, MD, received a grant from Perceptive Informatics, Inc; consults for GE Healthcare, FluoroPharma and Astellas; and serves on the speakers bureau for Astellas. Jeanne M. DeCara, MD, served as a consultant for Epsilon Imaging and Methylgene. Michael S. Ewer, MD, JD, consults or serves as advisory board member for Roche Laboratories, Cell Therapeutics, GlaxoSmithKline, and Boehringer Ingelheim. Scott D. Flamm, MD, MBA, serves on advisory boards for Philips Healthcare, Bayer Healthcare, and TeraRecon and received institutional research support from Siemens Healthcare. Thomas Force, MD consults for GlaxoSmithKline. Bonnie Ky, MD, FASE, received an investigator-initiated award from Pfizer, Inc. Thomas Marwick, MBBS, PhD, MPH, received research funding from the National Health and Medical Research Council in Australia and the Royal Hobart Hospital Foundation, an equipment grant from Philips Medical Systems and Siemens, and a project grant from GE Medical Systems. Igal A. Sebag, MD, FASE, serves on the speakers bureau for Lantheus. NR 240 TC 128 Z9 131 U1 4 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2014 VL 27 IS 9 BP 911 EP 939 DI 10.1016/j.echo.2014.07.012 PG 29 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO5CN UT WOS:000341359600001 PM 25172399 ER PT J AU Stern, KWD Gauvreau, K Geva, T Benavidez, OJ AF Stern, Kenan W. D. Gauvreau, Kimberlee Geva, Tal Benavidez, Oscar J. TI The Impact of Procedural Sedation on Diagnostic Errors in Pediatric Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Pediatric and congenital heart disease; Echocardiography; Diagnostic errors; Procedural sedation ID CONGENITAL HEART-SURGERY; RISK-FACTORS; CHLORAL HYDRATE; INTRANASAL MIDAZOLAM; ADVERSE EVENTS; INFANTS; DISEASE AB Background: Infants and young children frequently have difficulty remaining still for an echocardiographic examination, potentially leading to poor study quality, increasing the likelihood of diagnostic errors. Sedation is believed to improve echocardiographic quality, but its effectiveness has not been demonstrated. The aim of this study was to test the hypothesis that sedation would improve study quality and reduce diagnostic errors. Methods: Outpatient echocardiograms from children aged <= 36 months obtained from January 2008 to June 2009 were examined. Variables related to image quality, report completeness, and sedation use were collected. Diagnostic errors were identified and categorized. Multivariate analysis identified the odds ratios (OR) and 95% confidence intervals (CI) for risk factors for potentially preventable diagnostic errors and the impact of sedation on these errors. Results: Among 2,003 echocardiographic examinations, sedation was used in 498 (25%). The overall diagnostic error rate was 6.5%. Most errors (66%) were potentially preventable. Multivariate analysis identified the following risk factors for potentially preventable errors: precardiac procedure (OR, 2.19; 95% CI, 1.05-4.59; P = .04), moderate anatomic complexity (OR, 3.91; 95% CI, 2.25-6.81; P < .001), and high anatomic complexity (OR, 8.36; 95% CI, 3.57-19.6; P < .001). Sedation was independently associated with lower odds of potentially preventable diagnostic errors (OR, 0.47; 95% CI, 0.27-0.80; P = .006). Echocardiographic examinations with sedation had fewer image quality concerns (22% vs 60%) and fewer incomplete reports (3% vs 20%) (P < .001). Conclusions: Most echocardiographic diagnostic errors among infants and young children are potentially preventable. Sedation is associated with a lower likelihood of these diagnostic errors, fewer imaging quality concerns, and fewer incomplete reports. C1 [Stern, Kenan W. D.; Gauvreau, Kimberlee; Geva, Tal; Benavidez, Oscar J.] Harvard Univ, Sch Med, Dept Cardiol, Boston Childrens Hosp, Boston, MA USA. [Benavidez, Oscar J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Congenital Cardiol, Boston, MA USA. [Stern, Kenan W. D.; Gauvreau, Kimberlee; Geva, Tal; Benavidez, Oscar J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Stern, KWD (reprint author), Childrens Hosp Montefiore, Dept Pediat, Div Cardiol, 3415 Bainbridge Ave, Bronx, NY 10467 USA. EM kstern@montefiore.org FU Robert Wood Johnson Foundation's Harold Amos Medical Faculty Development Program; National Institutes of Health [2 T32 HL007572-27 A1]; Higgins Family Noninvasive Cardiac Imaging Research Fund; Program for Patient Safety and Quality of Boston Children's Hospital FX Dr Benavidez is supported by a grant from the Robert Wood Johnson Foundation's Harold Amos Medical Faculty Development Program. A T32 Training Grant from the National Institutes of Health supported Dr Stern (2 T32 HL007572-27 A1). The study was supported in part by the Higgins Family Noninvasive Cardiac Imaging Research Fund and by a research grant from the Program for Patient Safety and Quality of Boston Children's Hospital. NR 18 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2014 VL 27 IS 9 BP 949 EP 955 DI 10.1016/j.echo.2014.04.024 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO5CN UT WOS:000341359600003 PM 24930122 ER PT J AU Carroll, PR Parsons, JK Andriole, G Bahnson, RR Barocas, DA Catalona, WJ Dahl, DM Davis, JW Epstein, JI Etzioni, RB Giri, VN Hemstreet, GP Kawachi, MH Lange, PH Loughlin, KR Lowrance, W Maroni, P Mohler, J Morgan, TM Nadler, RB Poch, M Scales, C Shanefelt, TM Vickers, AJ Wake, R Shead, DA Ho, M AF Carroll, Peter R. Parsons, J. Kellogg Andriole, Gerald Bahnson, Robert R. Barocas, Daniel A. Catalona, William J. Dahl, Douglas M. Davis, John W. Epstein, Jonathan I. Etzioni, Ruth B. Giri, Veda N. Hemstreet, George P., III Kawachi, Mark H. Lange, Paul H. Loughlin, Kevin R. Lowrance, William Maroni, Paul Mohler, James Morgan, Todd M. Nadler, Robert B. Poch, Michael Scales, Chuck Shanefelt, Terrence M. Vickers, Andrew J. Wake, Robert Shead, Dorothy A. Ho, Maria TI Prostate Cancer Early Detection, Version 1.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID HEALTH INDEX PHI; SCREENING TRIAL; RANDOMIZED PROSTATE; FAMILY-HISTORY; FOLLOW-UP; FREE-PSA; AGE 50; ANTIGEN; RISK; MORTALITY AB The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for men choosing to participate in an early detection program for prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Overall, the 2014 update represents a more streamlined and concise set of recommendations. The panel stratified the age ranges at which initiating testing for prostate cancer should be considered. Indications for biopsy include both a cutpoint and the use of multiple risk variables in combination. In addition to other biomarkers of specificity, the Prostate Health Index has been included to aid biopsy decisions in certain men, given recent FDA approvals. C1 [Carroll, Peter R.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Parsons, J. Kellogg] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Andriole, Gerald] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Andriole, Gerald] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Bahnson, Robert R.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Bahnson, Robert R.] James Canc Hosp & Solove Res Inst, Columbus, OH USA. [Barocas, Daniel A.] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Catalona, William J.; Nadler, Robert B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Dahl, Douglas M.] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. [Davis, John W.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Epstein, Jonathan I.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Etzioni, Ruth B.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Giri, Veda N.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Hemstreet, George P., III] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Kawachi, Mark H.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Lange, Paul H.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Loughlin, Kevin R.] Dana FarberBrigham & Womens Canc Ctr, Boston, MA USA. [Lowrance, William] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Maroni, Paul] Univ Colorado, Canc Ctr, Boulder, CO 80309 USA. [Mohler, James] Roswell Pk Canc Inst, Buffalo, NY USA. [Morgan, Todd M.] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Poch, Michael] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Scales, Chuck] Duke Canc Inst, Durham, NC USA. [Shanefelt, Terrence M.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Vickers, Andrew J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Wake, Robert] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. RP Carroll, PR (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. OI Vickers, Andrew/0000-0003-1525-6503 FU NCI NIH HHS [P50 CA092629] NR 35 TC 31 Z9 34 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2014 VL 12 IS 9 BP 1211 EP 1219 PG 9 WC Oncology SC Oncology GA AO4ZM UT WOS:000341349900004 PM 25190691 ER PT J AU Denlinger, CS Ligibel, JA Are, M Baker, KS Demark-Wahnefried, W Dizon, D Friedman, DL Goldman, M Jones, L King, A Ku, GH Kvale, E Langbaum, TS Leonardi-Warren, K McCabe, MS Melisko, M Montoya, JG Mooney, K Morgan, MA Moslehi, JJ O'Connor, T Overholser, L Paskett, ED Peppercorn, J Raza, M Rodriguez, MA Syrjala, KL Urba, SG Wakabayashi, MT Zee, P McMillian, NR Freedman-Cass, DA AF Denlinger, Crystal S. Ligibel, Jennifer A. Are, Madhuri Baker, K. Scott Demark-Wahnefried, Wendy Dizon, Don Friedman, Debra L. Goldman, Mindy Jones, Lee King, Allison Ku, Grace H. Kvale, Elizabeth Langbaum, Terry S. Leonardi-Warren, Kristin McCabe, Mary S. Melisko, Michelle Montoya, Jose G. Mooney, Kathi Morgan, Mary Ann Moslehi, Javid J. O'Connor, Tracey Overholser, Linda Paskett, Electra D. Peppercorn, Jeffrey Raza, Muhammad Rodriguez, M. Alma Syrjala, Karen L. Urba, Susan G. Wakabayashi, Mark T. Zee, Phyllis McMillian, Nicole R. Freedman-Cass, Deborah A. TI Survivorship: Healthy Lifestyles, Version 2.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; BREAST-CANCER SURVIVORS; PHYSICAL-ACTIVITY; ADJUVANT CHEMOTHERAPY; COLORECTAL-CANCER; COLON-CANCER; BODY-MASS; EXERCISE INTERVENTIONS; PROSTATE-CANCER AB Healthy lifestyle habits have been associated with improved health outcomes and quality of life and, for some cancers, a reduced risk of recurrence and death. The NCCN Guidelines for Survivorship therefore recommend that cancer survivors be encouraged to achieve and maintain a healthy lifestyle, with attention to weight management, physical activity, and dietary habits. This section of the NCCN Guidelines focuses on recommendations regarding physical activity in survivors, including assessment for the risk of exercise-induced adverse events, exercise prescriptions, guidance for resistance training, and considerations for specific populations (eg, survivors with lymphedema, ostomies, peripheral neuropathy). In addition, strategies to encourage health behavioral change in survivors are discussed. C1 [Denlinger, Crystal S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Ligibel, Jennifer A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Are, Madhuri] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Baker, K. Scott] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Demark-Wahnefried, Wendy; Kvale, Elizabeth] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Dizon, Don] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Friedman, Debra L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Goldman, Mindy] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Jones, Lee] Mem Sloan Kettering Canc Ctr, New York, NY USA. [King, Allison] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [King, Allison] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Ku, Grace H.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA. [Langbaum, Terry S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Leonardi-Warren, Kristin] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Melisko, Michelle] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Montoya, Jose G.] Stanford Canc Inst, Stanford, CA USA. [Mooney, Kathi] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Morgan, Mary Ann] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Moslehi, Javid J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [O'Connor, Tracey] Roswell Pk Canc Inst, Buffalo, NY USA. [Overholser, Linda] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Paskett, Electra D.] Solove Res Inst, Columbus, OH USA. [Peppercorn, Jeffrey] Duke Canc Inst, Durham, NC USA. [Raza, Muhammad] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Rodriguez, M. Alma] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Syrjala, Karen L.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Wakabayashi, Mark T.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Zee, Phyllis] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RP Denlinger, CS (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. OI King, Allison/0000-0002-1951-6176 FU NCI NIH HHS [UM1 CA173642] NR 75 TC 12 Z9 12 U1 1 U2 20 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2014 VL 12 IS 9 BP 1222 EP 1237 PG 16 WC Oncology SC Oncology GA AO4ZM UT WOS:000341349900005 PM 25190692 ER PT J AU Zelenetz, AD Gordon, LI Wierda, WG Abramson, JS Advani, RH Andreadis, CB Bartlett, N Byrd, JC Czuczman, MS Fayad, LE Fisher, RI Glenn, MJ Harris, NL Hoppe, RT Horwitz, SM Kelsey, CR Kim, YH Krivacic, S LaCasce, AS Nademanee, A Porcu, P Press, O Rabinovitch, R Reddy, N Reid, E Saad, AA Sokol, L Swinnen, LJ Tsien, C Vose, JM Yahalom, J Zafar, N Dwyer, M Sundar, H AF Zelenetz, Andrew D. Gordon, Leo I. Wierda, William G. Abramson, Jeremy S. Advani, Ranjana H. Andreadis, C. Babis Bartlett, Nancy Byrd, John C. Czuczman, Myron S. Fayad, Luis E. Fisher, Richard I. Glenn, Martha J. Harris, Nancy Lee Hoppe, Richard T. Horwitz, Steven M. Kelsey, Christopher R. Kim, Youn H. Krivacic, Susan LaCasce, Ann S. Nademanee, Auayporn Porcu, Pierluigi Press, Oliver Rabinovitch, Rachel Reddy, Nishitha Reid, Erin Saad, Ayman A. Sokol, Lubomir Swinnen, Lode J. Tsien, Christina Vose, Julie M. Yahalom, Joachim Zafar, Nadeem Dwyer, Mary Sundar, Hema TI Non-Hodgkin's Lymphomas, Version 4.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID MANTLE-CELL LYMPHOMA; LOW-GRADE LYMPHOMA; PROGRESSION-FREE SURVIVAL; EUROPEAN-MCL-NETWORK; PROSPECTIVE RANDOMIZED-TRIAL; BENDAMUSTINE PLUS RITUXIMAB; WISCONSIN-ONCOLOGY-NETWORK; SINGLE-AGENT LENALIDOMIDE; HIGH-DOSE METHOTREXATE; PHASE-II MULTICENTER AB Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Mantle cell lymphoma (MCL) accounts for approximately 6% of all newly diagnosed NHL cases. Radiation therapy with or without systemic therapy is a reasonable approach for the few patients who present with early-stage disease. Rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR) is recommended for patients presenting with advanced-stage disease. Induction therapy followed by rituximab maintenance may provide extended disease control for those who are not candidates for HDT/ASCR. Ibrutinib, a Bruton tyrosine kinase inhibitor, was recently approved for the treatment of relapsed or refractory disease. This manuscript discusses the recommendations outlined in the NCCN Guidelines for NHL regarding the diagnosis and management of patients with MCL. C1 [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Advani, Ranjana H.] Stanford Canc Inst, Stanford, CA USA. [Andreadis, C. Babis] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Bartlett, Nancy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Bartlett, Nancy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY USA. [Fayad, Luis E.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Fisher, Richard I.] Fox Chase Cance, Philadelphia, PA USA. [Glenn, Martha J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Harris, Nancy Lee] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hoppe, Richard T.; Kim, Youn H.] Stanford Canc Inst, Stanford, CA USA. [Horwitz, Steven M.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Kelsey, Christopher R.] Duke Canc Inst, Durham, NC USA. [Krivacic, Susan; LaCasce, Ann S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Nademanee, Auayporn] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Press, Oliver] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Rabinovitch, Rachel] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Reddy, Nishitha] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Reid, Erin] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA. [Saad, Ayman A.] Univ Alabama Birmingham, Comprehens Canc Network, Birmingham, AL USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Swinnen, Lode J.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Tsien, Christina] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Vose, Julie M.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Ann Arbor, MI 48109 USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Zafar, Nadeem] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP Zelenetz, AD (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. OI Saad, Ayman /0000-0003-0003-0130 FU NCI NIH HHS [P30 CA006973] NR 92 TC 44 Z9 52 U1 0 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2014 VL 12 IS 9 BP 1282 EP 1303 PG 22 WC Oncology SC Oncology GA AO4ZM UT WOS:000341349900009 PM 25190696 ER PT J AU Daly, MB Pilarski, R Axilbund, JE Buys, SS Crawford, B Friedman, S Garber, JE Horton, C Kaklamani, V Klein, C Kohlmann, W Kurian, A Litton, J Madlensky, L Marcom, PK Merajver, SD Offit, K Pal, T Pasche, B Reiser, G Shannon, KM Swisher, E Voian, NC Weitzel, JN Whelan, A Wiesner, GL Dwyer, MA Kumar, R AF Daly, Mary B. Pilarski, Robert Axilbund, Jennifer E. Buys, Saundra S. Crawford, Beth Friedman, Susan Garber, Judy E. Horton, Carolyn Kaklamani, Virginia Klein, Catherine Kohlmann, Wendy Kurian, Allison Litton, Jennifer Madlensky, Lisa Marcom, P. Kelly Merajver, Sofia D. Offit, Kenneth Pal, Tuya Pasche, Boris Reiser, Gwen Shannon, Kristen Mahoney Swisher, Elizabeth Voian, Nicoleta C. Weitzel, Jeffrey N. Whelan, Alison Wiesner, Georgia L. Dwyer, Mary A. Kumar, Rashmi TI Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 1.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID HAMARTOMA-TUMOR-SYNDROME; RILEY-RUVALCABA-SYNDROME; REVISED DIAGNOSTIC-CRITERIA; AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS DISEASE; GERMLINE PTEN MUTATIONS; SYNDROME PLEASE STAND; COWDEN-SYNDROME; CANCER; GENE AB During the past few years, several genetic aberrations that may contribute to increased risks for development of breast and/or ovarian cancers have been identified. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian focus specifically on the assessment of genetic mutations in BRCA1/BRCA2, TP53, and PTEN, and recommend approaches to genetic testing/counseling and management strategies in individuals with these mutations. This portion of the NCCN Guidelines includes recommendations regarding diagnostic criteria and management of patients with Cowden Syndrome/PTEN hamartoma tumor syndrome. C1 [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Pilarski, Robert] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Pilarski, Robert] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Axilbund, Jennifer E.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Crawford, Beth] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Garber, Judy E.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Horton, Carolyn] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Kaklamani, Virginia] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Klein, Catherine] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Kohlmann, Wendy] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Kurian, Allison] Stanford Canc Inst, Stanford, CA USA. [Litton, Jennifer] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Madlensky, Lisa] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA. [Marcom, P. Kelly] Duke Canc Inst, Durham, NC USA. [Merajver, Sofia D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Offit, Kenneth] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Pal, Tuya] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Pasche, Boris] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Reiser, Gwen] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Shannon, Kristen Mahoney] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Swisher, Elizabeth] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Voian, Nicoleta C.] Roswell Pk Canc Inst, Buffalo, NY USA. [Weitzel, Jeffrey N.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Whelan, Alison] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Whelan, Alison] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Wiesner, Georgia L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Daly, MB (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RI Pilarski, Robert/E-3871-2011 NR 46 TC 41 Z9 42 U1 0 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2014 VL 12 IS 9 BP 1326 EP 1338 PG 13 WC Oncology SC Oncology GA AO4ZM UT WOS:000341349900011 PM 25190698 ER PT J AU Fugate, JE Lyons, JL Thakur, KT Smith, BR Hedley-Whyte, ET Mateen, FJ AF Fugate, Jennifer E. Lyons, Jennifer L. Thakur, Kiran T. Smith, Bryan R. Hedley-Whyte, E. Tessa Mateen, Farrah J. TI Infectious causes of stroke SO LANCET INFECTIOUS DISEASES LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; ISCHEMIC CEREBROVASCULAR EVENTS; VARICELLA-ZOSTER-VIRUS; HIV-POSITIVE PATIENTS; HERPES-SIMPLEX-VIRUS; CHAGAS HEART-DISEASE; OF-THE-LITERATURE; TUBERCULOUS MENINGITIS; RISK-FACTOR; BACTERIAL-MENINGITIS AB Most infectious pathogens have anecdotal evidence to support a link with stroke, but certain pathogens have more robust associations, in which causation is probable. Few dedicated prospective studies of stroke in the setting of infection have been done. The use of head imaging, a clinical standard of diagnostic care, to confirm stroke and stroke type is not universal. Data for stroke are scarce in locations where infections are probably most common, making it difficult to reach condusions on how populations differ in terms of risk of infectious stroke. The treatment of infections and stroke, when concomitant, is based on almost no evidence and requires dedicated efforts to understand variations that might exist. We highlight the present knowledge and emphasise the need for stronger evidence to assist in the diagnosis, treatment, and secondary prevention of stroke in patients in whom an infectious cause for stroke is probable. C1 [Fugate, Jennifer E.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Lyons, Jennifer L.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Thakur, Kiran T.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Smith, Bryan R.] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Mateen, Farrah J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC 720,55 Fruit St, Boston, MA 02114 USA. EM fmateen@mgh.harvard.edu NR 142 TC 18 Z9 19 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2014 VL 14 IS 9 BP 869 EP 880 DI 10.1016/S1473-3099(14)70755-8 PG 12 WC Infectious Diseases SC Infectious Diseases GA AO4WS UT WOS:000341342700030 PM 24881525 ER PT J AU Stupp, R Hegi, ME Gorlia, T Erridge, SC Perry, J Hong, YK Aldape, KD Lhermitte, B Pietsch, T Grujicic, D Steinbach, JP Wick, W Tarnawski, R Nam, DH Hau, P Weyerbrock, A Taphoorn, MJB Shen, CC Rao, N Thurzo, L Herrlinger, U Gupta, T Kortmann, RD Adamska, K McBain, C Brandes, AA Tonn, JC Schnell, O Wiegel, T Kim, CY Nabors, LB Reardon, DA van den Bent, MJ Hicking, C Markivskyy, A Picard, M Weller, M AF Stupp, Roger Hegi, Monika E. Gorlia, Thierry Erridge, Sara C. Perry, James Hong, Yong-Kil Aldape, Kenneth D. Lhermitte, Benoit Pietsch, Torsten Grujicic, Danica Steinbach, Joachim Peter Wick, Wolfgang Tarnawski, Rafal Nam, Do-Hyun Hau, Peter Weyerbrock, Astrid Taphoorn, Martin J. B. Shen, Chiung-Chyi Rao, Nalini Thurzo, Laszlo Herrlinger, Ulrich Gupta, Tejpal Kortmann, Rolf-Dieter Adamska, Krystyna McBain, Catherine Brandes, Alba A. Tonn, Joerg Christian Schnell, Oliver Wiegel, Thomas Kim, Chae-Yong Nabors, Louis Burt Reardon, David A. van den Bent, Martin J. Hicking, Christine Markivskyy, Andriy Picard, Martin Weller, Michael CA European Org Res Treatment Canc Canadian Brain Tumor Consortium CENTRIC Study Team TI Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID MALIGNANT GLIOMA; INTEGRIN ALPHA(V)BETA(3); RECURRENT GLIOBLASTOMA; CLINICAL-TRIAL; UNITED-STATES; TEMOZOLOMIDE; RADIOTHERAPY; EXPRESSION; BRAIN; BEVACIZUMAB AB Background Cilengitide is a selective alpha v beta 3 and alpha v beta 5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. Methods In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age >= 18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. Findings Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26.3 months (95% CI 23.8-28.8) in the cilengitide group and 26.3 months (23.9-34.7) in the control group (hazard ratio 1.02, 95% CI 0.81-1.29, p=0 86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). Interpretation The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. C1 [Stupp, Roger; Weller, Michael] Univ Spital Zurich, Zurich, Switzerland. [Stupp, Roger; Hegi, Monika E.; Lhermitte, Benoit] CHU Vaudois, CH-1011 Lausanne, Switzerland. [Stupp, Roger; Hegi, Monika E.; Lhermitte, Benoit] Univ Lausanne, Lausanne, Switzerland. [Gorlia, Thierry] EORTC Headquarters, Brussels, Belgium. [Erridge, Sara C.] Univ Edinburgh, Edinburgh Canc Ctr, Edinburgh, Midlothian, Scotland. [Perry, James] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Hong, Yong-Kil] Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea. [Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pietsch, Torsten; Herrlinger, Ulrich] Univ Bonn, Dept Neuropathol, Bonn, Germany. [Grujicic, Danica] Univ Belgrade, Clin Ctr Serbia, Clin Neurosurg, Belgrade, Serbia. [Grujicic, Danica] Univ Belgrade, Fac Med, Belgrade, Serbia. [Steinbach, Joachim Peter] Klinikum JW Goethe Univ Frankfurt, Frankfurt, Germany. [Wick, Wolfgang] Heidelberg Univ, Med Ctr, Heidelberg, Germany. [Wick, Wolfgang] German Canc Res Ctr, Heidelberg, Germany. [Tarnawski, Rafal] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Gliwice Branch, Gliwice, Poland. [Nam, Do-Hyun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Hau, Peter] Univ Klinikum Regensburg, Regensburg, Germany. [Weyerbrock, Astrid] Univ Freiburg Klinikum, Freiburg, Germany. [Taphoorn, Martin J. B.] Med Ctr Haaglanden, The Hague, Netherlands. [Shen, Chiung-Chyi] Taichung Vet Gen Hosp, Taichung, Taiwan. [Rao, Nalini] Bangalore Inst Oncol, Bangalore, Karnataka, India. [Thurzo, Laszlo] Szegedi Tudomanyegyet, Szeged, Hungary. [Gupta, Tejpal] Tata Mem Hosp, Navi Mumbai, India. [Kortmann, Rolf-Dieter] Univ Klinikum Leipzig, Leipzig, Germany. [Adamska, Krystyna] Greater Poland Canc Ctr, Poznan, Poland. [McBain, Catherine] Christie NHS FT, Manchester, Lancs, England. [Brandes, Alba A.] AUSL IRCCS Inst Neurol Sci, Bellaria Maggiore Hosp, Bologna, Italy. [Tonn, Joerg Christian; Schnell, Oliver] Klinikum Univ Munchen, Munich, Germany. [Wiegel, Thomas] Univ Hosp Ulm, Ulm, Germany. [Kim, Chae-Yong] Seoul Natl Univ, Bundang Hosp, SNU Coll Med, Seoul, South Korea. [Nabors, Louis Burt] Univ Alabama Birmingham, Birmingham, AL USA. [Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [van den Bent, Martin J.] Erasmus MC, Inst Canc, Rotterdam, Netherlands. [Hicking, Christine; Markivskyy, Andriy; Picard, Martin] Merck KGaA, Darmstadt, Germany. RP Stupp, R (reprint author), Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. EM roger.stupp@usz.ch RI Hegi, Monika/O-4796-2015; Tarnawski, Rafal/N-7526-2016 OI Hegi, Monika/0000-0003-0855-6495; FU Merck KGaA, Darmstadt, Germany FX Merck KGaA, Darmstadt, Germany. NR 33 TC 152 Z9 155 U1 9 U2 44 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2014 VL 15 IS 10 BP 1100 EP 1108 DI 10.1016/S1470-2045(14)70379-1 PG 9 WC Oncology SC Oncology GA AO4MH UT WOS:000341312500051 PM 25163906 ER PT J AU Gadgeel, SM Gandhi, L Riely, GJ Chiappori, AA West, HL Azada, MC Morcos, PN Lee, RM Garcia, L Yu, L Boisserie, F Di Laurenzio, L Golding, S Sato, J Yokoyama, S Tanaka, T Ou, SHI AF Gadgeel, Shirish M. Gandhi, Leena Riely, Gregory J. Chiappori, Alberto A. West, Howard L. Azada, Michele C. Morcos, Peter N. Lee, Ruey-Min Garcia, Linta Yu, Li Boisserie, Frederic Di Laurenzio, Laura Golding, Sophie Sato, Jotaro Yokoyama, Shumpei Tanaka, Tomohiro Ou, Sai-Hong Ignatius TI Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study SO LANCET ONCOLOGY LA English DT Article ID PROGRESSION; INHIBITION; CH5424802; THERAPY AB Background Patients with non-small-cell lung cancer (NSCLC) and ALK rearrangements generally have a progression-free survival of 8-11 months while on treatment with the ALK inhibitor crizotinib. However, resistance inevitably develops, with the brain a common site of progression. More potent ALK inhibitors with consistently demonstrable CNS activity and good tolerability are needed urgently. Alectinib is a novel, highly selective, and potent ALK inhibitor that has shown clinical activity in patients with crizotinib-naive ALK-rearranged NSCLC. We did a phase 1/2 study of alectinib to establish the recommended phase 2 dose of the drug and examine its activity in patients resistant or intolerant to crizotinib. Methods We enrolled patients with ALK-rearranged NSCLC who progressed on or were intolerant to crizotinib. We administered various oral doses of alectinib (300-900 mg twice a day) during the dose-escalation portion of the study (phase 1), to ascertain the recommended dose for phase 2. We used Response Evaluation Criteria in Solid Tumors criteria (version 1.1) to investigate the activity of alectinib in all patients with a baseline scan and at least one post-treatment scan (CT or MRI), with central radiological review of individuals with brain metastases. We assessed safety in all patients who received at least one dose of alectinib. Here, we present data for the phase 1 portion of the study, the primary objective of which was to establish the recommended phase 2 dose; phase 2 is ongoing. This trial is registered at ClinicalTrials.gov, number NCT01588028. Findings 47 patients were enrolled. Alectinib was well tolerated, with the most common adverse events being fatigue (14 [30%]; all grade 1-2), myalgia (eight [17%]; all grade 1-2), and peripheral oedema (seven [15%] grade 1-2, one [2%] grade 3). Dose-limiting toxic effects were recorded in two patients in the cohort receiving alectinib 900 mg twice a day; one individual had grade 3 headache and the other had grade 3 neutropenia. The most common grade 3-4 adverse events were increased levels of gamma-glutamyl transpeptidase (two [4%]), a reduction in the number of neutrophils (two [4%]), and hypophosphataemia (two [4%]). Three patients reported four grade 4 serious adverse events that were deemed unrelated to alectinib: acute renal failure; pleural effusion and pericardial effusion; and brain metastasis. At data cut-off (median follow-up 126 days [IQR 84-217]), 44 patients could be assessed for activity. Investigator-assessed objective responses were noted in 24 (55%) patients, with a confirmed complete response in one (2%), a confirmed partial response in 14 (32%), and an unconfirmed partial response in nine (20%). 16 (36%) patients had stable disease; the remaining four (9%) had progressive disease. Of 21 patients with CNS metastases at baseline, 11 (52%) had an objective response; six (29%) had a complete response (three unconfirmed) and five (24%) had a partial response (one unconfirmed); eight (38%) patients had stable disease and the remaining two (10%) had progressive disease. Pharmacokinetic data indicated that mean exposure (AUC(0-10)) after multiple doses of alectinib (300-600 mg twice a day) was dose-dependent. Interpretation Alectinib was well tolerated, with promising antitumour activity in patients with ALK-rearranged NSCLC resistant to crizotinib, including those with CNS metastases. On the basis of activity, tolerability, and pharmacokinetic data, we chose alectinib 600 mg twice a day as the recommended dose for phase 2. C1 [Gadgeel, Shirish M.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Gandhi, Leena] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chiappori, Alberto A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [West, Howard L.] Swedish Med Ctr, Seattle, WA USA. [Morcos, Peter N.; Lee, Ruey-Min; Yu, Li; Boisserie, Frederic; Di Laurenzio, Laura; Golding, Sophie] F Hoffmann La Roche & Co Ltd, Roche Innovat Ctr New York, Roche Pharmaceut Res & Early Dev Ctr, New York, NY USA. [Garcia, Linta] Chugai Pharma USA, Berkeley Hts, NJ USA. [Sato, Jotaro; Yokoyama, Shumpei; Tanaka, Tomohiro] Chugai Pharmaceut Co Ltd, Tokyo, Japan. [Azada, Michele C.; Ou, Sai-Hong Ignatius] Univ Calif Irvine, Sch Med, Chao Family Comprehens Canc Ctr, Orange, CA 92868 USA. RP Ou, SHI (reprint author), Univ Calif Irvine, Sch Med, Chao Family Comprehens Canc Ctr, Dept Med,Div Hematol Oncol, Orange, CA 92868 USA. EM ignatius.ou@uci.edu OI Gandhi, Leena/0000-0002-2398-9179 FU Chugai Pharmaceuticals; F Hoffmann La-Roche FX Chugai Pharmaceuticals, F Hoffmann La-Roche. NR 26 TC 218 Z9 228 U1 5 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2014 VL 15 IS 10 BP 1119 EP 1128 DI 10.1016/S1470-2045(14)70362-6 PG 10 WC Oncology SC Oncology GA AO4MH UT WOS:000341312500053 PM 25153538 ER PT J AU de Azambuja, E Holmes, AP Piccart-Gebhart, M Holmes, E Di Cosimo, S Swaby, RF Untch, M Jackisch, C Lang, I Smith, I Boyle, F Xu, BH Barrios, CH Perez, EA Azim, HA Kim, SB Kuemmel, S Huang, CS Vuylsteke, P Hsieh, RK Gorbunova, V Eniu, A Dreosti, L Tavartkiladze, N Gelber, RD Eidtmann, H Baselga, J AF de Azambuja, Evandro Holmes, Andrew P. Piccart-Gebhart, Martine Holmes, Eileen Di Cosimo, Serena Swaby, Ramona F. Untch, Michael Jackisch, Christian Lang, Istvan Smith, Ian Boyle, Frances Xu, Binghe Barrios, Carlos H. Perez, Edith A. Azim, Hatem A., Jr. Kim, Sung-Bae Kuemmel, Sherko Huang, Chiun-Sheng Vuylsteke, Peter Hsieh, Ruey-Kuen Gorbunova, Vera Eniu, Alexandru Dreosti, Lydia Tavartkiladze, Natalia Gelber, Richard D. Eidtmann, Holger Baselga, Jose TI Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response SO LANCET ONCOLOGY LA English DT Article ID CHEMOTHERAPY PLUS TRASTUZUMAB; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; PREDICTS; THERAPY; EVENTS; WOMEN AB Background Findings from the randomised phase 3 NeoALTTO trial in women with HER2-positive early breast cancer showed that the combination of lapatinib and trastuzumab significantly improved rates of pathological complete response compared with either drug alone. Here, we report data for the prespecified secondary endpoints of event-free and overall survival, and assess the association between these outcomes and pathological complete response. Methods We enrolled women with HER2-positive early breast cancer and randomly assigned them to receive oral lapatinib (1500 mg), intravenous trastuzumab (4 mg/kg loading dose followed by 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab (same dose as for single agent) in combination for 6 weeks, followed by an additional 12 weeks of the assigned anti-HER2 therapy in combination with weekly paclitaxel (80 mg/m(2)). Definitive surgery was done 4 weeks after the last dose of paclitaxel. After surgery, women received three cycles of FEC (fluorouracil 500 mg/m(2) plus epirubicin 100 mg/m(2) plus cyclophosphamide 500 mg/m(2)) given intravenously every 3 weeks, followed by 34 weeks of the same assigned neoadjuvant anti-HER2 therapy. The primary endpoint was pathological complete response. Secondary endpoints included event-free and overall survival (intention-to-treat analysis), and the association between pathological complete response and event-free or overall survival (analysed by landmark analysis at 30 weeks after randomisation). Follow-up is ongoing, and the trial is registered with ClinicalTrials.gov, number NCT00553358. Findings 455 patients were enrolled: 154 (34%) were assigned to the lapatinib group, 149 (33%) to the trastuzumab group, and 152 (33%) to the lapatinib plus trastuzumab group. At an event follow-up of 3.77 years (IQR 3.50-4.22), 3-year event-free survival was 78% (95% CI 70-84) in the lapatinib group, 76% (68-82) in the trastuzumab group, and 84% (77-89) in the combination group. Event-free survival did not differ between the lapatinib and trastuzumab groups (HR 1.06, 95% CI 0.66-1.69, p=0.81), nor between the combination and trastuzumab groups (0.78, 0.47-1.28, p=0.33). Median survival follow-up was 3.84 years (IQR 3.60-4.24), and 3-year overall survival was 93% (95% CI 87-96) for lapatinib, 90% (84-94) for trastuzumab, and 95% (90-98) for combination therapy. Overall survival did not significantly differ between the lapatinib and trastuzumab groups (HR 0.86, 95% CI 0.45-1 63, p=0.65), nor between the combination and trastuzumab groups (0.62, 0.30-1.25, p=0.19). Landmark analyses showed that 3-year event-free survival was significantly improved for women who achieved pathological complete response compared with those who did not (HR 0.38, 95% CI 0.22-0.63, p=0.0003), as was 3-year overall survival (0.35, 0.15-0.70, p=0.005). Adverse events occurred in 149 (99%) patients receiving lapatinib, 142 (96%) patients receiving trastuzumab, and 147 (99%) patients receiving combination therapy. The most common adverse events were diarrhoea, rash or erythema, hepatic adverse events, and neutropenia (not related to FEC administration), and were consistent with known safety profiles of lapatinib and trastuzumab. Three primary and eight secondary cardiac events occurred, with no significant difference in incidence between treatment groups for primary or any cardiac events. Interpretation Although event-free survival or overall survival did not differ between treatment groups, findings from our study confirm that patients who achieve pathological complete response after neoadjuvant anti-HER2 therapy have longer event-free and overall survival than do patients without pathological complete response. C1 [de Azambuja, Evandro; Azim, Hatem A., Jr.] Inst Jules Bordet, B-1000 Brussels, Belgium. [de Azambuja, Evandro; Azim, Hatem A., Jr.] Breast European Adjuvant Study Team, Brussels, Belgium. [Holmes, Andrew P.; Holmes, Eileen] Frontier Sci Scotland Ltd, Kincraig, Kingussie, England. [Piccart-Gebhart, Martine] Univ Libre Brussels, Inst Jules Bordet, Dept Med, Brussels, Belgium. [Di Cosimo, Serena] Ist Nazl Tumori, I-20133 Milan, Italy. [Di Cosimo, Serena] SOLTI Breast Canc Res Grp, Madrid, Spain. [Swaby, Ramona F.] GlaxoSmithKline, Collegeville, PA USA. [Untch, Michael] HELIOS Klin, Clin Gynaecol Gynaecol Oncol & Obstet, Buch, Germany. [Untch, Michael] HELIOS Klin, Breast Canc Ctr, Buch, Germany. [Jackisch, Christian] Sana Klinikum Offenbach, Offenbach, Germany. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Smith, Ian] Royal Marsden Hosp, London SW3 6JJ, England. [Smith, Ian] Inst Canc Res, London SW3 6JB, England. [Boyle, Frances] Univ Sydney, Mater Hosp, Patricia Ritchie Ctr Canc Care & Res, Sydney, NSW, Australia. [Xu, Binghe] Chinese Acad Med Sci, Canc Hosp, Beijing 100730, Peoples R China. [Barrios, Carlos H.] PUC RS Sch Med, Porto Alegre, RS, Brazil. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Kim, Sung-Bae] Univ Ulsan, Coll Med, Asian Med Ctr, Seoul, South Korea. [Kuemmel, Sherko] Kliniken Essen Mitte, Essen, Germany. [Huang, Chiun-Sheng] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Vuylsteke, Peter] Clin St Elizabeth, Namur, Belgium. [Hsieh, Ruey-Kuen] Mackay Mem Hosp, Taipei, Taiwan. [Eniu, Alexandru] Canc Inst Prof Dr Ion Chiricuta, Cluj Napoca, Romania. [Dreosti, Lydia] Univ Pretoria, Dept Med Oncol, ZA-0001 Pretoria, South Africa. [Tavartkiladze, Natalia] Odessa Oncol Ctr, Odessa, Ukraine. [Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Eidtmann, Holger] Univ Hosp Kiel, Kiel, Germany. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP de Azambuja, E (reprint author), Inst Jules Bordet, Blvd Waterloo 121, B-1000 Brussels, Belgium. EM evandro.azambuja@bordet.be RI Serena, Di Cosimo/E-9418-2017; OI Serena, Di Cosimo/0000-0002-4666-8052; Huang, Chiun-Sheng/0000-0002-6557-211X FU GlaxoSmithKline FX GlaxoSmithKline. NR 28 TC 89 Z9 91 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2014 VL 15 IS 10 BP 1137 EP 1146 DI 10.1016/S1470-2045(14)70320-1 PG 10 WC Oncology SC Oncology GA AO4MH UT WOS:000341312500055 PM 25130998 ER PT J AU Apora, E O'Brien, J Stephen, M Castillo, JJ AF Apora, Emmanuel O'Brien, Jennifer Stephen, Merin Castillo, Jorge J. TI Systemic lupus erythematosus is associated with increased incidence of hematologic malignancies: A meta-analysis of prospective cohort studies SO LEUKEMIA RESEARCH LA English DT Article DE Lupus; Lymphoma; Leukemia; Myeloma; Incidence; Meta-analysis ID NON-HODGKINS-LYMPHOMA; CANCER-RISK; SUBTYPES; BIAS AB Our objective was to define the risk of lymphoma, leukemia and myeloma in adult patients with SLE with a meta-analysis of prospective cohort studies. A literature search from 1995 to 2013 revealed eight studies evaluating this association. The outcome of interest was the standardized incidence ratio (SIR). Our study included 401 cases in a cohort of approximately 68,000 SLE patients, and showed an increased incidence of all hematologic malignancies (SIR 2.9), non-Hodgkin lymphoma (SIR 5.7), Hodgkin lymphoma (SIR 3.1), leukemia (SIR 2.3) and myeloma (SIR 1.5) in SLE patients compared with the general population. The increased SIR was consistent regardless of age, sex or geographical region. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Apora, Emmanuel; O'Brien, Jennifer] Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. [Apora, Emmanuel; O'Brien, Jennifer] Miriam Hosp, Dept Med, Providence, RI 02906 USA. Roger Williams Med Ctr, Div Hematol & Oncol, Providence, RI USA. [Castillo, Jorge J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 23 TC 5 Z9 5 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2014 VL 38 IS 9 BP 1067 EP 1071 DI 10.1016/j.leukres.2014.06.025 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA AO5AB UT WOS:000341351400014 PM 25052307 ER PT J AU Rafferty, EA AF Rafferty, Elizabeth A. TI Mammographic breast density: from Wolfe and beyond SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID CANCER; RISK; ASSOCIATION C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rafferty, EA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP PY 2014 VL 21 IS 9 BP 920 EP 921 DI 10.1097/gme.0000000000000308 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AO7JN UT WOS:000341529400003 PM 25072956 ER PT J AU Lezcano, C Lee, CW Larson, AR Menzies, AM Kefford, RF Thompson, JF Mihm, MC Ogino, S Long, GV Scolyer, RA Murphy, GF AF Lezcano, Cecilia Lee, Chung-Wei Larson, Allison R. Menzies, Alexander M. Kefford, Richard F. Thompson, John F. Mihm, Martin C., Jr. Ogino, Shuji Long, Georgina V. Scolyer, Richard A. Murphy, George F. TI Evaluation of stromal HGF immunoreactivity as a biomarker for melanoma response to RAF inhibitors SO MODERN PATHOLOGY LA English DT Article DE biomarker; HGF; melanoma; RAF inhibitor ID HEPATOCYTE GROWTH-FACTOR; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; CANCER-CELLS; SOLID TUMORS; GEFITINIB RESISTANCE; KINASE INHIBITORS; LUNG-CANCER; BRAF; MET AB Of more than 150 000 published studies evaluating new biomarkers, fewer than 100 biomarkers have been implemented for patient care. One reason for this is lack of rigorous testing by the medical community to validate claims for biomarker clinical relevance, and potential reluctance to publish negative results when confirmation is not obtained. Here we sought to determine the utility and reproducibility of immunohistochemical detection of hepatocyte growth factor (HGF) in melanoma tissue, an approach of potential assistance in defining patients with innate resistance to BRAF inhibitor therapy. To this end, a published and a revised method that retained sensitivity but with greater specificity for HGF detection, were evaluated in cells known to endogenously express HGF, and in models where HGF is upregulated via cytokine induction and via overexpression by gene transfection. Consequent patient evaluation in collaboration with the Melanoma Institute Australia of a cohort of 41 melanoma specimens with extensive clinical annotation failed to validate HGF immunohistochemistry as a predictor of response to BRAF inhibitors. Targeted therapies for advanced melanoma and other cancers show great promise, and rigorous validation studies are thus indicated for approaches that seek to personalize such therapies to maximize therapeutic efficacy. C1 [Lezcano, Cecilia; Lee, Chung-Wei; Ogino, Shuji; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lezcano, Cecilia; Lee, Chung-Wei; Larson, Allison R.; Mihm, Martin C., Jr.; Ogino, Shuji; Murphy, George F.] Harvard Univ, Sch Med, Boston, MA USA. [Larson, Allison R.; Mihm, Martin C., Jr.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Kefford, Richard F.; Thompson, John F.; Long, Georgina V.; Scolyer, Richard A.] Melanoma Inst Australia, Sydney, NSW, Australia. [Menzies, Alexander M.; Kefford, Richard F.; Thompson, John F.; Long, Georgina V.; Scolyer, Richard A.] Univ Sydney, Camperdown, NSW, Australia. [Kefford, Richard F.; Long, Georgina V.] Westmead Inst Canc Res, Sydney, NSW, Australia. [Thompson, John F.] Mater Hosp, Sydney, NSW, Australia. [Thompson, John F.; Scolyer, Richard A.] Royal Prince Alfred Hosp, Sydney, NSW, Australia. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Murphy, GF (reprint author), Brigham & Womens Hosp, Dept Pathol, 221 Longwood Ave,EBRC Suite 401, Boston, MA 02115 USA. EM gmurphy@rics.bwh.harvard.edu RI Larson, Allison/N-4263-2015; OI Larson, Allison/0000-0001-8534-7078; Scolyer, Richard/0000-0002-8991-0013 FU [NIH-P50 CA93683]; [R01 CA158467-02] FX NIH-P50 CA93683 and R01 CA158467-02 supported the present work. We thank Julie Howle, Jessica Hyman, Tracy Liaw, Katherine Carson, Raghwa Sharma and the staff at Melanoma Institute Australia and Westmead Medical Oncology Trials Centre. NR 49 TC 9 Z9 9 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2014 VL 27 IS 9 BP 1193 EP 1202 DI 10.1038/modpathol.2013.226 PG 10 WC Pathology SC Pathology GA AO8QU UT WOS:000341620100002 PM 24434899 ER PT J AU Doros, LA Rossi, CT Yang, JD Field, A Williams, GM Messinger, Y Cajaiba, MM Perlman, EJ Schultz, KA Cathro, HP Legallo, RD La Fortune, KA Chikwava, KR Faria, P Geller, JI Dome, JS Mullen, EA Gratias, EJ Dehner, LP Hill, DA AF Doros, Leslie A. Rossi, Christopher T. Yang, Jiandong Field, Amanda Williams, Gretchen M. Messinger, Yoav Cajaiba, Mariana M. Perlman, Elizabeth J. Schultz, Kris A. Cathro, Helen P. Legallo, Robin D. La Fortune, Kristin A. Chikwava, Kudakwashe R. Faria, Paulo Geller, James I. Dome, Jeffrey S. Mullen, Elizabeth A. Gratias, Eric J. Dehner, Louis P. Hill, D. Ashley TI DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma SO MODERN PATHOLOGY LA English DT Article DE cystic nephroma; DICER1; embryonal rhabdomyosarcoma; pleuropulmonary blastoma; renal cysts; renal sarcoma; Wilms tumor ID PARTIALLY DIFFERENTIATED NEPHROBLASTOMA; PLEUROPULMONARY BLASTOMA REGISTRY; INTEGRATIVE GENOMICS VIEWER; AMINO-ACID SUBSTITUTIONS; MULTILOCULAR CYST; STROMAL TUMOR; KIDNEY; ENTITY; RHABDOMYOSARCOMA; DIAGNOSIS AB The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor. We hypothesize that cystic nephroma, like the pleuropulmonary blastoma in the lung, represents a spectrum of abnormal renal organogenesis with risk for malignant transformation. Here we studied DICER1 mutations in a cohort of 20 cystic nephromas and 6 cystic partially differentiated nephroblastomas, selected independently of a familial association with pleuropulmonary blastoma and describe four cases of sarcoma arising in cystic nephroma, which have a similarity to the solid areas of type II or III pleuropulmonary blastoma. The genetic analyses presented here confirm that DICER1 mutations are the major genetic event in the development of cystic nephroma. Further, cystic nephroma and pleuropulmonary blastoma have similar DICER1 loss of function and 'hotspot' missense mutation rates, which involve specific amino acids in the RNase IIIb domain. We propose an alternative pathway with the genetic pathogenesis of cystic nephroma and DICER1-renal sarcoma paralleling that of type I to type II/III malignant progression of pleuropulmonary blastoma. C1 [Doros, Leslie A.; Rossi, Christopher T.; Dome, Jeffrey S.] George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Div Oncol, Washington, DC 20052 USA. [Doros, Leslie A.; Rossi, Christopher T.; Yang, Jiandong; Field, Amanda; Hill, D. Ashley] George Washington Univ, Sch Med & Hlth Sci, Dept Pathol, Washington, DC 20052 USA. [Doros, Leslie A.; Rossi, Christopher T.; Yang, Jiandong; Field, Amanda; Hill, D. Ashley] George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Washington, DC 20052 USA. [Yang, Jiandong; Field, Amanda; Hill, D. Ashley] Childrens Res Inst, Med Genet Res Ctr, Minneapolis, MN USA. [Williams, Gretchen M.; Messinger, Yoav; Schultz, Kris A.; Dehner, Louis P.; Hill, D. Ashley] Childrens Hosp & Clin Minnesota, Int Pleuropulm Blastoma Registry, Minneapolis, MN USA. [Cajaiba, Mariana M.] Vanderbilt Univ, Dept Pathol, Nashville, TN USA. [Perlman, Elizabeth J.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Cathro, Helen P.; Legallo, Robin D.; La Fortune, Kristin A.] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. [Chikwava, Kudakwashe R.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Faria, Paulo] Inst Nacl Canc, Div Pathol, Rio De Janeiro, Brazil. [Geller, James I.] Cincinnati Childrens Hosp Med Ctr, Div Oncol, Cincinnati, OH 45229 USA. [Mullen, Elizabeth A.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gratias, Eric J.] Univ Tennessee, Coll Med, Childrens Hosp Erlanger, Div Hematol Oncol, Chattanooga, TN USA. [Dehner, Louis P.] Washington Univ, Med Ctr, Lauren V Ackerman Lab Surg Pathol, St Louis, MO 63110 USA. [Hill, D. Ashley] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. RP Dehner, LP (reprint author), Washington Univ, Med Ctr, Lauren V Ackerman Div Surg Pathol, 660S Euclid Ave, St Louis, MO 63110 USA. EM dehner@path.wustl.edu; dashill@childrensnational.org FU National Institutes of Health [U10 CA98543, U24 CA114766]; National Cancer Institute (NCI); NCI [R01CA143167]; American Society of Clinical Oncology Young Investigator Award; Parson's Foundation; Hyundai Hope on Wheels FX This work is supported by National Institutes of Health grants U10 CA98543 and U24 CA114766 to the Children's Oncology Group. Tissue samples were provided by the Cooperative Human Tissue Network that is funded by the National Cancer Institute (NCI). Other investigators may have received samples from these same tissues. Dr Hill, Doros and Dr Rossi were supported in part by NCI R01CA143167, an American Society of Clinical Oncology Young Investigator Award (LD), The Parson's Foundation (DAH) and a grant from Hyundai Hope on Wheels. We thank the many physicians and families who contribute time and tissues that facilitate research, in particular the members of the Renal Tumor Biology Committee of the Children's Oncology Group. NR 38 TC 32 Z9 32 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2014 VL 27 IS 9 BP 1267 EP 1280 DI 10.1038/modpathol.2013.242 PG 14 WC Pathology SC Pathology GA AO8QU UT WOS:000341620100010 PM 24481001 ER PT J AU Jin, DQ Ni, TT Sun, JJ Wan, HY Amack, JD Yu, GJ Fleming, J Chiang, C Li, WY Papierniak, A Cheepala, S Conseil, G Cole, SPC Zhou, B Drummond, IA Schuetz, JD Malicki, J Zhong, TP AF Jin, Daqing Ni, Terri T. Sun, Jianjian Wan, Haiyan Amack, Jeffrey D. Yu, Guangju Fleming, Jonathan Chiang, Chin Li, Wenyan Papierniak, Anna Cheepala, Satish Conseil, Gwenaelle Cole, Susan P. C. Zhou, Bin Drummond, Iain A. Schuetz, John D. Malicki, Jarema Zhong, Tao P. TI Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport SO NATURE CELL BIOLOGY LA English DT Article ID LEFT-RIGHT ASYMMETRY; KUPFFERS VESICLE; EFFLUX TRANSPORTER; SENSORY NEURONS; LENGTH CONTROL; PRIMARY CILIUM; GTPASE RAB8; ZEBRAFISH; RESISTANCE; MULTIDRUG AB Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (Ikt) mutants show ciliogenesis defects, and the Ikt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4T8 4m mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis. C1 [Jin, Daqing; Sun, Jianjian; Yu, Guangju; Li, Wenyan; Zhong, Tao P.] Fudan Univ, Sch Life Sci, Dept Genet, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Ni, Terri T.; Wan, Haiyan; Zhong, Tao P.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Amack, Jeffrey D.] SUNY Upstate Med Univ, Dept Cell & Dev Biol, New York, NY 13210 USA. [Fleming, Jonathan; Chiang, Chin] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. [Papierniak, Anna; Malicki, Jarema] Univ Sheffield, ARC Ctr Dev & Biomed Genet, Sheffield S10 2TN, S Yorkshire, England. [Cheepala, Satish; Schuetz, John D.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38163 USA. [Conseil, Gwenaelle; Cole, Susan P. C.] Queens Univ, Div Canc Biol & Genet, Kingston, ON K7L 3N6, Canada. [Zhou, Bin] Chinese Acad Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China. [Drummond, Iain A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Cambridge, MA 02148 USA. RP Zhong, TP (reprint author), Fudan Univ, Sch Life Sci, Dept Genet, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. EM taozhong@fudan.edu.cn RI malicki, jarema/G-8611-2014; OI Amack, Jeffrey/0000-0002-5465-9754 FU National Basic Research Program of China [CMST2013CB945301, CMST2012CB944501]; National Natural Science Foundation of China [NSFC31172173]; Shanghai Pujiang Program [11PJ1401600]; National Institute of Health of America; Canadian Institutes of Health Research [MOP106513] FX We acknowledge P. Yuanyuan and J. Guan for assistance in fish care, X. Zhu for hRPE1 cells, J. Shah for IFT88-EYFP cells, C. Yi for cAMP assays, Q. Li for diagram drawing and L. Cai and G. Zhu for spin-disk confocal microscopy analysis. We are grateful to H. Ma, B. Appel, Z. Sun, J. Gamse and members of our laboratories for comments on the manuscript and helpful discussions. This research was supported in part by grants from the National Basic Research Program of China (CMST2013CB945301, CMST2012CB944501; T.P.Z.), National Natural Science Foundation of China (NSFC31172173; T.P.Z.) and Shanghai Pujiang Program (11PJ1401600; T.P.Z.) as well as the National Institute of Health of America (T.P.Z., J.D.S., J.M., I.A.D.) and Canadian Institutes of Health Research (MOP106513, S.P.C.C.). NR 50 TC 14 Z9 16 U1 0 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2014 VL 16 IS 9 BP 841 EP 851 DI 10.1038/ncb3029 PG 11 WC Cell Biology SC Cell Biology GA AO5SA UT WOS:000341404400005 PM 25173977 ER PT J AU Sevenich, L Bowman, RL Mason, SD Quail, DE Rapaport, F Elie, BT Brogi, E Brastianos, PK Hahn, WC Holsinger, LJ Massague, J Leslie, CS Joyce, JA AF Sevenich, Lisa Bowman, Robert L. Mason, Steven D. Quail, Daniela E. Rapaport, Franck Elie, Benelita T. Brogi, Edi Brastianos, Priscilla K. Hahn, William C. Holsinger, Leslie J. Massague, Joan Leslie, Christina S. Joyce, Johanna A. TI Analysis of tumour-and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S SO NATURE CELL BIOLOGY LA English DT Article ID BREAST-CANCER METASTASIS; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; PROTEOMIC IDENTIFICATION; TIGHT JUNCTION; MICROENVIRONMENT; PROTEASES; TARGETS; BARRIER; DISSEMINATION AB Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumour microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analysed tumour stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumour cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood brain barrier transmigration through proteolytic processing of the junctional adhesion molecule, JAM-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease. C1 [Sevenich, Lisa; Bowman, Robert L.; Mason, Steven D.; Quail, Daniela E.; Elie, Benelita T.; Massague, Joan; Joyce, Johanna A.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA. [Rapaport, Franck; Leslie, Christina S.] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10065 USA. [Brogi, Edi] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Brastianos, Priscilla K.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Brastianos, Priscilla K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02214 USA. [Holsinger, Leslie J.] Virobay Inc, Menlo Pk, CA 94025 USA. [Massague, Joan; Joyce, Johanna A.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10065 USA. [Massague, Joan; Joyce, Johanna A.] Mem Sloan Kettering Canc Ctr, Metastasis Res Ctr, New York, NY 10065 USA. RP Joyce, JA (reprint author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA. EM johanna@joycelab.org OI Brastianos, Priscilla/0000-0003-4470-8425; Massague, Joan/0000-0001-9324-8408 FU US National Cancer Institute program grant of the Integrative Cancer Biology Program [CA148967]; US National Cancer Institute program grant of Tumour Microenvironment Network [CA126518]; Health Research Science Board of New York; Alan and Sandra Gerry Metastasis Research Initiative; Deutsche Forschungsgemeinschaft [SE2234/1-1]; US National Cancer Institute F31 fellowship [CA167863]; Gerstner Sloan Kettering graduate program; US National Cancer Institute F32 fellowship [CA130329]; Canadian Institutes of Health Research FX We thank K. Simpson and X. Chen for excellent technical support, and members of the J.A.J. laboratory for insightful discussion. We thank L. Akkari, O. Olson and D. Yan for reading the manuscript,We are grateful to P. Bos for advice on the BBB assays and experimental brain metastasis model. We thank the MSKCC Core Facilities of Genomics, Molecular Cytology, Small Animal Imaging and Monoclonal Antibody Production for technical assistance. We thank H. Chapman (UCSF) for providing cathepsin S KO mice. This research was supported by the following: US National Cancer Institute program grants of the Integrative Cancer Biology Program (CA148967; J.A.J., C.S.L.) and Tumour Microenvironment Network (CA126518; J.A.J., J.M.), the Health Research Science Board of New York, and the Alan and Sandra Gerry Metastasis Research Initiative (J.A.J.), Deutsche Forschungsgemeinschaft (SE2234/1-1; L.S.), US National Cancer Institute F31 fellowship CA167863 and Gerstner Sloan Kettering graduate program (R.L.B.), US National Cancer Institute F32 fellowship CA130329 (S.D.M.), and Canadian Institutes of Health Research (D.F.Q.). NR 49 TC 40 Z9 42 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2014 VL 16 IS 9 BP 876 EP 888 DI 10.1038/ncb3011 PG 13 WC Cell Biology SC Cell Biology GA AO5SA UT WOS:000341404400008 PM 25086747 ER PT J AU He, XL Zhang, LG Chen, Y Remke, M Shih, D Lu, FH Wang, HB Deng, YQ Yu, Y Xia, Y Wo, XC Ramaswamy, V Hu, T Wang, F Zhou, WH Burns, DK Kim, SH Kool, M Pfister, SM Weinstein, LS Pomeroy, SL Gilbertson, RJ Rubin, JB Hou, YP Wechsler-Reya, R Taylor, MD Lu, QR AF He, Xuelian Zhang, Liguo Chen, Ying Remke, Marc Shih, David Lu, Fanghui Wang, Haibo Deng, Yaqi Yu, Yang Xia, Yong Wo, Xiaochong Ramaswamy, Vijay Hu, Tom Wang, Fan Zhou, Wenhao Burns, Dennis K. Kim, Se Hoon Kool, Marcel Pfister, Stefan M. Weinstein, Lee S. Pomeroy, Scott L. Gilbertson, Richard J. Rubin, Joshua B. Hou, Yiping Wechsler-Reya, Robert Taylor, Michael D. Lu, Q. Richard TI The G protein alpha subunit G alpha(s) is a tumor suppressor in Sonic hedgehog-driven medulloblastoma SO NATURE MEDICINE LA English DT Article ID PRIMARY CILIUM; SHH MEDULLOBLASTOMA; COUPLED RECEPTORS; KINASE-A; PATHWAY; CANCER; INHIBITOR; BRAIN; MICE; ACTIVATION AB Medulloblastoma, the most common malignant childhood brain tumor, exhibits distinct molecular subtypes and cellular origins. Genetic alterations driving medulloblastoma initiation and progression remain poorly understood. Herein, we identify GNAS, encoding the G protein G alpha(s), as a potent tumor suppressor gene that, when expressed at low levels, defines a subset of aggressive Sonic hedgehog (SHH)-driven human medulloblastomas. Ablation of the single Gnas gene in anatomically distinct progenitors in mice is sufficient to induce Shh-associated medulloblastomas, which recapitulate their human counterparts. G alpha(s) is highly enriched at the primary cilium of granule neuron precursors and suppresses Shh signaling by regulating both the cAMP-dependent pathway and ciliary trafficking of Hedgehog pathway components. Elevation in levels of a G alpha(s) effector, cAMP, effectively inhibits tumor cell proliferation and progression in Gnas-ablated mice. Thus, our gain- and loss-of-function studies identify a previously unrecognized tumor suppressor function for G alpha(s) that can be found consistently across Shh-group medulloblastomas of disparate cellular and anatomical origins, highlighting G protein modulation as a potential therapeutic avenue. C1 [He, Xuelian; Wang, Fan; Hou, Yiping] Sichuan Univ, Sch Preclin & Forens Med, Collaborat Innovat Ctr Biotherapy, Dept Forens Med,State Key Lab Biotherapy,West Ch, Chengdu 610064, Peoples R China. [He, Xuelian; Zhang, Liguo; Lu, Fanghui; Wang, Haibo; Deng, Yaqi; Lu, Q. Richard] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Brain Tumor Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. [He, Xuelian; Zhang, Liguo; Lu, Fanghui; Wang, Haibo; Deng, Yaqi; Lu, Q. Richard] Cincinnati Childrens Hosp Med Ctr, Canc Biol Canc & Blood Dis Inst, Cincinnati, OH 45229 USA. [Chen, Ying] Xiamen Univ, Sch Life Sci, Xiamen, Fujian, Peoples R China. [Remke, Marc; Shih, David; Wo, Xiaochong; Ramaswamy, Vijay; Taylor, Michael D.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Yu, Yang; Lu, Q. Richard] Sichuan Univ, Collaborat Innovat Ctr Biotherapy, State Key Lab Biotherapy, Dept Pediat,West China Hosp 2, Chengdu 610064, Peoples R China. [Xia, Yong] Sichuan Univ, Dept Neurosurg, West China Hosp, Chengdu 610064, Peoples R China. [Hu, Tom; Burns, Dennis K.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Zhou, Wenhao; Lu, Q. Richard] Fudan Univ, Key Lab Birth Defects, Childrens Hosp, Shanghai 200433, Peoples R China. [Kim, Se Hoon] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea. [Kool, Marcel; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany. [Weinstein, Lee S.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. [Pomeroy, Scott L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurol,Childrens Hosp, Boston, MA 02115 USA. [Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. [Rubin, Joshua B.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Wechsler-Reya, Robert] Sanford Burnham Med Res Inst, Tumor Dev Program, La Jolla, CA USA. RP Lu, QR (reprint author), Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Brain Tumor Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. EM richard.lu@cchmc.org RI Shih, David/H-3186-2011; Pfister, Stefan/F-6860-2013; OI Shih, David/0000-0002-9802-4937; Pfister, Stefan/0000-0002-5447-5322; Remke, Marc/0000-0002-9404-9993 FU US National Institutes of Health [R01 NS078092, R01 NS075243]; Ministry of Education of China [IRT0935]; Canadian Institutes of Health Research; Mildred-Scheel Foundation/German Cancer Aid FX We would like to thank A. Gilman, L. Lum, E. Hurlock, K. Campbell, J. Chan, H. Li, A. Hassan, D. He, E. Lu, L. He and W Ding for comments and technical support. We thank B. Fritzsch (University of Iowa) and J. Johnson (UT Southwestern) for Atoh1-Cre and Atoh1-GFP lines, respectively, C. Stiles (Harvard Medical School) for anti-Olig2, R. Rohatgi (Stanford University) for Ptch1-specific antibody and S. Scales (Genentech) for Gli2-, Gli3- and GPR161-specific antibodies. This study was funded in part by grants from the US National Institutes of Health (R01 NS078092 and R01 NS075243) to Q.R.L., the Ministry of Education of China (IRT0935) and from the Canadian Institutes of Health Research to M.D.T. and a postdoctoral fellowship by the Mildred-Scheel Foundation/German Cancer Aid (M.R.). NR 55 TC 28 Z9 28 U1 3 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD SEP PY 2014 VL 20 IS 9 BP 1035 EP 1042 DI 10.1038/nm.3666 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AO5RW UT WOS:000341404000016 PM 25150496 ER PT J AU Strosberg, JR Benson, AB Huynh, L Duh, MS Goldman, J Sahai, V Rademaker, AW Kulke, MH AF Strosberg, Jonathan R. Benson, Al B. Huynh, Lynn Duh, Mei Sheng Goldman, Jamie Sahai, Vaibhav Rademaker, Alfred W. Kulke, Matthew H. TI Clinical Benefits of Above-Standard Dose of Octreotide LAR in Patients With Neuroendocrine Tumors for Control of Carcinoid Syndrome Symptoms: A Multicenter Retrospective Chart Review Study SO ONCOLOGIST LA English DT Review DE Neuroendocrine tumor; Carcinoid syndrome symptoms; Somatostatin analogs; Flushing; Diarrhea; Above-standard dose ID MANAGEMENT; GUIDELINES AB Background. Octreotide LAR is used in patients for control of carcinoid syndrome (CS) and other symptoms of hormone hypersecretion. The aim of this study was to examine reasons for octreotide LAR dose escalation and observe CS symptom improvement in patients with neuroendocrine tumors (NETs) who under went octreotide LAR dose escalation at three cancer referral centers. Methods. Medical records for patients with diagnosis of carcinoid or pancreatic NET who had received one dose or more of octreotide LAR above 30 mg every 4 weeks from 2000 to 2012 were reviewed. Reasons for dose escalation and symptomatic outcomes were abstracted for each patient 3 months prior to and up to 12 months following the dose escalation. Results. Of the evaluated 239 NET patients, 53% were male, mean age at first dose escalation was 60 years (standard deviation [SD]: 11 years), and mean time from octreotide LAR initiation to first dose escalation was 1.7 years (SD: 2.0 years). The primary reasons reported for dose escalation were carcinoid or hormonal syndrome (62%) or radiographic progression (28%). The most common dose changes at the first dose escalation were 40 mg every 4 weeks (71%) and 60 mg every 4 weeks (18%). Of 90 patients in whom flushing was reported prior to first dose escalation, 73 (81%) were reported to have experienced improvement or resolution of their symptoms following the dose escalation. Of 107 patients who were reported to have experienced diarrhea before the first dose escalation, 85 (79%) were reported to have experienced improvement or resolution after first dose escalation. Conclusion. The goal of improved symptom control is a common reason for dose escalation of octreotide LAR. This study suggests that escalation to above the standard dose of octreotide LAR of 30 mg every 4 weeks may result in improved CS symptom control. C1 [Strosberg, Jonathan R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Gastrointestinal Oncol, Tampa, FL 33612 USA. [Benson, Al B.; Sahai, Vaibhav; Rademaker, Alfred W.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Huynh, Lynn; Duh, Mei Sheng] Anal Grp Inc, Boston, MA 02199 USA. [Goldman, Jamie] Univ S Florida, Dept Internal Med, Tampa, FL 33612 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Duh, MS (reprint author), Anal Grp Inc, 111 Huntington Ave,Tenth Floor, Boston, MA 02199 USA. EM mduh@analysisgroup.com FU Novartis Pharmaceuticals Corporation (East Hanover, NJ) FX We acknowledge Lauren Brais from the Dana-Farber Cancer Institute and Amir Shah from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University for medical chart abstraction and Kevin N. Tran and Francis Vekeman from Analysis Group, Inc. for analyzing the data and for providing substantive suggestions for revisions. This work was supported by Novartis Pharmaceuticals Corporation (East Hanover, NJ). Novartis reviewed the manuscript prior to submission but did not edit or amend or make suggestions that resulted in changes to the manuscript content or conclusion. Jonathan R. Strosberg, Al B. Benson, and Matthew H. Kulke served as coinvestigators on this project. NR 20 TC 21 Z9 21 U1 0 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD SEP PY 2014 VL 19 IS 9 BP 930 EP 936 DI 10.1634/theoncologist.2014-0120 PG 7 WC Oncology SC Oncology GA AO5VB UT WOS:000341412300006 PM 25096997 ER PT J AU Yonekawa, Y Hacker, HD Lehman, RE Beal, CJ Veldman, PB Vyas, NM Shah, AS Wu, D Eliott, D Gardiner, MF Kuperwaser, MC Rosa, RH Ramsey, JE Miller, JW Mazzoli, RA Lawrence, MG Arroyo, JG AF Yonekawa, Yoshihiro Hacker, Henry D. Lehman, Roy E. Beal, Casey J. Veldman, Peter B. Vyas, Neil M. Shah, Ankoor S. Wu, David Eliott, Dean Gardiner, Matthew F. Kuperwaser, Mark C. Rosa, Robert H., Jr. Ramsey, Jean E. Miller, Joan W. Mazzoli, Robert A. Lawrence, Mary G. Arroyo, Jorge G. TI Ocular Blast Injuries in Mass-Casualty Incidents The Marathon Bombing in Boston, Massachusetts, and the Fertilizer Plant Explosion in West, Texas SO OPHTHALMOLOGY LA English DT Article ID EYE INJURIES; DISASTER; FREEDOM; IRAQI AB Purpose: To report the ocular injuries sustained by survivors of the April 15, 2013, Boston Marathon bombing and the April 17, 2013, fertilizer plant explosion in West, Texas. Design: Multicenter, cross-sectional, retrospective, comparative case series. Participants: Seventy-two eyes of 36 patients treated at 12 institutions were included in the study. Methods: Ocular and systemic trauma data were collected from medical records. Main Outcome Measures: Types and severity of ocular and systemic trauma and associations with mechanisms of injury. Results: In the Boston cohort, 164 of 264 casualties were transported to level 1 trauma centers, and 22 (13.4%) required ophthalmology consultations. In the West cohort, 218 of 263 total casualties were transported to participating centers, of which 14 (6.4%) required ophthalmology consultations. Boston had significantly shorter mean distances to treating facilities (1.6 miles vs. 53.6 miles; P = 0.004). Overall, rigid eye shields were more likely not to have been provided than to have been provided on the scene (P<0.001). Isolated upper body and facial wounds were more common in West largely because of shattered windows (75.0% vs. 13.6%; P = 0.001), resulting in more open-globe injuries (42.9% vs. 4.5%; P = 0.008). Patients in Boston sustained more lower extremity injuries because of the ground-level bomb. Overall, 27.8% of consultations were called from emergency rooms, whereas the rest occurred afterward. Challenges in logistics and communications were identified. Conclusions: Ocular injuries are common and potentially blinding in mass-casualty incidents. Systemic and ocular polytrauma is the rule in terrorism, whereas isolated ocular injuries are more common in other calamities. Key lessons learned included educating the public to stay away from windows during disasters, promoting use of rigid eye shields by first responders, the importance of reliable communications, deepening the ophthalmology call algorithm, the significance of visual incapacitation resulting from loss of spectacles, improving the rate of early detection of ocular injuries in emergency departments, and integrating ophthalmology services into trauma teams as well as maintaining a voice in hospital-wide and community-based disaster planning. (C) 2014 by the American Academy of Ophthalmology. C1 [Yonekawa, Yoshihiro; Veldman, Peter B.; Shah, Ankoor S.; Wu, David; Eliott, Dean; Gardiner, Matthew F.; Miller, Joan W.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02215 USA. [Yonekawa, Yoshihiro; Kuperwaser, Mark C.; Arroyo, Jorge G.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. [Yonekawa, Yoshihiro; Shah, Ankoor S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston Childrens Hosp, Boston, MA 02215 USA. [Yonekawa, Yoshihiro; Veldman, Peter B.; Shah, Ankoor S.; Wu, David; Eliott, Dean; Miller, Joan W.] Harvard Univ, Sch Med, Dept Ophthalmol, Brigham & Womens Hosp, Boston, MA 02215 USA. [Yonekawa, Yoshihiro; Veldman, Peter B.; Shah, Ankoor S.; Wu, David; Eliott, Dean; Gardiner, Matthew F.; Miller, Joan W.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Gen Hosp, Boston, MA 02215 USA. [Hacker, Henry D.; Lehman, Roy E.; Rosa, Robert H., Jr.] Texas A&M Hlth Sci Ctr, Coll Med, Scott & White Eye Inst, Dept Ophthalmol, Temple, TX USA. [Beal, Casey J.] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA. [Vyas, Neil M.; Ramsey, Jean E.] Boston Univ, Sch Med, Dept Ophthalmol, Boston Med Ctr, Boston, MA 02118 USA. [Mazzoli, Robert A.] Dept Def & Vet Adm, Vis Ctr Excellence, Bethesda, MD USA. [Mazzoli, Robert A.; Lawrence, Mary G.] Uniformed Serv Univ Hlth Sci, Dept Ophthalmol, Bethesda, MD 20814 USA. RP Arroyo, JG (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Ophthalmol, 330 Brookline Ave,Shapiro Fifth Floor, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu OI Gardiner, Matthew/0000-0002-8864-2379 NR 22 TC 1 Z9 1 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2014 VL 121 IS 9 BP 1670 EP + DI 10.1016/j.ophtha.2014.04.004 PG 8 WC Ophthalmology SC Ophthalmology GA AO2KY UT WOS:000341151800014 PM 24841363 ER PT J AU Grob, SR Jakobiec, FA Rashid, A Yoon, MK AF Grob, Seanna R. Jakobiec, Frederick A. Rashid, Alia Yoon, Michael K. TI Chalazia Associated with Bortezomib Therapy for Multiple Myeloma SO OPHTHALMOLOGY LA English DT Editorial Material C1 [Grob, Seanna R.; Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Grob, Seanna R.; Jakobiec, Frederick A.; Rashid, Alia; Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Grob, SR (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2014 VL 121 IS 9 BP 1845 EP 1847 PG 5 WC Ophthalmology SC Ophthalmology GA AO2KY UT WOS:000341151800037 PM 24974380 ER PT J AU Michaela, G Bernd, H Bernhard, BB Thorsten, WL Clemens, B AF Michaela, Gessner Bernd, Hoppe Bernhard, Beck Bodo Thorsten, Weber Lutz Clemens, Bergwitz TI Rare Heterozygous None-synonymous Single Nucleotide Polymorphism In Slc34a3/npt2c Is Associated With Hypercalciuria And Renal Calcifications SO PEDIATRIC NEPHROLOGY LA English DT Meeting Abstract C1 [Michaela, Gessner; Bernhard, Beck Bodo; Thorsten, Weber Lutz] Univ Cologne, Cologne, Germany. [Bernd, Hoppe] Univ Bonn, Bonn, Germany. [Clemens, Bergwitz] 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 0931-041X EI 1432-198X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD SEP PY 2014 VL 29 IS 9 MA P496 BP 1836 EP 1837 PG 2 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA AO5IM UT WOS:000341377700602 ER PT J AU Hoche, F Frankenberg, E Rambow, J Theis, M Harding, JA Qirshi, M Seidel, K Barbosa-Sicard, E Porto, L Schmahmann, JD Kieslich, M AF Hoche, Franziska Frankenberg, Emily Rambow, Jennifer Theis, Marius Harding, Jessica Ann Qirshi, Mayyada Seidel, Kay Barbosa-Sicard, Eduardo Porto, Luciana Schmahmann, Jeremy D. Kieslich, Matthias TI Cognitive Phenotype in Ataxia-Telangiectasia SO PEDIATRIC NEUROLOGY LA English DT Article DE ataxia-telangiectasia; ATM; cerebellar cognitive affective syndrome; cerebellum; striatum; basal ganglia; cognition; cognitive development ID DEVELOPMENTAL DYSLEXIA; GENOTYPE-PHENOTYPE; CEREBELLAR ATROPHY; PREFRONTAL CORTEX; BASAL GANGLIA; RATING-SCALE; CHILDREN; MOTOR; CHILDHOOD; MUTATIONS AB BACKGROUND: Pediatric cerebrocerebellar neurodegenerative disorders such as ataxia-telangiectasia (AT) have not been examined in detail for neuropsychologic changes. Such studies may contribute to the further understanding of ataxia-telangiectasia and to the role of the cerebrocerebellar system in the development of cognitive function in childhood. METHODS: Twenty-two patients with the classic phenotype of ataxia-telangiectasia were grouped into early stage cerebellar disease (group AT-I) versus late stage cerebrocerebellar disease (group AT-II) and examined for neurocognitive features. Results were compared with those of healthy control subjects and with standard norms. RESULTS: Patients in AT-I group scored low average compared with standard norms on all tests and were impaired compared with healthy control subjects for verbal intelligence quotient (P < 0.001), vocabulary and comprehension (P = 0.007), processing speed (P = 0.005), visuospatial processing (P = 0.020), and working memory (P = 0.046). Patients in AT-II group scored below average compared with standard norms on all tests and were impaired compared with control subjects for attention (P < 0.001), working memory (P < 0.001), and abstract reasoning (P < 0.001). Comprehension scores were lower for patients in AT-II than in AT-I group (P = 0.002), whereas vocabulary scores showed no difference between groups (P = 0.480). CONCLUSION: Cognitive impairments in ataxia-telangiectasia present early, coinciding with cerebellar pathology and are characteristic of the cerebellar cognitive affective syndrome. Widespread and deeper cognitive deficits manifest in later stages of ataxia-telangiectasia when additional noncerebellar pathology develops. These results are the first indications of distinct cerebellar and extracerebellar and/or subcortical contributions to the range of cognitive domains affected in ataxia-telangiectasia and need to be confirmed in future studies. C1 [Hoche, Franziska; Harding, Jessica Ann; Schmahmann, Jeremy D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cognit Behav Neurol Unit,Dept Neurol,Ataxia Unit, Boston, MA 02114 USA. [Hoche, Franziska; Frankenberg, Emily; Rambow, Jennifer; Theis, Marius; Qirshi, Mayyada; Barbosa-Sicard, Eduardo; Kieslich, Matthias] Goethe Univ Frankfurt, Childrens Hosp, Dept Neuropediat, D-60054 Frankfurt, Germany. [Seidel, Kay] Goethe Univ Frankfurt, Dr Senckenberg Chronomed Inst, D-60054 Frankfurt, Germany. [Porto, Luciana] Goethe Univ Frankfurt, Childrens Hosp, Dept Pediat Neurol, Frankfurt, Germany. RP Hoche, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cognit Behav Neurol Unit,Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM fhoche@mgh.harvard.edu FU German Neuropediatric Society; Dr. Senckenberg Society Frankfurt; German Heredo-Ataxia Society (DHAG); National Ataxia Foundation; National Organization for Rare Disorders; Birmingham Foundation; MINDlink Foundation FX F.H. is indebted to Xavier Guell for skillful assistance. The authors are grateful to the patients and their families for participating in this research, study. This study was supported in part by the German Neuropediatric Society, Dr. Senckenberg Society Frankfurt, and the German Heredo-Ataxia Society (DHAG), the National Ataxia Foundation, the National Organization for Rare Disorders, the Birmingham Foundation and the MINDlink Foundation. NR 69 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 EI 1873-5150 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD SEP PY 2014 VL 51 IS 3 BP 297 EP 310 DI 10.1016/j.pediatrneurol.2014.04.027 PG 14 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AO4TT UT WOS:000341335000002 PM 25037873 ER PT J AU Elahi, D Angeli, FS Vakilipour, A Carlson, OD Tomas, E Egan, JM Habener, JF Shannon, RP AF Elahi, Dariush Angeli, Franca S. Vakilipour, Amin Carlson, Olga D. Tomas, Eva Egan, Josephine M. Habener, Joel F. Shannon, Richard P. TI GLP-1(32-36) amide, a novel pentapeptide cleavage product of GLP-1, modulates whole body glucose metabolism in dogs SO PEPTIDES LA English DT Article DE Glucagon-like peptide-1; Diabetes; Obesity; Insulin resistance; Glucose utilization ID GLUCAGON-LIKE PEPTIDE-1; INSULIN-SECRETION; RECEPTOR; HUMANS; MICE AB We have previously demonstrated in human subjects who under euglycemic clamp conditions GLP-1(9-36) amide infusions inhibit endogenous glucose production without substantial insulinotropic effects. An earlier report indicates that GLP-1(9-36) amide is cleaved to a nonapeptide, GLP-1(28-36) amide and a pentapeptide GLP-1(32-36) amide (LVKGR amide). Here we study the effects of the pentapeptide on whole body glucose disposal during hyperglycemic clamp studies. Five dogs underwent indwelling catheterizations. Following recovery, the dogs underwent a 180 min hyperglycemic clamp(basal glucose +98 mg/dl) in a cross-over design. Saline or pentapeptide (30 pmol kg(-1) min(-1)) was infused during the last 120 min after commencement of the hyperglycemic clamp in a primed continuous manner. During the last 30 min of the pentapeptide infusion, glucose utilization (M) significantly increased to 21.4 +/- 2.9 mg kg(-1) min(-1)c ompared to M of 14.3 +/- 1.1 mg kg(-1) min(-1) during the saline infusion (P = 0.026, paired t-test; P = 0.062, Mann-Whitney U test). During this interval, no significant differences in insulin(26.6 +/- 3.2 vs. 23.7 +/- 2.5 mu U/ml, P = NS) or glucagon secretion (34.0 +/- 2.1 vs. 31.7 +/- 1.8 pg/ml, P = NS) were observed. These findings demonstrate that under hyperglycemic clamp studies the pentapeptide modulates glucose metabolism by a stimulation of whole-body glucose disposal. Further, the findings suggest that the metabolic benefits previously observed during GLP-1(9-36) amide infusions in humans might be due, at least in part, to the metabolic effects of the pentapeptide that is cleaved from the pro-peptide, GLP-1(9-36) amide in the circulation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Elahi, Dariush; Angeli, Franca S.; Vakilipour, Amin; Shannon, Richard P.] Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. [Carlson, Olga D.; Egan, Josephine M.] NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [Tomas, Eva; Habener, Joel F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. [Tomas, Eva; Habener, Joel F.] Harvard Univ, Sch Med, Boston, MA USA. RP Elahi, D (reprint author), ICON Dev Solut, 8307 Gault Lane, San Antonio, TX 78209 USA. EM dariush.elahi@iconplc.com FU Department of Medicine at the Perelman School of Medicine; Intramural Research Program of the National Institutes on Aging; Laboratory of Molecular Endocrinology at the Massachusetts General Hospital [P30DK05751] FX We thank Drs. You-Tang Shen and Li Chen for performing the surgery in the dogs. This study was funded in part from the Department of Medicine at the Perelman School of Medicine, from the Intramural Research Program of the National Institutes on Aging, and from the Laboratory of Molecular Endocrinology at the Massachusetts General Hospital (Grant No. P30DK05751). NR 32 TC 3 Z9 4 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD SEP PY 2014 VL 59 BP 20 EP 24 DI 10.1016/j.peptides.2014.06.004 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA AO5ZT UT WOS:000341427300004 PM 24937653 ER PT J AU Thanos, S Bohm, MRR Horste, MMZ Prokosch-Willing, V Hennig, M Bauer, D Heiligenhaus, A AF Thanos, Solon Boehm, Michael R. R. Hoerste, Melissa Meyer Zu Prokosch-Willing, Verena Hennig, Maren Bauer, Dirk Heiligenhaus, Arndt TI Role of crystallins in ocular neuroprotection and axonal regeneration SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article DE Retina; Crystallins; Glaucoma injury; Axonal regrowth; Neuroprotection ID ALPHA-B-CRYSTALLIN; RETINAL GANGLION-CELLS; HEAT-SHOCK-PROTEIN; LENS EPITHELIAL-CELLS; EXPERIMENTAL AUTOIMMUNE UVEITIS; OPTIC-NERVE REGENERATION; A-CRYSTALLIN; GENE-EXPRESSION; MACULAR DEGENERATION; IN-VITRO AB Neuroprotection is an emerging challenge in ophthalmology due to the particularly exposed location of retinal neurons and to the steadily increasing rate of intraocular surgical and pharmacological treatments applied to various eye diseases. Within few decades neuroprotection has developed from strongly contested approaches to being recognized and introduced as a potentially clinical application. One of the groups of putative substances for neuroprotection comprises alpha A- and alpha B-crystallins, which are types of heat-shock proteins and are considered to be molecular chaperones. The beta/gamma-crystallins form their own superfamily and are characterized as proteins with a distinct structure containing four Greek key motifs. Besides being abundant in the ocular lens, crystallins are also expressed in both the developing and mature retina. Crystallins are dramatically up-regulated in numerous retinal pathologies, including mechanical injury, ischemic insults, age-related macular degeneration, uveoretinitis, and diabetic retinopathy. Crystallins of the alpha family are thought to play a crucial role in retinal neuron survival and inflammation. Crystallins of the beta/gamma superfamily are also small proteins with a possible emerging role in retinal tissue remodeling and repair. One of the typical retinal diseases associated with crystallins is the experimental glaucomatous neuropathy that is characterized by their expression. Another typical retinal disease is the atrophy that occurs after mechanical injury to the optic nerve, which is associated with the need to regrow retinal axons. We have shown in regenerative models in vivo and in vitro that beta B2-crystallin actively supports the regenerative growth of cut retinal axons, thereby offering targets for neuroprotective and regenerative treatments. In this review we discuss the discovery that beta B2-crystallin is clearly up-regulated in the regenerating retina in vitro. beta B2-Crystallin is produced and secreted during axon elongation, while beta/gamma-crystallins promote axon growth both in vivo and in vitro by acting either directly by uptake into cells, or indirectly by enhancing the production of ciliary neurotrophic factor from astrocytes to synergistically promote axon regrowth. We also discuss methods to induce the continuous production of crystallins at the site of injury and repair based on the use of transfected neural progenitor cells. This review ultimately leads to the conclusion that the postinjury fate of neurons cannot be seen merely as inevitable, but instead should be regarded as a challenge to shaping the neuroprotective and regenerative conditions that promote cell survival and axon repair. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Thanos, Solon; Boehm, Michael R. R.; Prokosch-Willing, Verena; Heiligenhaus, Arndt] Inst Expt Ophthalmol, Berlin, Germany. [Thanos, Solon; Boehm, Michael R. R.] Univ Munster, Sch Med, Ctr Excellence Cells In Mot CiM, D-48149 Munster, Germany. [Hoerste, Melissa Meyer Zu] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hoerste, Melissa Meyer Zu] Univ Essen Gesamthsch, Eye Clin, Essen, Germany. [Hennig, Maren; Bauer, Dirk; Heiligenhaus, Arndt] Franziskus Hosp Munster, Dept Ophthalmol, Munster, Germany. RP Thanos, S (reprint author), Univ Munster, Sch Med, Inst Expt Ophthalmol, Albert Schweitzer Campus 1,D15, D-48149 Munster, Germany. EM solon@uni-muenster.de FU Deutsche Forschungsgemeinschaft (DFG) [Th 386/20-1, ME 4162/1-1]; Interdisciplinary Clinical Research Center (IZKF); Innovative Medical Research (IMF) FX The authors are indebted to Magdalena Reis for typing the manuscript and Mechthild Wissing and Mechthild Langkamp-Flock for technical assistance. The work was supported by the Deutsche Forschungsgemeinschaft (DFG: Grant No. Th 386/20-1 to S.T.), the Interdisciplinary Clinical Research Center (IZKF), and the Innovative Medical Research (IMF). M.M.z.H. was supported by a DFG Fellowship to conduct research at MEEI (Grant No. ME 4162/1-1). All tissue materials used for in vitro explants in this study were obtained from cadavers after the animals had died. NR 167 TC 15 Z9 16 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD SEP PY 2014 VL 42 BP 145 EP 161 DI 10.1016/j.preteyeres.2014.06.004 PG 17 WC Ophthalmology SC Ophthalmology GA AO6NT UT WOS:000341469500007 PM 24998680 ER PT J AU Clapp, JD Grubaugh, AL Allen, JG Oldham, JM Fowler, JC Hardesty, S Frueh, BC AF Clapp, Joshua D. Grubaugh, Anouk L. Allen, Jon G. Oldham, John M. Fowler, J. Christopher Hardesty, Susan Frueh, B. Christopher TI Interpersonal Change Following Intensive Inpatient Treatment SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID THERAPEUTIC ALLIANCE; PSYCHOMETRIC PROPERTIES; PSYCHODYNAMIC THERAPY; PERSONALITY-DISORDERS; SYMPTOM IMPROVEMENT; TREATMENT RESPONSE; PSYCHOTHERAPY; BEHAVIOR; OUTCOMES; INVENTORY AB Objective: Persons admitted for inpatient psychiatric care often present with interpersonal difficulties that disrupt adaptive social relations and complicate the provision of treatment. Whereas domains of psychosocial functioning in this population demonstrate clear growth in response to intervention, the impact of treatment on more complex patterns of interpersonal behavior has been largely overlooked within the existing literature. Interpersonal profiles characteristic of psychiatric inpatients were identified in the current study to determine rates of transition to adaptive functioning following hospitalization. Methods: Personality disturbance was assessed in 513 psychiatric inpatients using the Inventory of Interpersonal Problems. Scores were analyzed within a series of latent profile models to isolate unique interpersonal profiles at admission and at discharge. Longitudinal modeling was then employed to determine rates of transition from dysfunctional to adaptive profiles. Relationships with background characteristics, clinical presentation, and treatment response were explored. Results: Normative, Submissive, and Hostile/Withdrawn profiles emerged at both admission and discharge. Patients in the Normative profile demonstrated relatively moderate symptoms. Submissive and Hostile/Withdrawn profiles were related to known risk factors and elevated psychopathology. Approximately half of the patients who had been identified as Submissive or Hostile/Withdrawn transitioned to the Normative profile by discharge. Transition status evidenced modest associations with background characteristics and clinical presentation. Treatment engagement and reduction of clinical symptoms were strongly associated with adaptive transition. Conclusion: Maladaptive interpersonal profiles characteristic of psychiatric inpatients demonstrated categorical change following inpatient hospitalization. Enhanced therapeutic engagement and overall reductions in psychiatric symptoms appear to increase potential for interpersonal change. C1 [Clapp, Joshua D.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Grubaugh, Anouk L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Grubaugh, Anouk L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Allen, Jon G.; Oldham, John M.; Fowler, J. Christopher; Hardesty, Susan; Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Allen, Jon G.; Oldham, John M.; Fowler, J. Christopher; Hardesty, Susan] Baylor Coll Med, Houston, TX 77030 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. RP Clapp, JD (reprint author), Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. EM jclapp@uwyo.edu FU Menninger Foundation; McNair Medical Institute; National Institute of Mental Health; NIMH [T32-MH18869] FX Research was supported in part by funding from the Menninger Foundation, the McNair Medical Institute, and the National Institute of Mental Health. Dr. Clapp was an NIMH-sponsored psychology intern at the Medical University of South Carolina (T32-MH18869) during the development of this project. Dr. Frueh is a McNair Scholar. We are grateful for the assistance of Steve Herrera, MA, and all the research assistants at the Menninger Clinic. NR 44 TC 1 Z9 1 U1 0 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 2014 VL 77 IS 3 BP 247 EP 262 PG 16 WC Psychiatry SC Psychiatry GA AO4WF UT WOS:000341341400007 PM 25162133 ER PT J AU Szafranski, DD Gros, DF Menefee, DS Wanner, JL Norton, PJ AF Szafranski, Derek D. Gros, Daniel F. Menefee, Deleene S. Wanner, Jill L. Norton, Peter J. TI Predictors of Length of Stay Among OEF/OIF/OND Veteran Inpatient PTSD Treatment Noncompleters SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOMETRIC PROPERTIES; BEHAVIORAL ACTIVATION; PROLONGED EXPOSURE; AFGHANISTAN; DEPRESSION; THERAPY; DROPOUT; SAMPLE; IRAQ AB High rates of attrition occur in outpatient and inpatient evidence-based treatments (EBTs) targeting newly returning veterans from Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF) and Operation New Dawn (OND) with posttraumatic stress disorder (PTSD). Traditionally, research has examined attrition as a dichotomous variable (i.e., noncompleters vs. completers) and focused almost exclusively on outpatient EBTs for PTSD. These studies have provided little information to inpatient psychiatric providers about timing-related predictors of treatment discontinuation. The present study attempted to mend these gaps by examining attrition as a continuous variable and investigated predictors of length of stay (LOS) among 282 OEF/OIF/OND male veterans, 69 of which did not complete the full 25-day intensive, multimodal inpatient PTSD EBT program. At admission, participants completed a series of clinician-rated, biological, and self-report assessments. Linear regression analyses were used to identify predictors of shorter LOS. The results demonstrated that less improvement in symptom reduction, overall functioning, and greater number of drugs used at admission were significant and unique predictors of shorter LOS. Overall, these findings reveal clinically relevant, timing-related predictors of attrition and provide generalizable clinical information to inpatient psychiatric providers. C1 [Szafranski, Derek D.; Norton, Peter J.] Univ Houston, Dept Psychol, Houston, TX 77204 USA. [Szafranski, Derek D.; Menefee, Deleene S.; Wanner, Jill L.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Menefee, Deleene S.; Wanner, Jill L.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Szafranski, DD (reprint author), Univ Houston, Dept Psychol, 126 Heyne Bldg, Houston, TX 77204 USA. EM ddszafranski@gmail.com NR 38 TC 2 Z9 2 U1 0 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 2014 VL 77 IS 3 BP 263 EP 274 PG 12 WC Psychiatry SC Psychiatry GA AO4WF UT WOS:000341341400008 PM 25162134 ER PT J AU Bentley, KH Gallagher, MW Carl, JR Barlow, DH AF Bentley, Kate H. Gallagher, Matthew W. Carl, Jenna R. Barlow, David H. TI Development and Validation of the Overall Depression Severity and Impairment Scale SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE depression; screening; psychometrics; item response theory ID DSM-IV ANXIETY; NATIONAL COMORBIDITY SURVEY; MOOD DISORDERS; STRUCTURAL RELATIONSHIPS; PSYCHOMETRIC EVALUATION; SYMPTOMATOLOGY QIDS; LIFETIME PREVALENCE; SURVEY REPLICATION; MAJOR DEPRESSION; COMMUNITY SAMPLE AB The need to capture severity and impairment of depressive symptomatology is widespread. Existing depression scales are lengthy and largely focus on individual symptoms rather than resulting impairment. The Overall Depression Severity and Impairment Scale (ODSIS) is a 5-item, continuous measure designed for use across heterogeneous mood disorders and with subthreshold depressive symptoms. This study examined the psychometric properties of the ODSIS in outpatients in a clinic for emotional disorders (N = 100), undergraduate students (N = 566), and community-based adults (N = 189). Internal consistency, latent structure, item response theory, classification accuracy, convergent and discriminant validity, and differential item functioning analyses were conducted. ODSIS scores exhibited excellent internal consistency, and confirmatory factor analyses supported a unidimensional structure. Item response theory results demonstrated that the ODSIS provides more information about individuals with high levels of depression than those with low levels of depression. Responses on the ODSIS discriminated well between individuals with and without a mood disorder and depression-related severity across clinical and subclinical levels. A cut score of 8 correctly classified 82% of outpatients as with or without a mood disorder; it evidenced a favorable balance of sensitivity and specificity and of positive and negative predictive values. The ODSIS demonstrated good convergent and discriminant validity, and results indicate that items function similarly across clinical and nonclinical samples. Overall, findings suggest that the ODSIS is a valid tool for measuring depression-related severity and impairment. The brevity and ease of use of the ODSIS support its utility for screening and monitoring treatment response across a variety of settings. C1 [Bentley, Kate H.; Carl, Jenna R.; Barlow, David H.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Gallagher, Matthew W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Gallagher, Matthew W.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Bentley, KH (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM khb@bu.edu NR 61 TC 17 Z9 17 U1 7 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD SEP PY 2014 VL 26 IS 3 BP 815 EP 830 DI 10.1037/a0036216 PG 16 WC Psychology, Clinical SC Psychology GA AO6WA UT WOS:000341491800012 PM 24708078 ER PT J AU Cicero, DC Martin, EA Becker, TM Docherty, AR Kerns, JG AF Cicero, David C. Martin, Elizabeth A. Becker, Theresa M. Docherty, Anna R. Kerns, John G. TI Correspondence Between Psychometric and Clinical High Risk for Psychosis in an Undergraduate Population SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE schizotypy; psychometric high risk; clinical high risk; psychotic-like experiences; prodrome ID WISCONSIN SCHIZOTYPY SCALES; PERSISTENT NEGATIVE SYMPTOMS; AGE-OF-ONSET; UNTREATED PSYCHOSIS; PRODROMAL SYNDROMES; SOCIAL ANHEDONIA; SELF-REPORT; AT-RISK; 1ST-EPISODE SCHIZOPHRENIA; INTERRATER RELIABILITY AB Despite the common use of either psychometric or clinical methods for identifying individuals at risk for psychosis, previous research has not examined the correspondence and extent of convergence of these 2 approaches. Undergraduates (n = 160), selected from a larger pool, completed 3 self-report schizotypy scales: the Magical Ideation Scale, the Perceptual Aberration Scale, and the Revised Social Anhedonia Scale. They were administered the Structured Interview for Prodromal Syndromes. First, high correlations were observed for self-report and interview-rated psychotic-like experiences (rs between .48 and .61, p < .001). Second, 77% of individuals who identified as having a risk for psychosis with the self-report measures reported at least 1 clinically meaningful psychotic-like experience on the Structured Interview for Prodromal Syndromes. Third, receiver operating characteristic curve analyses showed that the self-report scales can be used to identify which participants report clinically meaningful positive symptoms. These results suggest that mostly White undergraduate participants who identify as at risk with the psychometric schizotypy approach report clinically meaningful psychotic-like experiences in an interview format and that the schizotypy scales are moderately to strongly correlated with interview-rated psychotic-like experiences. The results of the current research provide a baseline for comparing research between these 2 approaches. C1 [Cicero, David C.] Univ Hawaii Manoa, Dept Psychol, Honolulu, HI 96822 USA. [Martin, Elizabeth A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Becker, Theresa M.] Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. [Docherty, Anna R.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Stat Genet, Richmond, VA 23284 USA. [Kerns, John G.] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA. RP Cicero, DC (reprint author), Univ Hawaii Manoa, Dept Psychol, Sakamaki Hall,C400,2530 Dole St, Honolulu, HI 96822 USA. EM dcicero@hawaii.edu RI Cicero, David/E-2046-2016; OI Cicero, David/0000-0002-5666-9139; Docherty, Anna/0000-0001-7139-7007 FU NIMH NIH HHS [F31 MH086190, MH086190, T32 MH020030] NR 85 TC 14 Z9 14 U1 3 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD SEP PY 2014 VL 26 IS 3 BP 901 EP 915 DI 10.1037/a0036432 PG 15 WC Psychology, Clinical SC Psychology GA AO6WA UT WOS:000341491800020 PM 24708081 ER PT J AU Schacht, JP Anton, RF Randall, P Li, XB Henderson, S Myrick, H AF Schacht, Joseph P. Anton, Raymond F. Randall, PatrickK. Li, Xingbao Henderson, Scott Myrick, Hugh TI Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals SO PSYCHOPHARMACOLOGY LA English DT Article DE Varenicline; Alcohol; fMRI; Neuroimaging; Craving ID PARTIAL AGONIST VARENICLINE; RECEPTOR PARTIAL AGONIST; NICOTINIC ACETYLCHOLINE-RECEPTORS; INDUCED BRAIN ACTIVATION; ETHANOL-CONSUMPTION; DOPAMINE RELEASE; CUE REACTIVITY; DOUBLE-BLIND; NALTREXONE; RESPONSES AB The alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas. This pilot study tested varenicline's effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals. Thirty-five such individuals (mean age = 30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC). Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas. These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption. C1 [Schacht, Joseph P.; Anton, Raymond F.; Randall, PatrickK.; Li, Xingbao; Henderson, Scott; Myrick, Hugh] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Myrick, Hugh] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM schacht@musc.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); Charleston Alcohol Research Center [P50 AA010761]; [K99 AA021419]; [K05 AA017435] FX Portions of this work were presented at the 34th Annual Meeting of the Research Society on Alcoholism (June 2011, Atlanta) and the 52nd Annual Meeting of the American College on Neuropsychopharmacology (December 2013, Hollywood, FL). This research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), including the Charleston Alcohol Research Center (P50 AA010761). NIAAA had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the paper, or in the decision to submit for publication. Drs. Schacht and Anton are supported by K99 AA021419 and K05 AA017435, respectively. NR 45 TC 13 Z9 13 U1 8 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2014 VL 231 IS 18 BP 3799 EP 3807 DI 10.1007/s00213-014-3518-1 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AO5GG UT WOS:000341371300013 PM 24647921 ER PT J AU Woodberry, KA Serur, RA Hallinan, SB Mesholam-Gately, RI Giuliano, AJ Wojcik, JD Keshavan, MS Frazier, JA Goldstein, JM Shenton, ME McCarley, RW Seidman, LJ AF Woodberry, Kristen A. Serur, Rachael A. Hallinan, Sean B. Mesholam-Gately, Raquelle I. Giuliano, Anthony J. Wojcik, Joanne D. Keshavan, Matcheri S. Frazier, Jean A. Goldstein, Jill M. Shenton, Martha E. McCarley, Robert W. Seidman, Larry J. TI Frequency and pattern of childhood symptom onset reported by first episode schizophrenia and clinical high risk youth SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Child; Psychosis; Psychotic-like; SIPS; Prodrome; Early onset ID AUDITORY VOCAL HALLUCINATIONS; PSYCHOTIC SYMPTOMS; BIRTH-COHORT; RETROSPECTIVE REPORTS; ADULT SCHIZOPHRENIA; UNTREATED PSYCHOSIS; PRODROMAL PHASE; DISORDER; DURATION; EXPERIENCES AB Background: Psychosis prevention and early intervention efforts in schizophrenia have focused increasingly on sub-threshold psychotic symptoms in adolescents and young adults. Although many youth report symptom onset prior to adolescence, the childhood incidence of prodromal-level symptoms in those with schizophrenia or related psychoses is largely unknown. Methods: This study reports on the retrospective recall of prodromal-level symptoms from 40 participants in a first-episode of schizophrenia (FES) and 40 participants at "clinical high risk" (CHR) for psychosis. Onset of positive and non-specific symptoms was captured using the Structured Interview for Prodromal Syndromes. Frequencies are reported according to onset during childhood (prior to age 13), adolescence (13-17), or adulthood (18+). Results: Childhood-onset of attenuated psychotic symptoms was not rare. At least 11% of FES and 23% of CHR reported specific recall of childhood-onset of unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most recalled experiencing non-specific symptoms prior to positive symptoms. CHR and FES did not differ significantly in the timing of positive and non-specific symptom onset. Other than being younger at assessment, those with childhood onset did not differ demographically from those with later onset. Conclusion: Childhood-onset of initial psychotic-like symptoms may be more common than previous research has suggested. Improved characterization of these symptoms and a focus on their predictive value for subsequent schizophrenia and other major psychoses are needed to facilitate screening of children presenting with attenuated psychotic symptoms. Accurate detection of prodromal symptoms in children might facilitate even earlier intervention and the potential to alter pre-illness trajectories. (C) 2014 Elsevier B.V. All rights reserved. C1 [Woodberry, Kristen A.; Serur, Rachael A.; Hallinan, Sean B.; Mesholam-Gately, Raquelle I.; Giuliano, Anthony J.; Wojcik, Joanne D.; Keshavan, Matcheri S.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Woodberry, Kristen A.; Mesholam-Gately, Raquelle I.; Giuliano, Anthony J.; Wojcik, Joanne D.; Keshavan, Matcheri S.; Goldstein, Jill M.; Shenton, Martha E.; McCarley, Robert W.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Giuliano, Anthony J.] Worcester Recovery Ctr & Hosp, Dept Psychol, Worcester, MA USA. [Frazier, Jean A.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Frazier, Jean A.] Univ Massachusetts Mem Hlth Care, Worcester, MA USA. [Goldstein, Jill M.; Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goldstein, Jill M.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Shenton, Martha E.; McCarley, Robert W.] Vet Affairs Boston Healthcare Syst, Brockton, MA USA. [Shenton, Martha E.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Woodberry, KA (reprint author), Commonwealth Res Ctr, 75 Fenwood Rd, Boston, MA 02115 USA. EM kwoodber@bidmc.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Veterans Affairs Merit Awards; Veterans Affairs Schizophrenia Center; National Institutes of Health [P50 MH 080272, UO1 MH081928]; Commonwealth Research Center of the Massachusetts Department of Mental Health [SCDMH82101008006]; National Alliance for Research in Schizophrenia and Depression Distinguished Investigator Award; University of Massachusetts [IDDRC P30HD0004147]; Clinical Translational Science Award [UL1RR025758]; National Center for Research Resources [M01RR01032, P41RR14075]; Beth Israel Deaconess Medical Center; Shared Instrumentation Grants [1S10RR023401, 1S10RR019307, 1S10RR023043] FX Funding was provided by Veterans Affairs Merit Awards to M. E. S. and R. W. M., Veterans Affairs Schizophrenia Center to R. W. M. and M. E. S., the National Institutes of Health (P50 MH 080272 to R. W. M.; UO1 MH081928 to L.J.S.), the Commonwealth Research Center of the Massachusetts Department of Mental Health (SCDMH82101008006 to L.J.S.), National Alliance for Research in Schizophrenia and Depression Distinguished Investigator Award to M. E. S., University of Massachusetts (IDDRC P30HD0004147 to J.A.F.), Clinical Translational Science Award (UL1RR025758) and General Clinical Research Center Grant (M01RR01032) from the National Center for Research Resources to Harvard University and Beth Israel Deaconess Medical Center, the National Center for Research Resources (P41RR14075), and Shared Instrumentation Grants (1S10RR023401, 1S10RR019307, 1S10RR023043). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 53 TC 8 Z9 8 U1 7 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2014 VL 158 IS 1-3 BP 45 EP 51 DI 10.1016/j.schres.2014.05.017 PG 7 WC Psychiatry SC Psychiatry GA AO4MW UT WOS:000341314800008 PM 24924404 ER PT J AU Sebro, R Oliveira, A Palmer, WE AF Sebro, Ronnie Oliveira, Adriana Palmer, William E. TI MR Arthrography of the Shoulder: Technical Update and Clinical Applications SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE magnetic resonance arthrography advances; shoulder; rotator cuff; labrum ID MAGNETIC-RESONANCE ARTHROGRAPHY; ROTATOR CUFF TEARS; GLENOHUMERAL JOINT INJECTION; POSTERIOR LABROCAPSULAR COMPLEX; LABRAL-LIGAMENTOUS COMPLEX; PARTIAL-THICKNESS TEARS; GLENOID LABRUM; ARTHROSCOPIC CORRELATION; SUPRASPINATUS TENDON; EXTERNAL ROTATION AB Direct MR arthrography of the shoulder is a safe, relatively easy procedure that can increase diagnostic confidence in the evaluation of rotator cuff and labroligamentous disorders compared with conventional MR imaging of the shoulder. Surgeons more often request MR arthrography in younger patients who may have internal impingement or subtle shoulder subluxation rather than obvious cuff rupture, repeated dislocation, or arthropathy. This article describes the advances in glenohumeral injection and MR protocol techniques, imaging pitfalls, anatomical variants, common lesions associated with internal derangement of the shoulder, and MR arthrography of the postoperative shoulder. C1 [Sebro, Ronnie; Oliveira, Adriana; Palmer, William E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Palmer, WE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM wpalmer@mgh.harvard.edu NR 166 TC 4 Z9 4 U1 1 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 EI 1098-898X J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD SEP PY 2014 VL 18 IS 4 BP 352 EP 364 DI 10.1055/s-0034-1384825 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO4WJ UT WOS:000341341800003 PM 25184391 ER PT J AU Tao, ZM Ghoroghchian, PP AF Tao, Zhimin Ghoroghchian, P. Peter TI Microparticle, nanoparticle, and stem cell-based oxygen carriers as advanced blood substitutes SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID LIPOSOME-ENCAPSULATED HEMOGLOBIN; HUMAN EMBRYONIC STEM; NITRIC-OXIDE; POLYMERIC NANOPARTICLES; HEMORRHAGIC-SHOCK; GASEOUS LIGANDS; VESICLES; DELIVERY; DESIGN; TRIAL AB Here, we discuss recent advances in the development of artificial red blood cell (RBC) substitutes, illustrating lessons learned from initial attempts using perfluorocarbon (PFC) emulsions and acellular hemoglobin-based oxygen carriers (HBOCs). We also highlight novel oxygen-containing microparticles, nanoparticles, and stem cell-derived RBC products, with emphasis on improvements in biocompatibility and oxygen delivery. In addition, we envision future developments for the rational design of advanced blood substitutes that aim to address unmet clinical needs. C1 [Tao, Zhimin; Ghoroghchian, P. Peter] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Ghoroghchian, P. Peter] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ghoroghchian, PP (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ppg@mit.edu FU National Blood Foundation; National Heart, Lung, and Blood Institute [R43 HL103388-01]; Kentucky Cabinet for Economic Development's Department of Commercialization and Innovation [KSTC-184-512-10-091]; Charles W. and Jennifer C. Johnson Clinical Investigator Fund FX P.P.G. acknowledges support from the National Blood Foundation, the National Heart, Lung, and Blood Institute (R43 HL103388-01), the Kentucky Cabinet for Economic Development's Department of Commercialization and Innovation (KSTC-184-512-10-091), and the Charles W. (1955) and Jennifer C. Johnson Clinical Investigator Fund. NR 75 TC 9 Z9 9 U1 12 U2 97 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD SEP PY 2014 VL 32 IS 9 SI SI BP 466 EP 473 DI 10.1016/j.tibtech.2014.05.001 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AO6QW UT WOS:000341477600007 PM 24929580 ER PT J AU Bechis, SK Eisner, BH AF Bechis, Seth K. Eisner, Brian H. TI Obesity in Percutaneous Nephrolithotomy. Is Body Mass Index Really Important? EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material ID OUTCOMES C1 [Bechis, Seth K.; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02138 USA. RP Bechis, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02138 USA. NR 8 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD SEP PY 2014 VL 84 IS 3 BP 542 EP 543 DI 10.1016/j.urology.2014.03.063 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA AO5EL UT WOS:000341366000013 PM 25168530 ER PT J AU Thrall, JH AF Thrall, James H. TI Appropriateness and Imaging Utilization: "Computerized Provider Order Entry and Decision Support" SO ACADEMIC RADIOLOGY LA English DT Article DE Appropriateness criteria; utilization; computerized physician order entry (CPOE) AB Modern imaging methods have been transformative in improving medical card. Cross-sectional imaging has largely eliminated the need for invasive "exploratory" surgery and is widely used to triage acutely ill patients. However, how to best use medical imaging with ongoing concerns related to overall costs and radiation risks remains controversial. Imaging saves lives, but overuse of imaging can add unnecessary costs to the health system and add to the radiation burden of the population. In this article, the American College of Radiology Appropriateness Criteria (ACRAC) are reviewed, while the Massachusetts General Hospital experience with a computerized physician (provider) order entry system and other approaches to utilization management are discussed. There are strong evidence-based indicators of appropriateness for a substantial percentage of common imaging applications and where this is the case, decision support systems based on ACRAC or other criteria can and should be used. Standardize health care delivery and elimination of wasteful practice variation can be achieved without the art of medicine being ignored or devalued. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 25 New Chardon St,Suite 400, Boston, MA 02114 USA. EM jhthrall@mac.com NR 9 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2014 VL 21 IS 9 BP 1083 EP 1087 DI 10.1016/j.acra.2014.02.019 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AN6KV UT WOS:000340704300002 PM 25107862 ER PT J AU Williams, EC Rubinsky, AD Chavez, LJ Lapham, GT Rittmueller, SE Achtmeyer, CE Bradley, KA AF Williams, Emily C. Rubinsky, Anna D. Chavez, Laura J. Lapham, Gwen T. Rittmueller, Stacey E. Achtmeyer, Carol E. Bradley, Katharine A. TI An early evaluation of implementation of brief intervention for unhealthy alcohol use in the US Veterans Health Administration SO ADDICTION LA English DT Article DE Alcohol; brief intervention; implementation; unhealthy alcohol use; veterans ID RANDOMIZED CONTROLLED-TRIAL; ELECTRONIC CLINICAL REMINDER; PRIMARY-CARE PHYSICIANS; SERVICES-TASK-FORCE; RE-AIM FRAMEWORK; AT-RISK DRINKING; PREVENTIVE-SERVICES; USE DISORDERS; AUDIT-C; COUNSELING INTERVENTIONS AB Aims The US Veterans Health Administration [Veterans Affairs (VA)] used performance measures and electronic clinical reminders to implement brief intervention for unhealthy alcohol use. We evaluated whether documented brief intervention was associated with subsequent changes in drinking during early implementation. Design Observational, retrospective cohort study using secondary clinical and administrative data. Setting Thirty VA facilities. Participants Outpatients who screened positive for unhealthy alcohol use [Alcohol Use Disorders Identification Test Consumption (AUDIT-C >= 5)] in the 6 months after the brief intervention performance measure (n = 22 214) and had follow-up screening 9-15 months later (n = 6210; 28%). Measurements Multi-level logistic regression estimated the adjusted prevalence of resolution of unhealthy alcohol use (follow-up AUDIT-C < 5 with <= 2 point reduction) for patients with and without documented brief intervention (documented advice to reduce or abstain from drinking). Findings Among 6210 patients with follow-up alcohol screening, 1751 (28%) had brief intervention and 2922 (47%) resolved unhealthy alcohol use at follow-up. Patients with documented brief intervention were older and more likely to have other substance use disorders, mental health conditions, poor health and more severe unhealthy alcohol use than those without (P-values < 0.05). Adjusted prevalences of resolution were 47% [95% confidence interval (CI) = 42-52%] and 48% (95% CI = 42-54%) for patients with and without documented brief intervention, respectively (P = 0.50). Conclusions During early implementation of brief intervention in the US Veterans Health Administration, documented brief intervention was not associated with subsequent changes in drinking among outpatients with unhealthy alcohol use and repeat alcohol screening. C1 [Williams, Emily C.; Rubinsky, Anna D.; Chavez, Laura J.; Lapham, Gwen T.; Rittmueller, Stacey E.; Achtmeyer, Carol E.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR&D, Seattle, WA 98101 USA. [Williams, Emily C.; Chavez, Laura J.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Achtmeyer, Carol E.] VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98101 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov FU US Department of Veterans Affairs (VA) Quality Enhancement Research Initiative [RRP 11-268]; VA Health Services Research and Development [IIR 08-314, CDA 12-276]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative (QUERI); VA Center of Excellence for Substance Abuse Treatment and Education (CESATE) FX This study was supported by funding from the US Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (RRP 11-268; Principle Investigator E.C.W.) and VA Health Services Research and Development (IIR 08-314; Principle Investigator K.A.B.). E.C.W. is supported by El Career Development Award from VA Health Services Research and Development (CDA 12-276) and is an investigator with the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work at Washington University in St Louis. IRI is supported through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative (QUERI). K.A.B. and A.D.R. were supported by the VA Center of Excellence for Substance Abuse Treatment and Education (CESATE) for their work on this project. The views expressed in this paper are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the University of Washington or Group Health Research Institute. NR 91 TC 12 Z9 12 U1 4 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD SEP PY 2014 VL 109 IS 9 BP 1472 EP 1481 DI 10.1111/add.12600 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AN4OE UT WOS:000340566600015 PM 24773590 ER PT J AU Zanni, MV Fitch, KV Feldpausch, M Han, A Lee, H Lu, MT Abbara, S Ribaudo, H Douglas, PS Hoffmann, U Lo, J Grinspoon, SK AF Zanni, Markella V. Fitch, Kathleen V. Feldpausch, Meghan Han, Allison Lee, Hang Lu, Michael T. Abbara, Suhny Ribaudo, Heather Douglas, Pamela S. Hoffmann, Udo Lo, Janet Grinspoon, Steven K. TI 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III cholesterol guidelines applied to HIV-infected patients with/without subclinical high-risk coronary plaque SO AIDS LA English DT Article DE atherosclerosis; cholesterol guidelines; computed tomography angiography; HIV ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; CT ANGIOGRAPHY; ATHEROSCLEROSIS; EVENTS AB Background: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines are being applied to HIV-infected patients but have not been validated in this at-risk population, which is known to have a high prevalence of subclinical high-risk morphology (HRM) coronary atherosclerotic plaque. Objective: To compare recommendations for statins among HIV-infected subjects with/without HRM coronary plaque according to 2013 ACC/AHA versus 2004 Adult Treatment Panel III guidelines. Methods/design: Data from 108 HIV-infected subjects without known cardiovascular disease (CVD) or lipid-lowering treatment who underwent contrast-enhanced computed tomography angiography were analyzed. Recommendations for statin therapy according to 2013 versus 2004 guidelines were assessed among those with/without HRM coronary plaque. Results: Among all subjects, 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was 3.3% (1.6, 6.6), yet 36% of subjects had HRM coronary plaque. Among those with HRM coronary plaque, statins would be recommended for 26% by 2013 guidelines versus 10% by 2004 guidelines (P = 0.04). Conversely, among those without HRM coronary plaque, statins would be recommended for 19% by 2013 guidelines versus 7% by 2004 guidelines (P = 0.005). In multivariate modeling, while 10-year ASCVD risk score related to HRM coronary plaque burden (P = 0.02), so too did other factors not incorporated into 2013 guidelines. Conclusion: The 2013 ACC/AHA cholesterol guidelines recommend statin therapy for a higher percentage of subjects with and without HRM coronary plaque relative to 2004 guidelines. However, even by 2013 guidelines, statin therapy would not be recommended for the majority (74%) of HIV-infected subjects with subclinical HRM coronary plaque. Outcome studies are needed to determine the utility of new statin recommendations and the contribution of HRM coronary plaque to CVD events among HIV-infected subjects. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Zanni, Markella V.; Fitch, Kathleen V.; Feldpausch, Meghan; Han, Allison; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Lu, Michael T.; Abbara, Suhny; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiovasc Imaging Sect, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Ribaudo, Heather] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Douglas, Pamela S.] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA. RP Zanni, MV (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM mzanni@mgh.harvard.edu FU Bristol Myers Squibb, Inc.; National Institutes of Health (NIH) [K24 DK064545, R01 HL095123-04, K23 HL092792]; NIH [M01-RR-01066, 1 UL1 RR025758-01]; National Center for Research Resources [UM1 AI068634, P30 DK040561]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8KL2TR000168-05]; National Heart, Lung, and Blood Institute [5T32 HL076136] FX This work was supported by Bristol Myers Squibb, Inc. and the National Institutes of Health (NIH) via K24 DK064545 and R01 HL095123-04 to S. K. G. and K23 HL092792 to J.L. The work was also supported by the NIH via M01-RR-01066 and 1 UL1 RR025758-01 to the Harvard Clinical and Translational Science Center, from the National Center for Research Resources, via UM1 AI068634 to the Center for Biostatistics in AIDS Research and via P30 DK040561 to the Nutrition Obesity Research Center at Harvard. Finally, this work was supported by a KL2 Medical Research Investigator Training (MeRIT) award to M.V.Z. from the Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8KL2TR000168-05. M. T. L. was supported by a grant from the National Heart, Lung, and Blood Institute (5T32 HL076136). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the NIH. NR 24 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD SEP PY 2014 VL 28 IS 14 BP 2061 EP 2070 DI 10.1097/QAD.0000000000000360 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AO1NM UT WOS:000341079800007 PM 25265074 ER PT J AU Palmer, CD Tomassilli, J Sirignano, M Romero-Tejeda, M Arnold, KB Che, D Lauffenburger, DA Jost, S Allen, T Mayer, KH Altfeld, M AF Palmer, Christine D. Tomassilli, Julia Sirignano, Michael Romero-Tejeda, Marisol Arnold, Kelly B. Che, Denise Lauffenburger, Douglas A. Jost, Stephanie Allen, Todd Mayer, Kenneth H. Altfeld, Marcus TI Enhanced immune activation linked to endotoxemia in HIV-1 seronegative MSM SO AIDS LA English DT Article ID MEN; SEX; PROLIFERATION; TRANSMISSION; ACQUISITION; SENESCENCE; PREVENTION; INFECTION; CELLS; WOMEN AB This study assessed cellular and soluble markers of immune activation in HIV-1 seronegative MSM. MSM immune profiles were characterized by an increased expression of CD57 on T cells and endotoxemia. Endotoxin presence was linked to recent high-risk exposure and associated with elevated cytokine levels and decreased CD4(+)/CD8(+) T cell ratios. Taken together, these data show elevated levels of inflammation linked to periods of endotoxemia resulting in a significantly different immune phenotype in a subset of MSM at a high risk of HIV-1 acquisition. C1 [Palmer, Christine D.; Sirignano, Michael; Romero-Tejeda, Marisol; Jost, Stephanie; Allen, Todd; Altfeld, Marcus] Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA USA. [Palmer, Christine D.; Sirignano, Michael; Romero-Tejeda, Marisol; Jost, Stephanie; Allen, Todd; Altfeld, Marcus] MIT, Cambridge, MA 02139 USA. [Palmer, Christine D.; Sirignano, Michael; Romero-Tejeda, Marisol; Jost, Stephanie; Allen, Todd; Altfeld, Marcus] Harvard Univ, Cambridge, MA 02138 USA. [Tomassilli, Julia; Mayer, Kenneth H.] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Fenway Hlth, Boston, MA USA. [Tomassilli, Julia; Mayer, Kenneth H.] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Med, Boston, MA USA. [Arnold, Kelly B.; Che, Denise; Lauffenburger, Douglas A.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Altfeld, Marcus] Leibniz Inst Expt Virol, Heinrich Pette Inst, Dept Viral Immunol, Hamburg, Germany. RP Altfeld, M (reprint author), Leibniz Inst Expt Virol, Heinrich Pette Inst, Res Unit Viral Immunol, Martinistr 52, D-20251 Hamburg, Germany. EM marcus.altfeld@hpi.uni-hamburg.de RI Allen, Todd/F-5473-2011 FU Ragon Institute; NIH [P01 AI074415] FX Funding for this study was provided by the Ragon Institute and NIH [grant number P01 AI074415]. NR 21 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD SEP PY 2014 VL 28 IS 14 BP 2162 EP 2166 DI 10.1097/QAD.0000000000000386 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AO1NM UT WOS:000341079800019 PM 25003719 ER PT J AU Khan, NH Almukhtar, RM AF Khan, N. H. Almukhtar, R. M. TI Editorial: early corticosteroids in ulcerative colitis - authors' reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID REMISSION; DISEASE C1 [Khan, N. H.; Almukhtar, R. M.] Southeast Louisiana Vet Hlth Care Syst, Gastroenterol Sect, Dept Internal Med, New Orleans, LA 70112 USA. [Khan, N. H.] Univ Penn, Gastroenterol Sect, Perelman Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Almukhtar, R. M.] Tulane Univ, Hlth Sci Ctr, Dept Internal Med, Sect Gastroenterol & Hepatol, New Orleans, LA 70118 USA. [Almukhtar, R. M.] Louisiana State Univ, Hlth Sci Ctr, Dept Epidemiol, New Orleans, LA USA. RP Khan, NH (reprint author), Southeast Louisiana Vet Hlth Care Syst, Gastroenterol Sect, Dept Internal Med, New Orleans, LA 70112 USA. EM nabeel.khan@va.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP PY 2014 VL 40 IS 6 BP 728 EP 728 DI 10.1111/apt.12898 PG 1 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA AN4LS UT WOS:000340559900015 PM 25123385 ER PT J AU Patil, S Tadigotla, VR Shreffler, W AF Patil, S. Tadigotla, V. R. Shreffler, W. TI Next generation sequencing of the IgE repertoire reveals high identity with other memory compartments SO ALLERGY LA English DT Meeting Abstract CT European-Academy-of-Allergy-and-Clinical-Immunology Congress CY JUN 07-11, 2014 CL Copenhagen, DENMARK SP European Acad Allergy & Clin Immunol C1 [Patil, S.; Shreffler, W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Tadigotla, V. R.] Courtagen, Woburn, 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 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2014 VL 69 SU 99 SI SI MA 61 BP 28 EP 28 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA AO2HL UT WOS:000341139400062 ER PT J AU Jartti, T Nieminen, R Vuorinen, T Lehtinen, P Vahlberg, T Gern, J Camargo, CA Ruuskanen, O AF Jartti, T. Nieminen, R. Vuorinen, T. Lehtinen, P. Vahlberg, T. Gern, J. Camargo, C. A., Jr. Ruuskanen, O. TI The effect of prednisolone in the first rhinovirus-induced wheeze: a randomised controlled trial with 12-month follow-up SO ALLERGY LA English DT Meeting Abstract CT European-Academy-of-Allergy-and-Clinical-Immunology Congress CY JUN 07-11, 2014 CL Copenhagen, DENMARK SP European Acad Allergy & Clin Immunol C1 [Jartti, T.; Nieminen, R.; Lehtinen, P.; Ruuskanen, O.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Vuorinen, T.; Vahlberg, T.] Univ Turku, Turku, Finland. [Gern, J.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Camargo, C. A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol Emergency Med & M, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2014 VL 69 SU 99 SI SI MA 124 BP 56 EP 57 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA AO2HL UT WOS:000341139400125 ER PT J AU Patil, S Ogunniyi, A Ma, A Swenson, T Calatroni, A Moon, J Love, JC Shreffler, W AF Patil, S. Ogunniyi, A. Ma, A. Swenson, T. Calatroni, A. Moon, J. Love, J. C. Shreffler, W. TI Induction of Arah2-specific memory B cells identified using a novel tetramer-based approach occurs early and transiently during peanut oral immunotherapy SO ALLERGY LA English DT Meeting Abstract CT European-Academy-of-Allergy-and-Clinical-Immunology Congress CY JUN 07-11, 2014 CL Copenhagen, DENMARK SP European Acad Allergy & Clin Immunol C1 [Patil, S.; Shreffler, W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ogunniyi, A.; Love, J. C.] MIT, Cambridge, MA 02139 USA. [Ma, A.; Swenson, T.; Moon, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Calatroni, A.] Rho Inc, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2014 VL 69 SU 99 SI SI MA 187 BP 85 EP 85 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA AO2HL UT WOS:000341139400188 ER PT J AU Patil, S Schneider, M Ma, A Swenson, T Shreffler, WG AF Patil, S. Schneider, M. Ma, A. Swenson, T. Shreffler, W. G. TI Basophil activation testing measures in peanut oral immunotherapy SO ALLERGY LA English DT Meeting Abstract CT European-Academy-of-Allergy-and-Clinical-Immunology Congress CY JUN 07-11, 2014 CL Copenhagen, DENMARK SP European Acad Allergy & Clin Immunol C1 [Patil, S.; Shreffler, W. G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Schneider, M.] BUHLMANN Labs, Schonenbuch, Switzerland. [Ma, A.; Swenson, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2014 VL 69 SU 99 SI SI MA 1621 BP 103 EP 104 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA AO2HL UT WOS:000341139400229 ER PT J AU Bergroth, E Aakula, M Remes, S Korppi, M Piedra, PA Camargo, CA Jartti, T AF Bergroth, E. Aakula, M. Remes, S. Korppi, M. Piedra, P. A. Camargo, C. A., Jr. Jartti, T. TI Hospitalisation for rhinovirus-induced bronchiolitis is associated with increased risk of using regular asthma controller medication during the subsequent 12 months SO ALLERGY LA English DT Meeting Abstract CT European-Academy-of-Allergy-and-Clinical-Immunology Congress CY JUN 07-11, 2014 CL Copenhagen, DENMARK SP European Acad Allergy & Clin Immunol C1 [Bergroth, E.] Cent Hosp Cent Finland, Dept Pediat, Jyvaskyla, Finland. [Bergroth, E.; Remes, S.] Kuopio Univ Hosp, Dept Pediat, SF-70210 Kuopio, Finland. [Aakula, M.; Jartti, T.] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Korppi, M.] Tampere Univ, Pediat Res Ctr, FIN-33101 Tampere, Finland. [Korppi, M.] Tampere Univ Hosp, Tampere, Finland. [Piedra, P. A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Piedra, P. A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, 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 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2014 VL 69 SU 99 SI SI MA 406 BP 179 EP 180 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA AO2HL UT WOS:000341139400433 ER PT J AU Koistinen, A Nieminen, R Vuorinen, T Soderlund-Venermo, M Camargo, CA Ruuskanen, O Jartti, T AF Koistinen, A. Nieminen, R. Vuorinen, T. Soderlund-Venermo, M. Camargo, C. A., Jr. Ruuskanen, O. Jartti, T. TI Vitamin D, virus etiology, and atopy in Finnish children with first wheeze SO ALLERGY LA English DT Meeting Abstract CT European-Academy-of-Allergy-and-Clinical-Immunology Congress CY JUN 07-11, 2014 CL Copenhagen, DENMARK SP European Acad Allergy & Clin Immunol C1 [Koistinen, A.; Nieminen, R.; Ruuskanen, O.; Jartti, T.] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Vuorinen, T.] Univ Turku, Dept Virol, Turku, Finland. [Soderlund-Venermo, M.] Univ Helsinki, Dept Virol, Haartman Inst, Helsinki, Finland. [Camargo, C. A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, C. A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2014 VL 69 SU 99 SI SI MA 454 BP 197 EP 198 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA AO2HL UT WOS:000341139400480 ER PT J AU Wang, L Sesso, HD Glynn, RJ Christen, WG Bubes, V Manson, JE Buring, JE Gaziano, JM AF Wang, Lu Sesso, Howard D. Glynn, Robert J. Christen, William G. Bubes, Vadim Manson, JoAnn E. Buring, Julie E. Gaziano, J. Michael TI Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID BETA-CAROTENE SUPPLEMENTATION; LONG-TERM SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; PROSTATE-CANCER; COLORECTAL-CANCER; ALPHA-TOCOPHEROL; EPIDEMIOLOGIC EVIDENCE; ANTIOXIDANT VITAMINS; PREVENTION AB Background: Recent posttrial analysis of a completed randomized trial found an increased risk of prostate cancer among healthy men taking high-dose vitamin E supplements. Trials that examined the effect of vitamin C supplements on cancer risk are few. Objective: We examined whether vitamin E or vitamin C supplementation affects the risk of cancer events during posttrial follow-up of the Physicians' Health Study II. Design: Beginning in 1997, a total of 14,641 US male physicians aged >= 50 y were randomly assigned to receive 400 IU of vitamin E every other day, 500 mg of vitamin C daily, or their respective placebos. The vitamin E and vitamin C treatment ended in 2007, and observational follow-up continued through June 2011. Results: This study included an additional 356 cases of incident prostate cancer and 771 total cancers that developed during a mean (maximum) of 2.8 (3.8) y of posttrial observation. During an overall mean of 10.3 (13.8) y, there were a total of 1373 incident prostate cancers and 2669 total cancers documented. In comparison with placebo, vitamin E supplementation had no effect on the incidence of prostate cancer (HR: 0.99; 95% CI: 0.89, 1.10) or total cancers (HR: 1.02; 95% CI: 0.95, 1.10). There was also no effect of vitamin C supplementation on total cancers (HR: 1.02; 95% CI: 0.94, 1.10) or incident prostate cancer (HR: 1.03; 95% CI: 0.93, 1.15). Neither vitamin E nor vitamin C supplementation had effects on other site-specific cancers overall. Stratification by known cancer risk factors, history of cancer, other randomized treatment, and follow-up time showed no significant interactions. Conclusion: In this large-scale randomized trial in men, vitamin E and C supplementation had no immediate or long-term effects on the risk of total cancers, prostate cancer, or other site-specific cancers. C1 [Wang, Lu; Sesso, Howard D.; Glynn, Robert J.; Christen, William G.; Bubes, Vadim; Manson, JoAnn E.; Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Sesso, Howard D.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Manson, JoAnn E.; Buring, Julie E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Wang, L (reprint author), 900 Commonwealth Ave East, Boston, MA 02215 USA. EM lwang@research.bwh.harvard.edu FU NIH [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; BASF Corporation; National Heart, Lung, and Blood Institute [HL095649] FX Supported by grants from the NIH (CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595) and an investigator-initiated grant from BASF Corporation. Study agents and packaging were provided by BASF Corporation, Pfizer (formerly Wyeth, American Home Products, and Lederle), and DSM Nutritional Products Inc (formerly Roche Vitamins). LW was supported by a K99/R00 grant (HL095649) from the National Heart, Lung, and Blood Institute. NR 34 TC 17 Z9 19 U1 0 U2 13 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2014 VL 100 IS 3 BP 915 EP 923 DI 10.3945/ajcn.114.085480 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AN6WJ UT WOS:000340738800023 PM 25008853 ER PT J AU Garcia-Manero, G Gartenberg, G Steensma, DP Schipperus, MR Breems, DA de Paz, R Valcarcel, D Kranenburg, B Reddy, M Komrokji, RS AF Garcia-Manero, Guillermo Gartenberg, Gary Steensma, David P. Schipperus, Martin R. Breems, Dimitri A. de Paz, Raquel Valcarcel, David Kranenburg, Britte Reddy, Manjula Komrokji, Rami S. TI A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ANTI-INTERLEUKIN-6 MONOCLONAL-ANTIBODY; CYTOKINES; HEPCIDIN; CELLS; PROLIFERATION; INFLAMMATION; EXPRESSION; LYMPHOMA; THERAPY; DISEASE AB Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double-blind, placebo-controlled, phase 2 study assessed the efficacy and safety of siltuximab, a chimeric anti-IL-6 monoclonal antibody, in patients with low-and intermediate-1-risk MDS who require transfusions for MDS anemia. Patients were randomized in a 2: 1 ratio to siltuximab 15 mg kg(-1) every 4 weeks+best supportive care (BSC) or placebo+BSC for 12 weeks. The primary endpoint was reduction in red blood cell (RBC) transfusions to treat MDS anemia, defined as >= 50% relative decrease and >= 2-unit absolute decrease in RBC transfusions. Fifty and 26 patients were randomized to the siltuximab and placebo groups, respectively. The study did not meet its prespecified hypothesis, with six (12%) patients in the siltuximab group and one (3.8%) in the placebo group having reductions in RBC transfusions (P=0.271). At the time of the planned futility analysis, the prespecified cutoff criteria were not met, and the study was terminated early due to lack of efficacy. No unexpected safety findings were observed. In conclusion, compared to placebo, treatment with siltuximab did not reduce RBC transfusions in transfusion-dependent patients with low- and intermediate-1-risk MDS. Future studies might explore siltuximab in patients with less iron overload and with elevated IL-6 levels and/or using higher doses for MDS. (C) 2014 Wiley Periodicals, Inc. C1 [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77025 USA. [Gartenberg, Gary] Janssen Res & Dev LLC, Raritan, NJ USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schipperus, Martin R.] Haga Teaching Hosp, The Hague, Netherlands. [Breems, Dimitri A.] Hosp Network Antwerp, Antwerp, Belgium. [de Paz, Raquel] Univ Hosp La Paz, Madrid, Spain. [Valcarcel, David] Univ Autonoma Barcelona, Hosp Vall dHebron, E-08193 Barcelona, Spain. [Kranenburg, Britte] Janssen Biol Europe, Leiden, Netherlands. [Reddy, Manjula] Janssen Res & Dev LLC, Spring House, PA USA. [Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Garcia-Manero, G (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe,Box 428, Houston, TX 77025 USA. EM ggarciam@mdanderson.org OI Steensma, David/0000-0001-5130-9284 FU Janssen Research Development FX Contract grant sponsor: Janssen Research & Development. NR 24 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2014 VL 89 IS 9 BP E156 EP E162 DI 10.1002/ajh.23780 PG 7 WC Hematology SC Hematology GA AN6BT UT WOS:000340679400005 PM 24888488 ER PT J AU Pena, JRA Saidman, SL Girouard, TC Meister, E Dzik, WH Makar, RS AF Pena, Jeremy Ryan A. Saidman, Susan L. Girouard, Timothy C. Meister, Erin Dzik, Walter H. Makar, Robert S. TI Anti-HLA alloantibodies in surgical patients refractory to platelet transfusion SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID BLOOD-DONORS; ANTIBODIES; ALLOIMMUNIZATION; MANAGEMENT; PREVALENCE; EXPRESSION; PREVENTION; REDUCTION; PREGNANCY; STRATEGY AB Alloimmune platelet refractoriness (alloPR) among actively bleeding surgical patients with thrombocytopenia represents a life-threatening problem. Here we present three cases in which surgical bleeding was complicated by life-threatening thrombocytopenia and alloPR. We demonstrate that the human leukocyte antigens (HLA) antibodies associated with alloPR are broadly reactive and in high concentration, are not removed by hemodilution, and are not absorbed by transfusion of multiple doses of platelet concentrates. HLA alloPR may be under-recognized among surgical patients. Research is needed to develop pre-operative screening methods that will identify patients in need of specialized platelet support using HLA compatible donor products. (C) 2014 Wiley Periodicals, Inc. C1 [Pena, Jeremy Ryan A.] Beth Israel Deaconess Med Ctr, Div Lab & Transfus Med, Dept Pathol, Boston, MA 02215 USA. [Pena, Jeremy Ryan A.; Saidman, Susan L.; Girouard, Timothy C.; Meister, Erin; Dzik, Walter H.; Makar, Robert S.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. RP Pena, JRA (reprint author), Beth Israel Deaconess Med Ctr, Div Lab & Transfus Med, 330 Brookline Ave YA-309, Boston, MA 02215 USA. EM jrpena@bidmc.harvard.edu FU Luick Fund; NIH/NHLBI [K12HL087164-07] FX Contract grant sponsor: Luick Fund, a gift of the Luick family to the Blood Transfusion Service, Department of Pathology, MGH.; Contract grant sponsor: NIH/NHLBI; Contract grant number: K12HL087164-07. NR 26 TC 6 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2014 VL 89 IS 9 BP E133 EP E137 DI 10.1002/ajh.23757 PG 5 WC Hematology SC Hematology GA AN6BT UT WOS:000340679400001 PM 24816643 ER PT J AU Kozel, BA Bayliss, SJ Berk, DR Waxler, JL Knutsen, RH Danback, JR Pober, BR AF Kozel, Beth A. Bayliss, Susan J. Berk, David R. Waxler, Jessica L. Knutsen, Russell H. Danback, Joshua R. Pober, Barbara R. TI Skin Findings in Williams Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Williams syndrome; elastin; skin wrinkling; graying of hair; skin; biomechanics ID SUPRAVALVULAR AORTIC-STENOSIS; DOMINANT CUTIS LAXA; ELASTIN GENE; BEUREN-SYNDROME; FRAMESHIFT MUTATIONS; VOIDING DYSFUNCTION; HAIR; DISEASE; FIBERS; DIVERTICULITIS AB Previous examination in a small number of individuals with Williams syndrome (also referred to as Williams-Beuren syndrome) has shown subtly softer skin and reduced deposition of elastin, an elastic matrix protein important in tissue recoil. No quantitative information about skin elasticity in individuals with Williams syndrome is available; nor has there been a complete report of dermatologic findings in this population. To fill this knowledge gap, 94 patients with Williams syndrome aged 750 years were recruited as part of the skin and vascular elasticity (WS-SAVE) study. They underwent either a clinical dermatologic assessment by trained dermatologists (2010 WSA family meeting) or measurement of biomechanical properties of the skin with the DermaLab (TM) suction cup (2012 WSA family meeting). Clinical assessment confirmed that soft skin is common in this population (83%), as is premature graying of the hair (80% of those 20 years or older), while wrinkles (92%), and abnormal scarring (33%) were detected in larger than expected proportions. Biomechanical studies detected statistically significant differences in dP (the pressure required to lift the skin), dT (the time required to raise the skin through a prescribed gradient), VE (viscoelasticity), and E (Young's modulus) relative to matched controls. The RT (retraction time) also trended longer but was not significant. The biomechanical differences noted in these patients did not correlate with the presence of vascular defects also attributable to elastin insufficiency (vascular stiffness, hypertension, and arterial stenosis) suggesting the presence of tissue specific modifiers that modulate the impact of elastin insufficiency in each tissue. (C) 2014 Wiley Periodicals, Inc. C1 [Kozel, Beth A.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Bayliss, Susan J.; Berk, David R.; Danback, Joshua R.] Washington Univ, Sch Med, Dept Dermatol, St Louis, MO 63110 USA. [Waxler, Jessica L.; Pober, Barbara R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Knutsen, Russell H.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Pober, Barbara R.] Frank Netter Sch Med, Dept Med Sci, Hamden, CT USA. RP Kozel, BA (reprint author), Washington Univ, Sch Med, 660 S Euclid,Campus Box 8208, St Louis, MO 63110 USA. EM Kozel_b@kids.wustl.edu FU Children's Discovery Institute of Washington University, School of Medicine and St. Louis Children's Hospital; Child Health Research Center in Developmental Biology [NIH K12-HD01487]; Genetic Basis of Inflammatory Airway Disease [NIH K12-HL089968] FX Grant sponsor: Children's Discovery Institute of Washington University, School of Medicine and St. Louis Children's Hospital; Grant sponsor: Child Health Research Center in Developmental Biology; Grant number: NIH K12-HD01487; Grant sponsor: Genetic Basis of Inflammatory Airway Disease; Grant number: NIH K12-HL089968. NR 38 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2014 VL 164 IS 9 BP 2217 EP 2225 DI 10.1002/ajmg.a.36628 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AN5YO UT WOS:000340669200012 PM 24920525 ER PT J AU Peacock, ZS Klein, KP Mulliken, JB Kaban, LB AF Peacock, Zachary S. Klein, Katherine P. Mulliken, John B. Kaban, Leonard B. TI The Habsburg Jaw-Re-examined SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE maxillary retrognathia; mandibular prognathism; midfacial deficiency; class III skeletal malocclusion; maxillary hypoplasia; maxillary retrusion; mandibular hyperplasia; exorbitism; medical disease in portraits; everted lower lip; nasal dorsal hump ID CLASS-III MALOCCLUSION; MANDIBULAR PROGNATHISM; GENETICS AB "Habsburg Jaw" is a frequently used eponymous designation for patients with mandibular prognathism, hyperplasia, or overgrowth. The purpose of this study was to evaluate portraits of the Spanish Habsburgs to determine the relative contributions of maxillary deficiency and mandibular prognathism to overall facial appearance. Representative portraits of the Spanish Habsburgs were assessed by 4 investigators for the presence of 11 anatomic features of maxillary deficiency and 7 of mandibular prognathism. Each characteristic was given a binary score of 1 if present and 0 if absent. Thus, the maximum score would be 11 for maxillary deficiency and 7 for mandibular prognathism. A semi-quantitative scale was established to determine the likelihood of each diagnosis: Maxillary deficiency: 0-4.99 (unlikely), 5-7.99 (likely), 8-11 (very likely); mandibular prognathism: 0-2.99 (unlikely), 3-5.99 (likely), 6-7 (very likely). Six of 7 Habsburg rulers were considered either likely or very likely to have maxillary deficiency, whereas 3/7 were assessed as likely and 4 unlikely to have mandibular prognathism. The results of this study suggest that the primary deformity of the "Habsburg Jaw" is maxillary deficiency rather than absolute mandibular prognathism. (C) 2014 Wiley Periodicals, Inc. C1 [Peacock, Zachary S.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Klein, Katherine P.] Harvard Univ, Sch Dent Med, Div Dent, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mulliken, John B.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM lkaban@partners.org NR 24 TC 0 Z9 0 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2014 VL 164 IS 9 BP 2263 EP 2269 DI 10.1002/ajmg.a.36639 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AN5YO UT WOS:000340669200018 PM 24942320 ER PT J AU Bayram, Y Pehlivan, D Karaca, E Gambin, T Jhangiani, SN Erdin, S Gonzaga-Jauregui, C Wiszniewski, W Muzny, D Elcioglu, NH Yildirim, MS Bozkurt, B Zamani, AG Boerwinkle, E Gibbs, RA Lupski, JR AF Bayram, Yavuz Pehlivan, Davut Karaca, Ender Gambin, Tomasz Jhangiani, Shalini N. Erdin, Serkan Gonzaga-Jauregui, Claudia Wiszniewski, Wojciech Muzny, Donna Elcioglu, Nursel H. Yildirim, M. Selman Bozkurt, Banu Zamani, Ayse Gul Boerwinkle, Eric Gibbs, Richard A. Lupski, James R. CA Baylor Hopkins Ctr Mendelian Geno TI Whole Exome Sequencing Identifies Three Novel Mutations in ANTXR1 in Families with GAPO Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE GAPO syndrome; ANTXR1; whole exome sequencing ID OF-THE-LITERATURE; PROTEINS; GENOMICS; GLAUCOMA; DISEASE; PATIENT; GROWTH; SERVER AB GAPO syndrome (OMIM#230740) is the acronym for growth retardation, alopecia, pseudoanodontia, and optic atrophy. About 35 cases have been reported, making it among one of the rarest recessive conditions. Distinctive craniofacial features including alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, mid-facial hypoplasia, hypertelorism, and thickened eyelids and lips make GAPO syndrome a clinically recognizable phenotype. While this genomic study was in progress mutations in ANTXR1 were reported to cause GAPO syndrome. In our study we performed whole exome sequencing (WES) for five affected individuals from three Turkish kindreds segregating the GAPO trait. Exome sequencing analysis identified three novel homozygous mutations including; one frameshift (c.1220_1221insT; p.Ala408Cysfs*2), one splice site (c.411A> G; p.Gln137Gln), and one non-synonymous (c.1150G> A; p.Gly384Ser) mutation in the ANTXR1 gene. Our studies expand the allelic spectrum in this rare condition and potentially provide insight into the role of ANTXR1 in the regulation of the extracellular matrix. (C) 2014 Wiley Periodicals, Inc. C1 [Bayram, Yavuz; Pehlivan, Davut; Karaca, Ender; Gambin, Tomasz; Gonzaga-Jauregui, Claudia; Wiszniewski, Wojciech; Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Jhangiani, Shalini N.; Muzny, Donna; Boerwinkle, Eric; Gibbs, Richard A.; Lupski, James R.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Erdin, Serkan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Elcioglu, Nursel H.] Marmara Univ, Fac Med, Dept Pediat Genet, Istanbul, Turkey. [Yildirim, M. Selman; Zamani, Ayse Gul] Necmettin Erbakan Univ, Meram Med Fac, Dept Genet, Konya, Turkey. [Bozkurt, Banu] Selcuk Univ Konya, Dept Ophthalmol, Fac Med, Konya, Turkey. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Lupski, JR (reprint author), Baylor Coll Med, Dept Mol & Human Genet, One Baylor Plaza,Room 604B, Houston, TX 77030 USA. EM jlupski@bcm.edu RI Erdin, Serkan/B-4988-2008; Zamani, Ayse Gul/A-6567-2016; OI Erdin, Serkan/0000-0001-6587-2625; Zamani, Ayse Gul/0000-0003-0329-9047; Gonzaga-Jauregui, Claudia/0000-0002-4667-3679; Gambin, Tomasz/0000-0002-0941-4571 FU United States National Human Genome Research Institute/National Heart Blood and Lung Institute [U54HG006542] FX Grant sponsor: United States National Human Genome Research Institute/National Heart Blood and Lung Institute; Grant number: U54HG006542. NR 34 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2014 VL 164 IS 9 BP 2328 EP 2334 DI 10.1002/ajmg.a.36678 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AN5YO UT WOS:000340669200027 PM 25045128 ER PT J AU Broussard, CS Frey, MT Hernandez-Diaz, S Greene, MF Chambers, CD Sahin, L Sharp, BAC Honein, MA AF Broussard, Cheryl S. Frey, Meghan T. Hernandez-Diaz, Sonia Greene, Michael F. Chambers, Christina D. Sahin, Leyla Sharp, Beth A. Collins Honein, Margaret A. TI Developing a systematic approach to safer medication use during pregnancy: summary of a Centers for Disease Control and Prevention-convened meeting SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE Centers for Disease Control and Prevention; expert review; medications; pregnancy; teratogens ID RECOMMENDATIONS; WOMEN; LACTATION; INFECTION; FETAL; BIRTH; RISK; CDC AB To address information gaps that limit informed clinical decisions on medication use in pregnancy, the Centers for Disease Control and Prevention (CDC) solicited expert input on a draft prototype outlining a systematic approach to evaluating the quality and strength of existing evidence for associated risks. The draft prototype outlined a process for the systematic review of available evidence and deliberations by a panel of experts to inform clinical decision making for managing health conditions in pregnancy. At an expert meeting convened by the CDC in January 2013, participants divided into working groups discussed decision points within the prototype. This report summarizes their discussions of best practices for formulating an expert review process, developing evidence summaries and treatment guidance, and disseminating information. There is clear recognition of current knowledge gaps and a strong collaboration of federal partners, academic experts, and professional organizations willing to work together toward safer medication use during pregnancy. C1 [Broussard, Cheryl S.; Frey, Meghan T.; Honein, Margaret A.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Frey, Meghan T.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Greene, Michael F.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Greene, Michael F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chambers, Christina D.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Chambers, Christina D.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Sahin, Leyla] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Maternal Hlth Team,Pediat & Maternal Hlth Staff, Silver Spring, MD USA. [Sharp, Beth A. Collins] Agcy Healthcare Res & Qual, Rockville, MD USA. RP Broussard, CS (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. FU Centers for Disease Control and Prevention (CDC) FX This work was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention (CDC) administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the CDC (M.T.F.). NR 35 TC 11 Z9 11 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2014 VL 211 IS 3 BP 208 EP U667 DI 10.1016/j.ajog.2014.05.040 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AO4HO UT WOS:000341297900007 PM 24881821 ER PT J AU Goldfarb, IT Little, S Brown, J Riley, LE AF Goldfarb, Ilona T. Little, Sarah Brown, Joelle Riley, Laura E. TI Use of the combined tetanus-diphtheria and pertussis vaccine during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE pertussis; pregnancy; Tdap; vaccination ID INFLUENZA VACCINATION; POSTPARTUM WOMEN; ATTITUDES; IMMUNIZATION; KINETICS AB OBJECTIVE: A recent increase in pertussis cases prompted the Advisory Committee on Immunization Practices to recommend administering the perinatal tetanus, diphtheria, and pertussis (Tdap) vaccine during each pregnancy. We sought to describe uptake of Tdap and identify predictors of vaccination in pregnancy. STUDY DESIGN: We conducted a retrospective study of all women delivering at a university hospital between February and June 2013. Demographic, pregnancy, and vaccination data were abstracted from the medical record. The relationship between maternal age, parity, gestational age, race/ethnicity, marital status, prenatal provider/site, insurance, influenza vaccination status, and Tdap vaccine was described by univariate analysis. Independent predictors were identified by multivariable logistic regression. RESULTS: In our cohort of 1467 women, 1194 (81.6%) received a Tdap vaccine. After adjusting for potential confounders, 3 factors were found to be independent predictors of receiving the vaccine. Patients were more likely to receive Tdap if they had been vaccinated against influenza during this pregnancy (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.4-2.3). Black women were less likely to receive Tdap when compared with other women (aOR, 0.42; 95% CI, 0.27-0.67). Also, women who delivered preterm were less likely to receive the Tdap vaccine (aOR, 0.33; 95% CI, 0.22-0.48). CONCLUSION: A high overall Tdap vaccination rate was observed following implementation of the Advisory Committee on Immunization Practices guidelines. Black women, however, had significantly lower vaccine uptake than other women. Further research is needed to understand and minimize this disparity. Women who delivered prematurely also had a decreased rate of Tdap vaccination; vaccinating earlier should be considered to better capture this population. C1 [Goldfarb, Ilona T.; Brown, Joelle; Riley, Laura E.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Little, Sarah] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med,Sch Med, Boston, MA 02115 USA. RP Goldfarb, IT (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St Founders 4, Boston, MA 02114 USA. EM igoldfarb@partners.org NR 23 TC 3 Z9 3 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2014 VL 211 IS 3 AR 299.e1 DI 10.1016/j.ajog.2014.05.029 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AO4HO UT WOS:000341297900040 PM 24858200 ER PT J AU Worley, MJ Guseh, SH Rauh-Hain, A Esselen, KM Muto, MG Feltmate, CM Berkowitz, RS del Carmen, MG Schorge, JO Horowitz, NS AF Worley, Michael J., Jr. Guseh, Stephanie H. Rauh-Hain, Alejandro Esselen, Katharine M. Muto, Michael G. Feltmate, Colleen M. Berkowitz, Ross S. del Carmen, Marcela G. Schorge, John O. Horowitz, Neil S. TI What is the optimal treatment for obese patients with advanced ovarian carcinoma? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE neoadjuvant chemotherapy; obesity; ovarian cancer; primary debulking surgery ID ADVANCED-STAGE OVARIAN; BODY-MASS INDEX; NEOADJUVANT CHEMOTHERAPY NACT; BREAST-CANCER CHEMOTHERAPY; GYNECOLOGIC-ONCOLOGY-GROUP; PRIMARY DEBULKING SURGERY; PHASE-III TRIAL; DOSE-INTENSITY; US ADULTS; CARBOPLATIN AB OBJECTIVE: The purpose of this study was to compare primary debulking surgery (PDS) vs neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) among obese patients. STUDY DESIGN: Medical records of patients with a body mass index (BMI) of >= 30 kg/m(2) with ovarian/fallopian tube/primary peritoneal carcinoma between January 2005 and December 2010 were reviewed. Patients were separated by PDS or NACT-IDS. Preoperative characteristics, surgical procedures, and postoperative and oncologic outcomes were compared. RESULTS: Of 117 patients, 95 women (81.2%) underwent PDS, and 22 women (18.8%) underwent NACT-IDS. Patients who underwent NACT-IDS were more likely to have stage IV disease (63.6% vs 26.3%; P = .001) and a low surgical complexity score (n = 14; 63.6%). There were no other differences between groups with respect to preoperative characteristics or postoperative morbidity. Compared with the NACT-IDS group, the PDS group had an improved progression-free survival (PFS; 15 vs 11 months; P = .006) and overall survival (OS; 53 vs 32 months; P = .036). Seventy-eight patients (66.7%) had a BMI of 30-34.9 kg/m(2). Within this subset of obese patients, the PDS group had an improved PFS (15 vs 10 months; P = .011) and OS (58 vs 32 months; P = .033), compared with the NACT-IDS group. Among patients with a BMI of >= 35 kg/m(2), there was no difference in PFS (14 vs 12 months; P = .316) or OS (38 vs 32 months; P = .640) when the PDS and NACT-IDS groups were compared. CONCLUSION: Patients with a BMI of 30-34.9 kg/m(2) who undergo PDS have improved oncologic outcomes, compared with those women who undergo NACT-IDS. Patients with a BMI of >= 35 kg/m(2) who undergo PDS have similar oncologic outcomes to those who undergo NACT-IDS. Complication rates were similar at all BMIs, regardless of treatment approach. C1 [Worley, Michael J., Jr.; Esselen, Katharine M.; Muto, Michael G.; Feltmate, Colleen M.; Berkowitz, Ross S.; Horowitz, Neil S.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. [Guseh, Stephanie H.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Rauh-Hain, Alejandro; del Carmen, Marcela G.; Schorge, John O.] Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02114 USA. RP Horowitz, NS (reprint author), Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM nhorowitz@partners.org NR 44 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2014 VL 211 IS 3 AR 231.e1 DI 10.1016/j.ajog.2014.03.059 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AO4HO UT WOS:000341297900015 PM 24704062 ER PT J AU Liu, YN Yuan, JZ Tan, TY Jia, WZ Lugea, A Mareninova, O Waldron, RT Pandol, SJ AF Liu, Yannan Yuan, Jingzhen Tan, Tanya Jia, Wenzhuo Lugea, Aurelia Mareninova, Olga Waldron, Richard T. Pandol, Stephen J. TI Genetic inhibition of protein kinase C epsilon attenuates necrosis in experimental pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE apoptosis; necrosis; inhibitors of apoptotic proteins (IAPs); Bcl-2 family proteins; receptor-interacting protein kinase (RIP) ID NF-KAPPA-B; RECEPTOR-INTERACTING PROTEIN; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; CELL-DEATH; ACINAR-CELLS; PROGRAMMED NECROSIS; ZYMOGEN ACTIVATION; INDUCED APOPTOSIS; TNF-ALPHA; BCL-2 AB Understanding the regulation of death pathways, necrosis and apoptosis, in pancreatitis is important for developing therapies directed to the molecular pathogenesis of the disease. Protein kinase C epsilon (PKC epsilon) has been previously shown to regulate inflammatory responses and zymogen activation in pancreatitis. Furthermore, we demonstrated that ethanol specifically activated PKCe in pancreatic acinar cells and that PKCe mediated the sensitizing effects of ethanol on inflammatory response in pancreatitis. Here we investigated the role of PKCe in the regulation of death pathways in pancreatitis. We found that genetic deletion of PKCe resulted in decreased necrosis and severity in the in vivo cerulein-induced pancreatitis and that inhibition of PKCe protected the acinar cells from CCK-8 hyperstimulation-induced necrosis and ATP reduction. These findings were associated with upregulation of mitochondrial Bak and Bcl-2/Bcl-xL, proapoptotic and prosurvival members in the Bcl-2 family, respectively, as well as increased mitochondrial cytochrome c release, caspase activation, and apoptosis in pancreatitis in PKCe knockout mice. We further confirmed that cerulein pancreatitis induced a dramatic mitochondrial translocation of PKCe, suggesting that PKCe regulated necrosis in pancreatitis via mechanisms involving mitochondria. Finally, we showed that PKCe deletion downregulated inhibitors of apoptosis proteins, c-IAP2, survivin, and c-FLIPs while promoting cleavage/inactivation of receptor-interacting protein kinase (RIP). Taken together, our findings provide evidence that PKCe activation during pancreatitis promotes necrosis through mechanisms involving mitochondrial proapoptotic and prosurvival Bcl-2 family proteins and upregulation of nonmitochondrial pathways that inhibit caspase activation and RIP cleavage/inactivation. Thus PKCe is a potential target for prevention and/or treatment of acute pancreatitis. C1 [Liu, Yannan; Yuan, Jingzhen; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Liu, Yannan; Yuan, Jingzhen; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.] South Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Liu, Yannan; Jia, Wenzhuo] Beijing Hosp, Beijing, Peoples R China. [Tan, Tanya] St Georges Univ, Sch Med, St Georges, Grenada. [Lugea, Aurelia; Waldron, Richard T.; Pandol, Stephen J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Yuan, JZ (reprint author), UCLA VA Greater Los Angeles Healthcare Syst, West Los Angeles VA Healthcare Ctr, South Calif Res Ctr Alcohol Liver & Pancreat Dis, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM jzyuan@ucla.edu FU Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (NIH) [P50-A11999]; UCLA Center of Excellence in Pancreatic Diseases (NIH) [1P01AT0003960-01]; Department of Veterans Affairs Merits Grant; Southern California Research Center for Liver and Pancreatic Diseases FX This study was supported by the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (NIH Grant P50-A11999); UCLA Center of Excellence in Pancreatic Diseases (NIH Grant 1P01AT0003960-01); the Department of Veterans Affairs Merits Grant; and Lee Summer Student Research Award from Southern California Research Center for Liver and Pancreatic Diseases (to T. Tan). NR 57 TC 5 Z9 5 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP G550 EP G563 DI 10.1152/ajpgi.00432.2013 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA AO1SP UT WOS:000341094700006 PM 25035113 ER PT J AU Yarbrough, WM Baicu, C Mukherjee, R Van Laer, A Rivers, WT McKinney, RA Prescott, CB Stroud, RE Freels, PD Zellars, KN Zile, MR Spinale, FG AF Yarbrough, William M. Baicu, Catalin Mukherjee, Rupak Van Laer, An Rivers, William T. McKinney, Richard A. Prescott, Corey B. Stroud, Robert E. Freels, Parker D. Zellars, Kia N. Zile, Michael R. Spinale, Francis G. TI Cardiac-restricted overexpression or deletion of tissue inhibitor of matrix metalloproteinase-4: differential effects on left ventricular structure and function following pressure overload-induced hypertrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE remodeling; tissue inhibitors of metalloproteinase; pressure-overload hypertrophy ID AORTIC-VALVE REPLACEMENT; MYOCARDIAL FIBROSIS; HEART-FAILURE; MICE; DISEASE; REGRESSION; INDUCTION; DYSFUNCTION; INFARCTION; EXPRESSION AB Historically, the tissue inhibitors of matrix metalloproteinases (TIMPs) were considered monochromatic in function. However, differential TIMP profiles more recently observed with left ventricular (LV) dysfunction and matrix remodeling suggest more diverse biological roles for individual TIMPs. This study tested the hypothesis that cardiac-specific overexpression (TIMP-4OE) or deletion (knockout; TIMP-4KO) would differentially affect LV function and structure following pressure overload (LVPO). LVPO (transverse aortic constriction) was induced in mice (3.5 +/- 0.1 mo of age, equal sex distribution) with TIMP-4OE (n = 38), TIMP4-KO (n = 24), as well as age/strain-matched wild type (WT, n = 25), whereby indexes of LV remodeling and function such as LV mass and ejection fraction (LVEF) were determined at 28 days following LVPO. Following LVPO, both early (7 days) and late (28 days) survival was similar to 25% lower in the TIMP-4KO group (P < 0.05). While LVPO increased LV mass in all groups, the relative hypertrophic response was attenuated with TIMP-4OE. With LVPO, LVEF was similar between WT and TIMP-4KO (48 +/- 2% and 45 +/- 3%, respectively) but was higher with TIMP-4OE (57 +/- 2%, P < 0.05). With LVPO, LV myocardial collagen expression (type I, III) increased by threefold in all groups (P < 0.05), but surprisingly this response was most robust in the TIMP-4KO group. These unique findings suggest that increased myocardial TIMP-4 in the context of a LVPO stimulus may actually provide protective effects with respect to survival, LV function, and extracellular matrix (ECM) remodeling. These findings challenge the canonical belief that increased levels of specific myocardial TIMPs, such as TIMP-4 in and of themselves, contribute to adverse ECM accumulation following a pathological stimulus, such as LVPO. C1 [Freels, Parker D.; Zellars, Kia N.; Spinale, Francis G.] Univ S Carolina, Sch Med, WJB Dorn Vet Affairs Med Ctr, Columbia, SC USA. [Baicu, Catalin; Mukherjee, Rupak; Van Laer, An; Rivers, William T.; McKinney, Richard A.; Prescott, Corey B.; Stroud, Robert E.; Zile, Michael R.] Med Univ S Carolina, Div Cardiothorac Surg & Adult Cardiol, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Yarbrough, William M.] Sisters Char Providence Hosp, Columbia, SC USA. RP Spinale, FG (reprint author), Univ S Carolina, Sch Med, Cardiovasc Translat Res Ctr, CBA, 6439 Garners Ferry Rd, Columbia, SC 29208 USA. EM cvctrc@uscmed.sc.edu FU National Institutes of Health [HL-11090, HL-089944]; Veterans Affairs Health Administration; Research Service of the Department of Veterans Affairs FX This work was supported by National Institutes of Health Grants HL-11090 and HL-089944 and a Merit Award from the Veterans Affairs Health Administration. F. G. Spinale and M. R. Zile are supported by the Research Service of the Department of Veterans Affairs. NR 37 TC 3 Z9 3 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP H752 EP H761 DI 10.1152/ajpheart.00063.2014 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA AO1NZ UT WOS:000341081200013 PM 24993046 ER PT J AU Gooz, MB Maldonado, EN Dang, YJ Amria, MY Higashiyama, S Abboud, HE Lemasters, JJ Bell, PD AF Gooz, Monika Beck Maldonado, Eduardo N. Dang, Yujing Amria, May Y. Higashiyama, Shigeki Abboud, Hanna E. Lemasters, John J. Bell, P. Darwin TI ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ADAM17; glycolysis; ERK; cell proliferation; polycystic kidney disease (PKD) ID CONVERTING-ENZYME TACE; GROWTH; ALPHA; EGFR; RECEPTORS; POLARIS; CANCER; CILIA; MICE AB Polycystic kidney disease (PKD) is a common genetic disorder leading to cyst formation in the kidneys and other organs that ultimately results in kidney failure and death. Currently, there is no therapy for slowing down or stopping the progression of PKD. In this study, we identified the disintegrin metalloenzyme 17 (ADAM17) as a key regulator of cell proliferation in kidney tissues of conditional knockout Ift88(-/-) mice and collecting duct epithelial cells from Ift88(orpk) mice, animal models of autosomal recessive polycystic kidney disease (ARPKD). Using Western blotting, an enzyme activity assay, and a growth factor-shedding assay in the presence or absence of the specific ADAM17 inhibitor TMI-005, we show that increased expression and activation of ADAM17 in the cystic kidney and in collecting duct epithelial cells originating from the Ift88(orpk) mice (designated as PKD cells) lead to constitutive shedding of several growth factors, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, and transforming growth factor-alpha (TGF-alpha). Increased growth factor shedding induces activation of the EGFR/MAPK/ERK pathway and maintains higher cell proliferation rate in PKD cells compared with control cells. PKD cells also displayed increased lactate formation and extracellular acidification indicative of aerobic glycolysis (Warburg effect), which was blocked by ADAM17 inhibition. We propose that ADAM17 is a key promoter of cellular proliferation in PKD cells by activating the EGFR/ERK axis and a proproliferative glycolytic phenotype. C1 [Gooz, Monika Beck; Dang, Yujing; Amria, May Y.; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Maldonado, Eduardo N.; Lemasters, John J.] Med Univ S Carolina, Dept Drug Discovery & Pharmaceut Sci, Charleston, SC 29425 USA. [Higashiyama, Shigeki] Ehime Univ, Dept Biochem & Mol Genet, Matsuyama, Ehime 790, Japan. [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Nephrol, San Antonio, TX 78229 USA. [Lemasters, John J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Gooz, MB (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,CSB829,MS 629, Charleston, SC 29425 USA. EM beckm@musc.edu FU National Institutes of Health (NIH) [NIDDK P30 DK074038, R01 DK32032]; Veterans Administration (Ralph H. Johnson VA Medical Center); Dialysis Clinic, Inc. FX This work was supported by grants from the National Institutes of Health (NIH NIDDK P30 DK074038 and R01 DK32032), a Merit Grant from the Veterans Administration (Ralph H. Johnson VA Medical Center), and grants from the Dialysis Clinic, Inc. NR 26 TC 6 Z9 6 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP F551 EP F559 DI 10.1152/ajprenal.00218.2014 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AO1QA UT WOS:000341086900007 ER PT J AU Siroky, BJ Yin, H Dixon, BP Reichert, RJ Hellmann, AR Ramkumar, T Tsuchihashi, Z Bunni, M Dillon, J Bell, PD Sampson, JR Bissler, JJ AF Siroky, Brian J. Yin, Hong Dixon, Bradley P. Reichert, Ryan J. Hellmann, Anna R. Ramkumar, Thiruvamoor Tsuchihashi, Zenta Bunni, Marlene Dillon, Joshua Bell, P. Darwin Sampson, Julian R. Bissler, John J. TI Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE tuberous sclerosis complex; angiomyolipoma; angiotensin II type 1 receptor; pericyte; perivascular epithelioid cell tumor; mammalian target of rapamycin ID TUBEROUS SCLEROSIS COMPLEX; GROWTH-FACTOR; ER STRESS; CELLS; LYMPHANGIOLEIOMYOMATOSIS; EXPRESSION; NEOPLASMS; PROTEIN; KIDNEY; MICE AB Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in patients with TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-beta, desmin, alpha-smooth muscle actin, and VEGF receptor 2 but did not express the adipocyte marker S100 or the endothelial marker CD31. Sera of TSC patients exhibited increased vascular mural cell-secreted peptides, such as VEGF-A, VEGF-D, soluble VEGF receptor 2, and collagen type IV. These findings suggest that angiomyolipomas may arise from renal pericytes. ANG II treatment of angiomyolipoma cells in vitro resulted in an exaggerated intracellular Ca2+ response and increased proliferation, which were blocked by the ANG II type 2 receptor antagonist valsartan. Blockade of ANG II signaling may have preventative therapeutic potential for angiomyolipomas. C1 [Siroky, Brian J.; Dixon, Bradley P.; Reichert, Ryan J.; Hellmann, Anna R.] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. [Yin, Hong] Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA. [Ramkumar, Thiruvamoor] Novartis Inst Biomed Res, Cambridge, MA USA. [Tsuchihashi, Zenta] Daiichi Sankyo, Parsippany, NJ USA. [Bunni, Marlene; Dillon, Joshua; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Tsuchihashi, Zenta] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Hellmann, Anna R.; Sampson, Julian R.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF10 3AX, S Glam, Wales. [Bissler, John J.] Univ Tennessee, Le Bonheur Childrens Hosp, Coll Med, Tuberous Sclerosis Complex Ctr Excellence, Memphis, TN USA. RP Bissler, JJ (reprint author), Le Bonheur Childrens Hosp, Div Pediat, 848 Adams Ave, Memphis, TN 38138 USA. EM jbissler@uthsc.edu FU Rothberg Courage Award from Tuberous Sclerosis Alliance; Tuberous Sclerosis Alliance; Wales Gene Park FX This work was supported by a Rothberg Courage Award from the Tuberous Sclerosis Alliance (to J. J. Bissler), a Fellowship Award from the Tuberous Sclerosis Alliance (to B. J. Siroky), and the Wales Gene Park (to J. R. Sampson). NR 56 TC 8 Z9 8 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP F560 EP F570 DI 10.1152/ajprenal.00569.2013 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AO1QA UT WOS:000341086900008 PM 24920756 ER PT J AU Tregellas, JR AF Tregellas, Jason R. TI Right Versus Left Hippocampal Activity as a Biomarker in Schizophrenia Response SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Tregellas, Jason R.] Univ Colorado, Sch Med, Denver VA Med Ctr, Res Serv, Aurora, CO 80204 USA. [Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. RP Tregellas, JR (reprint author), Univ Colorado, Sch Med, Denver VA Med Ctr, Res Serv, Aurora, CO 80204 USA. RI Tregellas, Jason/J-3637-2015 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2014 VL 171 IS 9 BP 1001 EP 1001 DI 10.1176/appi.ajp.2014.14050687r PG 1 WC Psychiatry SC Psychiatry GA AO1MU UT WOS:000341077000020 PM 25178756 ER PT J AU Samols, MA Su, A Ra, S Cappel, MA Louissant, A Knudson, RA Ketterling, RP Said, J Binder, S Harris, NL Feldman, AL Kim, J Kim, YH Gratzinger, D AF Samols, Mark A. Su, Albert Ra, Seong Cappel, Mark A. Louissant, Abner, Jr. Knudson, Ryan A. Ketterling, Rhett P. Said, Jonathan Binder, Scott Harris, Nancy Lee Feldman, Andrew L. Kim, Jinah Kim, Youn H. Gratzinger, Dita TI Intralymphatic Cutaneous Anaplastic Large Cell Lymphoma/Lymphomatoid Papulosis Expanding the Spectrum of CD30-positive Lymphoproliferative Disorders SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE anaplastic large cell lymphoma; intravascular; CD30(+) cutaneous lymphoproliferative disorder; lymphatic ID CD30-POSITIVE LYMPHOPROLIFERATIVE DISORDERS; EPSTEIN-BARR-VIRUS; OF-THE-LITERATURE; LARGE T-CELL; LYMPHOMATOID PAPULOSIS; INTRAVASCULAR LYMPHOMA; MYCOSIS-FUNGOIDES; RARE VARIANT; PROLIFERATION; TRANSLOCATIONS AB Intravascular large B-cell lymphomas and EBV+ NK/T-cell lymphomas commonly follow an aggressive clinical course. We recently reported an entirely intravascular anaplastic large cell lymphoma (ALCL) in the skin with a surprisingly indolent clinical course; interestingly, this lymphoma involved the lymphatic rather than the blood vasculature. We hypothesized that intravascular skin-limited ALCL is distinct from aggressive systemic intravascular lymphomas in its intralymphatic localization and clinical course. We now describe 18 cases of cutaneous intravascular large cell lymphoproliferations from 4 institutions. All 12 intravascular large T-cell lesions were intralymphatic; the majority (9) were CD30(+) T-cell lymphoproliferative disorders (TLPDs), 5 further classified as intravascular ALK(-) ALCL. One ALK(+) ALCL and 2 benign microscopic intravascular T-cell proliferations were also intralymphatic. A single case of otherwise typical cutaneous follicle center lymphoma contained intralymphatic centroblasts. The clinical and pathologic characteristics of the CD30(+) TLPDs were similar to those of their extravascular counterparts, including extralymphatic dermal involvement in a subset, DUSP22-IRF4 translocations in half of tested ALK(-) ALCLs, and associated mycosis fungoides in 1; most were skin-limited at baseline and remained so at relapse. All 5 cases of intravascular large B-cell lymphoma involved the blood vasculature and behaved in a clinically aggressive manner; the ALK(+) ALCL, although intralymphatic, was systemic and clinically aggressive. We propose that cutaneous ALK(-) ALCL and related CD30(+) ALK(-) TLPDs involving the lymphatics are part of an expanding spectrum of CD30(+) TLPDs. The identification of intralymphatic as distinct from blood vascular localization may provide critical prognostic and therapeutic information. C1 [Samols, Mark A.; Kim, Jinah; Gratzinger, Dita] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Kim, Youn H.] Stanford Univ, Sch Med, Dept Dermatol, Stanford, CA 94305 USA. [Su, Albert; Ra, Seong; Said, Jonathan; Binder, Scott] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Ra, Seong] San Diego Pathologists Med Grp, San Diego, CA USA. [Cappel, Mark A.] Mayo Clin, Dept Dermatol, Jacksonville, FL 32224 USA. [Louissant, Abner, Jr.; Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Knudson, Ryan A.; Ketterling, Rhett P.; Feldman, Andrew L.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RP Gratzinger, D (reprint author), Stanford Univ, Sch Med, Dept Pathol, 300 Pasteur Dr,L235, Stanford, CA 94305 USA. EM ditag@stanford.edu OI Gratzinger, Dita/0000-0002-9182-8123 NR 35 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2014 VL 38 IS 9 BP 1203 EP 1211 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA AO1TE UT WOS:000341096800005 PM 24805854 ER PT J AU Cornejo, KM Young, RH AF Cornejo, Kristine M. Young, Robert H. TI Adult Granulosa Cell Tumors of the Testis A Report of 32 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testis; adult granulosa cell tumor; sex cord-stromal tumor; prognosis ID OF-THE-LITERATURE; GONADAL STROMAL TUMOR; CLINICOPATHOLOGICAL ANALYSIS; SERTOLI; FOXL2; OVARY; MUTATION; CLASSIFICATION; ANDROBLASTOMA; GYNECOMASTIA AB The clinicopathologic features of 32 adult granulosa cell tumors (AGCT) of the testis are presented. The patients were from 14 to 87 years of age (mean 40.0 y) and underwent orchiectomy (n = 30) or wedge excision (n = 2). None had endocrine-related symptoms. The tumors measured 0.5 to 6.0 cm (mean 2.8 cm) and were predominantly well circumscribed and yellow-tan, except for 1, which had infiltrative borders. The predominant pattern was diffuse, but insular, spindled, micro-follicular (Call-Exner bodies), trabecular, corded, watered-silk, palisading, and pseudopapillary patterns were also present. The cells contained round to ovoid nuclei with frequent longitudinal nuclear grooves, indistinct cell borders, and varying amounts of eosinophilic cytoplasm. Most tumors contained limited amounts of fibrocollagenous stroma. The mitotic count ranged from 0 to 18/10 high-power fields (HPF) (mean 4.9/10 HPF, x 400). Two tumors had prominent necrosis, and 1 had vessel invasion. Follow-up information was available for 19 patients, with a mean of 51.0 months (range, 1 to 169 mo). All were without evidence of disease except 1 who had lung metastasis at 24 months. Our findings indicate that the morphologic spectrum of testicular AGCT is similar to that of ovarian AGCT. The majority of testicular examples have a good prognosis (compared with a malignant behavior in 2 of 7 cases in 1 prior series). Lymphovascular invasion, infiltrative borders, and size >4cm may help in identifying cases with aggressive behavior, as these features were present in the one case with metastasis in our series. Mitotic counts varied and do not appear to be of prognostic significance on the basis of our experience. C1 [Cornejo, Kristine M.; Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Cornejo, Kristine M.; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cornejo, KM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA. EM kcornejo@partners.org NR 40 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2014 VL 38 IS 9 BP 1242 EP 1250 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA AO1TE UT WOS:000341096800010 PM 24705318 ER PT J AU Lawton, KA Brown, MV Alexander, D Li, Z Wulff, JE Lawson, R Jaffa, M Milburn, MV Ryals, JA Bowser, R Cudkowicz, ME Berry, JD AF Lawton, Kay A. Brown, Meredith V. Alexander, Danny Li, Zhen Wulff, Jacob E. Lawson, Robert Jaffa, Matt Milburn, Mike V. Ryals, John A. Bowser, Robert Cudkowicz, Merit E. Berry, James D. CA Northeast ALS Consortium TI Plasma metabolomic biomarker panel to distinguish patients with amyotrophic lateral sclerosis from disease mimics SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE Biomarker; metabolomics; diagnostics ID URIC-ACID LEVELS; CEREBROSPINAL-FLUID; OXIDATIVE STRESS; MASS-SPECTROMETRY; MOTOR-NEURONS; ALS; IDENTIFICATION; DISCOVERY; PROGRESSION; CREATININE AB Our objective was to identify plasma biomarkers of ALS that can aid in distinguishing patients with ALS from those with disease mimics. In this multi-center study, plasma samples were collected from 172 patients recently diagnosed with ALS, 50 healthy controls, and 73 neurological disease mimics. Samples were analyzed using metabolomics. Using all identified biochemicals detected in > 50% of all samples in the metabolomics analysis, samples were classified as ALS or mimic with 65% sensitivity and 81% specificity by LASSO analysis (AUC of 0.76). A subset panel of 32 candidate biomarkers classified these diagnosis groups with a specificity of 90%/sensitivity 58% (AUC of 0.81). Creatinine was lower in subjects with lower revised ALS Functional Rating Scale (ALSFRS-R) scores. In conclusion, ALS can be distinguished from neurological disease mimics by global biochemical profiling of plasma samples. Our analysis identified ALS versus mimics with relatively high sensitivity. We identified a subset of 32 metabolites that identify patients with ALS with a high specificity. Interestingly, lower creatinine correlates significantly with a lower ALSFRS-R score. Finally, molecules previously reported to be important in disease pathophysiology, such as urate, are included in our metabolite panel. C1 [Lawton, Kay A.; Brown, Meredith V.; Alexander, Danny; Li, Zhen; Wulff, Jacob E.; Milburn, Mike V.; Ryals, John A.] Metabolon Inc, Durham, NC USA. [Lawson, Robert; Jaffa, Matt; Cudkowicz, Merit E.; Berry, James D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bowser, Robert] Barrow Neurol Inst, Phoenix, AZ 85013 USA. RP Berry, JD (reprint author), Massachusetts Gen Hosp, Neurol Clin Res Inst, Dept Neurol, 1256 Bigelow,55 Fruit St, Boston, MA 02155 USA. EM jdberry@partners.org FU ALS Association; National Institutes of Health; National Institutes of Health (NIH)/National Center for Research Resources/General Clinical Research Centers Program; North Carolina Biotechnology Center Industrial Fellowship Program; Northeast ALS Consortium (NEALS); NEALS Biofluid Repository Committee FX The project was supported, in part, by support from the following: ALS Association; National Institutes of Health; and National Institutes of Health (NIH)/National Center for Research Resources/General Clinical Research Centers Program. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, or ALS Association. The authors thank the Metabolon platform team and chemical spectra analysts for contributing to data acquisition. Support for MB was received from the North Carolina Biotechnology Center Industrial Fellowship Program.; The authors would also like to acknowledge project input and support from the Northeast ALS Consortium (NEALS), the NEALS Biofluid Repository Committee and the committee Co-Chairs, Robert Bowser and Terry Heiman-Patterson. The authors thank Lucie Bruijn and ALSA for guidance, the NEALS Consortium for sample collection, Daniela Grasso for overseeing protocol development, informed consent design, supervising clinical operations, and research coordination. NR 51 TC 18 Z9 19 U1 0 U2 14 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD SEP PY 2014 VL 15 IS 5-6 BP 362 EP 370 DI 10.3109/21678421.2014.908311 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AN8BY UT WOS:000340827800006 PM 24984169 ER PT J AU Mcelhiney, M Rabkin, JG Goetz, R Katz, J Miller, RG Forshew, DA David, W Cudkowicz, M Glass, JD Appel, S Simpson, E Mitsumoto, H AF Mcelhiney, Martin Rabkin, Judith G. Goetz, Raymond Katz, Jonathan Miller, Robert G. Forshew, Dallas A. David, William Cudkowicz, Merit Glass, Jonathan D. Appel, Stanley Simpson, Ericka Mitsumoto, Hiroshi TI Seeking a measure of clinically meaningful change in ALS SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE Clinically meaningful changes; ALSFRS-R; quality of life ID PATIENT-REPORTED OUTCOMES; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; RATING-SCALE; TRIAL; MULTICENTER; CANCER; TIME AB We sought to identify a method to assess 'clinically meaningful change' perceived by patients, caregivers and clinical raters in relation to changes in ALSFRS-R scores at three-month intervals. In this five-site study, 81 patient-caregiver dyads were interviewed at baseline, three, and six months to assess changes in ALSFRS-R in relation to perceived occurrence of change, its magnitude and impact. Ratings by patients, caregivers and clinical raters were analyzed over three-month intervals within and between respondent groups. We found that patients, clinical raters, and caregivers agreed about 80% of the time about whether change occurred, and in what direction, on each of three visits. The perceived magnitude of change for the four domains measured by the ALSFRS-R was correlated with ratings of impact within respondent groups and across time. We also found moderate associations between changes in ALSFRS-R domain scores and judgments of symptom impact as rated by patient, caregiver and clinical rater. Independent measures (Quality of Life, Goal Assessment Scaling) showed no consistent correlations with ALSFRS-R change scores. In conclusion, the use of scales to assess the perceived magnitude and impact of change corresponding with the domains of the ALSFRS-R may be a step towards understanding of the clinical meaning of changes in that measure. C1 [Mcelhiney, Martin; Rabkin, Judith G.; Goetz, Raymond] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Mcelhiney, Martin; Rabkin, Judith G.; Goetz, Raymond] Columbia Univ, Ctr Med, Dept Psychiat, New York, NY 10027 USA. [Katz, Jonathan; Miller, Robert G.; Forshew, Dallas A.] Calif Pacific Med Ctr, Dept Neurol, New York, NY USA. [David, William; Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Res Inst, Boston, MA 02114 USA. [Glass, Jonathan D.] Emory Univ, Sch Med, Emory ALS Res Ctr, Atlanta, GA 30322 USA. [Appel, Stanley; Simpson, Ericka] Methodist Hosp, Methodist Neurol Inst, New York, NY USA. [Mitsumoto, Hiroshi] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. RP Mcelhiney, M (reprint author), New York State Psychiat Inst & Hosp, New York, NY 10032 USA. EM mcelhin@nyspi.columbia.edu FU NINDS NIH HHS [T32 NS007480] NR 24 TC 3 Z9 3 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD SEP PY 2014 VL 15 IS 5-6 BP 398 EP 405 DI 10.3109/21678421.2014.942668 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AN8BY UT WOS:000340827800011 PM 25124889 ER PT J AU Bozik, ME Mitsumoto, H Brooks, BR Rudnicki, SA Moore, DH Zhang, B Ludolph, A Cudkowicz, ME Van den Berg, LH Mather, J Petzinger, T Archibald, D AF Bozik, Michael E. Mitsumoto, Hiroshi Brooks, Benjamin R. Rudnicki, Stacy A. Moore, Dan H. Zhang, Bing Ludolph, Albert Cudkowicz, Merit E. Van den Berg, Leonard H. Mather, James Petzinger, Thomas, Jr. Archibald, Donald TI A post hoc analysis of subgroup outcomes and creatinine in the phase III clinical trial (EMPOWER) of dexpramipexole in ALS SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE Clinical trials; biomarker; mitochondria; therapy; risk ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MULTIPLE-SCLEROSIS; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; SURVIVAL; MULTICENTER; RILUZOLE; EFFICACY AB Our objective was to compare the phase II and phase III (EMPOWER) studies of dexpramipexole in ALS and evaluate potential EMPOWER responder subgroups and biomarkers based on significant inter-study population differences. In a post hoc analysis, we compared the baseline population characteristics of both dexpramipexole studies and analyzed EMPOWER efficacy outcomes and laboratory measures in subgroups defined by significant inter-study differences. Results showed that, compared with phase II, the proportion of El Escorial criteria (EEC) definite participants decreased (p = 0.005), riluzole use increased (p = 0.002), and mean symptom duration increased (p = 0.037) significantly in EMPOWER. Baseline creatinine (p < 0.001) and on-study creatinine change (p < 0.001) correlated significantly with ALSFRS-R in EMPOWER. In the EMPOWER subgroup defined by EEC-definite ALS, riluzole use, and < median symptom duration (15.3 months), dexpramipexole-treated participants had reduced ALSFRS-R slope decline (p = 0.015), decreased mortality (p = 0.011), and reduced creatinine loss (p = 0.003). In conclusion, significant differences existed between the phase II and EMPOWER study populations in ALS clinical trials of dexpramipexole. In a post hoc analysis of EMPOWER subgroups defined by these differences, potential clinical benefits of dexpramipexole were identified in the subgroup of riluzole-treated, short-symptom duration, EEC-definite ALS participants. Creatinine loss correlated with disease progression and was reduced in dexpramipexole-treated participants, suggesting it as a candidate biomarker. C1 [Bozik, Michael E.; Mather, James; Petzinger, Thomas, Jr.; Archibald, Donald] Knopp Biosci LLC, Pittsburgh, PA 15203 USA. [Mitsumoto, Hiroshi] Columbia Univ, Ctr Med, New York, NY USA. [Brooks, Benjamin R.] Univ N Carolina, Sch Med, Carolinas Neuromuscular ALS MDA Ctr, Carolinas Healthcare Syst, Charlotte, NC 28223 USA. [Rudnicki, Stacy A.] Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. [Moore, Dan H.] Calico Comp, Livermore, CA USA. [Zhang, Bing] MacroStat Inc, Hockessin, DE USA. [Ludolph, Albert] Univ Ulm, D-89069 Ulm, Germany. [Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Res Inst, Boston, MA 02114 USA. [Van den Berg, Leonard H.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, Utrecht, Netherlands. RP Bozik, ME (reprint author), Knopp Biosci LLC, 2100 Wharton St, Pittsburgh, PA 15203 USA. EM michael.bozik@knoppbio.com FU Knopp Biosciences; Biogen Idec FX The phase II and phase III dexpramipexole studies were sponsored by Knopp Biosciences and Biogen Idec, respectively. Knopp Biosciences was involved in the design and conduct (collection/analysis of data) of the phase II dexpramipexole trial and Biogen Idec and Knopp Biosciences were involved in the design and conduct (collection/analysis of data) of the EMPOWER trial. NR 35 TC 16 Z9 17 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD SEP PY 2014 VL 15 IS 5-6 BP 406 EP 413 DI 10.3109/21678421.2014.943672 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AN8BY UT WOS:000340827800012 PM 25125035 ER PT J AU Paganoni, S Macklin, EA Lee, A Murphy, A Chang, J Zipf, A Cudkowicz, M Atassi, N AF Paganoni, Sabrina Macklin, Eric A. Lee, Alexandra Murphy, Alyssa Chang, Judith Zipf, Amanda Cudkowicz, Merit Atassi, Nazem TI Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS) SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE Diagnosis; predictor; delay; timeline ID NEUROLOGY; PATIENT AB The objective of this study was to characterize the diagnostic timelines and their predictors in people with amyotrophic lateral sclerosis (ALS). Patients were identified through ALS billing codes. Time from presenting symptom to first doctor visit, first doctor visit to suspected ALS diagnosis, suspected to confirmed ALS diagnosis, and presenting symptom to confirmed ALS diagnosis (total diagnostic time) were collected. Regression models were used to analyze the predictors of diagnostic delay. Three hundred and four ALS patients were included in the analysis. Median total diagnostic time was 11.5 months. Diagnostic timelines were longer in patients with age > 60 years (p < 0.001), sporadic ALS (p = 0.043), and limb onset (p = 0.010). The presence of fasciculations, slurred speech, and lower extremity weakness when symptoms were first noted were independent predictors of shorter time to ALS diagnosis (p = 0.04, p = 0.02, and p = 0.04, respectively). About half of the patients (52%) received an alternative diagnosis and each patient saw an average of three different physicians before ALS diagnosis was confirmed. In conclusion, diagnostic timelines in ALS are long, and patients see many physicians and receive multiple alternative diagnoses before the diagnosis of ALS is confirmed. Older age, sporadic disease, and limb onset can delay ALS diagnosis. C1 [Paganoni, Sabrina; Lee, Alexandra; Murphy, Alyssa; Chang, Judith; Zipf, Amanda; Cudkowicz, Merit; Atassi, Nazem] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res NCRI,Dept Neurol, Boston, MA 02114 USA. [Paganoni, Sabrina] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Atassi, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res NCRI, 55 Fruit St,Bigelow 1256, Boston, MA 02114 USA. EM natassi@partners.org OI Macklin, Eric/0000-0003-1618-3502 FU Harvard NeuroDiscovery Center FX This study was funded in part by support from the Harvard NeuroDiscovery Center. NR 13 TC 15 Z9 15 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD SEP PY 2014 VL 15 IS 5-6 BP 453 EP 456 DI 10.3109/21678421.2014.903974 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AN8BY UT WOS:000340827800019 PM 24981792 ER PT J AU Badgaiyan, RD Weise, S Wack, DS Melo, MFV AF Badgaiyan, Rajendra D. Weise, Steven Wack, David S. Melo, Marcos F. Vidal TI Attenuation of Regional Cerebral Blood Flow During Memory Processing After Coronary Artery Bypass Surgery SO ANESTHESIA AND ANALGESIA LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; OFF-PUMP; ON-PUMP; MODALITIES; VULNERABILITY; PET AB Reports of memory impairment after cardiac surgery are controversial. To address this controversy, we used positron emission tomography to examine changes in regional cerebral blood flow (rCBF) during memory processing before and after elective coronary artery bypass grafting surgery. In postoperative scans, we observed significantly reduced rCBF in 2 of the most important memory processing areas; the medial temporal lobe (P = 0.023) and the prefrontal cortex (P = 0.002). The results suggest postoperative attenuation of rCBF in brain areas involved in memory processing. These reductions could be used to evaluate severity of memory impairment after coronary artery bypass grafting surgery in patients at risk. C1 [Badgaiyan, Rajendra D.] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. [Weise, Steven] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wack, David S.] SUNY Buffalo, Dept Nucl Med, Buffalo, NY 14260 USA. [Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Melo, Marcos F. Vidal] Harvard Univ, Sch Med, Boston, MA USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM VidalMelo.Marcos@mgh.harvard.edu FU Society of Cardiovascular Anesthesiologists FX This study was funded by a grant of the Society of Cardiovascular Anesthesiologists to Dr. Vidal Melo. NR 24 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2014 VL 119 IS 3 BP 550 EP 553 DI 10.1213/ANE.0000000000000334 PG 4 WC Anesthesiology SC Anesthesiology GA AN6KY UT WOS:000340704600010 PM 24977634 ER PT J AU Cotten, JF AF Cotten, Joseph F. TI The Latest Pharmacologic Ventilator SO ANESTHESIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Cotten, JF (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM jcotten@partners.org FU NHLBI NIH HHS [HL117871, R01 HL117871] NR 6 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2014 VL 121 IS 3 BP 442 EP 444 PG 3 WC Anesthesiology SC Anesthesiology GA AO2YO UT WOS:000341194600002 PM 25222671 ER PT J AU Costa, ELV Melo, MFV AF Vieira Costa, Eduardo Leite Melo, Marcos F. Vidal TI Diaphragmatic Electrical Activity A New Tool to Assess Lung Hyperinflation? SO ANESTHESIOLOGY LA English DT Editorial Material ID END-EXPIRATORY PRESSURE; VENTILATION C1 [Vieira Costa, Eduardo Leite] Univ Sao Paulo, Div Pulm, Heart Inst Incor, Cardiopulm Dept, Sao Paulo, Brazil. [Vieira Costa, Eduardo Leite] Hosp Sirio Libanes, Res & Educ Inst, Sao Paulo, Brazil. [Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Melo, MFV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. EM mvidalmelo@partners.org FU NHLBI NIH HHS [1R01HL121228-01, R01 HL121228] NR 10 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2014 VL 121 IS 3 BP 447 EP 449 PG 3 WC Anesthesiology SC Anesthesiology GA AO2YO UT WOS:000341194600004 PM 25046571 ER PT J AU Tao, GR Zhang, J Zhang, L Dong, YL Yu, BW Crosby, G Culley, DJ Zhang, YY Xie, ZC AF Tao, Guorong Zhang, Jie Zhang, Lei Dong, Yuanlin Yu, Buwei Crosby, Gregory Culley, Deborah J. Zhang, Yiying Xie, Zhongcong TI Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3 beta Activation in Young Mice SO ANESTHESIOLOGY LA English DT Article ID DEVELOPING RAT-BRAIN; ALZHEIMERS-DISEASE; PROTEIN-TAU; TRANSGENIC MICE; EARLY EXPOSURE; MOUSE MODEL; NEUROFIBRILLARY DEGENERATION; MICROGLIAL ACTIVATION; COGNITIVE-IMPAIRMENT; PHOSPHATASE-ACTIVITY AB Background: Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane is a commonly used anesthetic in children. Tau phosphorylation contributes to cognitive dysfunction. The authors therefore assessed the effects of sevoflurane on Tau phosphorylation and the underlying mechanisms in young mice. Methods: Six-day-old wild-type and Tau knockout mice were exposed to sevoflurane. The authors determined the effects of sevoflurane anesthesia on Tau phosphorylation, levels of the kinases and phosphatase related to Tau phosphorylation, interleukin-6 and postsynaptic density protein-95 in hippocampus, and cognitive function in both young wild-type and Tau knockout mice. Results: Anesthesia with 3% sevoflurane 2 h daily for 3 days induced Tau phosphorylation (257 vs. 100%, P = 0.0025, n = 6) and enhanced activation of glycogen synthase kinase 3 beta, which is the kinase related to Tau phosphorylation in the hippocampus of postnatal day-8 wild-type mice. The sevoflurane anesthesia decreased hippocampus postsynaptic density protein-95 levels and induced cognitive impairment in the postnatal day-31 mice. Glycogen synthase kinase 3 beta inhibitor lithium inhibited the sevoflurane-induced glycogen synthase kinase 3 beta activation, Tau phosphorylation, increased levels of interleukin-6, and cognitive impairment in the wild-type young mice. Finally, the sevoflurane anesthesia did not induce an increase in interleukin-6 levels, reduction in postsynaptic density protein-95 levels in hippocampus, or cognitive impairment in Tau knockout young mice. Conclusions: These data suggested that sevoflurane induced Tau phosphorylation, glycogen synthase kinase 3 beta activation, increase in interleukin-6 and reduction in postsynaptic density protein-95 levels in hippocampus of young mice, and cognitive impairment in the mice. Future studies will dissect the cascade relation of these effects. C1 [Tao, Guorong; Zhang, Jie; Zhang, Lei; Dong, Yuanlin; Zhang, Yiying; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Tao, Guorong; Zhang, Jie; Zhang, Lei; Dong, Yuanlin; Zhang, Yiying; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Tao, Guorong; Yu, Buwei] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Anesthesiol, Shanghai 200030, Peoples R China. [Zhang, Jie] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Anesthesiol, Wuhan 430074, Peoples R China. [Zhang, Lei] Tongji Univ, Sch Med, East Hosp, Dept Anesthesiol, Shanghai 200092, Peoples R China. [Crosby, Gregory; Culley, Deborah J.] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Crosby, Gregory; Culley, Deborah J.] Harvard Univ, Sch Med, Boston, MA USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@mgh.harvard.edu FU National Institutes of Health, Bethesda, Maryland [R21AG038994, R01 GM088801, R01 AG041274]; Alzheimer's Association, Chicago, Illinois; Cure Alzheimer's Fund, Wellesley, Massachusetts; National Institutes of Health [R01 GM088817] FX This research was supported by grant nos. R21AG038994, R01 GM088801, and R01 AG041274 from the National Institutes of Health, Bethesda, Maryland; Investigator-initiated Research Grant from Alzheimer's Association, Chicago, Illinois; and Cure Alzheimer's Fund, Wellesley, Massachusetts (to Dr. Xie); and was partially supported by grant no. R01 GM088817 (to Dr. Crosby) from the National Institutes of Health. Anesthetic sevoflurane was generously provided by the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. NR 75 TC 12 Z9 14 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2014 VL 121 IS 3 BP 510 EP 527 PG 18 WC Anesthesiology SC Anesthesiology GA AO2YO UT WOS:000341194600011 PM 24787352 ER PT J AU Permaul, P Kanchongkittiphon, W Phipatanakul, W AF Permaul, Perdita Kanchongkittiphon, Watcharoot Phipatanakul, Wanda TI Childhood asthma and obesity-what is the true link? SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID BODY-MASS INDEX; AIRWAY INFLAMMATION; INCIDENT ASTHMA; CHILDREN; ADOLESCENTS; PREVALENCE; PREGNANCY; ASSOCIATION; OVERWEIGHT; LEPTIN C1 [Permaul, Perdita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Permaul, Perdita; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Kanchongkittiphon, Watcharoot; Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA. RP Permaul, P (reprint author), Massachusetts Gen Hosp, Div Pediat Allergy & Immunol, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM ppermaul@partners.org FU NIH [R01 AI 073964, R01AI 073964-02S1, K24 AI 106822, U10HL098102]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award) [UL1 TR001102]; Harvard University FX This study was supported by NIH grants R01 AI 073964, R01AI 073964-02S1, K24 AI 106822 and U10HL098102 ( PI: Phipatanakul). This work was conducted with the support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, the National Center for Research Resources, or the National Institutes of Health. NR 28 TC 11 Z9 11 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD SEP PY 2014 VL 113 IS 3 BP 244 EP 246 DI 10.1016/j.anai.2014.07.001 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA AO4IU UT WOS:000341301500003 PM 25091715 ER PT J AU Chawla, N Yabroff, KR Mariotto, A McNeel, TS Schrag, D Warren, JL AF Chawla, Neetu Yabroff, K. Robin Mariotto, Angela McNeel, Timothy S. Schrag, Deborah Warren, Joan L. TI Limited validity of diagnosis codes in Medicare claims for identifying cancer metastases and inferring stage SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Cancer; Metastasis; SEER; Registry; Medicare claims; Stage at diagnosis ID BREAST-CANCER; LUNG-CANCER; SURVIVAL; IDENTIFICATION; CHEMOTHERAPY; RECURRENCE; ALGORITHM; GEORGIA; DISEASE; UTILITY AB Purpose: Researchers are using diagnosis codes from health claims to identify metastatic disease in cancer patients. The validity of this approach has not been established. Methods: We used the linked 2005-2007 Surveillance, Epidemiology and End Results (SEER)-Medicare data to assess the validity of metastasis codes at diagnosis from claims compared with stage reported by SEER cancer registries. The cohort included 80,052 incident breast, lung, and colorectal cancer patients aged 65 years and older. Using gold-standard SEER data, we evaluated sensitivity, specificity, positive predictive value, and negative predictive value of claims-based stage, survival by stage classification, and patient factors associated with stage misclassification using multivariable regression. Results: For patients with a registry report of distant metastatic cancer, the sensitivity, specificity, and positive predictive value of claims never simultaneously exceeded 80% for any cancer: lung (42.7%, 94.8%, and 88.1%), breast (51.0%, 98.3%, and 65.8%), and Colorectal (72.8%, 93.8%, and 68.5%). Misclassification of stage from Medicare claims was significantly associated with inaccurate estimates of stage-specific survival (P < .001). In adjusted analysis, patients who were older, black, or living in low-income areas were more likely to have their stage misclassified in claims. Conclusions: Diagnosis codes in Medicare claims have limited validity for inferring cancer stage and metastatic disease. Published by Elsevier Inc. C1 [Chawla, Neetu] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Chawla, Neetu; Yabroff, K. Robin; Warren, Joan L.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Mariotto, Angela] NCI, Data Modeling Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [McNeel, Timothy S.] Informat Management Serv Inc, Calverton, MD USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chawla, N (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Rockville, MD 20850 USA. EM neetu.chawla@nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 FU Intramural NIH HHS [Z99 CA999999] NR 27 TC 7 Z9 7 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2014 VL 24 IS 9 BP 666 EP 672 DI 10.1016/j.annepidem.2014.06.099 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AN8OX UT WOS:000340864600007 PM 25066409 ER PT J AU Serpell, J Sidhu, S Vallance, N Panizza, B Randolph, G AF Serpell, Jonathan Sidhu, Stan Vallance, Neil Panizza, Ben Randolph, Gregory TI Consensus statement on intra-operative electrophysiological recurrent laryngeal nerve monitoring during thyroid surgery SO ANZ JOURNAL OF SURGERY LA English DT Editorial Material ID RISK-FACTORS; PALSY; IDENTIFICATION; INJURY C1 [Serpell, Jonathan; Sidhu, Stan] Australian & New Zealand Endocrine Surg, St Leonards, NSW, Australia. [Vallance, Neil] Australian Soc Otolaryngol Head & Neck Surg, St Leonards, NSW, Australia. [Panizza, Ben] Australian & New Zealand Head & Neck Canc Soc, St Leonards, NSW, Australia. [Randolph, Gregory] Massachusetts Eye & Ear Infirm, Div Thyroid, Boston, MA 02114 USA. [Randolph, Gregory] Massachusetts Eye & Ear Infirm, Parathyroid Surg Div, Boston, MA 02114 USA. [Randolph, Gregory] Massachusetts Gen Hosp, Div Surg Oncol & Endocrine Surg, Boston, MA 02114 USA. [Randolph, Gregory] Harvard Univ, Sch Med, Boston, MA USA. RP Serpell, J (reprint author), Australian & New Zealand Endocrine Surg, St Leonards, NSW, Australia. RI Panizza, Benedict/G-6590-2012 NR 17 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1445-1433 EI 1445-2197 J9 ANZ J SURG JI ANZ J. Surg. PD SEP PY 2014 VL 84 IS 9 BP 603 EP 604 DI 10.1111/ans.12590 PG 2 WC Surgery SC Surgery GA AO3RJ UT WOS:000341252000004 PM 25302349 ER PT J AU Lim, S Meigs, JB AF Lim, Soo Meigs, James B. TI Links Between Ectopic Fat and Vascular Disease in Humans SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE body fat distribution; cardiovascular diseases; fatty liver; insulin resistance; intra-abdominal fat ID TYPE-2 DIABETIC-PATIENTS; VISCERAL ADIPOSE-TISSUE; ANGIOTENSIN-ALDOSTERONE SYSTEM; HEPATIC INSULIN-RESISTANCE; IMPAIRED GLUCOSE-TOLERANCE; CORONARY-ARTERY-DISEASE; OBSTRUCTIVE SLEEP-APNEA; METABOLIC RISK-FACTORS; CHRONIC KIDNEY-DISEASE; C-REACTIVE PROTEIN AB The average of overweight individual can have differential fat depots in target organs or specific compartments of the body. This ectopic fat distribution may be more of a predictive factor for cardiovascular risk than obesity. Abdominal visceral obesity, a representative ectopic fat, is robustly associated with insulin resistance and cardiovascular risk. Fat depots in the liver and muscle tissue cause adverse cardiometabolic risk by affecting glucose and lipid metabolism. Pericardial fat and perivascular fat affect coronary atherosclerosis, cardiac function, and hemodynamics. Fat around the neck is associated with systemic vascular resistance. Fat around the kidney may increase blood pressure and induce albuminuria. Fat accumulation in or around the pancreas alters glucose metabolism, conferring cardiovascular risk. Ectopic fat may act as an active endocrine and paracrine organ that releases various bioactive mediators that influence insulin resistance, glucose and lipid metabolism, coagulation, and inflammation, which all contribute to cardiovascular risk. Because both obese and apparently lean individuals can have ectopic fat, regional fat distribution may play an important role in the development of cardiovascular diseases in both nonobese and obese people. C1 [Lim, Soo] Seoul Natl Univ, Bundang Hosp, Coll Med, Dept Internal Med, Songnam, South Korea. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. RP Meigs, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA. EM jmeigs@partners.org FU [K24 DK080140] FX J.B. Meigs is supported by K24 DK080140. NR 107 TC 28 Z9 30 U1 1 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2014 VL 34 IS 9 BP 1820 EP 1826 DI 10.1161/ATVBAHA.114.303035 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AN8UX UT WOS:000340881600010 PM 25035342 ER PT J AU Subramanian, S Liu, CY Aviv, A Ho, JE Courchesne, P Muntendam, P Larson, MG Cheng, S Wang, TJ Mehta, NN Levy, D AF Subramanian, Subha Liu, Chunyu Aviv, Abraham Ho, Jennifer E. Courchesne, Paul Muntendam, Pieter Larson, Martin G. Cheng, Susan Wang, Thomas J. Mehta, Nehal N. Levy, Daniel TI Stromal Cell-Derived Factor 1 as a Biomarker of Heart Failure and Mortality Risk SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cardiovascular diseases; chemokine CXCL12; epidemiology; heart failure; mortality; myocardial infarction; stem cells ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; ENDOTHELIAL PROGENITOR CELLS; TELOMERE LENGTH; FACTOR-I; ATHEROSCLEROSIS; NUMBER; BLOOD; POPULATION; EXPRESSION AB Objective-CXCL12 encodes stromal cell-derived factor 1 alpha (SDF-1), which binds to the receptor encoded by CXCR4. Variation at the CXCL12 locus is associated with coronary artery disease and endothelial progenitor cell numbers, whereas variation at the CXCR4 locus is associated with leukocyte telomere length, which has been shown to be associated with coronary artery disease. Therefore, we examined the relationships of plasma SDF-1 levels to cardiovascular disease (CVD)-related outcomes, risk factors, leukocyte telomere length, and endothelial progenitor cells. Approach and Results-SDF-1 was measured in 3359 Framingham Heart Study participants. We used Cox regression to examine relationships of SDF-1 to new-onset CVD, myocardial infarction, heart failure, and all-cause mortality; we used linear regression to evaluate associations of SDF-1 with risk factors, leukocyte telomere length, and CD34+ cell phenotypes. In multivariable models, higher SDF-1 levels were associated with older age, lower levels of high-density lipoprotein-cholesterol and cigarette smoking. Higher SDF-1 levels were associated with lower CD34+ cell frequency (P=0.02) but not with leukocyte telomere length. During follow-up (median, 9.3 years), there were 263 new-onset CVD events, 160 myocardial infarctions, 200 heart failure events, and 385 deaths. After adjusting for clinical risk factors, SDF-1 levels were associated with heart failure (P=0.04) and all-cause mortality (P=0.003) but not with CVD (P=0.39) or myocardial infarction (P=0.10). The association of SDF-1 levels with myocardial infarction was attenuated after adjustment for high-density lipoprotein-cholesterol. Conclusions-After adjusting for traditional CVD risk factors, SDF-1 is associated with heart failure and all-cause mortality risk. Additional studies are needed to determine whether measurement of SDF-1 levels has clinical use. C1 [Subramanian, Subha; Liu, Chunyu; Ho, Jennifer E.; Courchesne, Paul; Larson, Martin G.; Cheng, Susan; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Subramanian, Subha; Liu, Chunyu; Courchesne, Paul; Levy, Daniel] NHLBI, Populat Sci Branch, Bethesda, MD 20892 USA. [Subramanian, Subha; Liu, Chunyu; Courchesne, Paul; Mehta, Nehal N.; Levy, Daniel] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Aviv, Abraham] Rutgers State Univ, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07102 USA. [Ho, Jennifer E.; Levy, Daniel] Boston Univ, Med Ctr, Cardiovasc Med Sect, Dept Med, Boston, MA 02215 USA. [Muntendam, Pieter] BG Med Inc, Waltham, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Cheng, Susan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. [Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA. RP Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM levyd@nih.gov OI Ho, Jennifer/0000-0002-7987-4768 FU National Institutes of Health (NIH) [N01-HC-25195]; Division of Intramural Research of the National Heart, Lung, and Blood Institute; NIH [R01AG030678, R01HD071180] FX The Framingham Heart Study of the National Heart, Lung, and Blood Institute is funded by National Institutes of Health (NIH) contract N01-HC-25195; the Division of Intramural Research of the National Heart, Lung, and Blood Institute also supported this research. The research of Dr Aviv was supported by NIH grants R01AG030678 and R01HD071180. NR 23 TC 17 Z9 17 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2014 VL 34 IS 9 BP 2100 EP 2105 DI 10.1161/ATVBAHA.114.303579 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AN8UX UT WOS:000340881600043 PM 25060794 ER PT J AU Duong, HK Savani, BN Copelan, E Devine, S Costa, LJ Wingard, JR Shaughnessy, P Majhail, N Perales, MA Cutler, CS Bensinger, W Litzow, MR Mohty, M Champlin, RE Leather, H Giralt, S Carpenter, PA AF Duong, Hien K. Savani, Bipin N. Copelan, Ed Devine, Steven Costa, Luciano J. Wingard, John R. Shaughnessy, Paul Majhail, Navneet Perales, Miguel-Angel Cutler, Corey S. Bensinger, William Litzow, Mark R. Mohty, Mohamad Champlin, Richard E. Leather, Helen Giralt, Sergio Carpenter, Paul A. TI Peripheral Blood Progenitor Cell Mobilization for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Peripheral blood; Progenitor cell mobilization; Hematopoietic transplantation ID COLONY-STIMULATING FACTOR; NON-HODGKINS-LYMPHOMA; LARGE-VOLUME LEUKAPHERESIS; VERSUS-HOST-DISEASE; IDENTICAL SIBLING TRANSPLANTATION; SINGLE-CENTER EXPERIENCE; HIGH-DOSE CHEMOTHERAPY; FACTOR G-CSF; PLUS G-CSF; STEM-CELLS AB Peripheral blood progenitor cell mobilization practices vary significantly among institutions. Effective mobilization regimens include growth factor alone, chemotherapy and growth factor combined, and, more recently, incorporation of plerixafor with either approach. Many institutions have developed algorithms to improve stem cell mobilization success rates and cost-effectiveness. However, an optimal stem cell mobilization regimen has not been defined. Practical guidelines are needed to address important clinical questions, including which growth factor is optimal, what chemotherapy and dose is most effective, and when to initiate leukapheresis. We present recommendations, based on a comprehensive review of the literature, from the American Society of Blood and Marrow Transplantation. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [Duong, Hien K.; Majhail, Navneet] Cleveland Clin Fdn, Blood & Marrow Transplant Program, Dept Blood & Marrow Transplant, Cleveland, OH 44195 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA. [Copelan, Ed] Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA. [Devine, Steven] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Costa, Luciano J.] Med Univ S Carolina, Dept Med, Div Hematol & Oncol, Charleston, SC 29425 USA. [Wingard, John R.; Leather, Helen] Univ Florida, Hlth Canc Ctr, Div Hematol Oncol, Gainesville, FL USA. [Shaughnessy, Paul] Texas Transplant Inst, Dept Adult Bone Marrow Transplant, San Antonio, TX USA. [Perales, Miguel-Angel; Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, New York, NY 10021 USA. [Perales, Miguel-Angel; Giralt, Sergio] Weill Cornell Med Coll, New York, NY USA. [Cutler, Corey S.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Bensinger, William; Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Litzow, Mark R.] Mayo Clin, Div Palliat Med, Div Hematol, Rochester, MN USA. [Mohty, Mohamad] St Antoine Hosp, Dept Haematol, Paris, France. [Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX 77030 USA. RP Duong, HK (reprint author), Cleveland Clin Fdn, Blood & Marrow Transplant Program, 9500 Euclid Ave,Desk R25, Cleveland, OH 44195 USA. EM duongh@ccf.org OI Shaughnessy, Paul/0000-0003-4023-3864 FU Sanofi; Celgene; Amgen; Chugai FX H.K.D. has received research support from Sanofi and Celgene and is on the Speaker's Bureau for Sanofi and Celgene. W.B. has received research support from Amgen and has consulted for Amgen. S.D. has received research support from Sanofi. M.M. has received honoraria and research support from Amgen, Chugai, and Sanofi, whose products are discussed in this work. L.J.C. has received research support for Onyx, Celgene, BMS, and Novartis; has consulted for Onyx and Sanofi; and is on the Speaker's Bureau for Sanofi. M.A.P. has consulted for Sanofi. P.S. is on Speaker's Bureau and has served on Advisory Board for Sanofi and is on Speaker's Bureau for Millenium. NR 114 TC 26 Z9 28 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2014 VL 20 IS 9 BP 1262 EP 1273 DI 10.1016/j.bbmt.2014.05.003 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AO0GD UT WOS:000340986200003 PM 24816581 ER PT J AU El-Jawahri, A Pidala, J Inamoto, Y Chai, XY Khera, N Wood, WA Cutler, C Arora, M Carpenter, PA Palmer, J Flowers, M Weisdorf, D Pavletic, S Jaglowski, S Jagasia, M Lee, SJ Chen, YB AF El-Jawahri, Areej Pidala, Joseph Inamoto, Yoshi Chai, Xiaoyu Khera, Nandita Wood, William A. Cutler, Corey Arora, Mukta Carpenter, Paul A. Palmer, Jeanne Flowers, Mary Weisdorf, Daniel Pavletic, Steven Jaglowski, Samantha Jagasia, Madan Lee, Stephanie J. Chen, Yi-Bin TI Impact of Age on Quality of Life, Functional Status, and Survival in Patients with Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Quality-of-life; Functional status; Chronic graft-versus-host disease; Age ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELL TRANSPLANTATION; HEALTH SURVEY SF-36; HEMATOLOGIC MALIGNANCIES; RISK-ASSESSMENT; PATIENTS OLDER; SCALE; CYTOGENETICS; VALIDATION AB Although older patients undergoing allogeneic hematopoietic stem cell transplantation (HCT) may experience higher morbidity, the impact of chronic graft-versus-host disease (GVHD) on quality of life (QOL) and survival outcomes for older compared with younger patients is currently unknown. We utilized data of patients with moderate or severe chronic GVHD (N = 522, 1661 follow-up visits, a total of 2183 visits) from the Chronic GVHD Consortium, a prospective observational multicenter cohort. We examined the relationship between age group (adolescent and young adult, "AYA," 18 to 40 years; "middle-aged," 41 to 59 years; and "older," >= 60 years) and QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT]), physical functioning (Human Activity Profile [HAP]), functional status (2-minute walk test [2MWT]), nonrelapse mortality, and overall survival. Because of multiple testing, P values < .01 were considered significant. This study included 115 (22%) AYA, 279 (53%) middle-aged, and 128 (25%) older patients with moderate (58%) or severe (42%) chronic GVHD. Despite more physical limitations in older patients as measured by worse functional status (shorter 2MWT [P < .001] and lower HAP scores [P < .001]) relative to AYA and middle-aged patients, older patients reported better QOL (FACT-BMT, P = .004) compared with middle-aged patients and similar to AYA patients (P = .99). Nonrelapse mortality and overall survival were similar between the age groups. Therefore, despite higher physical and functional limitations, older patients who are selected to undergo HSCT and survive long enough to develop moderate or severe chronic GVHD have preserved QOL and similar overall survival and nonrelapse mortality when compared with younger patients. Therefore, we did not find evidence that older age is associated with worse outcomes in patients with moderate or severe chronic GVHD. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [El-Jawahri, Areej; Chen, Yi-Bin] Massachusetts Gen Hosp, Ctr Canc, Div Bone Marrow Transplantat, Boston, MA 02114 USA. [El-Jawahri, Areej; Chen, Yi-Bin] Harvard Univ, Sch Med, Boston, MA USA. [Pidala, Joseph] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Inamoto, Yoshi; Chai, Xiaoyu; Carpenter, Paul A.; Flowers, Mary; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Khera, Nandita] Mayo Clin, Div Hematol Oncol, Phoenix, AZ USA. [Wood, William A.] Univ North Carolina Hosp, Linenberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Arora, Mukta; Weisdorf, Daniel] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Palmer, Jeanne] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA. [Pavletic, Steven] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Jaglowski, Samantha] Ohio State Univ, Med Ctr, Div Hematol Oncol, Columbus, OH 43210 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplant Program, Nashville, TN USA. RP El-Jawahri, A (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, 12 N Grove St,Lawrence House,Second Floor, Boston, MA 02114 USA. EM ael-jawahri@partners.org OI Wood, William/0000-0001-7439-2543 FU National Institutes of Health [CA118953, CA163438]; NIH Office of Rare Diseases Research at the National Center for Advancing Translational Sciences; National Cancer Institute; Fred Hutchinson Cancer Research Center FX This work was supported by grants CA118953 and CA163438 from the National Institutes of Health. The Chronic GVHD Consortium (U54 CA163438) is a part of the NIH Rare Diseases Clinical Research Network, supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Sciences, the National Cancer Institute, and the Fred Hutchinson Cancer Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 37 TC 8 Z9 8 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2014 VL 20 IS 9 BP 1341 EP 1348 DI 10.1016/j.bbmt.2014.05.001 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AO0GD UT WOS:000340986200013 PM 24813171 ER PT J AU Sobecks, RM Leis, JF Gale, RP Ahn, KW Zhu, XC Sabloff, M de Lima, M Brown, JR Inamoto, Y Hale, GA Aljurf, MD Kamble, RT Hsu, JW Pavletic, SZ Wirk, B Seftel, MD Lewis, ID Alyea, EP Cortes, J Kalaycio, ME Maziarz, RT Saber, W AF Sobecks, Ronald M. Leis, Jose F. Gale, Robert Peter Ahn, Kwang Woo Zhu, Xiaochun Sabloff, Mitchell de Lima, Marcos Brown, Jennifer R. Inamoto, Yoshihiro Hale, Gregory A. Aljurf, Mahmoud D. Kamble, Rammurti T. Hsu, Jack W. Pavletic, Steven Z. Wirk, Baldeep Seftel, Matthew D. Lewis, Ian D. Alyea, Edwin P. Cortes, Jorge Kalaycio, Matt E. Maziarz, Richard T. Saber, Wael TI Outcomes of Human Leukocyte Antigen-Matched Sibling Donor Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia: Myeloablative Versus Reduced-Intensity Conditioning Regimens SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic lymphocytic leukemia; Reduced-intensity conditioning; Myeloablative allogeneic hematopoietic cell transplantation; Outcomes ID VERSUS-HOST-DISEASE; MARROW TRANSPLANTATION; FOLLOW-UP; INTERNATIONAL-BLOOD; CLL3X TRIAL; GRAFT; FLUDARABINE; RITUXIMAB AB Allogeneic hematopoietic cell transplantation (HCT) can cure some chronic lymphocytic leukemia (CLL) subjects. This study compared outcomes of myeloablative (MA) and reduced-intensity conditioning (RIC) transplants from HLA-matched sibling donors (MSD) for CLL. From 1995 to 2007, information regarding 297 CLL subjects was reported to the Center of International Blood and Marrow Transplant Research; of these, 163 underwent MA and 134 underwent RIC MSD HCT. The MA subjects underwent transplantation less often after 2000 and less commonly received antithymocyte globulin (4% versus 13%, P = .004) or prior antibody therapy (14% versus 53%; P < .001). RIC was associated with a greater likelihood of platelet recovery and less grade 2 to 4 acute graft-versus-host disease compared with MA conditioning. One- and 5-year treatment-related mortality (TRM) were 24% (95% confidence intervals [CI], 16% to 33%) versus 37% (95% Cl, 30% to 45%; P = .023), and 40% (95% Cl, 29% to 51%) versus 54% (95% Cl, 46% to 62%; P = .036), respectively, and the relapse/progression rates at 1 and 5 years were 21% (95% Cl, 14% to 29%) versus 10% (95% Cl, 6% to 15%; P = .020), and 35% (95% Cl, 26% to 46%) versus 17% (95% CI, 12% to 24%; P = .003), respectively. MA conditioning was associated with better progression-free (PFS) (relative risk, .60; 95% CI, .37 to .97; P = .038) and 3-year survival in transplantations before 2001, but for subsequent years, RIC was associated with better PFS and survival (relative risk, 1.49 [95% CI, .92 to 2.421; P = .10; and relative risk, 1.86 [95% Cl, 1.11 to 3.13]; P = .019). Pretransplantation disease status was the most important predictor of relapse (P = .003) and PFS (P = .0007) for both forms of transplantation conditioning. MA and RIC MSD transplantations are effective for CLL. Future strategies to decrease TRM and reduce relapses are warranted. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [Sobecks, Ronald M.; Kalaycio, Matt E.] Cleveland Clin, Taussig Canc Inst, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. [Leis, Jose F.] Mayo Clin Arizona, Dept Hematol Oncol, Phoenix, AZ USA. [Leis, Jose F.] Phoenix Childrens Hosp, Phoenix, AZ USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Hematol Res Ctr, Dept Med, Div Expt Med, London, England. [Ahn, Kwang Woo; Zhu, Xiaochun; Saber, Wael] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ahn, Kwang Woo] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Sabloff, Mitchell] Univ Ottawa, Dept Med, Div Hematol, Ottawa, ON, Canada. [Sabloff, Mitchell] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [de Lima, Marcos] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Inamoto, Yoshihiro] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, Dept Hematol Oncol, St Petersburg, FL 33701 USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia. [Kamble, Rammurti T.] Baylor Coll Med, Dept Hematol Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Hsu, Jack W.] Shands HealthCare, Dept Med, Div Hematol & Oncol, Gainesville, FL USA. [Hsu, Jack W.] Univ Florida, Gainesville, FL USA. [Pavletic, Steven Z.] NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Wirk, Baldeep] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Seftel, Matthew D.] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada. [Lewis, Ian D.] Royal Adelaide Hosp, Adelaide, SA 5000, Australia. [Alyea, Edwin P.; Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Leukemia, Houston, TX 77030 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. RP Sobecks, RM (reprint author), Cleveland Clin, Taussig Canc Inst, Dept Hematol & Med Oncol, 9500 Euclid Ave,R35, Cleveland, OH 44195 USA. EM sobeckr@ccf.org FU National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. NR 35 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2014 VL 20 IS 9 BP 1390 EP 1398 DI 10.1016/j.bbmt.2014.05.020 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AO0GD UT WOS:000340986200020 PM 24880021 ER PT J AU Torlen, J Ringden, O Le Rademacher, J Batiwalla, M Chen, JF Erkers, T Ho, V Kebriaei, P Keever-Taylor, C Kindwall-Keller, T Lazarus, HM Laughlin, MJ Lill, M O'Brien, T Perales, MA Rocha, V Savani, BN Szwajcer, D Valcarcel, D Eapen, M AF Torlen, Johan Ringden, Olle Le Rademacher, Jennifer Batiwalla, Minoo Chen, Junfang Erkers, Tom Ho, Vincent Kebriaei, Partow Keever-Taylor, Carolyn Kindwall-Keller, Tamila Lazarus, Hillard M. Laughlin, Mary J. Lill, Michael O'Brien, Tracey Perales, Miguel-Angel Rocha, Vanderson Savani, Bipin N. Szwajcer, David Valcarcel, David Eapen, Mary TI Low CD34 Dose Is Associated with Poor Survival after Reduced-Intensity Conditioning Allogeneic Transplantation for Acute Myeloid Leukemia and Myelodygplastic Syndrome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Cellular content; Peripheral blood graft; Hematological malignancy ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; PERIPHERAL-BLOOD; BONE-MARROW; RISK-FACTORS; UNRELATED DONORS; CHRONIC GRAFT; OUTCOMES; ENGRAFTMENT; RELAPSE AB Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34(+) dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34(+) dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4 x 10(6) CD34(+)/kg was associated with higher nonrelapse mortality (hazard ratio [HR], 2.03; P = .001), overall mortality (HR, 1.48; P = .008), and lower neutrophil (odds ratio [OR], .76; P = .03) and platelet (OR, .76; P = .03) recovery. PBPC from unrelated donors with CD34(+) dose <6 x 10(6) CD34(+)/kg was also associated with higher nonrelapse (HR, 1.38; P = .02) and overall mortality (HR, 1.20; P = .05). In contrast to reports after myeloablative HCT, CD34(+) dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34(+) doses >4 x 10(6) CD34(+)/kg and >6 x 10(6) CD34(+)/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [Torlen, Johan; Ringden, Olle] Karolinska Univ Hosp Huddinge, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Ringden, Olle; Erkers, Tom] Karolinska Inst, Div Therapeut Immunol, Stockholm, Sweden. [Le Rademacher, Jennifer] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Le Rademacher, Jennifer; Chen, Junfang; Eapen, Mary] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Batiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Ho, Vincent] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Kebriaei, Partow] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Keever-Taylor, Carolyn; Eapen, Mary] Med Coll Wisconsin, Dept Med, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Kindwall-Keller, Tamila] Univ Virginia Hlth Syst, Div Hematol Oncol, Charlottesville, VA USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Laughlin, Mary J.] Novartis Pharmaceut Inc, Stem Cell Therapeut Program, E Hanover, NJ USA. [Lill, Michael] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [O'Brien, Tracey] Sydney Childrens Hosp, Ctr Childrens Canc & Blood Disorders, Sydney, NSW, Australia. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, Dept Med, Bone Marrow Transplant Serv, New York, NY 10021 USA. [Rocha, Vanderson] Oxford Univ Hosp, Churchill Hosp, Dept Clin Haematol, Oxford, England. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Szwajcer, David] Univ Manitoba, Dept Hematol, Winnipeg, MB, Canada. [Valcarcel, David] Hosp Valle De Hebron, Dept Hematol, Barcelona, Spain. RP Eapen, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. EM meapen@mcw.edu FU National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID) [U24-CA076518]; NHLBI [5U10HL069294]; National Cancer Institute; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad Pharmaceuticals; Be The Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Terumo BCT; Teva Neuroscience, Inc.; Texas Instruments Inc.; WellPoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) U24-CA076518; a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and National Cancer Institute; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad Pharmaceuticals; Be The Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *Terumo BCT; *Teva Neuroscience, Inc.; *Texas Instruments Inc.; and *WellPoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government. NR 29 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2014 VL 20 IS 9 BP 1418 EP 1425 DI 10.1016/j.bbmt.2014.05.021 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AO0GD UT WOS:000340986200023 PM 24892261 ER PT J AU Sood, A Trinh, QD AF Sood, Akshay Quoc-Dien Trinh TI Perioperative aspirin: To give or not to give? SO BJU INTERNATIONAL LA English DT Editorial Material ID SURGERY C1 [Sood, Akshay] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg,Med Sch, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Surg & Publ Hlth,Med Sch, Boston, MA 02115 USA. RP Sood, A (reprint author), Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. EM trinh.qd@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD SEP PY 2014 VL 114 IS 3 BP 318 EP 319 DI 10.1111/bju.12525 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA AO3OI UT WOS:000341241000004 PM 25156500 ER PT J AU Greaney, ML Puleo, E Sprunck-Harrild, K Syngal, S Suarez, EG Emmons, KM AF Greaney, Mary L. Puleo, Elaine Sprunck-Harrild, Kim Syngal, Sapna Suarez, Elizabeth Gonzalez Emmons, Karen M. TI Changes in colorectal cancer screening intention among people aged 18-49 in the United States SO BMC PUBLIC HEALTH LA English DT Article DE Colorectal cancer; Cancer screening; Screening intentions; Low-income population ID SOCIODEMOGRAPHICALLY-DIVERSE ADULTS; SERVICES TASK-FORCE; LOW-INCOME; ETHNIC DISPARITIES; RANDOMIZED-TRIAL; SOCIAL-CONTEXT; WORKING-CLASS; POPULATION; HEALTH; OLDER AB Background: To determine whether exposure to a peer-led intervention focused on colorectal cancer (CRC) screening, physical activity, and multi-vitamin intake can lead to increased intentions to be screened for CRC once age eligible among adults under the age of 50. Methods: Participants were residents of low-income housing sites, and CRC screening intentions were assessed at baseline and at follow-up (approximately 2 years later) to determine changes in screening intentions and factors associated with changes in intentions. Results: Participants (n = 692) were 78.4% female, 42.6% Hispanic and 50.8% black. At follow-up, 51% maintained their intention to be screened and 14.6% newly intended to get screened. Individuals newly intending to get screened were more likely to have participated in the intervention, be older, male, and born in Puerto Rico or the United States compared to those who maintained their intention not to get screened (p < 0.05). Conclusion: Exposure to CRC prevention messages before the age of 50 can increase screening intentions among individuals who did not initially intend to get screened. Peer-led interventions to promote CRC screening should include individual less than 50 years of age, as this may contribute to increased screening at the recommended age threshold. C1 [Greaney, Mary L.] Univ Rhode Isl, Kingston, RI 02881 USA. [Greaney, Mary L.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. [Puleo, Elaine] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Sprunck-Harrild, Kim; Suarez, Elizabeth Gonzalez; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02215 USA. [Syngal, Sapna] Brigham & Womens Hosp, Boston, MA 02215 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Greaney, ML (reprint author), Univ Rhode Isl, 25 West Independence Way, Kingston, RI 02881 USA. EM mgreaney@mail.uri.edu FU NIH [R01 CA098864, 1K05 CA124415, K24CA11343] FX This research was supported by grants from NIH (R01 CA098864, 1K05 CA124415). Sapna Syngal, MD was supported by supported by NIH Grant K24CA11343. We would like to thank all the individuals who participated in the Open Doors to Health Study. Additionally, we would like to thank Serena Houghton University of Massachusetts, School of Public Health and Health Sciences, for her statistical support. NR 38 TC 0 Z9 0 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD SEP 1 PY 2014 VL 14 AR 901 DI 10.1186/1471-2458-14-901 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO3CG UT WOS:000341205300001 PM 25179871 ER PT J AU Mahal, BA Ziehr, DR Hyatt, AS Neubauer-Sugar, EH O'Farrell, DA O'Leary, MP Steele, GS Niedermayr, TR Beard, CJ Martin, NE Orio, PF D'Amico, AV Devlin, PM Nguyen, PL AF Mahal, Brandon A. Ziehr, David R. Hyatt, Andrew S. Neubauer-Sugar, Emily H. O'Farrell, Desmond A. O'Leary, Michael P. Steele, Graeme S. Niedermayr, Thomas R. Beard, Clair J. Martin, Neil E. Orio, Peter F. D'Amico, Anthony V. Devlin, Phillip M. Nguyen, Paul L. TI Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate cancer in previously irradiated patients: Initial experience and short-term results SO BRACHYTHERAPY LA English DT Article DE Prostate cancer; Brachytherapy; Rectal spacer; Hydrogel spacer; Salvage; Prior pelvic irradiation; Prior pelvic radiation ID QUALITY-OF-LIFE; POLYETHYLENE-GLYCOL HYDROGEL; EXTERNAL-BEAM RADIOTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; SALVAGE LOCAL THERAPY; RADIATION-THERAPY; CRYOSURGICAL ABLATION; RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; DIABETES-MELLITUS AB BACKGROUND: Salvage brachytherapy in patients with prior pelvic radiation carries a risk of rectal injury. Herein, we report our initial experience using a hydrogel spacer between the prostate and the rectum during salvage brachytherapy. METHODS AND MATERIALS: A total of 11 patients with prostate cancer and prior radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation therapy [EBRT], and 4 rectal cancer EBRT) received I-125 brachytherapy after attempted placement of 10 cc of a diluted hydrogel spacer between the prostate and rectum. RESULTS: Spacing was achieved in 8 of the 11(73%) patients but was not possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and adhesions. For the 8 patients in whom spacing was accomplished, the median space between the prostate and rectum was 10.9 mm (prior EBRT) vs. 7.7 mm (prior brachytherapy), p = 0.048. Median followup was 15.7 months. One patient developed a prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient developed lymph node positive recurrence. The 16-month prostate-specific antigen failure-free survival rate was 89%. Compared with baseline, Expanded Prostate Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was significantly worse at 3 and 6 months but not significantly worse by 1 year. There were no significant changes throughout the study period in bowel or sexual QoL. CONCLUSION: Hydrogel spacer placements may be feasible in most patients with prior pelvic radiation. Further followup is needed to determine whether spacer placement will produce long-term improvements in toxicity or QoL. (C) 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Mahal, Brandon A.; Ziehr, David R.; Hyatt, Andrew S.; Neubauer-Sugar, Emily H.; O'Farrell, Desmond A.; Niedermayr, Thomas R.; Beard, Clair J.; Martin, Neil E.; Orio, Peter F.; D'Amico, Anthony V.; Devlin, Phillip M.; Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mahal, Brandon A.; Ziehr, David R.; Hyatt, Andrew S.; Neubauer-Sugar, Emily H.; O'Farrell, Desmond A.; Niedermayr, Thomas R.; Beard, Clair J.; Martin, Neil E.; Orio, Peter F.; D'Amico, Anthony V.; Devlin, Phillip M.; Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [O'Leary, Michael P.; Steele, Graeme S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU David and Cynthia Chapin; Prostate Cancer Foundation; Fitz's Cancer Warriors FX This work is supported by David and Cynthia Chapin, the Prostate Cancer Foundation, Fitz's Cancer Warriors, and a grant from an anonymous family foundation. NR 48 TC 7 Z9 7 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD SEP-OCT PY 2014 VL 13 IS 5 BP 442 EP 449 DI 10.1016/j.brachy.2014.05.001 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AO1JK UT WOS:000341068200002 PM 24880584 ER PT J AU Hsu, ICJ Yamada, Y Assimos, DG D'Amico, AV Davis, BJ Frank, SJ Gottschalk, AR Gustafson, GS McLaughlin, PW Nguyen, PL Rosenthal, SA Taira, A Vapiwala, N Merrick, G AF Hsu, I-Chow Joe Yamada, Yoshiya Assimos, Dean G. D'Amico, Anthony V. Davis, Brian J. Frank, Steven J. Gottschalk, Alexander R. Gustafson, Gary S. McLaughlin, Patrick W. Nguyen, Paul L. Rosenthal, Seth A. Taira, Al V. Vapiwala, Neha Merrick, Gregory TI A critical ACR Appropriateness Criteria omission Response SO BRACHYTHERAPY LA English DT Letter ID DOSE-RATE BRACHYTHERAPY; LOCALIZED PROSTATE-CANCER; PHASE-II; MONOTHERAPY C1 [Hsu, I-Chow Joe; Gottschalk, Alexander R.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94115 USA. [Yamada, Yoshiya] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Assimos, Dean G.] Univ Alabama Birmingham, Sch Med, Amer Urol Assoc, Dept Urol, Birmingham, AL USA. [D'Amico, Anthony V.] Amer Soc Clin Oncol, Joint Ctr Radiat Therapy, Dept Radiat Oncol, Boston, MA USA. [Davis, Brian J.] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Frank, Steven J.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Gustafson, Gary S.] William Beaumont Hosp, Dept Radiat Oncol, Troy, MI USA. [McLaughlin, Patrick W.] Univ Michigan, Dept Radiat Oncol, Novi, MI USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Rosenthal, Seth A.] Radiol Associates Sacramento, Dept Radiat Oncol, Sacramento, CA USA. [Taira, Al V.] Mt View Oncol, Western Radiat Oncol, Dept Radiat Oncol, Mountain View, CA USA. [Vapiwala, Neha] Univ Penn, Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Merrick, Gregory] Schiffler Canc Ctr, Dept Radiat Oncol, Wheeling, WV USA. [Merrick, Gregory] Wheeling Jesuit Univ, Wheeling, WV USA. RP Hsu, ICJ (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94115 USA. FU NCI NIH HHS [P30 CA016672] NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD SEP-OCT PY 2014 VL 13 IS 5 BP 523 EP 525 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AO1JK UT WOS:000341068200014 PM 24880587 ER PT J AU De Buck, SS Jakab, A Boehm, M Bootle, D Juric, D Quadt, C Goggin, TK AF De Buck, Stefan S. Jakab, Annamaria Boehm, Markus Bootle, Douglas Juric, Dejan Quadt, Cornelia Goggin, Timothy K. TI Population pharmacokinetics and pharmacodynamics of BYL719, a phosphoinositide 3-kinase antagonist, in adult patients with advanced solid malignancies SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE BYL719; cancer; phosphoinositide 3-kinase; population pharmacokinetics; RECIST; transit compartment ID LUNG-CANCER PATIENTS; INSULIN-SECRETION; DRUG DEVELOPMENT; PIK3CA GENE; TUMOR SIZE; PI3K; MUTATIONS; SURVIVAL; PATHWAY; MODEL AB AIMS The aim was to characterize the population pharmacokinetics of BYL719 in cancer patients and assess the time course of tumour response in relation to drug exposure and dosing schedule. METHODS Plasma samples and longitudinal tumour size measurements were collected from 60 patients with advanced solid malignancies who received oral BYL719 once daily (30-450 mg) or twice daily at 120 mg or 200 mg. Non-linear mixed effect modelling was employed to develop the population pharmacokinetic and pharmacodynamic model. RESULTS The pharmacokinetics were best described by a one compartment disposition model and transit compartments accounting for the lag time in absorption. The typical population oral clearance and volume of distribution estimates with their between-subject variability (BSV) were 10 l h(-1) (BSV 26%) and 108 l (BSV 28%), respectively. The estimated optimal number of transit compartments was 8.1, with a mean transit time to the absorption compartment of 1.28 h (BSV 32%). The between-occasion variability in the rate and extent of absorption was 46% and 26%, respectively. Tumour growth was modelled using a turnover model characterized by a zero order growth rate of 0.581 cm week(1) and a first order death rate of 0.0123 week(-1). BYL719 inhibited tumour growth with an IC50 of 100 ng ml(-1) (BSV 154%). Model-based predictions showed potential for additional anti-tumour activity of twice daily dosing at total daily dose below 400 mg, but a loss of efficacy if administered less frequently than once daily. CONCLUSIONS The proposed model provides a valuable approach for planning future clinical studies and for designing optimized dosing regimens with BYL719. C1 [De Buck, Stefan S.; Goggin, Timothy K.] Novartis Pharmaceut AG, Oncol Clin Pharmacol, CH-4002 Basel, Switzerland. [Jakab, Annamaria] Novartis Inst Biomed Res, Dept Drug Metab & Pharmacokinet, Cambridge, MA USA. [Boehm, Markus; Bootle, Douglas; Quadt, Cornelia] Novartis Pharmaceut AG, Oncol Translat Med, CH-4002 Basel, Switzerland. [Juric, Dejan] Massachusetts Gen Hosp, Ctr Canc, Termeer Ctr Targeted Therapies, Boston, MA 02114 USA. RP De Buck, SS (reprint author), Novartis Pharmaceut AG, Oncol Clin Pharmacol, WSJ 103-5-09-9, CH-4002 Basel, Switzerland. EM stefan.de_buck@novartis.com FU Novartis Pharma A.G. FX This study was supported by Novartis Pharma A.G. The authors would like to thank all laboratory staff of the Drug Metabolism and Bioanalytics group for providing the BYL719 plasma concentration data and metabolism data used in this study. The authors are also grateful to Antonin Schmitt for his advice and valuable comments. We also acknowledge the clinical investigators and study coordinators at Massachusetts General Hospital Cancer Center (M. Frisbie, C. Caldwell), University of Texas MD Anderson Cancer Center (A. Gonzalez, J. Bendell, F. Janku, T. Helgason, D. Westerhold), Sarah Cannon Research Institute (S. Burris, J. Bendell, J. Infante, T. Jew), Vanderbilt-Ingram Cancer Center (J. Berlin, W. Van Meulen), Vall d'Hebron Institute of Oncology (J. Tabernero, J. Rodon, G. Argiles, L. Martinez), University of Oxford Churchill Hospital (M. Middleton, A. Gupta, W. Saka, N. Hayward), Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis (J. Schellens, M. Roelvink, S. Marchetti, E. Harms) and Universitatsklinikum Essen (M. Schuler) for conducting the study and technicians for technical support. NR 32 TC 6 Z9 6 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0306-5251 EI 1365-2125 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD SEP PY 2014 VL 78 IS 3 BP 543 EP 555 DI 10.1111/bcp.12378 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AN8ZG UT WOS:000340894300010 PM 24617631 ER PT J AU Zhou, YS Liu, X Xu, L Hunter, ZR Cao, Y Yang, G Carrasco, R Treon, SP AF Zhou, Yangsheng Liu, Xia Xu, Lian Hunter, Zachary R. Cao, Yang Yang, Guang Carrasco, Ruben Treon, Steven P. TI Transcriptional repression of plasma cell differentiation is orchestrated by aberrant over-expression of the ETS factor SPIB in Waldenstrom macroglobulinaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE waldenstrom Macroglobulinaemia; POU2F2; POU1AF1; SPIB ID MYD88 L265P; FACTOR E2-2; LYMPHOMA; REGULATOR; DEPENDS; BLIMP-1; GENES; XBP-1 AB In Waldenstrom macroglobulinaemia (WM), the mechanism(s) responsible for repression of B-cell differentiation remains unknown. We found that expression of SPIB and ID2 were significantly increased and decreased, respectively, in WM lymphoplasmacytic cells (LPC). Ectopic expression of SPIB in healthy donor CD19(+) cells inhibited plasmacytic differentiation in conjunction with decreased transcription of IRF4 and XBP1 spliced form. In primary WM LPC, knock-down of SPIB induced plasmacytic differentiation in conjunction with increased transcription of PRDM1, XBP1 spliced form, IRF4 and ID2. Knock-down of SPIB also led to decreased BCL2 expression. Given that SPIB is a direct target of POU2AF1 (OBF1) in complex with POU2F2 or POU2F1, we next examined their expression in WM LPC. POU2F2 transcription, as well as POU2F2 and POU2AF1 protein expression was higher in WM LPC. Ectopic expression of POU2F2 in healthy donor CD19(+) cells induced transcription of SPIB and suppressed transcription of PRDM1 and IRF4. Chromatin immunoprecipitation analysis in BCWM. 1 WM cells confirmed binding of POU2F2 and POU2AF1 in SPIB and ID2 promoters. These findings establish a molecular hierarchy among POU2F2, SPIB and ID2 during B-cell differentiation, and suggest that aberrant expression of these transcription factors plays an important role in arresting plasmacytic differentiation in WM. C1 [Zhou, Yangsheng; Liu, Xia; Xu, Lian; Hunter, Zachary R.; Cao, Yang; Yang, Guang; Carrasco, Ruben; Treon, Steven P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Zhou, Yangsheng; Liu, Xia; Xu, Lian; Hunter, Zachary R.; Cao, Yang; Yang, Guang; Carrasco, Ruben; Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zhou, Yangsheng; Liu, Xia; Xu, Lian; Hunter, Zachary R.; Cao, Yang; Yang, Guang; Carrasco, Ruben; Treon, Steven P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 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 Hunter, Zachary/0000-0002-1689-1691 FU Peter Bing; International Waldenstrom's Macroglobulinemia Foundation; Coyote Fund for WM; Waldenstrom's Cancer Fund; Bailey Family Fund for WM; D'Amato Family Fund for Genomic Discovery; Edward and Linda Nelson Fund for WM Research; Bauman Family Trust; Tannenhauser Family Foundation FX The authors gratefully acknowledge the generous support of Peter Bing, the International Waldenstrom's Macroglobulinemia Foundation, the Coyote Fund for WM, the Waldenstrom's Cancer Fund, the Bailey Family Fund for WM, the D'Amato Family Fund for Genomic Discovery, the Edward and Linda Nelson Fund for WM Research, the Bauman Family Trust, the Tannenhauser Family Foundation, and the WM patients who provided samples for their support of these studies. NR 27 TC 5 Z9 5 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2014 VL 166 IS 5 BP 677 EP 689 DI 10.1111/bjh.12936 PG 13 WC Hematology SC Hematology GA AN5ZE UT WOS:000340671000008 PM 24801987 ER PT J AU Sancey, L Lux, F Kotb, S Roux, S Dufort, S Bianchi, A Cremillieux, Y Fries, P Coll, JL Rodriguez-Lafrasse, C Janier, M Dutreix, M Barberi-Heyob, M Boschetti, F Denat, F Louis, C Porcel, E Lacombe, S Le Duc, G Deutsch, E Perfettini, JL Detappe, A Verry, C Berbeco, R Butterworth, KT Mcmahon, SJ Prise, KM Perriat, P Tillement, O AF Sancey, L. Lux, F. Kotb, S. Roux, S. Dufort, S. Bianchi, A. Cremillieux, Y. Fries, P. Coll, J-L Rodriguez-Lafrasse, C. Janier, M. Dutreix, M. Barberi-Heyob, M. Boschetti, F. Denat, F. Louis, C. Porcel, E. Lacombe, S. Le Duc, G. Deutsch, E. Perfettini, J-L Detappe, A. Verry, C. Berbeco, R. Butterworth, K. T. Mcmahon, S. J. Prise, K. M. Perriat, P. Tillement, O. TI The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID NEUTRON-CAPTURE THERAPY; GOLD NANOPARTICLES; RADIATION-THERAPY; IN-VIVO; CONTRAST AGENTS; MOTEXAFIN GADOLINIUM; IONIZING-RADIATION; BREAST-CANCER; QUANTUM DOTS; MRI AB A new efficient type of gadolinium-based theranostic agent (AGuIX (R)) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. C1 [Sancey, L.; Lux, F.; Kotb, S.; Janier, M.; Verry, C.; Tillement, O.] Univ Lyon 1, Univ Lyon, Inst Lumiere Mat, Team FENNEC,UMR5306, Villeurbanne, France. [Detappe, A.] Univ Franche Comte, CNRS UFC, Inst UTINAM, UMR 6213, F-25030 Besancon, France. [Roux, S.; Detappe, A.] Nano H SAS, St Quentin Fallavier, France. [Roux, S.; Fries, P.; Detappe, A.] Inst Albert Bonniot, INSERM, Unite 823, Grenoble, France. [Roux, S.; Fries, P.; Detappe, A.] UJF, Grenoble, France. [Dufort, S.; Bianchi, A.; Detappe, A.] Univ Bordeaux Segalen, Ctr Resonance Magnet Syst Biol, CNRS, UMR5536, Bordeaux, France. [Cremillieux, Y.; Detappe, A.] Univ Saarland, Med Ctr, Clin Diagnost & Intervent Radiol, Homburg, Germany. [Coll, J-L; Detappe, A.] Univ Hosp Lyon Sud, Hosp Civils Lyon, Dept Biochem & Mol Biol, Med Unit Mol Oncol & Transfer, Pierre Benite, France. [Janier, M.; Detappe, A.] Ctr Univ, Res Ctr, Inst Curie, Equipe Dutreix, Paris, France. [Dutreix, M.; Detappe, A.] Univ Lorraine, Ctr Alexis Vautrin, CRAN, UMR 7039, Vandoeuvre Les Nancy, France. [Barberi-Heyob, M.; Detappe, A.] CheMatech, Dijon, France. [Boschetti, F.; Detappe, A.] Univ Bourgogne, Inst Chim Mol, UMR CNRS 5260, Dijon, France. [Louis, C.; Porcel, E.; Detappe, A.] Univ Paris Sud 11, Lab Collis Atom & Mol, UMR 8625, Orsay, France. [Lacombe, S.; Detappe, A.] European Synchrotron Radiat Facil, F-38043 Grenoble, France. [Le Duc, G.; Deutsch, E.; Detappe, A.] Univ Paris Sud, INSERM 1030, LERMIT, Inst Gustave Roussy Villejuif Labex,Lab Radiother, Paris, France. [Perfettini, J-L; Detappe, A.; Verry, C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Perfettini, J-L; Detappe, A.; Verry, C.] Harvard Univ, Sch Med, Boston, MA USA. [Berbeco, R.; Butterworth, K. T.; Mcmahon, S. J.] UJF CEA CHU, INSERM, Grenoble Inst Neurosci, U836, La Tronche, France. [Prise, K. M.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast, Antrim, North Ireland. [Prise, K. M.] INSA Lyon, MATEIS, CNRS, UMR 5510, Villeurbanne, France. RP Lux, F (reprint author), Univ Lyon 1, Univ Lyon, Inst Lumiere Mat, Team FENNEC,UMR5306, Villeurbanne, France. EM francois.lux@univ-lyon1.fr RI Prise, Kevin/N-7872-2015 OI Prise, Kevin/0000-0001-6134-7946 FU University of Lyon [ANR-11-LABX-0063, ANR-11-IDEX-0007]; ANR FX This work was supported by the LABEX PRIMES (ANR-11-LABX-0063) of the University of Lyon, within the "Investissements d'Avenir" program (ANR-11-IDEX-0007) co-ordinated by the French National Research Agency (ANR), as well as the ANR TheraGuIma. We would also like to express our gratitude to French programs ANR-12-RPIB-0010 Multimage and ANR-12-P2N-0009-Gd-Lung. We wish to thank the European Network PINET (FP7-PEOPLE-2010-ITN-264864) and the COST action TD1004 "theranostics imaging and therapy: an action to develop novel nanosized systems for imaging-guided drug delivery". NR 59 TC 26 Z9 26 U1 3 U2 56 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PD SEP PY 2014 VL 87 IS 1041 AR 20140134 DI 10.1259/bjr.20140134 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO4LM UT WOS:000341309700016 PM 24990037 ER PT J AU Dal-Bianco, JP Beaudoin, J Handschumacher, MD Levine, RA AF Dal-Bianco, Jacob P. Beaudoin, Jonathan Handschumacher, Mark D. Levine, Robert A. TI Basic Mechanisms of Mitral Regurgitation SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Review ID SYSTOLIC ANTERIOR MOTION; OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY; OUTFLOW TRACT OBSTRUCTION; LEFT-VENTRICULAR DYSFUNCTION; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; PAPILLARY-MUSCLE DYSFUNCTION; MYXOMATOUS VALVE DISEASE; VALVULAR HEART-DISEASE; MYOCARDIAL-INFARCTION; FUNCTIONAL-ANATOMY AB Any structural or functional impairment of the mitral valve (MV) apparatus that exhausts MV tissue redundancy available for leaflet coaptation will result in mitral regurgitation (MR). The mechanism responsible for MV malcoaptation and MR can be dysfunction or structural change of the left ventricle, the papillary muscles, the chordae tendineae, the mitral annulus, and the MV leaflets. The rationale for MV treatment depends on the MR mechanism and therefore it is essential to identify and understand normal and abnormal MV and MV apparatus function. C1 [Dal-Bianco, Jacob P.; Handschumacher, Mark D.; Levine, Robert A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Beaudoin, Jonathan] Inst Univ Cardiol & Pneumol Quebec, Dept Cardiol, Quebec City, PQ, Canada. RP Levine, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. EM rlevine@partners.org FU Leducq Foundation, Paris, France [07CVD04]; National Institutes of Health [K24 HL67434, R01 HL72265, HL109506] FX This work was supported in part by grant 07CVD04 of the Leducq Foundation, Paris, France, for the Leducq Transatlantic MITRAL Network, and by National Institutes of Health grants K24 HL67434, R01 HL72265, and HL109506. NR 155 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X EI 1916-7075 J9 CAN J CARDIOL JI Can. J. Cardiol. PD SEP PY 2014 VL 30 IS 9 BP 971 EP 981 DI 10.1016/j.cjca.2014.06.022 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4RQ UT WOS:000341329500003 PM 25151282 ER PT J AU Rassi, AN Pibarot, P Elmariah, S AF Rassi, Andrew N. Pibarot, Philippe Elmariah, Sammy TI Left Ventricular Remodelling in Aortic Stenosis SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Review ID PROSTHESIS-PATIENT MISMATCH; PRESERVED EJECTION FRACTION; CARDIOVASCULAR MAGNETIC-RESONANCE; EUROSCORE MULTINATIONAL DATABASE; LOW TRANSVALVULAR GRADIENTS; CHRONIC PRESSURE-OVERLOAD; EUROPEAN CARDIAC-SURGERY; PARADOXICAL LOW-FLOW; HIGH-RISK PATIENTS; VALVE-REPLACEMENT AB Aortic stenosis (AS) is a progressive condition associated with high mortality if not treated. The hemodynamic effects of AS have serious implications for the left ventricle. In this review, we describe the responses of the left ventricle to AS by highlighting the process of adaptive remodelling, which begins as a beneficial compensatory mechanism but ultimately transitions to a maladaptive process with potentially irreversible consequences. We discuss the impact of left ventricular (LV) remodelling on diastolic and systolic function and on the development of symptoms. In addition, we review the adverse consequences of maladaptive LV remodelling on clinical outcomes before and after aortic valve replacement. The relative irreversibility of maladaptive remodelling and the clear relationship between its progression and clinical outcomes suggest a need to incorporate measures of LV performance beyond simply systolic function when deciding on the timing of valve replacement. C1 [Rassi, Andrew N.; Elmariah, Sammy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Pibarot, Philippe] Univ Laval, Quebec Heart & Lung Inst, Quebec City, PQ, Canada. RP Elmariah, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM selmariah@mgh.harvard.edu NR 86 TC 6 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X EI 1916-7075 J9 CAN J CARDIOL JI Can. J. Cardiol. PD SEP PY 2014 VL 30 IS 9 BP 1004 EP 1011 DI 10.1016/j.cjca.2014.04.026 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4RQ UT WOS:000341329500006 PM 25151283 ER PT J AU Gronchi, A Colombo, C Raut, CP AF Gronchi, Alessandro Colombo, Chiara Raut, Chandrajit P. TI Surgical Management of Localized Soft Tissue Tumors SO CANCER LA English DT Article; Proceedings Paper CT AACR Annual Meeting CY APR 05-09, 2014 CL San Diego, CA DE sarcoma; gastrointestinal stromal tumor; desmoid; surgery; prognosis; survival; outcome ID GASTROINTESTINAL STROMAL TUMORS; ENDOSCOPIC-ULTRASOUND-SURVEY; CLINICAL-PRACTICE GUIDELINES; PROGRESSION-FREE SURVIVAL; FRENCH SARCOMA GROUP; PROGNOSTIC-FACTORS; SINGLE INSTITUTION; DESMOID TUMORS; RETROPERITONEAL SARCOMAS; RADIATION-THERAPY AB Soft tissue tumors are rare and can arise from a variety of soft tissues and viscera in a variety of body sites. Their management requires a thorough understanding of the biology of the different histologies and molecular subtypes as well as the constraints of specific anatomic sites. The surgical approach has undergone significant changes thanks to a better understanding of the natural history of the different histologic subtypes, the importance of site, and the different sensitivity to available drugs. The soft tissue tumor family includes 3 major, distinct categories: desmoid-type fibromatosis, soft tissue sarcoma, and gastrointestinal stromal tumor. In general, limb-sparing and function-sparing approaches should be used when feasible for tumors located in the extremities and girdles. Resections of adherent structures/viscera, which may be close but not invaded, may be needed in tumors arising in the retroperitoneum/abdomen to minimize microscopic intralesional margins, maximize local tumor control, and possibly improve survival. Margins of resection and the use of adjuvant/neadjuvant radiation therapy and/or chemotherapy are contingent on an accurate histologic diagnosis. Treatment planning should include multidisciplinary consultation to determine optimal therapy, taking into consideration tumor histology, site and extent of the disease, its natural history and sensitivity to available treatments, surgical challenges, and-of course-quality of life. (C) 2014 American Cancer Society. C1 [Gronchi, Alessandro; Colombo, Chiara] Sci Inst Res & Treatment IRCCS Fdn, Natl Canc Inst, Dept Surg, Sarcoma Serv, Milan, Italy. [Raut, Chandrajit P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Ctr Sarcoma & Bone Oncol,De, Boston, MA 02115 USA. RP Gronchi, A (reprint author), Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, Via Venezian 1, I-20133 Milan, Italy. EM alessandro.gronchi@istitutotumori.mi.it RI Colombo, Chiara/C-4303-2017; OI Colombo, Chiara/0000-0001-8031-5528; Gronchi, Alessandro/0000-0002-4703-3534 NR 70 TC 14 Z9 14 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2014 VL 120 IS 17 BP 2638 EP 2648 DI 10.1002/cncr.28715 PG 11 WC Oncology SC Oncology GA AN4LJ UT WOS:000340559000004 PM 24752977 ER PT J AU Locati, LD Licitra, L Agate, L Ou, SHI Boucher, A Jarzab, B Qin, SK Kane, MA Wirth, LJ Chen, C Kim, S Ingrosso, A Pithavala, YK Bycott, P Cohen, EEW AF Locati, Laura D. Licitra, Lisa Agate, Laura Ou, Sai-Hong I. Boucher, Andree Jarzab, Barbara Qin, Shukui Kane, Madeleine A. Wirth, Lori J. Chen, Connie Kim, Sinil Ingrosso, Antonella Pithavala, Yazdi K. Bycott, Paul Cohen, Ezra E. W. TI Treatment of Advanced Thyroid Cancer With Axitinib: Phase 2 Study With Pharmacokinetic/Pharmacodynamic and Quality-of-Life Assessments SO CANCER LA English DT Article; Proceedings Paper CT AACR Annual Meeting CY APR 05-09, 2014 CL San Diego, CA DE axitinib; MD Anderson Symptom Inventory; metastatic disease; pharmacokinetic; pharmacodynamic; quality of life; radioactive iodine-refractory; thyroid cancer; tyrosine kinase inhibitor ID RENAL-CELL CARCINOMA; SOLID TUMORS; DOUBLE-BLIND; II TRIAL; SORAFENIB; POPULATION; EFFICACY; CABOZANTINIB; VANDETANIB; INHIBITOR AB BACKGROUND: In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed. METHODS: Patients (N = 52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters, and patient-reported outcomes assessed with the MD Anderson Symptom Inventory questionnaire. RESULTS: The overall ORR was 35% (18 partial responses), and 18 patients had stable disease for >= 16 weeks. The median PFS was 16.1 months, and the median OS was 27.2 months. All-causality, grade >= 3 adverse events (>5%) were fatigue, dyspnea, diarrhea, decreased weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Patients who had greater axitinib exposure had a longer median PFS. Quality of life was maintained during treatment with axitinib, and no significant deterioration in symptoms or interference in daily life caused by symptoms, assessed on MD Anderson Symptom Inventory subscales, were observed. CONCLUSIONS: Axitinib has activity and a manageable safety profile while maintaining quality of life, and it represents an additional treatment option for patients with advanced thyroid cancer. (C) 2014 American Cancer Society. C1 [Locati, Laura D.; Licitra, Lisa] Fdn IRCCS, Ist Nazl Tumori, Head & Neck Med Oncol Unit, Milan, Italy. [Agate, Laura] Univ Pisa, Endocrine Unit, Pisa, Italy. [Ou, Sai-Hong I.] Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA. [Boucher, Andree] Univ Montreal, Dept Med, Ctr Hosp, Montreal, PQ H3C 3J7, Canada. [Jarzab, Barbara] Marii Sklodowskiej Curie Inst, Ctr Oncol, Gliwice, Poland. [Qin, Shukui] Nanjing Bayi Hosp, Nanjing, Jiangsu, Peoples R China. [Kane, Madeleine A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Wirth, Lori J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Chen, Connie] Pfizer Oncol, New York, NY USA. [Kim, Sinil; Bycott, Paul] Pfizer Oncol, San Diego, CA USA. [Ingrosso, Antonella] Pfizer Oncol, Milan, Italy. [Pithavala, Yazdi K.] Pfizer Oncol, Clin Pharmacol, San Diego, CA USA. [Cohen, Ezra E. W.] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. [Kim, Sinil] Pfizer Inc, Groton, CT USA. RP Locati, LD (reprint author), Fdn IRCCS, Ist Nazl Tumori, Via Venezian 1, Milan, Italy. EM laura.locati@istitutotumori.mi.it RI Locati, Laura /B-8163-2017; Licitra, Lisa/C-6271-2017 OI Locati, Laura /0000-0003-3315-2580; Licitra, Lisa/0000-0003-0623-4118 FU Pfizer Inc. FX This study was sponsored by Pfizer Inc. Medical writing support was provided by Lilliam Poltorack, PharmD, and Joanna Bloom, PhD, of Engage Scientific Solutions, and was funded by Pfizer Inc. NR 36 TC 29 Z9 31 U1 4 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2014 VL 120 IS 17 BP 2694 EP 2703 DI 10.1002/cncr.28766 PG 10 WC Oncology SC Oncology GA AN4LJ UT WOS:000340559000010 PM 24844950 ER PT J AU Pensa, S Neoh, K Resemann, HK Kreuzaler, PA Abell, K Clarke, NJ Reinheckel, T Kahn, CR Watson, CJ AF Pensa, S. Neoh, K. Resemann, H. K. Kreuzaler, P. A. Abell, K. Clarke, N. J. Reinheckel, T. Kahn, C. R. Watson, C. J. TI The PI3K regulatory subunits p55 alpha and p50 alpha regulate cell death in vivo SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID MAMMARY-GLAND INVOLUTION; ACUTE-PHASE RESPONSE; PHOSPHATIDYLINOSITOL 3-KINASE; NUCLEAR TRANSLOCATION; STAT3; MICE; REGRESSION; P85-ALPHA; APOPTOSIS; INTERACT AB The phosphatidylinositol 3-kinase (PI3K) regulatory subunits p55 alpha and p50 alpha are coordinately transcriptionally upregulated by signal transducer and activator of transcription 3 (Stat3) at the onset of mammary gland involution, a process that requires Stat3. Deletion of both p55 alpha and p50 alpha subunits in vivo abrogated mammary epithelial cell death during involution. This was associated also with reduced cytosolic levels and activity of the cysteine protease cathepsin L, which is implicated in lysosomal-mediated programmed cell death (LM-PCD) and is upregulated in involution. Furthermore, involution is delayed in cathepsin L-deficient mice suggesting that the p55 alpha/p50 alpha subunits mediate cell death in part by elevating the level of cathepsin L resulting in increased cytosolic activity. Surprisingly, we found that p55 alpha/p50 alpha localize to the nucleus where they bind to chromatin and regulate transcription of a subset of inflammatory/acute phase genes that are also Stat3 targets. Our findings reveal a novel role for these PI3K regulatory subunits as regulators of LM-PCD in vivo. C1 [Pensa, S.; Neoh, K.; Resemann, H. K.; Kreuzaler, P. A.; Abell, K.; Watson, C. J.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Kreuzaler, P. A.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Abell, K.] LEO Pharma AS, Ballerup, Denmark. [Clarke, N. J.] GlaxoSmithKline, Stevenage, Herts, England. [Reinheckel, T.] Univ Freiburg, Inst Mol Med & Cell Res, D-79106 Freiburg, Germany. [Reinheckel, T.] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79106 Freiburg, Germany. [Kahn, C. R.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Watson, CJ (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM cjw53@cam.ac.uk FU BBSRC; MRC [BB/D012937/1, MR/J001023/1]; Marie Curie IEF fellowship (EU Marie Curie grant) [273365]; BBSRC CASE PhD studentship; Cambridge Cancer Center; Trinity College fellowship; Excellence Initiative of the German Federal and State Governments [EXC 294]; Deutsche Forschungsgemeinschaft [SFB 850] FX We thank Maximilian Blanck and Ivan Ferrer-Vicens for immunofluorescence studies, Helen Skelton for tissue histology and the Watson lab members for helpful discussions. This work was funded by BBSRC and MRC grants (BB/D012937/1 and MR/J001023/1) awarded to CJW, SP is the recipient of a Marie Curie IEF fellowship (EU Marie Curie grant no. 273365), KN was supported by a BBSRC CASE PhD studentship, HKR is funded by a Cambridge Cancer Center PhD studentship and PAK is the recipient of a Trinity College fellowship. TR was supported by the Excellence Initiative of the German Federal and State Governments (EXC 294), and the Deutsche Forschungsgemeinschaft SFB 850 project B7. NR 25 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD SEP PY 2014 VL 21 IS 9 BP 1442 EP 1450 DI 10.1038/cdd.2014.59 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AN5WO UT WOS:000340662900011 PM 24902901 ER PT J AU Kobraei, EM Ricci, JA Vasconez, HC Rinker, BD AF Kobraei, Edward M. Ricci, Joseph A. Vasconez, Henry C. Rinker, Brian D. TI A comparison of techniques for myelomeningocele defect closure in the neonatal period SO CHILDS NERVOUS SYSTEM LA English DT Article DE Myelomeningocele; Fasciocutaneous; Myocutaneous; Neural tube defect; Spina bifida ID PLASTIC SURGICAL ASPECTS; NEURAL-TUBE DEFECTS; SOFT-TISSUE CLOSURE; MENINGOMYELOCELE DEFECTS; WOUND CLOSURE; REPAIR; RISK AB Numerous techniques have been described for repair of myelomeningoceles, but outcome data is scarce. A retrospective review was performed in 32 consecutive patients who underwent neonatal myelomeningocele repair and extra-dural closure to determine the influence of repair type on outcome. All procedures for myelomeningocele closure were classified into one of three groups, which included primary closure, myocutaneous flaps, and fasciocutaneous flaps. Defect size ranged from 1 to 48 cm(2). Primary skin closure was performed in 3 patients, fasciocutaneous flaps in 13 patients, and myocutaneous flaps in 16 patients. The overall complication rate was 18 %. No difference in the complication rates among the primary closure, myocutaneous, and fasciocutaneous flap groups was observed in our analysis. While not statistically significant, our data documents an association of fasciocutaneous flaps with postoperative complications that were not evident with primary skin closure or myocutaneous flaps (odds ratio 3.8; p = 0.15). The occurrence of one or more complications was associated with a longer hospital stay. Myocutaneous flaps provide a secure repair and should be considered for smaller myelomeningocele defects in addition to the larger defects where they are more traditionally used. We propose a tissue-based classification of closure techniques strictly for multi-institution outcome comparison that may ultimately inform clinical decision-making. C1 [Kobraei, Edward M.; Ricci, Joseph A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02163 USA. [Vasconez, Henry C.; Rinker, Brian D.] Univ Kentucky, Albert B Chandler Med Ctr, Coll Med, Div Plast Surg, Lexington, KY 40536 USA. RP Kobraei, EM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, 55 Fruit St,WACC 435, Boston, MA 02163 USA. EM eddiekobra@gmail.com NR 20 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0256-7040 EI 1433-0350 J9 CHILD NERV SYST JI Childs Nerv. Syst. PD SEP PY 2014 VL 30 IS 9 BP 1535 EP 1541 DI 10.1007/s00381-014-2430-7 PG 7 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA AN8UB UT WOS:000340879100010 PM 24802545 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Venous Thromboembolism Risk in Patients With Inflammatory Bowel Disease: Defining the Benefits of Pharmacologic Prophylaxis Reply SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2014 VL 12 IS 9 BP 1577 EP 1578 DI 10.1016/j.cgh.2014.04.029 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2EI UT WOS:000341127900032 PM 24793024 ER PT J AU Maguire, LH Chan, AT AF Maguire, Lillias H. Chan, Andrew T. TI Are We Overinterpreting Serum Vitamin D Data? Reply SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter ID CROHNS-DISEASE; REDUCED RISK C1 [Maguire, Lillias H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Maguire, LH (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2014 VL 12 IS 9 BP 1579 EP 1579 DI 10.1016/j.cgh.2014.07.002 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2EI UT WOS:000341127900035 PM 25008157 ER PT J AU Tirumani, H Vassa, R Fasih, N Ojili, V AF Tirumani, Harika Vassa, Ravi Fasih, Najla Ojili, Vijayanadh TI Small bowel obstruction in the emergency department: MDCT features of common and uncommon causes SO CLINICAL IMAGING LA English DT Review DE Small bowel obstruction; Emergency department; MDCT; Acute small bowel obstruction; Subacute small bowel obstruction ID IMAGING FINDINGS; GALLSTONE ILEUS; CYSTIC-FIBROSIS; HELICAL CT; HERNIAS; COMPLICATIONS; MANAGEMENT; DIAGNOSIS; EMPHASIS; PITFALLS AB Small bowel obstruction is a common condition encountered by the radiologist in the emergency department. Though intestinal adhesions and obstructed hernias are the most common causes of acute small bowel obstruction, a variety of uncommon and rare conditions can cause acute and subacute bowel obstruction. Imaging plays a key role in the workup of bowel obstruction by identifying the cause, level, and degree of bowel obstruction. In this article, we present a comprehensive review of the multi-detector computed tomography features of common and uncommon causes of acute and subacute small bowel obstruction. (C) 2014 Elsevier Inc. All rights reserved. C1 [Tirumani, Harika] Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, Boston, MA 02212 USA. [Vassa, Ravi; Ojili, Vijayanadh] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Fasih, Najla] Ottawa Hosp, Dept Diagnost Imaging, Ottawa, ON K1Y 4E9, Canada. RP Ojili, V (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Harika_Tirumani@Dfci.Harvard.Edu; ravivassa@gmail.com; nfasih2@gmail.com; ojili@uthscsa.edu NR 32 TC 6 Z9 6 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD SEP-OCT PY 2014 VL 38 IS 5 BP 580 EP 588 DI 10.1016/j.clinimag.2014.04.010 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO3GG UT WOS:000341217100004 PM 24861419 ER PT J AU Cabral, FC Krajewski, KM Rosenthal, MH Hirsch, MS Howard, SA AF Cabral, Fernanda C. Krajewski, Katherine M. Rosenthal, Michael H. Hirsch, Michelle S. Howard, Stephanie A. TI Teratoma with malignant transformation: report of three cases and review of the literature SO CLINICAL IMAGING LA English DT Review DE Testicular cancer; Teratoma with malignant transformation; Computed tomography; Nonseminomatous germ cell tumor ID GERM-CELL TUMORS; TESTICULAR CANCER; METASTASES; CHEMOTHERAPY; MANAGEMENT; PATTERNS; DISEASE; TESTIS AB Teratoma with malignant transformation is an uncommon, very aggressive germ cell tumor that has undergone transformation of a somatic teratomatous component to a histologic type identical to a somatic malignancy. We review the clinical presentation, imaging appearances, and prognosis of this entity and highlight its aggressive behavior by reporting on three patients with metastatic testicular nonseminomatous germ cell tumor with histologically proved malignant transformation. Published by Elsevier Inc. C1 [Cabral, Fernanda C.; Krajewski, Katherine M.; Rosenthal, Michael H.; Howard, Stephanie A.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging,Med Sch, Boston, MA 02115 USA. [Hirsch, Michelle S.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. RP Cabral, FC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM fcabral@partners.org RI Rosenthal, Michael/D-4080-2015 NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD SEP-OCT PY 2014 VL 38 IS 5 BP 589 EP 593 DI 10.1016/j.clinimag.2014.04.011 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AO3GG UT WOS:000341217100005 PM 24908364 ER PT J AU Weisbord, SD Mor, MK Sevick, MA Shields, AM Roffman, BL Palevsky, PM Arnold, RM Green, JA Fine, MJ AF Weisbord, Steven D. Mor, Maria K. Sevick, Mary Ann Shields, Anne Marie Roffman, Bruce L. Palevsky, Paul M. Arnold, Robert M. Green, Jamie A. Fine, Michael J. TI Associations of Depressive Symptoms and Pain with Dialysis Adherence, Health Resource Utilization, and Mortality in Patients Receiving Chronic Hemodialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; MANAGEMENT STRATEGIES; HOSPITALIZATION; PREVALENCE; SEVERITY; TERM; METAANALYSIS; VALIDATION; FLUOXETINE AB Background and objectives Depressive symptoms and pain are common in patients receiving chronic hemodialysis, yet their effect on dialysis adherence, health resource utilization, and mortality is not fully understood. This study sought to characterize the longitudinal associations of these symptoms with dialysis adherence, emergency department (ED) visits, hospitalizations, and mortality. Design, setting, participants, & measurements As part of a trial comparing symptom management strategies in patients receiving chronic hemodialysis, this study prospectively assessed depressive symptoms using the Patient Health Questionnaire 9, and pain using the Short-Form McGill Pain Questionnaire, monthly between 2009 and 2011. This study used negative binomial, Poisson, and proportional hazards regression to analyze the longitudinal associations of depressive symptoms and pain, scaled based on 5-point increments in symptom scores, with missed and abbreviated hemodialysis treatments, ED visits, hospitalizations, and mortality, respectively. Results Among 286 patients, moderate-to-severe depressive symptoms were identified on 788 of 4452 (18%) assessments and pain was reported on 3537 of 4459 (79%) assessments. Depressive symptoms were independently associated with missed (incident rate ratio [IRR], 1.21; 95% confidence interval [95% CI], 1.10 to 1.33) and abbreviated (IRR, 1.08; 95% CI, 1.03 to 1.14) hemodialysis treatments, ED visits (IRR, 1.24; 95% CI, 1.12 to 1.37), hospitalizations (IRR, 1.19; 95% CI, 1.10 to 1.30), and mortality (IRR, 1.40; 95% CI, 1.11 to 1.77). Pain was independently associated with abbreviated hemodialysis treatments (IRR, 1.03; 95% CI, 1.01 to 1.06) and hospitalizations (IRR, 1.05; 95% CI, 1.00 to 1.10). Severe pain was independently associated with abbreviated hemodialysis treatments (IRR, 1.16; 95% CI, 1.06 to 1.28), ED visits (IRR, 1.58; 95% CI, 1.28 to 1.94), and hospitalizations (IRR, 1.22; 95% CI, 1.03 to 1.45), but not mortality (hazard ratio, 1.71; 95% CI, 0.81 to 2.96). Conclusions Depressive symptoms and pain are independently associated with dialysis nonadherence and health services utilization. Depressive symptoms are also associated with mortality. Interventions to alleviate these symptoms have the potential to reduce costs and improve patient-centered outcomes. C1 [Weisbord, Steven D.; Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Mor, Maria K.; Shields, Anne Marie; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Arnold, Robert M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Palliat Care, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann; Roffman, Bruce L.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Green, Jamie A.] Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA. RP Weisbord, SD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv Line, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU US Department of Veterans Affairs Health Services Research and Development Merit Review award [IIR 07-190] FX This work was supported by a US Department of Veterans Affairs Health Services Research and Development Merit Review award (IIR 07-190). The opinions expressed in this article are those of the authors and do not represent the views of the US Department of Veterans Affairs or the US Government. NR 43 TC 12 Z9 13 U1 2 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2014 VL 9 IS 9 BP 1594 EP 1602 DI 10.2215/CJN.00220114 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AO3ZE UT WOS:000341275200015 PM 25081360 ER PT J AU Berns, JS Ellison, DH Linas, SL Rosner, MH AF Berns, Jeffrey S. Ellison, David H. Linas, Stuart L. Rosner, Mitchell H. TI Training the Next Generation's Nephrology Workforce SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID LUPUS NEPHRITIS; NEXT-GENERATION; KIDNEY-DISEASE; RHEUMATOLOGISTS; COMPETENCE; FELLOWS; REQUIREMENTS; ULTRASOUND; PROGRAMS AB The subspecialty of nephrology faces several critical challenges, including declining interest among medical students and internal medicine residents and worrisome declines in the number of applicants for nephrology fellowships. There is an urgent need to more clearly define the subspecialty and its scope of practice, reinvigorate meaningful research training and activities among trainees, and ensure that fellows who complete training and enter the practice of nephrology are experts in the broad scope of nephrology. This need requires a critical look at fellowship training programs and training requirements. A new workforce analysis is also needed that is not focused on primarily meeting estimated future clinical needs but rather, ensuring that there is alignment of supply and demand for nephrology trainees, which will ensure that those entering nephrology fellowships are highly qualified and capable of becoming outstanding nephrologists and that there are desirable employment opportunities for them when they complete their training. C1 [Berns, Jeffrey S.] Univ Penn, Hosp Univ Penn, Renal Electrolyte & Hypertens Div, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Div Nephrol, Portland, OR 97201 USA. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. [Linas, Stuart L.] Univ Colorado, Div Nephrol, Denver Hlth Med Ctr, Denver, CO 80202 USA. [Rosner, Mitchell H.] Univ Virginia, Sch Med, Div Nephrol, Charlottesville, VA 22908 USA. RP Berns, JS (reprint author), Hosp Univ Penn, 3400 Spruce St,1 Founders Pavil, Philadelphia, PA 19104 USA. EM bernsj@uphs.upenn.edu NR 35 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2014 VL 9 IS 9 BP 1639 EP 1644 DI 10.2215/CJN.00560114 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AO3ZE UT WOS:000341275200020 PM 24970877 ER PT J AU Tafti, BA Mandelkern, M Berenji, GR AF Tafti, Bashir Akhavan Mandelkern, Mark Berenji, Gholam Reza TI Subclinical Seizures as a Pitfall in F-18-FDG PET Imaging of Temporal Lobe Epilepsy SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE PET; epilepsy; subclinical seizure; MRI; electroencephalography ID POSITRON-EMISSION-TOMOGRAPHY; STATUS EPILEPTICUS C1 [Tafti, Bashir Akhavan; Mandelkern, Mark; Berenji, Gholam Reza] Vet Adm Greater Los Angeles Hlth Care Syst, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Berenji, GR (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gholam.berenji@va.gov NR 8 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 2014 VL 39 IS 9 BP 819 EP 821 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AN6SU UT WOS:000340728300023 PM 24873791 ER PT J AU Pu, X Hildebrandt, MAT Lu, C Roth, JA Stewart, DJ Zhao, Y Heist, RS Ye, Y Chang, DW Su, L Minna, JD Lippman, SM Spitz, MR Christiani, DC Wu, X AF Pu, X. Hildebrandt, M. A. T. Lu, C. Roth, J. A. Stewart, D. J. Zhao, Y. Heist, R. S. Ye, Y. Chang, D. W. Su, L. Minna, J. D. Lippman, S. M. Spitz, M. R. Christiani, D. C. Wu, X. TI Inflammation-Related Genetic Variations and Survival in Patients With Advanced Non-Small Cell Lung Cancer Receiving First-Line Chemotherapy SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; STATISTICS; PROMOTES; LEUKEMIA; PATHWAY; RISK AB Accurate prognostic prediction is challenging for patients with advanced-stage non-small cell lung cancer (NSCLC). We systematically investigated genetic variants within inflammation pathways as potential prognostic markers for advanced-stage NSCLC patients treated with first-line chemotherapy. A discovery phase in 502 patients and an internal validation phase in 335 patients were completed at the MD Anderson Cancer Center. External validation was performed in 371 patients at Harvard University. A missense single-nucleotide polymorphism (SNP) in the gene encoding the major histocompatibility complex class II, DO-beta chain (HLA-DOB:rs2071554), predicted to influence protein function, was significantly associated with poor survival in the discovery (hazard ratio (HR): 1.46; 95% confidence interval (CI): 1.02-2.09), internal validation (HR: 1.51; 95% CI: 1.02-2.25), and external validation (HR: 1.52; 95% CI: 1.01-2.29) populations. KLRK1:rs2900420 was associated with reduced risk in the discovery (HR: 0.76; 95% CI: 0.60-0.96), internal validation (HR: 0.77; 95% CI: 0.61-0.99), and external validation (HR: 0.80; 95% CI: 0.63-1.02) populations. A strong cumulative effect on overall survival was observed for these SNPs. Genetic variations in inflammation-related genes could have potential to complement prediction of prognosis. C1 [Pu, X.; Hildebrandt, M. A. T.; Ye, Y.; Chang, D. W.; Wu, X.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Lu, C.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Roth, J. A.] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA. [Stewart, D. J.] Ottawa Hosp Canc Ctr, Div Med Oncol, Ottawa, ON, Canada. [Zhao, Y.; Su, L.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Heist, R. S.; Christiani, D. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Minna, J. D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. [Lippman, S. M.] Univ Calif San Diego, Rebecca & John Moores Canc Ctr, San Diego, CA 92103 USA. [Spitz, M. R.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. RP Wu, X (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. EM xwu@mdanderson.org FU National Cancer Institute [R01 CA111646, P50 CA070907, R01 CA127219, R01 CA074386, R01 CA092824, P50 CA090578]; National Institutes of Health through MD Anderson's Cancer Center Support grant [CA016672] FX This work was supported by National Cancer Institute grants R01 CA111646, P50 CA070907, R01 CA127219, R01 CA074386, R01 CA092824, and P50 CA090578, as well as by the National Institutes of Health through MD Anderson's Cancer Center Support grant CA016672. NR 35 TC 1 Z9 1 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2014 VL 96 IS 3 BP 360 EP 369 DI 10.1038/clpt.2014.89 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AN7VS UT WOS:000340809700023 PM 24755914 ER PT J AU Arafat, SN Robert, MC Shukla, AN Dohlman, CH Chodosh, J Ciolino, JB AF Arafat, Samer N. Robert, Marie-Claude Shukla, Anita N. Dohlman, Claes H. Chodosh, James Ciolino, Joseph B. TI UV Cross-linking of Donor Corneas Confers Resistance to Keratolysis SO CORNEA LA English DT Article DE corneal collagen cross-linking; gamma (gamma) irradiation; collagenase; keratolysis ID BOSTON KERATOPROSTHESIS; GAMMA-IRRADIATION; MATRIX METALLOPROTEINASES; PROGRESSIVE KERATOCONUS; BIOMECHANICAL PROPERTY; BACTERIAL KERATITIS; MELT; ULCERATION; MOLECULES; PROTEASES AB Purpose: The aim of this study was to develop a modified ex vivo corneal cross-linking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis. Methods: Ex vivo cross-linking of human corneas was performed using Barron artificial anterior chambers. The corneas were deepithelialized, pretreated with riboflavin solution (0.1% riboflavin/20% dextran), and irradiated with ultraviolet A (UV-A) light (lambda = 370 nm, irradiance = 3 mW/cm(2)) for various durations. The combined effect of UV-A and gamma (gamma) irradiation was also assessed using the commercially available gamma-irradiated corneal donors. The corneas were then trephined and incubated at 37 degrees C with 0.3% collagenase A solution. The time to dissolution of each cornea was compared across treatments. Results: Deepithelialized corneas (no UV light, no riboflavin) dissolved in 5.8 +/- 0.6 hours. Cross-linked corneas demonstrated increased resistance to dissolution, with a time to dissolution of 17.8 +/- 2.6 hours (P < 0.0001). The corneal tissues' resistance to collagenase increased with longer UV-A exposure, reaching a plateau at 30 minutes. Cross-linking both the anterior and posterior corneas did not provide added resistance when compared with cross-linking the anterior corneas only (P > 0.05). gamma-irradiated corneas dissolved as readily as deepithelialized controls regardless of whether they were further cross-linked (5.6 +/- 1.2 hours) or not (6.1 +/- 0.6 hours) (P = 0.43). Conclusions: Collagen cross-linking of the deepithelialized anterior corneal surface for 30 minutes conferred optimal resistance to in vitro keratolysis by collagenase A. C1 [Arafat, Samer N.; Robert, Marie-Claude; Shukla, Anita N.; Dohlman, Claes H.; Chodosh, James; Ciolino, Joseph B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Arafat, Samer N.; Robert, Marie-Claude] Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA 02114 USA. RP Ciolino, JB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM joseph_ciolino@meei.harvard.edu FU Boston Keratoprosthesis Research Fund (Massachusetts Eye and Ear Infirmary), Boston, Massachusetts; National Institutes of Health, National Eye Institute, Bethesda, Maryland [NEI 1K08EY019686]; Research to Prevent Blindness, New York, New York FX Supported in part by the Boston Keratoprosthesis Research Fund (Massachusetts Eye and Ear Infirmary), Boston, Massachusetts, and the National Institutes of Health, National Eye Institute, Bethesda, Maryland (NEI 1K08EY019686 to J. B. Ciolino) and an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, from Research to Prevent Blindness, New York, New York. NR 42 TC 9 Z9 9 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD SEP PY 2014 VL 33 IS 9 BP 955 EP 959 PG 5 WC Ophthalmology SC Ophthalmology GA AN4UZ UT WOS:000340585400016 PM 25014151 ER PT J AU Harrington, RA Popma, CJ Gibson, CM AF Harrington, Robert A. Popma, Christopher J. Gibson, Charles Michael TI Advances in understanding percutaneous coronary intervention pharmacology: ischemia, bleeding, the ISAR research group, and a commitment to progress SO CORONARY ARTERY DISEASE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES; CLINICAL-OUTCOMES; ANTIPLATELET THERAPY; ACUITY TRIAL; IMPACT; BIVALIRUDIN; PREDICTORS; INHIBITORS C1 [Harrington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Popma, Christopher J.; Gibson, Charles Michael] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc Med, Boston, MA 02215 USA. [Gibson, Charles Michael] Harvard Univ, Sch Med, Boston, MA USA. RP Harrington, RA (reprint author), Stanford Univ, Dept Med, 300 Pasteur Dr,S-102, Stanford, CA 94305 USA. EM robert.harrington@stanford.edu NR 23 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD SEP PY 2014 VL 25 IS 6 BP 453 EP 455 DI 10.1097/MCA.0000000000000137 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AN4LW UT WOS:000340560300001 PM 25072657 ER PT J AU Hsieh, SJ Zhuo, HJ Benowitz, NL Thompson, BT Liu, KD Matthay, MA Calfee, CS AF Hsieh, S. Jean Zhuo, Hanjing Benowitz, Neal L. Thompson, B. Taylor Liu, Kathleen D. Matthay, Michael A. Calfee, Carolyn S. CA Natl Heart Lung Blood Inst Acute Resp Distress Syndrome TI Prevalence and Impact of Active and Passive Cigarette Smoking in Acute Respiratory Distress Syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; acute respiratory distress syndrome; cigarette smoking; lung injury; mortality ID ACUTE LUNG INJURY; ALCOHOL SCREENING SCORES; SECONDHAND SMOKE; UNITED-STATES; RISK-FACTORS; METABOLITE 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANOL; ETHANOL INGESTION; BARRIER FUNCTION; CLINICAL-TRIAL; MORTALITY AB Objectives: Cigarette smoke exposure has recently been found to be associated with increased susceptibility to trauma-and transfusion-associated acute respiratory distress syndrome. We sought to determine 1) the incidence of cigarette smoke exposure in a diverse multicenter sample of acute respiratory distress syndrome patients and 2) whether cigarette smoke exposure is associated with severity of lung injury and mortality in acute respiratory distress syndrome. Design: Analysis of the Albuterol for the Treatment of Acute Lung Injury and Omega Acute Respiratory Distress Syndrome Network studies. Setting: Acute Respiratory Distress Syndrome Network hospitals. Patients: Three hundred eighty-one patients with acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: 4-(Methylnitrosamino)1-(3-pyridyl)-1-butanol, a validated tobacco-specific marker, was measured in urine samples from subjects enrolled in two National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network randomized controlled trials. Urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels were consistent with active smoking in 36% of acute respiratory distress syndrome patients and with passive smoking in 41% of nonsmokers (vs 20% and 40% in general population, respectively). Patients with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels in the active smoking range were younger and had a higher incidence of alcohol misuse, fewer comorbidities, lower severity of illness, and less septic shock at enrollment compared with patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels. Despite this lower severity of illness, the severity of lung injury did not significantly differ based on biomarker-determined smoking status. Cigarette smoke exposure was not significantly associated with death after adjusting for differences in age, alcohol use, comorbidities, and severity of illness. Conclusions: In this first multicenter study of biomarker-determined cigarette smoke exposure in acute respiratory distress syndrome patients, we found that active cigarette smoke exposure was significantly more prevalent among acute respiratory distress syndrome patients compared to population averages. Despite their younger age, better overall health, and lower severity of illness, smokers by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol had similar severity of lung injury as patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. These findings suggest that active cigarette smoking may increase susceptibility to acute respiratory distress syndrome in younger, healthier patients. C1 [Hsieh, S. Jean] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care Med, Bronx, NY 10467 USA. [Zhuo, Hanjing; Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Benowitz, Neal L.] Univ Calif San Francisco, Div Clin Pharmacol & Expt Therapeut, San Francisco, CA 94143 USA. [Benowitz, Neal L.; Calfee, Carolyn S.] Univ Calif San Francisco, Ctr Tobacco Control Res & Educ, San Francisco, CA 94143 USA. [Thompson, B. Taylor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care Med,Dept Med, Boston, MA USA. [Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. [Liu, Kathleen D.; Matthay, Michael A.; Calfee, Carolyn S.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Matthay, Michael A.; Calfee, Carolyn S.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care, San Francisco, CA USA. RP Hsieh, SJ (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care Med, Bronx, NY 10467 USA. EM shsieh@montefiore.org RI Brown, Samuel/E-6846-2015; OI Brown, Samuel/0000-0003-1206-6261; Hsieh, S. Jean/0000-0002-2716-4609 FU Albert Einstein College of Medicine Institute of Clinical and Translational Research [8KL2TR0000088-05]; National Institute on Aging (NIA) National Institutes of Health (NIH) [8KL2TR0000088-05, 1R03AG040673GEMSSTAR]; Einstein-Montefiore Clinical and Translational Science Awards [1 UL1 TR001073-01, 1 TL1 TR001072-01, 1 KL2 TR001071-01]; NIH [DA12393, HL090833, HL110969, UL1 RR024131]; University of California; San Francisco Comprehensive Cancer Center; Flight Attendants Medical Research Institute; GlaxoSmithKline; National Heart, Lung, and Blood Institute (NHLBI) (Acute Respiratory Distress Syndrome Network) [N01-HR-56165-56713, HL51856]; National Institute of Allergy and Infectious Diseases; NHLBI; U.S. Department of Health and Human Services [HHSN268200536165C, HHSN268200536166C, HHSN268200536167C, HHSN268200536168C]; Flight Attendant Medical Research Institute; U.S. Department of Health and Human Services. [1 UL1 TR001073-01, 1 TL1 TR001072-01, 1 KL2 TR001071-01, HHSN268200536169C, HHSN268200536170C, HHSN268200536171C, HHSN268200536172C, HHSN268200536173C, HHSN268200536174C, HHSN268200536175C, HHSN268200536176C, HHSN268200536179C] FX Dr. Hsieh's institution received grant support from the Albert Einstein College of Medicine Institute of Clinical and Translational Research (8KL2TR0000088-05), (Mentored career development award) and from the National Institute on Aging (NIA) National Institutes of Health (NIH) (8KL2TR0000088-05) (Grants for Early Medical/Surgical Specialists Transition into Aging Research Award (1R03AG040673GEMSSTAR). Her institution received grant support from 1 UL1 TR001073-01, 1 TL1 TR001072-01, and 1 KL2 TR001071-01 (Einstein-Montefiore Clinical and Translational Science Awards). Dr. Benowitz provided expert testimony against tobacco companies, consulted for Pfizer and GlaxoSmithKline, received grant support from the NIH (DA12393) and University of California, San Francisco Comprehensive Cancer Center, and received royalties from McGraw Hill. His institution received grant support from the NIH and the Flight Attendants Medical Research Institute. Dr. Thompson's institution received grant support from the NIH. Dr. Liu served as board member for Astute Biomedical (Clinical Events Adjudication Committee), Complexa (Scientific Advisory Board), and Cytopheryx (Data Safety Monitoring Board); consulted for Abbvie and Chemocentryx; received support from Abbott (gift of reagents for biomarker assays) and CMIC Group (gift of reagents for biomarker assays); has stock options with Amgen; and received support for travel from the American Thoracic Society and the American Society of Nephrology. Dr. Liu and her institution received grant support from the NIH. Dr. Matthay served as board member for Roche-Genentech (chair of Data Safety Monitoring Board); consulted for GlaxoSmithKline and Cerus; received grant support from GlaxoSmithKline, National Heart, Lung, and Blood Institute (NHLBI) (Acute Respiratory Distress Syndrome Network N01-HR-56165-56713, HL51856), and National Institute of Allergy and Infectious Diseases; and received support for article research from the NIH. His institution received grant support from the NHLBI. Dr. Calfee received grant support from the NIH and GlaxoSmithKline, received support for travel from American Thoracic Society, and received support for article research from the NIH (HL090833, HL110969, and UL1 RR024131). The NHLBI ARDS Network received grant support from the U.S. Department of Health and Human Services (HHSN268200536165C through HHSN268200536176C, HHSN268200536179C; 1 UL1 TR001073-01, 1 TL1 TR001072-01, and 1 KL2 TR001071-01 [Einstein-Montefiore CTSA]). Her institution received grant support from the Flight Attendant Medical Research Institute and the NIH and consulted for Cerus. Dr. Zhuo has disclosed that she does not have any potential conflicts of interest. NR 49 TC 13 Z9 13 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2014 VL 42 IS 9 BP 2058 EP 2068 DI 10.1097/CCM.0000000000000418 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA AN7LF UT WOS:000340780800029 PM 24942512 ER PT J AU Legrand, M Mebazaa, A Ronco, C Januzzi, JL AF Legrand, Matthieu Mebazaa, Alexandre Ronco, Claudio Januzzi, James L., Jr. TI When Cardiac Failure, Kidney Dysfunction, and Kidney Injury Intersect in Acute Conditions: The Case of Cardiorenal Syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute kidney injury; biomarkers; mortality; outcome; renal failure; treatment ID DECOMPENSATED HEART-FAILURE; GELATINASE-ASSOCIATED LIPOCALIN; IMPAIRED RENAL-FUNCTION; BETA-TRACE PROTEIN; MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; VENOUS CONGESTION; PROGNOSTIC VALUE; TUBULAR DAMAGE; CYSTATIN C AB Objective: To review and describe diagnostic and prognostic value of biomarkers of renal function and renal injury in the cardiorenal syndrome complicating acutely decompensated heart failure. Data Sources: PubMed search and review of relevant medical literature. Study Selection: Two reviewers screened and selected studies in English with diagnostic or prognostic assessment of biomarkers of renal injury. Data Extraction: Narrative review of the medical literature. Data Synthesis: Cardiorenal syndrome has a complex pathophysiology and has a generally poor prognosis in patients with acutely decompensated heart failure. Among the methods to recognize risk for cardiorenal syndrome may be the use of circulating or urinary biomarkers, which may allow for more accurate early diagnosis and risk stratification; use of biomarkers may provide important pathophysiologic understanding beyond risk prediction. However, different phenotypes of patients with acute renal dysfunction may be present, which has ramifications with respect to response to treatment strategies. Addition of biomarkers of renal injury may provide additional prognostic value to biomarkers of renal or cardiac function, but more data are needed. Conclusions: Biomarkers reflecting renal function and injury are likely to better phenotype subgroups of patients with cardiorenal syndrome and to provide unique prognostic information. Future studies are needed relative to strategies using such biomarkers to guide care of affected patients. C1 [Legrand, Matthieu; Mebazaa, Alexandre] Grp Hosp St Louis Lariboisiere, AP HP, Dept Anesthesiol, Paris, France. [Legrand, Matthieu; Mebazaa, Alexandre] Hop Univ St Louis Lariboisiere, Crit Care & Burn Unit, Paris, France. [Legrand, Matthieu; Mebazaa, Alexandre] Univ Paris Diderot, Paris, France. [Legrand, Matthieu; Mebazaa, Alexandre] Inserm UMR942, Paris, France. [Ronco, Claudio] San Bortolo Hosp, Dept Nephrol Dialysis & Transplantat, Vicenza, Italy. [Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02163 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02163 USA. EM jjanuzzi@partners.org FU Alere; Pfizer; BRAHMS; Bioporto; Orion; Thermo-Fisher; Edwards; Critical Diagnostics; Roche Diagnostics; Novartis; Amgen; Zensun; Radiometer; Boeringer Ingelheim; Siemens; BG Medicine; Singulex FX Dr. Legrand has received lecture fees from Alere, travel grants from Pfizer, and research funds from BRAHMS and Bioporto. Dr. Mebazaa served as board member for Critical Diagnostics, The Medicine Company, Cardiorentis, and Bayer and lectured for Alere, Bayer, Edwards Life Sciences, The Medicines Company, Novartis, Orion, Servier, Thermo-Fisher, and Vifor Pharma. He receives fees for lectures from Orion, Alere, Thermo-Fisher, and Edwards, consulting income from Bayer, Cardiorentis, Novartis, Vifor, and The Medicines Company, and grants from Critical Diagnostics. Dr. Ronco received support for development of educational presentations from GE; consulted for Alere, Astute, Abbvie, and General Electric; and lectured for FMC, Gambro, and B. Braun. His institution consulted for ASAHI and received support for travel from FMC and Gambro. Dr. Januzzi received support for participation in review activities from Radiometer. He received consulting fees from Roche Diagnostics, Critical Diagnostics, Novartis, Amgen, Zensun, Radiometer, and Boeringer Ingelheim. His institution received grant support from Roche Diagnostics, Siemens, Critical Diagnostics, BG Medicine, Singulex, and Thermo-Fisher. Drs. Legrand, Januzzi, and Mebazaa are members of the Global research onacute conditions team network. NR 63 TC 11 Z9 11 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2014 VL 42 IS 9 BP 2109 EP 2117 DI 10.1097/CCM.0000000000000404 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA AN7LF UT WOS:000340780800035 PM 24810531 ER PT J AU Mangiavini, L Merceron, C Araldi, E Khatri, R Gerard-O'Riley, R Wilson, TL Rankin, EB Giaccia, AJ Schipani, E AF Mangiavini, Laura Merceron, Christophe Araldi, Elisa Khatri, Richa Gerard-O'Riley, Rita Wilson, Tremika LeShan Rankin, Erinn B. Giaccia, Amato J. Schipani, Ernestina TI Loss of VHL in mesenchymal progenitors of the limb bud alters multiple steps of endochondral bone development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Endochondral bone development; Limb bud mesenchyme; Von Hippel-Lindau; Hypoxia Inducible Factor ID HYPOXIA-INDUCIBLE FACTORS; LINDAU TUMOR-SUPPRESSOR; UNFOLDED PROTEIN RESPONSE; GROWTH-PLATE; SKELETAL DEVELOPMENT; ENDOPLASMIC-RETICULUM; CHONDROCYTE SURVIVAL; CELLULAR ADAPTATION; HIF-ALPHA; FACTOR-I AB Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-l alpha (HIF-1 alpha) and HIF-2 alpha are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia. We have previously demonstrated that the transcription factor HIF-l alpha is essential for survival and differentiation of growth plate chondrocytes, whereas HIF-2 alpha is not necessary for fetal growth plate development. We have also shown that VHL is important for endochondral bone development, since loss of VHL in chondrocytes causes severe dwarfism. In this study, in order to expand our understanding of the role of VHL in chondrogenesis, we conditionally deleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondrocyte lineage. Deficiency of VHL in limb bud mesenchyme does not alter the timely differentiation of mesenchymal cells into chondrocytes. However, it causes structural collapse of the cartilaginous growth plate as a result of impaired proliferation, delayed terminal differentiation, and ectopic death of chondrocytes. This phenotype is associated to delayed replacement of cartilage by bone. Notably, loss of HIF-2 alpha fully rescues the late formation of the bone marrow cavity in VHL mutant mice, though it does not affect any other detectable abnormality of the VHL mutant growth plates. Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements. (C) 2014 Elsevier Inc. All rights reserved. C1 [Mangiavini, Laura; Merceron, Christophe; Wilson, Tremika LeShan; Schipani, Ernestina] Univ Michigan, Sch Med, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA. [Mangiavini, Laura; Merceron, Christophe; Gerard-O'Riley, Rita; Wilson, Tremika LeShan; Schipani, Ernestina] Indiana Univ, Dept Med, Sch Med, Div Endocrinol, Indianapolis, IN 46202 USA. [Mangiavini, Laura; Araldi, Elisa; Khatri, Richa; Wilson, Tremika LeShan; Rankin, Erinn B.; Schipani, Ernestina] Harvard Univ, Sch Med, Endocrine Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mangiavini, Laura] Milano Bicocca Univ, Dept Orthopaed & Traumatol, I-20900 Monza, MB, Italy. [Merceron, Christophe] INSERM, UMRS LIOAD 791, Ctr Osteoarticular & Dent Tissue Engn, Grp STEP Skeletal Tissue Engn & Physiopathol, F-44042 Nantes, France. [Merceron, Christophe] Univ Nantes, LUNAM, Fac Dent Surg, Nantes, France. [Rankin, Erinn B.; Giaccia, Amato J.] Stanford Univ, Dept Radiat Oncol, Div Radiat & Canc Biol, Stanford, CA 94303 USA. [Schipani, Ernestina] Univ Michigan, Sch Med, Dept Med, Div Endocrinol, Ann Arbor, MI 48109 USA. RP Schipani, E (reprint author), Univ Michigan, Sch Med, A Alfred Taubman Biomed Sci Res Bldg, Ann Arbor, MI 48109 USA. EM eschipan@med.umich.edu RI merceron, christophe/P-1306-2014; Mangiavini, Laura/K-6340-2016 OI Mangiavini, Laura/0000-0003-1892-1249 FU NIH [R01 (AR065403-01)]; People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7) under the Research Executive Agency [300388] FX This work was supported by the NIH R01 (AR065403-01) Grant (to ES and AJG). Christophe Merceron received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) registered under the Research Executive Agency Grant Agreement no. 300388. NR 64 TC 6 Z9 6 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2014 VL 393 IS 1 BP 124 EP 136 DI 10.1016/j.ydbio.2014.06.013 PG 13 WC Developmental Biology SC Developmental Biology GA AN6JO UT WOS:000340701000012 PM 24972088 ER PT J AU Raz, I Bhatt, DL Hirshberg, B Mosenzon, O Scirica, BM Umez-Eronini, A Im, K Stahre, C Buskila, A Iqbal, N Greenberger, N Lerch, MM AF Raz, Itamar Bhatt, Deepak L. Hirshberg, Boaz Mosenzon, Ofri Scirica, Benjamin M. Umez-Eronini, Amarachi Im, KyungAh Stahre, Christina Buskila, Alona Iqbal, Nayyar Greenberger, Norton Lerch, Markus M. TI Incidence of Pancreatitis and Pancreatic Cancer in a Randomized Controlled Multicenter Trial (SAVOR-TIMI 53) of the Dipeptidyl Peptidase-4 Inhibitor Saxagliptin SO DIABETES CARE LA English DT Article ID INCRETIN-BASED THERAPIES; ATLANTA CLASSIFICATION; CARDIOVASCULAR-DISEASE; CLINICAL-USE; RISK; POPULATION; RATIONALE; OUTCOMES; COHORT; EXENATIDE AB OBJECTIVE To determine the incidence of pancreatitis and pancreatic cancer in the SAVOR-TIMI 53 trial. RESEARCH DESIGN AND METHODS A total of 16,492 type 2 diabetic patients >= 40 years old with established cardiovascular (CV) disease or CV risk factors were randomized to saxagliptin or placebo and followed for 2.1 years. Outcome measures were investigator reported with blinded expert adjudication of total pancreatitis (acute and chronic) and reported cases of pancreatic cancer. RESULTS Trial investigators reported 35 events of pancreatitis in each treatment arm in 63 patients (33 [0.40%] in the saxagliptin arm and 30 [0.37%] in control arm), with a hazard ratio (HR) of 1.09 (95% CI 0.66-1.79, P = 0.80). Adjudication confirmed pancreatitis in 24 patients (26 events) in the saxagliptin arm (0.29%) and 21 patients (25 events) in placebo arm (0.26%), with an HR of 1.13 (0.63-2.06, P = 0.77). Cases of definite acute pancreatitis were confirmed in 17 (0.2%) vs. 9 (0.1%) (HR 1.88 [0.86-4.41], P = 0.17), definite plus possible pancreatitis in 22 vs. 16 (HR 1.36 [0.72-2.64], P = 0.42), and chronic pancreatitis in 2 vs. 6 (HR 0.33 [0.05-1.44], P = 0.18) in the saxagliptin and placebo arms, respectively. No differences in time to event onset, concomitant risk factors for pancreatitis, investigator-reported causality from study medication or disease severity, and outcome were found between treatment arms. The investigators reported 5 and 12 cases of pancreatic cancer in the saxagliptin and placebo arms, respectively (HR 0.42 [0.13-1.12], P = 0.09). CONCLUSIONS In the SAVOR-TIMI 53 trial, within 2.1 years of follow-up, risk for pancreatitis in type 2 diabetic patients treated with saxagliptin was low and apparently similar to placebo, with no sign of increased risk for pancreatic cancer. Further studies are needed to completely resolve the pancreatic safety issues with incretin-based therapy. C1 [Raz, Itamar; Mosenzon, Ofri; Buskila, Alona] Hadassah Hebrew Univ Hosp, Dept Med, Diabet Unit, Jerusalem, Israel. [Bhatt, Deepak L.; Scirica, Benjamin M.; Umez-Eronini, Amarachi; Im, KyungAh; Greenberger, Norton] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Bhatt, Deepak L.; Scirica, Benjamin M.; Umez-Eronini, Amarachi; Im, KyungAh; Greenberger, Norton] Harvard Univ, Sch Med, Boston, MA USA. [Hirshberg, Boaz] AstraZeneca Res & Dev, Wilmington, DE USA. [Stahre, Christina] AstraZeneca Res & Dev, Molndal, Sweden. [Iqbal, Nayyar] Bristol Myers Squibb Co, Princeton, NJ USA. [Lerch, Markus M.] Univ Med Greifswald, Greifswald, Germany. RP Raz, I (reprint author), Hadassah Hebrew Univ Hosp, Dept Med, Diabet Unit, Jerusalem, Israel. EM ntv502@netvision.net.il RI Lerch, Markus M./E-2206-2016 OI Lerch, Markus M./0000-0002-9643-8263 FU AstraZeneca; Bristol-Myers Squibb (BMS); Amarin; AstraZeneca/BMS; Eisai; Ethicon; Medtronic; Roche; Sanofi; Medicines Company; Hadassah University Hospital - Novo Nordisk; Brigham and Women's Hospital from AstraZeneca/BMS; Daichi-Sankyo; GlaxoSmithKline; Johnson Johnson; Gilead; Arena; Merck; Lexicon; BMS; St. Jude's Medical FX AstraZeneca and Bristol-Myers Squibb (BMS) funded the study.; I.R. discloses the following relationships: advisory board for Novo Nordisk, AstraZeneca/BMS, Sanofi, Merck Sharp & Dohme (MSD), and Eli Lilly; consultant for AstraZeneca/BMS, Insuline, and Andromeda Biotech Ltd.; and speaker's bureau for Novo Nordisk, AstraZeneca/BMS, Sanofi, MSD, Eli Lilly, and Novartis. D. L. B. discloses the following relationships: advisory board for Elsevier PracticeUpdate Cardiology, Medscape Cardiology, and Regado Biosciences; board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; chair of the American Heart Association Get With The Guidelines Steering Committee; data monitoring committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; honoraria from the American College of Cardiology (editor, CardioSource clinical trial summaries), 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 (continuing medical education steering committees); other editorial activities for Clinical Cardiology (associate editor) and the Journal of the American College of Cardiology (section editor, pharmacology); research grant funding from Amarin, AstraZeneca/BMS, Eisai, Ethicon, Medtronic, Roche, Sanofi, and The Medicines Company; and unfunded research for FlowCo, PLx Pharma, and Takeda. B. H. and C. S. are employees of AstraZeneca. O.M. discloses the following relationships: research grant support through Hadassah University Hospital funded by Novo Nordisk; speaker's bureau for AstraZeneca/BMS, Novo Nordisk, Eli Lilly, Sanofi, Novartis, and MSD; advisory board for AstraZeneca/BMS, Novo Nordisk, Eli Lilly, Sanofi, and Novartis; and grants paid to her institution as study physician by AstraZeneca/BMS. B. M. S. discloses the following relationships: research grant support through Brigham and Women's Hospital from AstraZeneca/BMS, Daichi-Sankyo, GlaxoSmithKline, Johnson & Johnson, Gilead, Eisai, Arena, and Merck; consulting fees from Gilead, Arena, Eisai, Lexicon, BMS, and St. Jude's Medical; and editorial board for Elsevier (PracticeUpdate Cardiology). A.U.-E. and K. I. disclose research grant support to the TIMI Study Group from AstraZeneca. A. B. is the Hadassah University Hospital Diabetes Unit Project Manager for the SAVOR-TIMI 53 trial. N.I. is an employee of BMS. M. M. L. discloses the following relationships: advisory board for Eli Lilly, Roche, Solvay, Abbott, MSD, and AstraZeneca; consultant for British Biotech, Bioserve, Centogene, Metanomics, Takeda, AstraZeneca/BMS, Sanochemia, Alpinia, and Novartis; and speaker's bureau for Menarini, Recordati, Falk, Nordmark, Solvay, Abbott, AbbVie, and Roche. No other potential conflicts of interest relevant to this article were reported. NR 35 TC 30 Z9 32 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2014 VL 37 IS 9 BP 2435 EP 2441 DI 10.2337/dc13-2546 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN8HX UT WOS:000340846300015 PM 24914244 ER PT J AU Walford, GA Porneala, BC Dauriz, M Vassy, JL Cheng, S Rhee, EP Wang, TJ Meigs, JB Gerszten, RE Florez, JC AF Walford, Geoffrey A. Porneala, Bianca C. Dauriz, Marco Vassy, Jason L. Cheng, Susan Rhee, Eugene P. Wang, Thomas J. Meigs, James B. Gerszten, Robert E. Florez, Jose C. TI Metabolite Traits and Genetic Risk Provide Complementary Information for the Prediction of Future Type 2 Diabetes SO DIABETES CARE LA English DT Article ID GENOME-WIDE ASSOCIATION; INSULIN-RESISTANCE; SUSCEPTIBILITY LOCI; COMMON VARIANT; BRANCHED-CHAIN; AMINO-ACIDS; RECLASSIFICATION; MELLITUS; GLUCOSE; SCORE AB OBJECTIVE A genetic risk score (GRS) comprised of single nucleotide polymorphisms (SNPs) and metabolite biomarkers have each been shown, separately, to predict incident type 2 diabetes. We tested whether genetic and metabolite markers provide complementary information for type 2 diabetes prediction and, together, improve the accuracy of prediction models containing clinical traits. RESEARCH DESIGN AND METHODS Diabetes risk was modeled with a 62-SNP GRS, nine metabolites, and clinical traits. We fit age- and sex-adjusted logistic regression models to test the association of these sources of information, separately and jointly, with incident type 2 diabetes among 1,622 initially nondiabetic participants from the Framingham Offspring Study. The predictive capacity of each model was assessed by area under the curve (AUC). RESULTS Two hundred and six new diabetes cases were observed during 13.5 years of follow-up. The AUC was greater for the model containing the GRS and metabolite measurements together versus GRS or metabolites alone (0.820 vs. 0.641, P < 0.0001, or 0.820 vs. 0.803, P = 0.01, respectively). Odds ratios for association of GRS or metabolites with type 2 diabetes were not attenuated in the combined model. The AUC was greater for the model containing the GRS, metabolites, and clinical traits versus clinical traits only (0.880 vs. 0.856, P = 0.002). CONCLUSIONS Metabolite and genetic traits provide complementary information to each other for the prediction of future type 2 diabetes. These novel markers of diabetes risk modestly improve the predictive accuracy of incident type 2 diabetes based only on traditional clinical risk factors. C1 [Walford, Geoffrey A.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. [Walford, Geoffrey A.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Walford, Geoffrey A.; Dauriz, Marco; Vassy, Jason L.; Cheng, Susan; Rhee, Eugene P.; Meigs, James B.; Gerszten, Robert E.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Porneala, Bianca C.; Dauriz, Marco; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Dauriz, Marco] Univ Verona, Sch Med, Dept Med, Div Endocrinol & Metab Dis, I-37100 Verona, Italy. [Dauriz, Marco] Hosp Trust Verona, I-37100 Verona, Italy. [Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. [Vassy, Jason L.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [Wang, Thomas J.] Vanderbilt Univ, Med Ctr, Div Cardiol, Nashville, TN USA. [Meigs, James B.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Walford, GA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. EM gwalford@partners.org; jcflorez@partners.org RI Dauriz, Marco/S-5843-2016 OI Dauriz, Marco/0000-0002-5542-5941 FU National Institutes of Health [NO1-HC-25195, R01-DK-HL081572, R01-DK-078616, K24-DK-080140]; American Heart Association; University of Verona; Ellison Foundation; [NIH-U01-HG006500]; [L30-DK-089597]; [K99-HL-107642] FX This work was supported by National Institutes of Health contracts NO1-HC-25195, R01-DK-HL081572, R01-DK-078616, and K24-DK-080140 and by the American Heart Association. M. D. is supported by research grants of the University of Verona. J.L.V. is supported by NIH-U01-HG006500 and L30-DK-089597. S.C. is supported in part by K99-HL-107642 and a grant from the Ellison Foundation. NR 35 TC 23 Z9 24 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2014 VL 37 IS 9 BP 2508 EP 2514 DI 10.2337/dc14-0560 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN8HX UT WOS:000340846300024 PM 24947790 ER PT J AU Espeland, MA Glick, HA Bertoni, A Brancati, FL Bray, GA Clark, JM Curtis, JM Egan, C Evans, M Foreyt, JP Ghazarian, S Gregg, EW Hazuda, HP Hill, JO Hire, D Horton, ES Hubbard, V Jakicic, JM Jeffery, RW Johnson, KC Kahn, SE Killean, T Kitabchi, AE Knowler, WC Kriska, A Lewis, CE Miller, M Montez, MG Murillo, A Nathan, DM Nyenwe, E Patricio, J Peters, AL Pi-Sunyer, X Pownall, H Redmon, B Rushing, J Ryan, DH Safford, M Tsai, AG Wadden, TA Wing, RR Yanovski, SZ Zhang, P AF Espeland, Mark A. Glick, Henry A. Bertoni, Alain Brancati, Frederick L. Bray, George A. Clark, Jeanne M. Curtis, Jeffrey M. Egan, Caitlin Evans, Mary Foreyt, John P. Ghazarian, Siran Gregg, Edward W. Hazuda, Helen P. Hill, James O. Hire, Don Horton, Edward S. Hubbard, Van S. Jakicic, John M. Jeffery, Robert W. Johnson, Karen C. Kahn, Steven E. Killean, Tina Kitabchi, Abbas E. Knowler, William C. Kriska, Andrea Lewis, Cora E. Miller, Marsha Montez, Maria G. Murillo, Anne Nathan, David M. Nyenwe, Ebenezer Patricio, Jennifer Peters, Anne L. Pi-Sunyer, Xavier Pownall, Henry Redmon, Bruce Rushing, Julia Ryan, Donna H. Safford, Monika Tsai, Adam G. Wadden, Thomas A. Wing, Rena R. Yanovski, Susan Z. Zhang, Ping CA Look AHEAD Res Grp TI Impact of an Intensive Lifestyle Intervention on Use and Cost of Medical Services Among Overweight and Obese Adults With Type 2 Diabetes: The Action for Health in Diabetes SO DIABETES CARE LA English DT Article ID DISEASE RISK-FACTORS; LOOK-AHEAD ACTION; WEIGHT-LOSS; CARDIOVASCULAR-DISEASE; CLINICAL-TRIAL; MELLITUS; INDIVIDUALS; PREVENTION; METFORMIN; SAVINGS AB OBJECTIVE To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial. RESEARCH DESIGN AND METHODS A total of 5,121 overweight or obese adults with type 2 diabetes were randomly assigned to an ILI that promoted weight loss or to a comparison condition of diabetes support and education (DSE). Use and costs of health-care services were recorded across an average of 10 years. RESULTS ILI led to reductions in annual hospitalizations (11%, P = 0.004), hospital days (15%, P = 0.01), and number of medications (6%, P < 0.001), resulting in cost savings for hospitalization (10%, P = 0.04) and medication (7%, P < 0.001). ILI produced a mean relative per-person 10-year cost savings of $5,280 (95% CI 3,385-7,175); however, these were not evident among individuals with a history of cardiovascular disease. CONCLUSIONS Compared with DSE over 10 years, ILI participants had fewer hospitalizations, fewer medications, and lower health-care costs. C1 [Espeland, Mark A.; Hire, Don; Rushing, Julia] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Glick, Henry A.; Wadden, Thomas A.] Univ Penn, Weight & Eating Disorder Program, Philadelphia, PA 19104 USA. [Bertoni, Alain] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Brancati, Frederick L.; Clark, Jeanne M.] Johns Hopkins Sch Med, Baltimore, MD USA. [Bray, George A.; Ryan, Donna H.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Curtis, Jeffrey M.; Killean, Tina; Knowler, William C.] NIDDK, Southwest Amer Indian Ctr, Phoenix, AZ USA. [Egan, Caitlin; Wing, Rena R.] Miriam Hosp, Brown Med Sch, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA. [Evans, Mary; Hubbard, Van S.; Yanovski, Susan Z.] NIDDK, NIH, Bethesda, MD USA. [Foreyt, John P.; Pownall, Henry] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Ghazarian, Siran; Peters, Anne L.] Roybal Comprehens Hlth Ctr, Los Angeles, CA USA. [Gregg, Edward W.; Zhang, Ping] Ctr Dis Control & Prevent, Atlanta, GA USA. [Hazuda, Helen P.; Montez, Maria G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hill, James O.; Miller, Marsha] Univ Colorado, Hlth Sci Ctr, Anschutz Hlth & Wellness Ctr, Aurora, CO USA. [Horton, Edward S.] Joslin Diabet Ctr, Dept Clin Epidemiol, Boston, MA 02215 USA. [Jakicic, John M.; Kriska, Andrea] Univ Pittsburgh, Diabet Unit, Dept Hlth & Phys Act, Pittsburgh, PA USA. [Jeffery, Robert W.; Redmon, Bruce] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Johnson, Karen C.; Kitabchi, Abbas E.; Nyenwe, Ebenezer] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Kahn, Steven E.; Murillo, Anne] Univ Washington, Dept Med, Seattle, WA USA. [Lewis, Cora E.; Safford, Monika] Univ Alabama Birmingham, Birmingham, AL USA. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Patricio, Jennifer; Pi-Sunyer, Xavier] St Lukes Roosevelt Hosp, Div Dept Med, New York, NY 10025 USA. [Tsai, Adam G.] Univ Colorado, Hlth Sci Ctr, Div Internal Med, Aurora, CO USA. RP Espeland, MA (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. EM mespelan@wakehealth.edu OI Redmon, J. Bruce/0000-0002-1883-9467; Kriska, Andrea/0000-0002-3522-0869; Kahn, Steven/0000-0001-7307-9002 FU Merck; Amgen; Amylin Pharmaceuticals, LLC; Bristol-Myers Squibb/AstraZeneca; GI Dynamic, Inc.; Gilead Sciences, Inc.; International Medical Press Global Partnership for Effective Diabetes Management; Janssen Pharmaceuticals, Inc.; Merck Research Laboratories, Inc.; Sanofi, Inc.; Vivus, Inc.; Theracos Pharmaceuticals, Inc.; Takeda Pharmaceuticals, Inc.; Eli Lilly and Company; GlaxoSmithKline; Medtronic MiniMed; Medscape; Novo Nordisk; Janssen; Takeda; Vivus; Eisai; diaDexus FX M.A.E. serves on monitoring boards for Terumo Medical Corporation and the Kowa Research Institute. He serves on a steering committee for Boehringer Ingelheim and has recently served on an advisory committee for Takeda Global Research. H. A. G. has twice been a sponsored lecturer by Merck. J.O.H. serves on advisory boards for Takeda and Novo Nordisk. E. S. H. has received consulting, advisory board, monitoring board, and speakers' board support from Amgen; Amylin Pharmaceuticals, LLC; Bristol-Myers Squibb/AstraZeneca; GI Dynamic, Inc.; Gilead Sciences, Inc.; International Medical Press Global Partnership for Effective Diabetes Management; Janssen Pharmaceuticals, Inc.; Merck Research Laboratories, Inc.; Sanofi, Inc.; Vivus, Inc.; Theracos Pharmaceuticals, Inc.; and Takeda Pharmaceuticals, Inc. E.N. has received research support from Eli Lilly and Company and GlaxoSmithKline. A. L. P. has consulted for Abbott Diabetes Care, Becton Dickinson, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Lilly, Medtronic MiniMed, and Sanofi; has been on the speakers' bureau for Bristol-Myers Squibb/AstraZeneca and Novo Nordisk; has received research grant funding from Medtronic MiniMed; and has received editorial fees from Medscape. D. H. R. was a paid consultant/advisor to Novo Nordisk, Janssen, Takeda, Vivus, and Eisai and has an equity position in Scientific Intake. M. S. has received salary support from Amgen and diaDexus and has served as a consultant for diaDexus. T. A. W. serves on advisory boards for Novo Nordisk and Orexigen and is a consultant to Boehringer Ingelheim. No other potential conflicts of interest relevant to this article were reported. NR 32 TC 39 Z9 39 U1 5 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2014 VL 37 IS 9 BP 2548 EP 2556 DI 10.2337/dc14-0093 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN8HX UT WOS:000340846300029 PM 25147253 ER PT J AU Berkowitz, SA Gao, X Tucker, KL AF Berkowitz, Seth A. Gao, Xiang Tucker, Katherine L. TI Food-Insecure Dietary Patterns Are Associated With Poor Longitudinal Glycemic Control in Diabetes: Results From the Boston Puerto Rican Health Study SO DIABETES CARE LA English DT Article ID LOW-INCOME; ADULTS; INTERVENTION; DISPARITIES; OBESITY; ECONOMICS; OUTCOMES; PROGRAM; DISEASE; COST AB OBJECTIVE To determine whether dietary patterns associated with food insecurity are associated with poor longitudinal glycemic control. RESEARCH DESIGN AND METHODS In a prospective, population-based, longitudinal cohort study, we ascertained food security (Food Security Survey Module), dietary pattern (Healthy Eating Index-2005 [HEI 2005]), and hemoglobin A(1c) (HbA(1c)) in Puerto Rican adults aged 45-75 years with diabetes at baseline (2004-2009) and HbA(1c) at similar to 2 years follow-up (2006-2012). We determined associations between food insecurity and dietary pattern and assessed whether those dietary patterns were associated with poorer HbA(1c) concentration over time, using multivariable-adjusted repeated subjects mixed-effects models. RESULTS There were 584 participants with diabetes at baseline and 516 at follow-up. Food-insecure participants reported lower overall dietary quality and lower intake of fruit and vegetables. A food insecurity*HEI 2005 interaction (P < 0.001) suggested that better diet quality was more strongly associated with lower HbA(1c) in food-insecure than food-secure participants. In adjusted models, lower follow-up HbA(1c) was associated with greater HEI 2005 score (beta = -0.01 HbA(1c)% per HEI 2005 point, per year, P = 0.003) and with subscores of total vegetables (beta = -0.09, P = 0.04) and dark green and orange vegetables and legumes (beta = -0.06, P = 0.048). Compared with the minimum total vegetable score, a participant with the maximum score showed relative improvements of HbA(1c) of 0.5% per year. CONCLUSIONS Food insecurity was associated with lower overall dietary quality and lower consumption of plant-based foods, which was associated with poor longitudinal glycemic control. C1 [Berkowitz, Seth A.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Berkowitz, Seth A.; Gao, Xiang] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gao, Xiang] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Tucker, Katherine L.] Univ Massachusetts, Dept Clin Lab & Nutr Sci, Lowell, MA USA. RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. EM saberkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297 FU Institutional National Research Service Award [T32HP10251]; Ryoichi Sasakawa Young Leaders Fellowship Fund; General Medicine Division at Massachusetts General Hospital; National Institute on Aging [P01-AG-023394]; National Heart, Lung, and Blood Institute [P50-HL-105185] FX S.A.B. was supported by an Institutional National Research Service Award T32HP10251, the Ryoichi Sasakawa Young Leaders Fellowship Fund, and the General Medicine Division at Massachusetts General Hospital. The Boston Puerto Rican Health Study was supported by the National Institute on Aging (P01-AG-023394) and the National Heart, Lung, and Blood Institute (P50-HL-105185). NR 30 TC 9 Z9 9 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2014 VL 37 IS 9 BP 2587 EP 2592 DI 10.2337/dc14-0753 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN8HX UT WOS:000340846300034 PM 24969578 ER PT J AU Skupien, J Warram, JH Niewczas, MA Gohda, T Malecki, M Mychaleckyj, JC Galecki, AT Krolewski, AS AF Skupien, Jan Warram, James H. Niewczas, Monika A. Gohda, Tomohito Malecki, Maciej Mychaleckyj, Josyf C. Galecki, Andrzej T. Krolewski, Andrzej S. TI Synergism Between Circulating Tumor Necrosis Factor Receptor 2 and HbA(1c) in Determining Renal Decline During 5-18 Years of Follow-up in Patients With Type 1 Diabetes and Proteinuria SO DIABETES CARE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; MARKERS; DISEASE; RISK; ESRD AB OBJECTIVE We studied the serum concentration of tumor necrosis factor receptor 2 (TNFR2) and the rate of renal decline, a measure of the intensity of the disease process leading to end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS A cohort of 349 type 1 diabetic patients with proteinuria was followed for 5-18 years. Serum TNFR2, glycated hemoglobin A(1c) (HbA(1c)), and other characteristics were measured at enrollment. We used a novel analytic approach, a joint longitudinal-survival model, fitted to serial estimates of glomerular filtration rate (eGFR) based on serum creatinine (median seven per patient) and time to onset of ESRD (112 patients) to estimate the rate of renal decline (eGFR loss). RESULTS At enrollment, all patients had chronic kidney disease stage 1-3. The mean (+/- SD) rate of eGFR loss during 5-18 years of follow-up was 25.2 (64.9) mL/min/1.73 m(2)/year. Serum TNFR2 was the strongest determinant of renal decline and ESRD risk (C-index 0.79). The rate of eGFR loss became steeper with rising concentration of TNFR2, and elevated HbA(1c) augmented the strength of this association (P = 0.030 for interaction). In patients with HbA(1c) 10.1% (87 mmol/mol), the difference in the rate of eGFR loss between the first and fourth quartiles of TNFR2 was 5.4 mL/min/1.73 m(2)/year, whereas it was only 1.9 in those with HbA(1c) < 7.9% (63 mmol/mol). CONCLUSIONS Circulating TNFR2 is a major determinant of renal decline in patients with type 1 diabetes and proteinuria. Elevated HbA(1c) magnifies its effect. Although the mechanisms of this synergism are unknown, our findings allow us to stratify patients according to risk of ESRD. C1 [Skupien, Jan; Warram, James H.; Niewczas, Monika A.; Gohda, Tomohito; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Skupien, Jan; Warram, James H.; Niewczas, Monika A.; Gohda, Tomohito; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Skupien, Jan; Malecki, Maciej] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. [Gohda, Tomohito] Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol, Tokyo 113, Japan. [Mychaleckyj, Josyf C.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Galecki, Andrzej T.] Univ Michigan Hlth Syst, Dept Biostat, Ann Arbor, MI USA. [Galecki, Andrzej T.] Univ Michigan Hlth Syst, Div Geriatr Med, Ann Arbor, MI USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU JDRF [3-2009-397, 1-2008-1018, 17-2013-8]; National Institutes of Health [DK-41526] FX This study was funded through JDRF fellowship grant 3-2009-397 (J.S.), JDRF research grants 1-2008-1018 and 17-2013-8 (A.S.K.), and National Institutes of Health grant DK-41526 (A.S.K.). NR 18 TC 8 Z9 8 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2014 VL 37 IS 9 BP 2601 EP 2608 DI 10.2337/dc13-1983 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN8HX UT WOS:000340846300036 PM 24898299 ER PT J AU Perreault, L Temprosa, M Mather, KJ Horton, E Kitabchi, A Larkin, M Montez, MG Thayer, D Orchard, TJ Hamman, RF Goldberg, RB AF Perreault, Leigh Temprosa, Marinella Mather, Kieren J. Horton, Ed Kitabchi, Abbas Larkin, Mary Montez, Maria G. Thayer, Debra Orchard, Trevor J. Hamman, Richard F. Goldberg, Ronald B. CA Diabet Prevention Program Res Grp TI Regression From Prediabetes to Normal Glucose Regulation Is Associated With Reduction in Cardiovascular Risk: Results From the Diabetes Prevention Program Outcomes Study SO DIABETES CARE LA English DT Article ID LIFE-STYLE INTERVENTION; CORONARY-HEART-DISEASE; WEIGHT-LOSS; BLOOD-PRESSURE; INSULIN-RESISTANCE; METABOLIC SYNDROME; RANDOMIZED-TRIAL; HISPANIC WOMEN; TYPE-2; TOLERANCE AB OBJECTIVE Restoration of normal glucose regulation (NGR) in people with prediabetes significantly decreases the risk of future diabetes. We sought to examine whether regression to NGR is also associated with a long-term decrease in cardiovascular disease (CVD) risk. RESEARCH DESIGN AND METHODS The Framingham (2008) score (as an estimate of the global 10-year CVD risk) and individual CVD risk factors were calculated annually for the Diabetes Prevention Program Outcomes Study years 1-10 among those patients who returned to NGR at least once during the Diabetes Prevention Program (DPP) compared with those who remained with prediabetes or those in whom diabetes developed during DPP (N = 2,775). RESULTS The Framingham scores by glycemic exposure did not differ among the treatment groups; therefore, pooled estimates were stratified by glycemic status and were adjusted for differences in risk factors at DPP baseline and in the treatment arm. During 10 years of follow-up, the mean Framingham 10-year CVD risk scores were highest in the prediabetes group (16.2%), intermediate in the NGR group (15.5%), and 14.4% in people with diabetes (all pairwise comparisons P < 0.05), but scores decreased over time for those people with prediabetes (18.6% in year 1 vs. 15.9% in year 10, P < 0.01). The lower score in the diabetes group versus other groups, a declining score in the prediabetes group, and favorable changes in each individual risk factor in all groups were explained, in part, by higher or increasing medication use for lipids and blood pressure. CONCLUSIONS Prediabetes represents a high-risk state for CVD. Restoration of NGR and/or medical treatment of CVD risk factors can significantly reduce the estimated CVD risk in people with prediabetes. C1 [Perreault, Leigh] Univ Colorado, Aurora, CO 80204 USA. [Temprosa, Marinella] George Washington Univ, Biostat Ctr, Rockville, MD USA. [Mather, Kieren J.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Horton, Ed] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kitabchi, Abbas] Univ Tennessee, Memphis, TN USA. [Larkin, Mary] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Montez, Maria G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Thayer, Debra] Medstar Hlth Res Inst, Hyattsville, MD USA. [Orchard, Trevor J.] Univ Pittsburgh, Pittsburgh, PA USA. [Hamman, Richard F.] Colorado Sch Publ Hlth, Aurora, CO USA. [Goldberg, Ronald B.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Perreault, L (reprint author), Univ Colorado, Anschutz Med Campus, Aurora, CO 80204 USA. EM leigh.perreault@ucdenver.edu OI orchard, trevor/0000-0001-9552-3215 FU National Institutes of Health (NIH) [5U01-DK-048375-12]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH; NIDDK; Intramural Research Program; Indian Health Service; National Institute of Child Health and Human Development; National Institute on Aging; National Eye Institute; National Heart, Lung, and Blood Institute; Office of Research on Women's Health; National Institute on Minority Health and Health Disparities; Centers for Disease Control and Prevention; American Diabetes Association; Bristol-Myers Squibb; Parke-Davis FX This work was supported by National Institutes of Health (NIH) grant 5U01-DK-048375-12. During the Diabetes Prevention Program Outcomes Study (DPPOS), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study and for the collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart, Lung, and Blood Institute, the Office of Research on Women's Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided additional funding and material support during the Diabetes Prevention Program (DPP), Lipha (Merck Sante) provided medication, and LifeScan Inc. donated materials during the DPP and DPPOS. The opinions expressed are those of the investigators and do not necessarily reflect the views of the funding agencies. NR 49 TC 16 Z9 16 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2014 VL 37 IS 9 BP 2622 EP 2631 DI 10.2337/dc14-0656 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN8HX UT WOS:000340846300039 PM 24969574 ER PT J AU Jalilvand, A Fisichella, PM AF Jalilvand, Anahita Fisichella, Piero Marco TI Superior mesenteric artery syndrome SO DIGESTIVE AND LIVER DISEASE LA English DT Editorial Material C1 [Jalilvand, Anahita] Loyola Univ, Med Ctr, Dept Surg, New Orleans, LA 70118 USA. [Fisichella, Piero Marco] Boston VA Healthcare Syst, Dept Surg, Boston, MA USA. RP Fisichella, PM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Boston VA Healthcare Syst, 1400 VFW Pkwy 112, West Roxbury, MA 02132 USA. EM piero.fisichella@va.gov NR 1 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1590-8658 EI 1878-3562 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD SEP PY 2014 VL 46 IS 9 BP 859 EP 859 DI 10.1016/j.dld.2014.03.021 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2LM UT WOS:000341154000017 PM 24791667 ER PT J AU Arney, J Street, RL Naik, AD AF Arney, Jennifer Street, Richard L., Jr. Naik, Aanand D. TI Factors Shaping Physicians' Willingness to Accommodate Medication Requests SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE patient-provider relationships; physician behavior; prescribing patterns/practices; patient-centered care; primary care ID GENERAL-PRACTITIONERS; DECISION-MAKING; COMMUNICATION; PRESCRIBE AB Medical decisions, including physicians' prescribing behaviors, are shaped by a complex interplay of clinical and nonclinical factors. We aim to determine how physician, patient, and relationship characteristics influence physicians' decisions to accommodate brand-name prescription drug requests. We applied multivariate logistic regression to data from the Attitudinal and Behavioral Effects of Direct-to-Consumer Promotion of Prescription Drugs physician survey. We used a national probability sample of 500 primary care and specialty physicians reporting on a clinical encounter that involved a prescription drug request. Independent variables include physician's assessment of the patient's understanding of risks and benefits of a requested medication, whether the patient had the condition the drug treats, duration of the clinical relationship, and physician's age, area of practice, years of experience, and gender. These variables were used to predict whether the physician prescribed the requested drug. Physicians were more willing to accommodate requests when they believed that patients had a clear understanding of the drug's risks and when patients had the condition the drug treats. Primary care practitioners, compared to specialists, had higher odds of prescribing a requested drug. We conclude that clinical and communicative factors shape physicians' decisions to prescribe requested brand-name drugs. Findings offer insight into the influence that direct-to-consumer advertising can have in medical encounters, and may guide efforts to enhance physician-patient communication and shared decision making. C1 [Arney, Jennifer] Univ Houston Clear Lake, Dept Sociol, Houston, TX 77058 USA. [Arney, Jennifer; Street, Richard L., Jr.; Naik, Aanand D.] Michael E DeBakey Dept Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Arney, Jennifer; Street, Richard L., Jr.; Naik, Aanand D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Arney, J (reprint author), Univ Houston Clear Lake, Dept Sociol, 2700 Bay Area Blvd, Houston, TX 77058 USA. EM Arney@bcm.edu FU Division of Graduate Studies at Arizona State University; National Science Foundation's Division of Social, Behavioral, and Economic Sciences [0828582]; Houston VA HSR&D Center of Excellence [HFP90-020]; National Institute on Aging [K23AG027144] FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Division of Graduate Studies at Arizona State University and by the National Science Foundation's Division of Social, Behavioral, and Economic Sciences (Award ID 0828582). Additional support was provided by the Houston VA HSR&D Center of Excellence (HFP90-020), and the National Institute on Aging (K23AG027144). NR 24 TC 2 Z9 2 U1 0 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 EI 1552-3918 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD SEP PY 2014 VL 37 IS 3 BP 349 EP 365 DI 10.1177/0163278712468756 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AN6PE UT WOS:000340716700004 PM 23232050 ER PT J AU Sun, DW Nakao, S Xie, F Zandi, S Bagheri, A Kanavi, MR Samiei, S Soheili, ZS Frimmel, S Zhang, ZY Ablonczy, Z Ahmadieh, H Hafezi-Moghadam, A AF Sun, Dawei Nakao, Shintaro Xie, Fang Zandi, Souska Bagheri, Abouzar Kanavi, Mozhgan Rezaei Samiei, Shahram Soheili, Zahra-Soheila Frimmel, Sonja Zhang, Zhongyu Ablonczy, Zsolt Ahmadieh, Hamid Hafezi-Moghadam, Ali TI Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis SO FASEB JOURNAL LA English DT Article DE retinopathy; endothelial injury; probe development; preventive care ID ENDOTHELIAL GROWTH-FACTOR; METABOLIC SYNDROME; RETINOPATHY; VESSELS; LEUKOCYTE; INJURY; MODEL AB Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26 +/- 2 vs. 3 +/- 1 mu m/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. C1 [Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Frimmel, Sonja; Zhang, Zhongyu; Hafezi-Moghadam, Ali] Brigham & Womens Hosp, Ctr Excellence Funct & Mol Imaging, Boston, MA 02115 USA. [Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Frimmel, Sonja; Zhang, Zhongyu; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Frimmel, Sonja; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Frimmel, Sonja; Hafezi-Moghadam, Ali] Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. [Sun, Dawei; Xie, Fang] Harbin Med Univ, Affiliated Hosp 2, Dept Ophthalmol, Harbin, Peoples R China. [Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Ahmadieh, Hamid] Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran. [Samiei, Shahram] High Inst Res & Educ Transfus Med, Blood Transfus Res Ctr, Tehran, Iran. [Soheili, Zahra-Soheila] Natl Inst Genet Engn & Biotechnol, Tehran, Iran. [Ablonczy, Zsolt] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. RP Hafezi-Moghadam, A (reprint author), Brigham & Womens Hosp, 221 Longwood Ave, Boston, MA 02115 USA. EM ahm@bwh.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU U.S. National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases through Diabetes Complications Consortium award [25732-30]; BrightFocus Foundation; Malaysian Palm Oil Board; National Natural Science Foundation of China grant [81171381]; Heilongjiang [LC2011C27]; NIH/National Eye Institute [R01-EY019065]; Research to Prevent Blindness; South Carolina Lions Association FX This work was supported by the U.S. National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases through Diabetes Complications Consortium award 25732-30, the BrightFocus Foundation, the Malaysian Palm Oil Board, National Natural Science Foundation of China grant 81171381, Heilongjiang overseas fund grant LC2011C27, NIH/National Eye Institute grant R01-EY019065 (Z.A.), an unrestricted grant of Research to Prevent Blindness to the Department of Ophthalmology at the Medical University of South Carolina, and the South Carolina Lions Association. D. S., S.N., F.X., S.Z., A.B., M.R.K., S.S., Z.S.S., S.F., and Z.A. performed the research; D.S., S.N.,Z.S.S., H.A., and A.H.-M. analyzed the data; and A. H.-M. wrote the paper. The authors declare no conflicts of interest. NR 22 TC 2 Z9 2 U1 1 U2 8 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 SEP PY 2014 VL 28 IS 9 BP 3942 EP 3951 DI 10.1096/fj.14-251934 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AN8HU UT WOS:000340845900012 PM 24903276 ER PT J AU Rivas, DA Lessard, SJ Rice, NP Lustgarten, MS So, K Goodyear, LJ Parnell, LD Fielding, RA AF Rivas, Donato A. Lessard, Sarah J. Rice, Nicholas P. Lustgarten, Michael S. So, Kawai Goodyear, Laurie J. Parnell, Laurence D. Fielding, Roger A. TI Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling SO FASEB JOURNAL LA English DT Article DE noncoding RNA; genomics; humans; resistance exercise ID NUTRITION EXAMINATION SURVEY; RESISTANCE EXERCISE; GENE-EXPRESSION; ENDURANCE EXERCISE; NATIONAL-HEALTH; UNITED-STATES; METABOLISM; MOUSE; MASS; AGE AB Older individuals have a reduced capacity to induce muscle hypertrophy with resistance exercise (RE), which may contribute to the age-induced loss of muscle mass and function, sarcopenia. We tested the novel hypothesis that dysregulation of microRNAs (miRNAs) may contribute to reduced muscle plasticity with aging. Skeletal muscle expression profiling of protein-coding genes and miRNA was performed in younger (YNG) and older (OLD) men after an acute bout of RE. 21 miRNAs were altered by RE in YNG men, while no RE-induced changes in miRNA expression were observed in OLD men. This striking absence in miRNA regulation in OLD men was associated with blunted transcription of mRNAs, with only 42 genes altered in OLD men vs. 175 in YNG men following RE, demonstrating a reduced adaptability of aging muscle to exercise. Integrated bioinformatics analysis identified miR-126 as an important regulator of the transcriptional response to exercise and reduced lean mass in OLD men. Manipulation of miR-126 levels in myocytes, in vitro, revealed its direct effects on the expression of regulators of skeletal muscle growth and activation of insulin growth factor 1 (IGF-1) signaling. This work identifies a mechanistic role of miRNA in the adaptation of muscle to anabolic stimulation and reveals a significant impairment in exercise-induced miRNA/mRNA regulation with aging. C1 [Rivas, Donato A.; Rice, Nicholas P.; Lustgarten, Michael S.; So, Kawai; Fielding, Roger A.] Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. [Parnell, Laurence D.] Tufts Univ, Jean Mayer Human Nutr Res Ctr Aging, USDA, Nutr Genom Lab, Boston, MA 02111 USA. [Lessard, Sarah J.; Goodyear, Laurie J.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Lessard, Sarah J.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Rivas, DA (reprint author), Tufts Univ, Jean Mayer Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. EM donato.rivas@tufts.edu OI Rivas, Donato/0000-0002-4500-6233 FU U.S. Department of Agriculture (USDA) [58-1950-0014]; Boston Claude D. Pepper Center Older American Independence Centers (OAIC) [1P30AG031679]; Boston Claude D. Pepper Center OAIC; William Randolph Hearst Fellowship in Clinical and Translational Research FX This material is based on the work supported by the U.S. Department of Agriculture (USDA), under agreement 58-1950-0014. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the USDA. The study was also supported by the Boston Claude D. Pepper Center Older American Independence Centers (OAIC; 1P30AG031679). D.A.R. is supported by a Research Career Development Core Fellowship from the Boston Claude D. Pepper Center OAIC. S.J.L. is supported by the William Randolph Hearst Fellowship in Clinical and Translational Research. NR 68 TC 21 Z9 22 U1 0 U2 9 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 SEP PY 2014 VL 28 IS 9 BP 4133 EP 4147 DI 10.1096/fj.14-254490 PG 15 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AN8HU UT WOS:000340845900030 PM 24928197 ER PT J AU Copeland, LA Sako, EY Zeber, JE Pugh, MJ Wang, CP MacCarthy, AA Restrepo, MI Mortensen, EM Lawrence, VA AF Copeland, Laurel A. Sako, Edward Y. Zeber, John E. Pugh, Mary Jo Wang, Chen-Pin MacCarthy, Andrea A. Restrepo, Marcos I. Mortensen, Eric M. Lawrence, Valerie A. TI Mortality after cardiac or vascular operations by preexisting serious mental illness status in the Veterans Health Administration SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Cardiovascular surgical procedures; Comorbidity; Mental disorders; Mortality; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; CARDIOVASCULAR-DISEASE; SCHIZOPHRENIC-PATIENTS; MAJOR DEPRESSION; BIPOLAR DISORDER; NATIONAL SAMPLE; CARE; AFFAIRS; PREVALENCE; ANESTHESIA AB Objective: To estimate 1-year mortality risk associated with preoperative serious mental illness (SMI) as defined by the Veterans Health Administration (schizophrenia, bipolar disorder, posttraumatic stress disorder [PTSD], major depression) following nonambulatory cardiac or vascular surgical procedures compared to patients without SMI. Cardiac/vascular operations were selected because patients with SMI are known to be at elevated risk of cardiovascular disease. Method: Retrospective analysis of system-wide data from electronic medical records of patients undergoing nonambulatory surgery (inpatient or day-of-surgery admission) October 2005-September 2009 with 1-year follow-up (N=55,864; 99% male; <30 days of postoperative hospitalization). Death was hypothesized to be more common among patients with preoperative SMI. Results: One in nine patients had SMI, mostly PTSD (6%). One-year mortality varied by procedure type and SMI status. Patients had vascular operations (64%; 23% died), coronary artery bypass graft (26%; 10% died) or other cardiac operations (11%; 15%-18% died). Fourteen percent of patients with PTSD died, 20% without SMI and 24% with schizophrenia, with other groups intermediate. In multivariable stratified models, SMI was associated with increased mortality only for patients with bipolar disorder following cardiac operations. Bipolar disorder and PTSD were negatively associated with death following vascular operations. Conclusions: SMI is not consistently associated with postoperative mortality in covariate-adjusted analyses. Published by Elsevier Inc. C1 [Copeland, Laurel A.; Zeber, John E.] Baylor Scott & White Hlth, Ctr Appl Hlth Res, Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Copeland, Laurel A.; Zeber, John E.] Texas A&M Hlth Sci Ctr, Dept Med, Bryan Coll Stn, TX USA. [Copeland, Laurel A.; Zeber, John E.] Sch Rural Publ Hlth, Bryan Coll Stn, TX USA. [Sako, Edward Y.; Pugh, Mary Jo; Wang, Chen-Pin; MacCarthy, Andrea A.; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Sako, Edward Y.; Pugh, Mary Jo; Wang, Chen-Pin; Restrepo, Marcos I.; Lawrence, Valerie A.] UT Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Mortensen, Eric M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Copeland, LA (reprint author), Scott & White Healthcare, Ctr Appl Hlth Res, Cent Texas Vet Hlth Care Syst, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM LaurelACopeland@gmail.com OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563; Copeland, Laurel/0000-0002-9478-0209 FU VHA, Health Services Research Development [IIR-09-335]; Center for Applied Health Research - Central Texas Veterans Health Care System, Temple, TX; VERDICT Research Center at South Texas Veterans Health Care System, San Antonio, TX; VA North Texas Health Care System, Dallas, TX FX This research was supported by the VHA, Health Services Research & Development, Grant No. IIR-09-335 (L.A. Copeland, principal investigator), with additional support from Center for Applied Health Research jointly sponsored by Central Texas Veterans Health Care System, Temple, TX, and Scott & White Healthcare System, Temple, TX; VERDICT Research Center at South Texas Veterans Health Care System, San Antonio, TX; and VA North Texas Health Care System, Dallas, TX. Views are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 53 TC 9 Z9 9 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP PY 2014 VL 36 IS 5 BP 502 EP 508 DI 10.1016/j.genhosppsych.2014.04.003 PG 7 WC Psychiatry SC Psychiatry GA AN8RT UT WOS:000340872400014 PM 24957928 ER PT J AU Minen, MT Tanev, K AF Minen, Mia T. Tanev, Kaloyan TI Influence of psychiatric comorbidities in migraineurs in the emergency department SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Psychiatric; Migraine; Emergency department; Narcotics; Healthcare utilization ID ANXIETY DISORDERS; BENIGN HEADACHE; MENTAL-ILLNESS; RISK-FACTORS; HEALTH-CARE; POPULATION; BURDEN; PROGRESSION; MANAGEMENT; IMPACT AB Objective: To examine how psychiatric comorbidities in migraineurs in the emergency department (ED) affect healthcare utilization and treatment tendencies. Method: This is a cross-sectional analysis of 2872 patients who visited our ED over a 10-year period and were given a principal diagnosis of migraine. Results: Compared to migraineurs without a psychiatric comorbidity, migraineurs with a psychiatric comorbidity had about three times more ED visits, six times more inpatient hospital stays and four times more outpatient visits. Migraineurs with psychiatric comorbidities received narcotics in the ED more often than migraineurs without psychiatric comorbidities (P<0.0001). In addition, migraineurs with psychiatric disorders were more likely to have a computed tomography scan of the head [Risk Ratio (RR) 1.42 (95% confidence interval (CI)= 1.28-1.56, P<0.001)] or a magnetic resonance image of the brain [RR 1.53 (95% CI=1.33-1.76, P<0.001)] than patients without a psychiatric disorder when visiting our hospital center. Conclusions: Migraineurs with psychiatric comorbidity who visit the ED have different healthcare utilization tendencies than migraineurs without psychiatric comorbidity who visit the ED. This is seen in the frequency of ED visits, outpatient visits and inpatient stays, in the medications administered to them and in the radiology tests they undergo. (C) 2014 Elsevier Inc. All rights reserved. C1 [Minen, Mia T.] Brigham & Womens Hosp, Graham Headache Ctr, Dept Neurol, Boston, MA 02130 USA. [Minen, Mia T.; Tanev, Kaloyan] Harvard Univ, Sch Med, Boston, MA USA. [Tanev, Kaloyan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Minen, MT (reprint author), Brigham & Womens Hosp, Graham Headache Ctr, Dept Neurol, 1153 Ctr St,Suite 4970, Boston, MA 02130 USA. EM MinenMD@gmail.com NR 33 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP PY 2014 VL 36 IS 5 BP 533 EP 538 DI 10.1016/j.genhosppsych.2014.05.004 PG 6 WC Psychiatry SC Psychiatry GA AN8RT UT WOS:000340872400019 PM 24950915 ER PT J AU Villablanca, EJ De Calisto, J Paredes, PT Cassani, B Nguyen, DD Gabrielsson, S Mora, JR AF Villablanca, Eduardo J. De Calisto, Jaime Paredes, Patricia Torregrosa Cassani, Barbara Nguyen, Deanna D. Gabrielsson, Susanne Mora, J. Rodrigo TI beta 7 integrins are required to give rise to intestinal mononuclear phagocytes with tolerogenic potential SO GUT LA English DT Article ID CD103(+) DENDRITIC CELLS; RETINOIC ACID; T-CELLS; ALDEHYDE DEHYDROGENASE; LY6C(HI) MONOCYTES; LAMINA PROPRIA; LYMPH-NODES; MICE; GUT; INFLAMMATION AB Background and objective While pro-inflammatory monocyte trafficking to the intestine has been partially characterised, the molecules required for migration of tolerogenic mononuclear phagocytes (dendritic cells (DC) and macrophages) are unknown. We hypothesised that the gut-homing receptor integrin alpha 4 beta 7 is required for this process. Methods We used a T cell-mediated colitis model to study the role of alpha 4 beta 7 in the innate immune compartment. We then performed competitive bone marrow (BM) reconstitution experiments to assess the requirement of alpha 4 beta 7 in the generation of intestinal retinoic acid (RA)-producing CD11c(hi) DC (ALDE(+)DC) and CD64 macrophages. Using mixed BM chimeras we also asked whether alpha 4 beta 7 is required to give rise to tolerogenic mononuclear phagocytes. Results Lack of beta 7 integrins in the innate immune compartment (beta 7(-/-)RAG2(-/-) mice) markedly accelerated T cell-mediated colitis, which was correlated with lower numbers and frequencies of ALDE(+)DC in mesenteric lymph nodes. Consistent with a role of alpha 4 beta 7 in the generation of intestinal mononuclear phagocytes, BM cells from beta 7(-/-) mice poorly reconstituted small intestine ALDE(+)DC and M. when compared to their wild type counterparts. In addition, mice lacking beta 7 integrins in the CD11c(hi) compartment showed decreased ability to induce Foxp3(+) T-REG and IL-10-producing T cells. Conclusions Mice lacking beta 7 integrins in the innate immune compartment are more susceptible to intestinal inflammation, which is correlated with a requirement of beta 7 integrins to reconstitute gut mononuclear phagocytes with tolerogenic potential. C1 [Villablanca, Eduardo J.; De Calisto, Jaime; Paredes, Patricia Torregrosa; Cassani, Barbara; Nguyen, Deanna D.; Mora, J. Rodrigo] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Villablanca, Eduardo J.; De Calisto, Jaime; Paredes, Patricia Torregrosa; Cassani, Barbara; Nguyen, Deanna D.; Mora, J. Rodrigo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Paredes, Patricia Torregrosa; Gabrielsson, Susanne] Karolinska Inst, Dept Med, Translat Immunol Unit, Stockholm, Sweden. [Paredes, Patricia Torregrosa; Gabrielsson, Susanne] Univ Hosp, Stockholm, Sweden. RP Villablanca, EJ (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 185 Cambridge St,CPZN7106, Boston, MA 02114 USA. EM Villablanca.Eduardo@mgh.harvard.edu RI Cassani, Barbara/K-3871-2016 OI Cassani, Barbara/0000-0002-4115-8109 FU Crohn's & Colitis Foundation of America (CCFA); CCFA; NIH [DP2 2009A054301] FX EJV was supported by grants from the Crohn's & Colitis Foundation of America (CCFA). JRM was supported by grants from CCFA and NIH DP2 2009A054301. NR 37 TC 14 Z9 14 U1 0 U2 4 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 SEP PY 2014 VL 63 IS 9 BP 1431 EP 1440 DI 10.1136/gutjnl-2013-305386 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO0QC UT WOS:000341014600015 PM 24030488 ER PT J AU de Freitas, LCC Phelan, E Liu, LB Gardecki, J Namati, E Warger, WC Tearney, GJ Randolph, GW AF Conti de Freitas, Luiz C. Phelan, Eimear Liu, Linbo Gardecki, Joseph Namati, Eman Warger, Willian C. Tearney, Guillermo J. Randolph, Gregory W. TI Optical coherence tomography imaging during thyroid and parathyroid surgery: A novel system of tissue identification and differentiation to obviate tissue resection and frozen section SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE parathyroidectomy; thyroidectomy; thyroid cancer; parathyroid adenoma; hyperparathyroidism ID HIGH-SPEED; ULTRAHIGH-RESOLUTION; LYMPH-NODES; DIAGNOSIS; CANCER; HYPOPARATHYROIDISM; WAVELENGTH; ULTRASOUND; NODULES AB Background. Optical coherence tomography (OCT) allows tissue histologic-like evaluation, but without tissue fixation or staining. We investigated OCT images from tissues obtained at thyroid and parathyroid surgeries to provide a preliminary assessment as to whether these images contain sufficient information for recognition and differentiation of normal neck tissues. Methods. Normal tissues were obtained from patients undergoing surgical treatment. Two new-generation OCT systems, including optical frequency domain imaging (OFDI) and mu OCT, were compared to representative hematoxylin-eosin histology. Results. Thyroid, fat, muscle, lymph nodes, and parathyroid tissues were evaluated. Histologic-like microscopic characteristics sufficient for tissue type identification was realized using both systems for all tissue types examined. Conclusion. This pilot study demonstrated that new-generation OCT systems are capable of recognizing and differentiating neck tissues encountered during thyroid and parathyroid surgeries. Further advances in OCT miniaturization and development of sterile intraoperative probe formats may allow OCT to offer an intraoperative "optical biopsy" without fixation, staining, or tissue resection. (C) 2013 Wiley Periodicals, Inc. C1 [Conti de Freitas, Luiz C.; Phelan, Eimear; Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Div Thyroid & Parathyroid Surg, Boston, MA 02114 USA. [Conti de Freitas, Luiz C.; Liu, Linbo; Gardecki, Joseph; Namati, Eman; Warger, Willian C.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Conti de Freitas, Luiz C.; Liu, Linbo; Gardecki, Joseph; Namati, Eman; Warger, Willian C.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. [Conti de Freitas, Luiz C.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Ophthalmol Otolaryngol Head & Neck Surg, Div Head & Neck Surg, Sao Paulo, Brazil. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM gregory_randolph@meei.harvard.edu RI de Freitas, Luiz/F-1226-2013 OI de Freitas, Luiz/0000-0002-2153-6512 FU National Institutes of Health [NIH R01 CA103769] FX Contract grant sponsor; The National Institutes of Health; contract grant number: NIH R01 CA103769. NR 38 TC 13 Z9 13 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD SEP PY 2014 VL 36 IS 9 BP 1329 EP 1334 DI 10.1002/hed.23452 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AN3OQ UT WOS:000340498200017 ER PT J AU Buchanan, R Beckett, RD AF Buchanan, Rachel Beckett, Robert D. TI Assessment of vaccination-related information for consumers available on Facebook (R) SO HEALTH INFORMATION AND LIBRARIES JOURNAL LA English DT Article DE consumer health information; health information needs; information seeking behaviour; social media; social networking ID PERTUSSIS; VACCINES; RUBELLA; AUTISM AB Objectives: To assess the magnitude, interest, purpose and validity of vaccination-related information on Facebook and to determine whether information varies by site viewpoint. Methods: The 10 largest vaccination-focused Facebook (R) pages, groups and places in each category were identified and classified by viewpoint (i.e. anti-, pro-, neutral) and purpose. Number of members, posts per week, likes, comments and shares per post were recorded. Posts were assessed for concordance with CDC and FDA recommendations. Results: Of 30 sites, 43% (n = 13) were anti-vaccination, 7% (n = 2) neutral and 50% (n = 15) pro-vaccination. Most sites were most popular with American users. Median members were similar between anti-vaccination (2703 members, range 337-33 631 members) and pro-vaccination sites (2142 members, range 456-61 565 members, P = 0.262); however, anti-vaccination sites accumulated more posts per week by authors (median 15 vs. 3, P = 0.031) and members (median 33 vs. 1, P < 0.001). Pro-vaccination sites more commonly had commercial purpose (53% [n = 8] vs. 8% [n = 1], P = 0.02). Anti-vaccination sites more commonly gave medical advice (54% [n = 7] vs. 0%, P = 0.004). Overall, 48% (n = 22) of author posts were concordant with regulatory recommendations; concordance was more common on pro-vaccination sites (78% [n = 21] vs. 5% [n = 1], P = 0.0002). Conclusion: Vaccination-related information is prevalent on Facebook regardless of viewpoint; however, anti-vaccination information generates more interest. Anti-vaccination sites were likely to provide medical advice and disagree with regulatory bodies. C1 [Buchanan, Rachel] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Beckett, Robert D.] Univ Manchester, Coll Pharm, Ft Wayne, IN 46845 USA. RP Beckett, RD (reprint author), Univ Manchester, Coll Pharm, 10627 Diebold Rd, Ft Wayne, IN 46845 USA. EM rdbeckett@manchester.edu NR 15 TC 4 Z9 4 U1 7 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1471-1834 EI 1471-1842 J9 HEALTH INFO LIBR J JI Heatlth Info. Libr. J. PD SEP PY 2014 VL 31 IS 3 BP 227 EP 234 DI 10.1111/hir.12073 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA AO2KV UT WOS:000341151500006 PM 25041499 ER PT J AU Hettich, J Ryan, SD de Souza, ON Timmers, LFSM Tsai, SL Atai, NA da Hora, CC Zhang, X Kothary, R Snapp, E Ericsson, M Grundmann, K Breakefield, XO Nery, FC AF Hettich, Jasmin Ryan, Scott D. de Souza, Osmar Norberto Saraiva Macedo Timmers, Luis Fernando Tsai, Shelun Atai, Nadia A. da Hora, Cintia C. Zhang, Xuan Kothary, Rashmi Snapp, Erik Ericsson, Maria Grundmann, Kathrin Breakefield, Xandra O. Nery, Flavia C. TI Biochemical and Cellular Analysis of Human Variants of the DYT1 Dystonia Protein, TorsinA/TOR1A SO HUMAN MUTATION LA English DT Article DE torsinA; TOR1A; dystonia; DYT1; endoplasmic reticulum; protein secretion; ER stress ID MOLECULAR-DYNAMICS-SIMULATION; ONSET TORSION DYSTONIA; NUCLEAR-ENVELOPE; MUTANT TORSINA; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; CELLS; MEMBRANE; MUTATION; ATPASES AB Early-onset dystonia is associated with the deletion of one of a pair of glutamic acid residues (c.904_906delGAG/c.907_909delGAG; p.Glu302del /Glu303del; Delta E 302/303) near the carboxyl-terminus of torsinA, a member of the AAA(+) protein family that localizes to the endoplasmic reticulum lumen and nuclear envelope. This deletion commonly underlies early-onset DYT1 dystonia. While the role of the disease-causing mutation, torsinA Delta E, has been established through genetic association studies, it is much less clear whether other rare human variants of torsinA are pathogenic. Two missense variations have been described in single patients: R288Q (c.863G>A; p.Arg288Gln; R288Q) identified in a patient with onset of severe generalized dystonia and myoclonus since infancy and F205I (c.613T>A, p.Phe205Ile; F205I) in a psychiatric patient with late-onset focal dystonia. In this study, we have undertaken a series of analyses comparing the biochemical and cellular effects of these rare variants to torsinA Delta E and wild-type (wt) torsinA to reveal whether there are common dysfunctional features. The results revealed that the variants, R288Q and F205I, are more similar in their properties to torsinA Delta E protein than to torsinAwt. These findings provide functional evidence for the potential pathogenic nature of these rare sequence variants in the TOR1A gene, thus implicating these pathologies in the development of dystonia. C (C) 2014 Wiley Periodicals, Inc. C1 [Hettich, Jasmin; Tsai, Shelun; Atai, Nadia A.; da Hora, Cintia C.; Zhang, Xuan; Breakefield, Xandra O.; Nery, Flavia C.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Hettich, Jasmin; Tsai, Shelun; Atai, Nadia A.; da Hora, Cintia C.; Zhang, Xuan; Breakefield, Xandra O.; Nery, Flavia C.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Hettich, Jasmin; Tsai, Shelun; Atai, Nadia A.; da Hora, Cintia C.; Zhang, Xuan; Breakefield, Xandra O.; Nery, Flavia C.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Hettich, Jasmin; Grundmann, Kathrin] Univ Tubingen, Dept Med Genet & Appl Genom, Tubingen, Germany. [Ryan, Scott D.; Kothary, Rashmi] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Ryan, Scott D.; Kothary, Rashmi] Univ Ottawa, Ottawa, ON, Canada. [de Souza, Osmar Norberto; Saraiva Macedo Timmers, Luis Fernando] Pontificia Univ Catolica Rio Grande do Sul, Lab Bioinformat Modeling & Simulat Biosyst LABIO, Porto Alegre, RS, Brazil. [Atai, Nadia A.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. [Snapp, Erik] Yeshiva Univ, Albert Einstein Coll Med, Dept Anat & Struct Biol, New York, NY 10033 USA. [Ericsson, Maria] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Nery, FC (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM nery.flavia@mgh.harvard.edu OI Kothary, Rashmi/0000-0002-9239-7310 FU NIH/NINDS [NS037409, P30NS045776]; NINDS; NIH [1S10RR023440-01A1]; National Research Council of Brazil (CNPq) [305984/2012-8, 559917/2010-4]; CAPES; Canadian Institute of Health Research; Dystonia Medical Research Foundation; Deutsche Forschungsgemeinschaft; Elitepostdoc Programme Baden Wurttemberg; IZKF University of Tuebingen FX Contract grant sponsors: NIH/NINDS grant (NS037409); NINDS funded Neuroscience MGH Vector Core; NIH/NINDS (P30NS045776); NIH grant (1S10RR023440-01A1); National Research Council of Brazil (CNPq) (grants 305984/2012-8 and 559917/2010-4); CAPES; Canadian Institute of Health Research; Dystonia Medical Research Foundation; Deutsche Forschungsgemeinschaft; Elitepostdoc Programme Baden Wurttemberg; IZKF University of Tuebingen NR 83 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD SEP PY 2014 VL 35 IS 9 BP 1101 EP 1113 DI 10.1002/humu.22602 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AN4KY UT WOS:000340557900009 PM 24930953 ER PT J AU Peralta, CA Katz, R Newman, AB Psaty, BM Odden, MC AF Peralta, Carmen A. Katz, Ronit Newman, Anne B. Psaty, Bruce M. Odden, Michelle C. TI Systolic and Diastolic Blood Pressure, Incident Cardiovascular Events, and Death in Elderly Persons The Role of Functional Limitation in the Cardiovascular Health Study SO HYPERTENSION LA English DT Article DE activities of daily living; aged; hypertension ID OLDER-ADULTS; HYPERTENSION; MORTALITY; ASSOCIATION; SURVIVAL; STROKE; DISEASE; FRAILTY; SPEED; RISK AB Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78 +/- 5 and 21% reported limitation in >= 1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP <= 65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of <= 65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders. C1 [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, Div Nephrol, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Odden, Michelle C.] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA. RP Peralta, CA (reprint author), San Francisco VA Med Ctr, Box 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute on Aging [AG023629, K01AG039387]; National Institutes of Diabetes and Digestive and Kidney Diseases [K23SK082793]; Robert Wood Johnson Harold Amos Award; American Heart Association Western States Affiliate [CRP7210088] FX This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by the National Institute on Aging (AG023629). A full list of principal Cardiovascular Health Study (CHS) investigators and institutions can be found at https://CHS-NHLBI.org. C.A. Peralta is supported by the National Institutes of Diabetes and Digestive and Kidney Diseases (K23SK082793) and a Robert Wood Johnson Harold Amos Award. M. C. Odden is supported by the American Heart Association Western States Affiliate (CRP7210088) and the National Institute on Aging (K01AG039387). The content is solely our responsibility and does not necessarily represent the official views of the National Institutes of Health. NR 28 TC 10 Z9 12 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD SEP PY 2014 VL 64 IS 3 BP 472 EP 480 DI 10.1161/HYPERTENSIONAHA.114.03831 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AN9MB UT WOS:000340929900009 PM 24935945 ER PT J AU Dubberke, ER Carling, P Carrico, R Donskey, CJ Loo, VG McDonald, LC Maragakis, LL Sandora, TJ Weber, DJ Yokoe, DS Gerding, DN AF Dubberke, Erik R. Carling, Philip Carrico, Ruth Donskey, Curtis J. Loo, Vivian G. McDonald, L. Clifford Maragakis, Lisa L. Sandora, Thomas J. Weber, David J. Yokoe, Deborah S. Gerding, Dale N. TI Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals: 2014 Update SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; HIGH-RISK ANTIBIOTICS; ENVIRONMENTAL CONTAMINATION; HYPOCHLORITE SOLUTION; COLONIZED PATIENTS; CONTACT ISOLATION; TOXIN PRODUCTION; ISOLATION ROOMS; UNITED-STATES; NORTH-AMERICA C1 [Dubberke, Erik R.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Carling, Philip] Boston Univ, Sch Med, Boston, MA 02118 USA. [Carrico, Ruth] Univ Louisville, Sch Med, Div Infect Dis, Louisville, KY 40292 USA. [Donskey, Curtis J.] Case Western Reserve Univ, Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH 44106 USA. [Loo, Vivian G.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [McDonald, L. Clifford] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA USA. [Maragakis, Lisa L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sandora, Thomas J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Weber, David J.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Yokoe, Deborah S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yokoe, Deborah S.] Harvard Univ, Sch Med, Boston, MA USA. [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA. RP Dubberke, ER (reprint author), Washington Univ, Sch Med, 660 South Euclid Ave,Box 8051, St Louis, MO 63110 USA. EM edubberk@dom.wustl.edu FU Sanofi Pasteur; ViroPharma; Optimer; Merck; Rebiotix; Steris; Pfizer; GOJO Industries FX E.R.D. reports serving as an advisor/consultant for Sanofi Pasteur, Merck, and Pfizer and receiving research grants/contracts from Sanofi Pasteur, ViroPharma, Optimer, Merck, and Rebiotix. P.C. reports serving as an advisor/consultant for Steris and holding a patent/copyright/license with Ecolab. R.C. reports serving on the speakers' bureau for Sanofi Pasteur, MedImmune, Abbott Diabetes Care, and 3M; performing technical writing for Ketchum; and receiving research grants/contracts from Sanofi Pasteur. C.J.D. reports serving as an advisor/consultant for Steris, GOJO Industries, and 3M; receiving honoraria from Ecolab; and receiving research grants/contracts from Merck, ViroPharma, Steris, and Pfizer. V.G.L. reports serving as an advisor/consultant for Optimer Pharmaceuticals. D.J.W. reports serving as an advisor/consultant for Johnson & Johnson and Clorox. D.N.G. reports serving as an advisor/consultant for Merck, Cubist, Novartis, Cangene, Actelion, ViroPharma, Rebiotix, and Sanofi Pasteur; receiving honoraria from Robert Michael; holding a patent/license (no royalties) with ViroPharma; and receiving research grant/contracts from GOJO Industries. L.C.M., L.L.M., T.J.S., and D.S.Y. report no conflicts of interest. NR 120 TC 0 Z9 0 U1 1 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 SU 2 BP 628 EP 645 DI 10.1086/676023 PG 18 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AO0QB UT WOS:000341014500008 ER PT J AU Yin, J Reisinger, HS Vander Weg, M Schweizer, ML Jesson, A Morgan, DJ Forrest, G Graham, M Pineles, L Perencevich, EN AF Yin, Jun Reisinger, Heather Schacht Vander Weg, Mark Schweizer, Marin L. Jesson, Andrew Morgan, Daniel J. Forrest, Graeme Graham, Margaret Pineles, Lisa Perencevich, Eli N. TI Establishing Evidence-Based Criteria for Directly Observed Hand Hygiene Compliance Monitoring Programs: A Prospective, Multicenter Cohort Study SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HEALTH-CARE SETTINGS; HAWTHORNE; INFECTIONS; RECOMMENDATIONS; PRECAUTIONS; GUIDELINE; HOSPITALS; FEEDBACK; TIME AB OBJECTIVE. Hand hygiene surveillance programs that rely on direct observations of healthcare worker activity may be limited by the Hawthorne effect. In addition, comparing compliance rates from period to period requires adequately sized samples of observations. We aimed to statistically determine whether the Hawthorne effect is stable over an observation period and statistically derive sample sizes of observations necessary to compare compliance rates. DESIGN. Prospective multicenter cohort study. SETTING. Five intensive care units and 6 medical/surgical wards in 3 geographically distinct acute care hospitals. METHODS. Trained observers monitored hand hygiene compliance during routine care in fixed 1-hour periods, using a standardized collection tool. We estimated the impact of the Hawthorne effect using empirical fluctuation processes and F tests for structural change. Standard sample-size calculation methods were used to estimate how many hand hygiene opportunities are required to accurately measure hand hygiene across various levels of baseline and target compliance. RESULTS. Exit hand hygiene compliance increased after 14 minutes of observation (from 56.2% to 60.5%; P<.001) and increased further after 50 minutes (from 60.5% to 66.0%; P<.001). Entry compliance increased after 38 minutes (from 40.4% to 43.4%; P=.005). Between 79 and 723 opportunities are required during each period, depending on baseline compliance rates (range, 35%-90%) and targeted improvement (5% or 10%). CONCLUSIONS. Limiting direct observation periods to approximately 15 minutes to minimize the Hawthorne effect and determining required number of hand hygiene opportunities observed per period on the basis of statistical power calculations would be expected to improve the validity of hand hygiene surveillance programs. C1 [Yin, Jun] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. [Reisinger, Heather Schacht; Vander Weg, Mark; Schweizer, Marin L.; Jesson, Andrew; Perencevich, Eli N.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Reisinger, Heather Schacht; Schweizer, Marin L.; Graham, Margaret; Perencevich, Eli N.] Iowa City Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA 52246 USA. [Vander Weg, Mark] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Morgan, Daniel J.; Pineles, Lisa] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Morgan, Daniel J.] Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA. [Forrest, Graeme] Portland VA Med Ctr, Portland, OR USA. RP Perencevich, EN (reprint author), Iowa City Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA 52246 USA. EM eli-perencevich@uiowa.edu FU Veterans Affairs Health Services Research and Development [09-099] FX Veterans Affairs Health Services Research and Development Investigator Initiated research grant 09-099 (to E.N.P.). NR 22 TC 5 Z9 7 U1 3 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 IS 9 BP 1163 EP 1168 DI 10.1086/677629 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AN6TI UT WOS:000340729900011 PM 25111925 ER PT J AU Yanke, E Carayon, P Safdar, N AF Yanke, Eric Carayon, Pascale Safdar, Nasia TI Translating Evidence into Practice Using a Systems Engineering Framework for Infection Prevention SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID CLOSTRIDIUM-DIFFICILE INFECTION; CARE-ASSOCIATED INFECTIONS; PATIENT SAFETY; ICU; ACQUISITION; MANAGEMENT; COMMUNITY; QUALITY; UNIT C1 [Yanke, Eric] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Carayon, Pascale] Univ Wisconsin, Ctr Qual & Prod Improvement, Dept Ind & Syst Engn, Madison, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med, Dept Med, Div Infect Dis, Madison, WI USA. RP Safdar, N (reprint author), UWMF Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu FU NCATS NIH HHS [9U54TR000021, UL1 TR000427]; NCRR NIH HHS [1UL1RR025011] NR 40 TC 3 Z9 3 U1 4 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 IS 9 BP 1176 EP 1182 DI 10.1086/677638 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AN6TI UT WOS:000340729900013 PM 25111927 ER PT J AU Lee, MS Eum, KD Fang, SC Rodrigues, EG Modest, GA Christiani, DC AF Lee, Mi-Sun Eum, Ki-Do Fang, Shona C. Rodrigues, Ema G. Modest, Geoffrey A. Christiani, David C. TI Oxidative stress and systemic inflammation as modifiers of cardiac autonomic responses to particulate air pollution SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Particulate air pollution; Oxidative stress; Systemic inflammation; Effect modifier; Heart rate variability; Environmental health ID HEART-RATE-VARIABILITY; CARDIOVASCULAR-DISEASE; POTENTIAL MECHANISMS; DNA-DAMAGE; DYSFUNCTION; INHALATION; EXPOSURE; MATTER; ASSOCIATION; NIGHTTIME AB Background: The role of oxidative stress and systemic inflammation on the association between personal exposures to ambient fine particulate matter <= 2.5 mu m in diameter (PM2.5) and cardiac autonomic dysfunction, indicated by reduction in heart rate variability (HRV), has not been examined. Methods: We performed a repeated measures study on community adults in a densely populated inner city neighborhood in Boston, Massachusetts. Continuous ambulatory electrocardiogram (ECG) monitoring and personal exposure to PM2.5 were measured for up to two consecutive days. Peripheral blood and spot urine samples were collected at 12-hour intervals for the measurements of markers of inflammation including C-reactive protein (CRP), fibrinogen, white blood cell (WBC) and platelet counts as well as for the analysis of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Results: After adjusting for confounders, we found a pronounced decrease in nighttime standard deviation of normal-to normal intervals (SDNN): an interquartile range (IQR) increase in PM2.5 (13.6 mu g/m(3)) was associated with an 8.4% decrease in SDNN (95% CI: -11.3 to -5.5). Compared with the lower eightieth percentile, significantly greater PM2.5 associated nighttime SDNN reductions were observed among subjects in the upper twentieth percentile of 8-OHdG by -25.3%, CRP by -24.9%, fibrinogen by -28.7%, WBC by -23.4%, and platelet counts by -24.0% (all P < 0.0001; all P-interaction < 0.01). Conclusions: These data suggest that oxidative stress and systemic inflammation exacerbate the adverse effects of PM2.5 on the cardiac autonomic function even at ambient levels of exposure. (C) 2014 Elsevier Ireland Ltd. All rights reserved C1 [Lee, Mi-Sun; Eum, Ki-Do; Fang, Shona C.; Rodrigues, Ema G.; Christiani, David C.] Harvard Univ, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Sch Publ Hlth, Boston, MA 02115 USA. [Fang, Shona C.] New England Res Inst Inc, Watertown, MA USA. [Modest, Geoffrey A.] Boston Univ, Sch Med, Uphams Corner Hlth Ctr, Boston, MA 02118 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Sch Publ Hlth, 665 Huntington Ave,Bldg 1 Room 1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU U.S. EPA STAR grant [RD-83083801]; NIH [ES00002] FX This study was supported by grants from the U.S. EPA STAR grant (RD-83083801) and NIH (ES00002). NR 25 TC 15 Z9 16 U1 5 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP PY 2014 VL 176 IS 1 BP 166 EP 170 DI 10.1016/j.ijcard.2014.07.012 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO0ZG UT WOS:000341040900035 PM 25074558 ER PT J AU Shogan, AN Rogers, DJ Hartnick, CJ Kerschner, JE AF Shogan, Andrea Nath Rogers, Derek J. Hartnick, Christopher J. Kerschner, Joseph E. TI Use of botulinum toxin in pediatric otolaryngology and laryngology SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Review DE Botox; Pediatric; Paradoxical vocal fold dysfunction ID VOCAL-FOLD MOTION; CRICOPHARYNGEAL ACHALASIA; MUSCULAR TORTICOLLIS; LARYNGEAL DYSTONIA; MANAGEMENT; REDUCTION; PARALYSIS; GRANULOMA; THERAPY AB The use of botulinum toxin in adult otolaryngology has been commonly used in conditions such as spasmodic dysphonia, cricopharyngeal spasm, palatal myoclonus, sialorrhea, and for cosmetic reasons. The current use of botulinum toxin in pediatric otolaryngology and laryngology has primarily been off label and in children older than 2 years of age. This review discusses the different applications of botulinum toxin in pediatric patients and its effectiveness in treating different pediatric conditions. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Shogan, Andrea Nath; Kerschner, Joseph E.] Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Div Pediat Otolaryngol, Milwaukee, WI 53226 USA. [Rogers, Derek J.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Pediat Otolaryngol, Boston, MA USA. RP Kerschner, JE (reprint author), Med Coll Wisconsin, Off Dean, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM jkerschner@mcw.edu NR 26 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD SEP PY 2014 VL 78 IS 9 BP 1423 EP 1425 DI 10.1016/j.ijporl.2014.06.026 PG 3 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA AO0FC UT WOS:000340983500001 PM 25048857 ER PT J AU Cohen, MS Ha, AY Kitsko, DJ Chi, DH AF Cohen, Michael S. Ha, Austin Y. Kitsko, Dennis J. Chi, David H. TI Surgical outcomes with subperiosteal pocket technique for cochlear implantation in very young children SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Cochlear implants; Hearing loss; Pediatrics ID SPEECH-PERCEPTION; TITANIUM SCREWS; MINIMAL ACCESS; AGE; FIXATION; COMPLICATIONS; LANGUAGE; SURGERY AB Objectives: As data continue to emerge demonstrating improved hearing outcomes associated with younger age at time of cochlear implantation, more children aged 12 months or younger are undergoing this procedure. Drilling a well to house the cochlear implant receiver/stimulator (R/S) may carry an increased risk in this group of patients as the calvarium is thin and drilling an adequate well may require exposure of the underlying dura. Our group has employed a technique in this age group which involves securing the R/S in a subperiosteal pocket without creating a bony well. We report our experience with six infants 12 months of age or younger undergoing cochlear implantation with the subperiosteal pocket technique. Methods: Cases were identified by searching an IRB approved research registry. Charts were reviewed for demographics, surgical technique, and clinical outcomes. Descriptive statistics were calculated. Results: Six patients 12 months of age or younger underwent cochlear implantation over a one year period. Simultaneous bilateral implantation was performed in all cases, for a total of 12 implanted ears. The average age at time of implantation was 9.8 months (SD 2.1 months). There were no postoperative wound complications. No evidence of device migration was noted in any patient as of the most recent follow-up appointment. There was one device hard failure at 32 months. Average length of follow-up was 28.4 months (SD 13.8 months). Conclusions: No wound complications or device migrations occurred in 12 cochlear implantations in six children aged 12 months or younger. Advantages of this technique include no risk to the dura in this location, smaller incisions, and shorter surgical time. A potential disadvantage is the increased device profile from the lack of a well. New thinner implant designs may minimize this concern. Further prospective study is justified to confirm our initial experience in this small group. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Cohen, Michael S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Ha, Austin Y.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Kitsko, Dennis J.; Chi, David H.] UPMC, Childrens Hosp Pittsburgh, Dept Pediat Otolaryngol, Pittsburgh, PA USA. RP Cohen, MS (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM michael_cohen@meei.harvard.edu NR 21 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD SEP PY 2014 VL 78 IS 9 BP 1545 EP 1547 DI 10.1016/j.ijporl.2014.07.002 PG 3 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA AO0FC UT WOS:000340983500027 PM 25064628 ER PT J AU Matthews, LT Heffron, R Mugo, NR Cohen, CR Hendrix, CW Celum, C Bangsberg, DR Baeten, JM AF Matthews, Lynn T. Heffron, Renee Mugo, Nelly R. Cohen, Craig R. Hendrix, Craig W. Celum, Connie Bangsberg, David R. Baeten, Jared M. CA Partners PrEP Study Team TI High Medication Adherence During Periconception Periods Among HIV-1-Uninfected Women Participating in a Clinical Trial of Antiretroviral Pre-exposure Prophylaxis SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE pregnancy; HIV-1 prevention; pre-exposure prophylaxis; adherence; safer conception; serodiscordant couples; sub-Saharan Africa ID HIV-SERODISCORDANT COUPLES; PLACEBO-CONTROLLED TRIAL; SERO-DISCORDANT COUPLES; SOUTH-AFRICA; CONTRACEPTIVE USE; POSITIVE MEN; DOUBLE-BLIND; PREVENTION; PREGNANCY; INFECTION AB Introduction: Pre-exposure prophylaxis (PrEP) may be an important safer conception strategy for HIV-1-uninfected women with HIV-1-infected partners. Understanding medication adherence in this population may inform whether PrEP is a feasible safer conception strategy. Methods: We evaluated predictors of pregnancy and adherence to study medication among HIV-1-uninfected women enrolled in a randomized placebo-controlled trial of PrEP among African HIV-1-serodiscordant couples. Participants were counseled on HIV-1 risk reduction, contraception, and adherence and tested for pregnancy at monthly study visits. Pill counts of dispensed drug were performed and, at a subset of visits, plasma was collected to measure active drug concentration. Results: Among 1785 women, pregnancy incidence was 10.2 per 100 person-years. Younger age, not using contraception, having an additional sexual partner, and reporting unprotected sex were associated with increased likelihood of pregnancy. Monthly clinic pill counts estimated that women experiencing pregnancy took 97% of prescribed doses overall, with at least 80% pill adherence for 98% of study months, and no difference in adherence in the periconception period compared with previous periods (P = 0.98). Tenofovir was detected in plasma at 71% of visits where pregnancy was discovered. By multiple measures, adherence was similar for women experiencing and not experiencing pregnancy (P > 0.1). Conclusions: In this clinical trial of PrEP, pregnancy incidence was 10% per year despite excellent access to effective contraception. Women experiencing pregnancy had high medication adherence, suggesting that PrEP may be an acceptable and feasible safer conception strategy for HIV-1-uninfected women with HIV-1-serodiscordant partners. C1 [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Matthews, Lynn T.; Bangsberg, David R.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Heffron, Renee; Mugo, Nelly R.; Celum, Connie; Baeten, Jared M.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Mugo, Nelly R.] Kenya Govt Med Res Ctr, Nairobi, Kenya. [Cohen, Craig R.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Bixby Ctr Global Reprod Hlth, San Francisco, CA USA. [Hendrix, Craig W.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Celum, Connie; Baeten, Jared M.] Univ Washington, Dept Med, Seattle, WA USA. [Celum, Connie; Baeten, Jared M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM ltmatthews@partners.org FU Bill & Melinda Gates Foundation [OOP47674]; National Institute of Mental Health; Eunice Kennedy Shriver National Institute of Child Health and Development of the National Institutes of Health [K23MH095655, K24MH87227, R21HD074439, K99HD076679, R01MH095507]; Gilead Sciences FX The Partners PrEP study was supported by research grant (OOP47674) from the Bill & Melinda Gates Foundation; Gilead Sciences provided medication. This analysis was also supported by the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Development of the National Institutes of Health under award numbers K23MH095655, K24MH87227, R21HD074439, K99HD076679, and R01MH095507.; C.H. has a contract with Gilead Sciences for partial support of a clinical study managed by Johns Hopkins University. The remaining authors have no conflicts of interest to disclose. NR 46 TC 16 Z9 16 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2014 VL 67 IS 1 BP 91 EP 97 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AN6SP UT WOS:000340727600014 PM 25118795 ER PT J AU Yehia, BR Fleishman, JA Agwu, AL Metlay, JP Berry, SA Gebo, KA AF Yehia, Baligh R. Fleishman, John A. Agwu, Allison L. Metlay, Joshua P. Berry, Stephen A. Gebo, Kelly A. CA HIV Res Network TI Health Insurance Coverage for Persons in HIV Care, 2006-2012 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; insurance; Medicare; Medicaid; Ryan White; Affordable Care Act ID UNITED-STATES; ANTIRETROVIRAL THERAPY; VIRAL SUPPRESSION; INFECTED PATIENTS; DISPARITIES; SERVICES; MORTALITY; CLINICS; DECLINE; ADULTS AB We examined trends in health insurance coverage among 36,999 HIV-infected adults in care at 11 US HIV clinics between 2006 and 2012. Aggregate health insurance coverage was stable during this time. The proportions of patient-years with private, Medicaid, Medicare, and no insurance during this period were 15.9%, 35.7%, 20.1%, and 28.4%, respectively. Medicaid coverage was more prevalent among women than men, blacks, and Hispanics than whites, and individuals with injection drug use risk compared with other transmission risk factors. Hispanics and younger age groups were more likely to be uninsured than other racial/ethnic and older age groups, respectively. C1 [Yehia, Baligh R.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Yehia, Baligh R.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Fleishman, John A.] Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, Rockville, MD USA. [Agwu, Allison L.; Berry, Stephen A.; Gebo, Kelly A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Metlay, Joshua P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Yehia, BR (reprint author), Univ Penn, Perelman Sch Med, 1021 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM byehia@upenn.edu FU Agency for Healthcare Research and Quality [HHSA290201100007C]; Health Resources and Services Administration [HHSH250201200008C]; National Institutes of Health [K23-MH097647]; Gilead Sciences; Tibotec FX Supported by the Agency for Healthcare Research and Quality (HHSA290201100007C), the Health Resources and Services Administration (HHSH250201200008C), and the National Institutes of Health (K23-MH097647 to B.R.Y.).; BRY received grants to his institution from Gilead Sciences. KAG received grants to her institution from Tibotec, and provided consultancy to Tibotec and Bristol-Myers Squibb. The remaining authors have no conflicts of interest to disclose. NR 29 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2014 VL 67 IS 1 BP 102 EP 106 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AN6SP UT WOS:000340727600015 PM 24977377 ER PT J AU Hyle, EP Naidoo, K Su, AE El-Sadr, WM Freedberg, KA AF Hyle, Emily P. Naidoo, Kogieleum Su, Amanda E. El-Sadr, Wafaa M. Freedberg, Kenneth A. TI HIV, Tuberculosis, and Noncommunicable Diseases: What Is Known About the Costs, Effects, and Cost-effectiveness of Integrated Care? SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV/AIDS; noncommunicable diseases; cost-effectiveness; integrated care; tuberculosis ID SUB-SAHARAN AFRICA; MIDDLE-INCOME COUNTRIES; COMBINATION ANTIRETROVIRAL THERAPY; CERVICAL INTRAEPITHELIAL NEOPLASIA; PRIMARY-HEALTH-CARE; QUALITY-OF-LIFE; RESOURCE-LIMITED SETTINGS; SOUTH-AFRICA; INFECTED WOMEN; WESTERN KENYA AB Unprecedented investments in health systems in low-and middle-income countries (LMICs) have resulted in more than 8 million individuals on antiretroviral therapy. Such individuals experience dramatically increased survival but are increasingly at risk of developing common noncommunicable diseases (NCDs). Integrating clinical care for HIV, other infectious diseases, and NCDs could make health services more effective and provide greater value. Cost-effectiveness analysis is a method to evaluate the clinical benefits and costs associated with different health care interventions and offers guidance for prioritization of investments and scale-up, especially as resources are increasingly constrained. We first examine tuberculosis and HIV as 1 example of integrated care already successfully implemented in several LMICs; we then review the published literature regarding cervical cancer and depression as 2 examples of NCDs for which integrating care with HIV services could offer excellent value. Direct evidence of the benefits of integrated services generally remains scarce; however, data suggest that improved effectiveness and reduced costs may be attained by integrating additional services with existing HIV clinical care. Further investigation into clinical outcomes and costs of care for NCDs among people living with HIV in LMICs will help to prioritize specific health care services by contributing to an understanding of the affordability and implementation of an integrated approach. C1 [Hyle, Emily P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [Hyle, Emily P.; Su, Amanda E.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Hyle, Emily P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Hyle, Emily P.; Su, Amanda E.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Naidoo, Kogieleum] Univ KwaZulu Natal, Ctr AIDS Programme Res South Afr, Durban, South Africa. [El-Sadr, Wafaa M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, Int Ctr AIDS Care & Treatment Programs ICAP, New York, NY USA. [Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res CFAR, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Hyle, EP (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ehyle@partners.org FU National Institute of Allergy and Infectious Diseases [R01 AI058736, T32 AI007433]; PEPFAR [P30 AI060354]; Comprehensive International Program of Research on AIDS, CIPRA [3 U19 AI051794]; CAPRISA AIDS Treatment Programme [5U3GPS001350-04]; TRuTH Study, TB Recurrence upon Treatment with TB Therapy and HAART [ZA.09.0263]; Columbia UniversitySouth Africa Fogarty AIDS International Training and Research Program (AITRP) [D43 TW000231] FX Supported by the National Institute of Allergy and Infectious Diseases (R01 AI058736, T32 AI007433); PEPFAR Supplement funding (P30 AI060354); Comprehensive International Program of Research on AIDS, CIPRA (3 U19 AI051794); CAPRISA AIDS Treatment Programme (5U3GPS001350-04); The TRuTH Study, TB Recurrence upon Treatment with TB Therapy and HAART (ZA.09.0263), Columbia UniversitySouth Africa Fogarty AIDS International Training and Research Program (AITRP, Grant D43 TW000231). NR 183 TC 10 Z9 10 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2014 VL 67 SU 1 BP S87 EP S95 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AO1PT UT WOS:000341086200010 PM 25117965 ER PT J AU Kelly, P Saloojee, H Chen, JY Chung, RT AF Kelly, Paul Saloojee, Haroon Chen, Jennifer Y. Chung, Raymond T. TI Noncommunicable Diseases in HIV Infection in Low- and Middle-Income Countries: Gastrointestinal, Hepatic, and Nutritional Aspects SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; noncommunicable disease; digestive disorders; malnutrition; liver disorders ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; FATTY LIVER-DISEASE; RANDOMIZED CONTROLLED-TRIAL; RISK-FACTORS; MICRONUTRIENT SUPPLEMENTATION; TROPICAL ENTEROPATHY; UNITED-STATES; ADULTS; CHILDREN AB The purpose of this review was to outline the interaction between HIV and noncommunicable diseases affecting the gastrointestinal (GI) tract, liver, and nutritional disorders in low-and middle-income countries (LMICs), and to identify research priorities. Noncommunicable GI tract disorders are only moderately influenced by HIV, and peptic ulceration is actually less common. However, the impact of HIV on GI cancers needs further investigation. HIV interacts strongly with environmental enteropathy, exacerbating malabsorption of nutrients and drugs. HIV has 2 major effects on noncommunicable liver disease: drug-induced liver injury and nonalcoholic fatty liver disease (particularly in persons of African genetic descent). The effect of HIV on nutrition was one of the first markers of the epidemic in the 1980s, and HIV continues to have major nutritional consequences. Childhood malnutrition and HIV frequently coexist in some regions, for example, southern Africa, resulting in powerful negative interactions with poorer responses to standard nutritional rehabilitation. HIV and nutritional care need to be better integrated, but many questions on how best to do this remain unanswered. Across the spectrum of GI, hepatic, and nutritional disorders in HIV infection, there is increasing evidence that the microbiome may play an important role in disease pathogenesis, but work in this area, especially in low-and middle-income countries, is in its infancy. C1 [Kelly, Paul] Queen Mary Univ London, Barts & London Sch Med, Blizard Inst, London E1 2AD, England. [Kelly, Paul] Univ Zambia, Sch Med, Dept Med, Lusaka, Zambia. [Saloojee, Haroon] Univ Witwatersrand, Dept Paediat & Child Hlth, Johannesburg, South Africa. [Chen, Jennifer Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kelly, P (reprint author), Queen Mary Univ London, Barts & London Sch Med, Blizard Inst, London E1 2AD, England. EM m.p.kelly@qmul.ac.uk FU FIC NIH HHS [R24 TW007988]; NIDDK NIH HHS [T32 DK007191] NR 89 TC 5 Z9 5 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2014 VL 67 SU 1 BP S79 EP S86 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AO1PT UT WOS:000341086200009 PM 25117963 ER PT J AU Roberts, AL Rosario, M Calzo, JP Corliss, HL Frazier, L Austin, SB AF Roberts, Andrea L. Rosario, Margaret Calzo, Jerel P. Corliss, Heather L. Frazier, Lindsay Austin, S. Bryn TI Masculine Boys, Feminine Girls, and Cancer Risk Behaviors: An 11-Year Longitudinal Study SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Masculinity; Femininity; Cigarette smoking; Cigar smoking; Chewing tobacco; Physical activity; Tanning; Cancer ID CHILDHOOD GENDER NONCONFORMITY; HIGH-SCHOOL-STUDENTS; PHYSICAL-ACTIVITY; POSTTRAUMATIC STRESS; SMOKING INITIATION; SEXUAL ORIENTATION; SUBSTANCE USE; SELF-CONTROL; ADOLESCENTS; CHILDREN AB Objective: Cancer risk behaviors often begin in adolescence and persist through adulthood. Tobacco use, indoor tanning, and physical inactivity are highly prevalent, socially patterned cancer risk behaviors, and their prevalence differs strongly by sex. It is therefore possible that these behaviors also differ by gender expression within the sexes due to social patterning. Methods: We examined whether five cancer risk behaviors differed by childhood gender expression within the sexes and whether patterns of media engagement (e.g., magazine readership and trying to look like media personalities) explained possible differences, in a U.S. populatione-based cohort (N = 9,435). Results: The most feminine girls had higher prevalence of indoor tanning (prevalence risk ratio [pRR] = 1.32, 95% confidence interval [CI] = 1.23e1.42) and physical inactivity (pRR = 1.16, 95% CI = 1.01-1.34) and lower prevalence of worse smoking trajectory (prevalence odds ratio = .75, 95% CI = .65-.88) and smoking cigars (pRR = .61, 95% CI = .47-.79) compared with least feminine girls. Media engagement accounted for part of the higher prevalence of indoor tanning. The most masculine boys were more likely to chew tobacco (pRR = 1.78, 95% CI = 1.14-2.79) and smoke cigars (pRR = 1.55, 95% CI = 1.17-2.06) but less likely to follow a worse smoking trajectory (prevalence odds ratio = .69, 95% CI = .55-.87) and be physically inactive (pRR = .54, 95% CI = .43-.69) compared with least masculine boys. Conclusions: We found some strong differences in patterns of cancer risk behaviors by gender expression within the sexes. Prevention efforts that challenge the "masculinity" of smoking cigarettes and cigars and chewing tobacco and the "femininity" of indoor tanning to reduce their appeal to adolescents should be explored. (C) 2014 Society for Adolescent Health and Medicine. All rights reserved. C1 [Roberts, Andrea L.; Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Rosario, Margaret] CUNY City Coll, Grad Ctr, Dept Psychol, New York, NY 10031 USA. [Calzo, Jerel P.; Corliss, Heather L.; Austin, S. Bryn] Boston Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA USA. [Calzo, Jerel P.; Corliss, Heather L.; Austin, S. Bryn] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Corliss, Heather L.; Austin, S. Bryn] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Frazier, Lindsay] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Frazier, Lindsay] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Roberts, AL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Landmark Bldg 111 WS 24,401 Pk Dr, Boston, MA 02115 USA. EM aroberts@hsph.harvard.edu FU NIH [HD066963, HD057368, CA50385]; Maternal and Child Health Bureau, Health Resources and Services Administration [MC00001]; Leadership Education in Adolescent Health Project [6T71-MC00009] FX This research was supported by NIH grants HD066963 and HD057368. S. Bryn Austin is supported by Maternal and Child Health Bureau, Health Resources and Services Administration, training grant MC00001 and Leadership Education in Adolescent Health Project 6T71-MC00009. The Nurses' Health Study II is funded in part by NIH CA50385. NR 43 TC 4 Z9 4 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2014 VL 55 IS 3 BP 373 EP 379 DI 10.1016/j.jadohealth.2014.02.020 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA AO2HE UT WOS:000341138400013 PM 24746678 ER PT J AU Plitt, A Giugliano, RP AF Plitt, Anna Giugliano, Robert P. TI Edoxaban: Review of Pharmacology and Key Phase I to III Clinical Trials SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Review DE edoxaban; factor Xa inhibitor; atrial fibrillation; venous thromboembolism ID FACTOR-XA INHIBITOR; NONVALVULAR ATRIAL-FIBRILLATION; ORAL ANTICOAGULANTS; VENOUS THROMBOEMBOLISM; STROKE PREVENTION; WARFARIN; PHARMACOKINETICS; PHARMACODYNAMICS; SAFETY; EPIDEMIOLOGY AB Vitamin K antagonists (VKAs) remain the standard therapy for anticoagulation in prevention and treatment of venous thromboembolism (VIE) and for the prevention of stroke in atrial fibrillation (AF). Due to numerous limitations of VKAs, target-specific oral anticoagulants have been developed. Edoxaban is a direct activated factor X inhibitor with attractive features among which are once daily dosing, no need for routine monitoring, and minimal drug-drug interactions. In patients undergoing orthopedic surgery, edoxaban was superior to enoxaparin in preventing VTE. Furthermore, a recent large-scale phase III trial in patients with symptomatic VTE demonstrated that edoxaban was noninferior to warfarin in preventing recurrent VTE and reduced bleeding. In the largest trial of anticoagulation in patients with AF to date, edoxaban was noninferior to warfarin in the prevention of stroke or systemic embolism and reduced bleeding and cardiovascular mortality. This review provides an overview of the pharmacology, clinical trial results, and potential indications for edoxaban. C1 [Plitt, Anna] Harvard Univ, Sch Med, Boston, MA USA. [Giugliano, Robert P.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Fl Off, Boston, MA 02115 USA. EM rgiugliano@partners.org FU Daiichi Sankyo; Janssen Pharmaceuticals; Merck; Pfizer; Bristol-Myers Squibb; Daiichi Sankyoo; Sanofi; Johnson Johnson; AstraZeneca FX The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Giugliano reports receiving consulting fees from Daiichi Sankyo, Janssen Pharmaceuticals, Merck, and Pfizer; lecture fees from Bristol-Myers Squibb, Daiichi Sankyoo, Merck, and Sanofi; and grant support through his institution from Daiichi Sankyoo, Merck, Johnson & Johnson, Sanofi, and AstraZeneca. NR 44 TC 6 Z9 6 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 EI 1940-4034 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD SEP PY 2014 VL 19 IS 5 BP 409 EP 416 DI 10.1177/1074248414523675 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA AO1HY UT WOS:000341064400001 PM 24607764 ER PT J AU Zhu, XX Park, J Golinski, J Qiu, JH Khuman, J Lee, CCH Lo, EH Degterev, A Whalen, MJ AF Zhu, Xiaoxia Park, Juyeon Golinski, Julianne Qiu, Jianhua Khuman, Jugta Lee, Christopher C. H. Lo, Eng H. Degterev, Alexei Whalen, Michael J. TI Role of Akt and mammalian target of rapamycin in functional outcome after concussive brain injury in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Akt; concussion; mice; necrostatin-1; rapamycin; traumatic brain injury ID CONTROLLED CORTICAL IMPACT; FRAGILE-X-SYNDROME; SYNAPTIC PLASTICITY; COGNITIVE DEFICITS; SPATIAL MEMORY; MTOR; KINASE; PHOSPHORYLATION; ACTIVATION; SURVIVAL AB Akt (protein kinase B) and mammalian target of rapamycin (mTOR) have been implicated in the pathogenesis of cell death and cognitive outcome after cerebral contusion in mice; however, a role for Akt/mTOR in. concussive brain injury has not been well characterized. In a mouse closed head injury (CHI) concussion traumatic brain injury (TBI) model, phosphorylation of Akt (p-Akt), mTOR (p-mTOR), and S6RP (p-S6RP) was increased by 24 hours in cortical and hippocampal brain homogenates (P<0.05 versus sham for each), and p-S6RP was robustly induced in IBA-1 + microglia and glial fibrillary acidic protein-positive (GFAP+) astrocytes. Pretreatment with inhibitors of Akt or mTOR individually by the intracerebroventricular route reduced phosphorylation of their respective direct substrates FOXO1 (P<0.05) or S6RP (P<0.05) after CHI, confirming the activity of inhibitors. Rapamycin pretreatment significantly worsened hidden platform (P<0.01) and probe trial (P<0.05) performance in CHI mice. Intracerebroventricular administration of necrostatin-1 (Nec-1) before CHI increased hippocampal Akt and S6RP phosphorylation and improved place learning (probe trials, P<0.001 versus vehicle), whereas co-administration of rapamycin or Akt inhibitor with Nec-1 eliminated improved, probe trial performance. These data suggest a beneficial role for Akt/mTOR signaling after concussion TBI independent of cell death that may contribute to improved outcome by Nec-1. C1 [Zhu, Xiaoxia; Park, Juyeon; Golinski, Julianne; Qiu, Jianhua; Khuman, Jugta; Lee, Christopher C. H.; Lo, Eng H.; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. [Zhu, Xiaoxia; Park, Juyeon; Golinski, Julianne; Qiu, Jianhua; Khuman, Jugta; Lee, Christopher C. H.; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. [Zhu, Xiaoxia] Fudan Univ, Huashan Hosp, Dept Rheumatol, Shanghai 200433, Peoples R China. [Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Degterev, Alexei] Tufts Univ, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. RP Whalen, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. EM mwhalen@partners.org FU Harvard Catalyst; Harvard University; affiliated academic health care centers [1UL1 TR001102-01]; NINDS [5RO1NS047447]; National Football League Players Association; Harvard Catalyst [1UL1 TR001102-01] FX This work was conducted with support from Harvard Catalyst and financial contributions from Harvard University and its affiliated academic health care centers, grant number 1UL1 TR001102-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. This work was supported by a grant from NINDS 5RO1NS047447 (MJW), a grant from the National Football League Players Association, and Harvard Catalyst (1UL1 TR001102-01). Authors have no disclosures or conflict of interest to report. NR 40 TC 7 Z9 7 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2014 VL 34 IS 9 BP 1531 EP 1539 DI 10.1038/jcbfm.2014.113 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA AO4WT UT WOS:000341342800014 PM 24938400 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Time Trends of US Hospitalization for Esophageal Disease SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE achalasia; dyskinesia; epidemiology of digestive disease; gastroesophageal reflux disease; Mallory-Weiss syndrome ID GASTROESOPHAGEAL-REFLUX DISEASE; PEPTIC-ULCER; ADENOCARCINOMA; METAANALYSIS; OBESITY AB Background and Aims: The occurrence of reflux disease seems to be rising in the United States. The aim of the present study was to follow the time trends of hospitalization for gastroesophageal reflux disease (GERD) and other esophageal disease during the past 4 decades. Methods: US hospital utilization data were available for individual years from 1970 to 2010 through the National Hospital Discharge Survey. Esophageal diagnoses were stratified by their ninth revision of the International Classification of Diseases codes. Annual hospitalizations were expressed as rates per 100,000 living US population. Results: GERD was by far the most common esophageal disorder resulting in hospitalization. However, in only 5% of instances did GERD-related diagnoses constitute the primary cause of hospitalization. Between 1970 and 2010 the rates of GERD-related hospitalizations increased in an exponential manner almost 10-fold. This rise affected both sex and all age groups alike. A 3-fold rise was noted in hospitalizations for esophageal adenocarcinoma. Other esophageal diagnoses, such as achalasia, dyskinesia, or stricture were characterized by falling or stable trends. Conclusions: US hospitalization data show a continued exponential rise in the occurrence of GERD without any signs of leveling off. These trends are likely to represent ongoing changes in the underlying incidence and prevalence of the disease. C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr GI P3, Div Gastroenterol, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 20 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 EI 1539-2031 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD SEP PY 2014 VL 48 IS 8 BP E71 EP E75 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AN6TC UT WOS:000340729100002 PM 24440940 ER PT J AU Rauch, SD AF Rauch, Steven D. TI IL-1 beta inhibition in autoimmune inner ear disease: can you hear me now? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID AUTOANTIBODIES AB Clinical vignette: A 51-year-old man with right-sided sudden hearing loss presents to the otology clinic. He has a 4-year history of episodic vertigo of several hours' duration and fluctuating, progressive sensorineural hearing loss in his left ear. The vertigo attacks have not occurred for the last 18 months, and the left ear hearing is consistently poor. The patient's right ear hearing has dropped in the last 36 hours. MRI imaging of brain and temporal bone are normal. A 2-week "burst and taper" of oral prednisone is administered with no effect. Over the next 3 months, serial audiograms show rapidly progressive loss of threshold and word recognition scores on the right side. A trial of high-dose prednisone (60 mg/d for 30 days) results in full recovery of the right ear hearing and substantial improvement in the left ear. As the prednisone dose is slowly tapered over several months, the hearing drops again. C1 [Rauch, Steven D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rauch, Steven D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Vestibular Div, Boston, MA 02114 USA. [Rauch, Steven D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM steven_rauch@meei.harvard.edu FU BestDoctors, Inc.; Blend Therapeutics; Eleven Biotherapeutics FX Steven D. Rauch receives consulting fees from BestDoctors, Inc. His spouse receives consulting fees from Blend Therapeutics and Eleven Biotherapeutics and holds stock in Biogen Idec. NR 16 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2014 VL 124 IS 9 BP 3685 EP 3687 DI 10.1172/JCI77197 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO2PQ UT WOS:000341168100004 PM 25133418 ER PT J AU Mizumura, K Cloonan, SM Nakahira, K Bhashyam, AR Cervo, M Kitada, T Glass, K Owen, CA Mahmood, A Washko, GR Hashimoto, S Ryter, SW Choi, AMK AF Mizumura, Kenji Cloonan, Suzanne M. Nakahira, Kiichi Bhashyam, Abhiram R. Cervo, Morgan Kitada, Tohru Glass, Kimberly Owen, Caroline A. Mahmood, Ashfaq Washko, George R. Hashimoto, Shu Ryter, Stefan W. Choi, Augustine M. K. TI Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; AUTOPHAGIC CELL-DEATH; MITOCHONDRIAL FISSION; SELECTIVE AUTOPHAGY; OXIDATIVE STRESS; MAMMALIAN-CELLS; TNF-ALPHA; PARKIN; MECHANISMS; NECROSIS AB The pathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear, but involves loss of alveolar surface area (emphysema) and airway inflammation (bronchitis) as the consequence of cigarette smoke (CS) exposure. Previously, we demonstrated that autophagy proteins promote lung epithelial cell death, airway dysfunction, and emphysema in response to CS; however, the underlying mechanisms have yet to be elucidated. Here, using cultured pulmonary epithelial cells and murine models, we demonstrated that CS causes mitochondrial dysfunction that is associated with a reduction of mitochondrial membrane potential. CS induced mitophagy, the autophagy-dependent elimination of mitochondria, through stabilization of the mitophagy regulator PINK1. CS caused cell death, which was reduced by administration of necrosis or necroptosis inhibitors. Genetic deficiency of PINK1 and the mitochondrial division/mitophagy inhibitor Mdivi-1 protected against CS-induced cell death and mitochondrial dysfunction in vitro and reduced the phosphorylation of MLKL, a substrate for RIP3 in the necroptosis pathway. Moreover, Pink1(-/-) mice were protected against mitochondrial dysfunction, airspace enlargement, and mucociliary clearance (MCC) disruption during CS exposure. Mdivi-1 treatment also ameliorated CS-induced MCC disruption in CS-exposed mice. In human COPD, lung epithelial cells displayed increased expression of PINK1 and RIP3. These findings implicate mitophagy-dependent necroptosis in lung emphysematous changes in response to CS exposure, suggesting that this pathway is a therapeutic target for COPD. C1 [Mizumura, Kenji; Cloonan, Suzanne M.; Nakahira, Kiichi; Ryter, Stefan W.; Choi, Augustine M. K.] New York Presbyterian Hosp, Joan & Sanford I Weill Dept Med, Weill Cornell Med Ctr, New York, NY USA. [Mizumura, Kenji; Cloonan, Suzanne M.; Nakahira, Kiichi; Bhashyam, Abhiram R.; Owen, Caroline A.; Washko, George R.; Ryter, Stefan W.; Choi, Augustine M. K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Mizumura, Kenji; Hashimoto, Shu] Nihon Univ, Sch Med, Div Resp Med, Tokyo, Japan. [Cervo, Morgan; Mahmood, Ashfaq] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Kitada, Tohru] Ottawa Hosp, Res Inst, Div Neurosci, Ottawa, ON, Canada. [Glass, Kimberly] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Glass, Kimberly] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Choi, AMK (reprint author), Weill Cornell Med Ctr, Joan & Sanford I Weill Dept Med, 525 East 68th St,Room M-522,Box 130, New York, NY 10065 USA. EM amc2056@med.cornell.edu FU NIH [P01 HL114501-01, P01 HL105339] FX We thank I.O. Rosas, E. Ifedigbo, H.C. Lam, Z.H. Chen, and C.H. An for their technical assistance. This work was supported by NIH grants P01 HL114501-01 and P01 HL105339 (to A.M.K. Choi). NR 71 TC 58 Z9 62 U1 2 U2 22 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2014 VL 124 IS 9 BP 3987 EP 4003 DI 10.1172/JCI74985 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO2PQ UT WOS:000341168100032 PM 25083992 ER PT J AU Jones, PS Aghi, MK Muzikansky, A Shih, HA Barker, FG Curry, WT AF Jones, Pamela S. Aghi, Manish K. Muzikansky, Alona Shih, Helen A. Barker, Fred G., II Curry, William T., Jr. TI Outcomes and patterns of care in adult skull base chordomas from the Surveillance, Epidemiology, and End Results (SEER) database SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Chordoma; Population study; Radiation therapy; Skull base tumors ID ENDOSCOPIC ENDONASAL APPROACH; CRANIAL BASE; CLIVAL CHORDOMAS; UNITED-STATES; FOLLOW-UP; PROGNOSTIC-FACTORS; MOBILE SPINE; RESECTION; MANAGEMENT; SURVIVAL AB This study aims to demonstrate survival rates and treatment patterns among patients with chordomas of the skull base using a large population database. Patients with cranial chordomas between 1973 and 2009 were identified from the USA Surveillance, Epidemiology, and End Results (SEER) public use database. Kaplan-Meier analysis was used to examine the effect of surgery and radiation on overall survival. We identified 394 patients with histologically-confirmed cranial chordomas. Median survival was 151 months. Most patients (89.09%) underwent surgery. Less than half (44.92%) received radiation after diagnosis. Patients who underwent surgical resection survived significantly longer than those who did not undergo resection, regardless of other treatments (151 versus 81 months, p < 0.001). Ten year survival was lower among patients receiving radiation (44.8% versus 61.4%, p = 0.66). Surgery predicted better overall survival by univariate analysis (hazard ratio [HR] 0.603, p = 0.0293); younger age at diagnosis (HR 1.028, p < 0.001), and later year of diagnosis (HR 0.971, p = 0.0027) were prognostic of improved survival in a multivariate model. In subgroup analysis of patients with documented tumor size, smaller tumor size (HR 1.021, p = 0.0067), younger age (HR 1.031, p = 0.001), and treatment within a higher volume registry (HR 0.490, p = 0.0129) predicted improved survival. Surgical intervention offers survival benefit for cranial chordomas. Findings of decreased survival in patients receiving radiation may be associated with selection. Studies examining surgical extent of resection data and radiation details are needed to determine the impact of radiotherapy. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Jones, Pamela S.; Barker, Fred G., II; Curry, William T., Jr.] Massachusetts Gen Hosp, Dept Neurosurg, Stephen L Harris Ctr Chordoma Care, Boston, MA 02114 USA. [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Curry, WT (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Stephen L Harris Ctr Chordoma Care, 55 Fruit St,Yawkey 9E-9026, Boston, MA 02114 USA. EM wcurry@mgh.harvard.edu NR 36 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2014 VL 21 IS 9 BP 1490 EP 1496 DI 10.1016/j.jocn.2014.02.008 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7XZ UT WOS:000340815600004 PM 24852903 ER PT J AU Jones, PS Aghi, MK Muzikansky, A Shih, HA Barker, FG Curry, WT AF Jones, Pamela S. Aghi, Manish K. Muzikansky, Alona Shih, Helen A. Barker, Fred G., II Curry, William T., Jr. TI Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Chondrosarcoma; Population study; Radiation therapy; Skull base tumors ID PROTON RADIATION-THERAPY; TERM-FOLLOW-UP; CHORDOMA; SURGERY; TUMORS; HEAD; NECK AB This study aims to demonstrate survival rates and treatment patterns among patients with chondrosarcomas of the skull base using a large population database. Patients with skull base chondrosarcomas between 1973 and 2009 were identified from the USA Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis was used to examine the effect of surgery and radiation on overall survival. We identified 226 patients with skull base chondrosarcomas. Median follow-up was 5.4 years. Median overall survival was 22 years, and 10 year survival was 68.2%. Most patients underwent surgery (92.5%). Few received radiation after diagnosis (38.1%). Ten year survival for all patients treated with surgery was significantly increased compared to those without surgery (69.3% versus 53.9%, p = 0.02). There was a significant difference in survival amongst treatment groups (p = 0.02), with median overall survival not yet reached for patients who received surgery and radiation (median follow-up 5.3 years), compared to 22 years for non-irradiated surgical patients. Surgery predicted better overall survival by univariate analysis (hazard ratio [HR] 0.420, p = 0.03). Female sex (HR 0.470, p = 0.011), younger age at diagnosis (HR 1.046, p < 0.0001), and later year of diagnosis (HR 0.949, p = 0.0006) were prognostic of improved survival in a multivariate model. In subgroup analysis of patients with documented tumor size, smaller tumor size (HR 1.054, p = 0.0003) and younger age (HR 1.021, p = 0.0067) predicted improved survival. This population based study further reaffirms the role of surgery as an effective treatment for skull base chondrosarcoma as previously reported in small case series. Adjuvant radiation may also confer survival benefit. Optimal treatment strategy has yet to be defined in the literature. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Jones, Pamela S.; Barker, Fred G., II; Curry, William T., Jr.] Massachusetts Gen Hosp, Dept Neurosurg, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Curry, WT (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Stephen E & Catherine Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E-9026, Boston, MA 02114 USA. EM wcurry@mgh.harvard.edu NR 20 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2014 VL 21 IS 9 BP 1497 EP 1502 DI 10.1016/j.jocn.2014.02.005 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7XZ UT WOS:000340815600005 PM 24792724 ER PT J AU Stapleton, CJ Fusco, MR Thomas, AJ Levy, EI Ogilvy, CS AF Stapleton, Christopher J. Fusco, Matthew R. Thomas, Ajith J. Levy, Elad I. Ogilvy, Christopher S. TI Traumatic pseudoaneurysms of the superficial temporal artery: Case series, anatomy, and multidisciplinary treatment considerations SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Blunt head injury; Embolization; Neurosurgery; Pseudoaneurysm; Superficial temporal artery ID CT ANGIOGRAPHY; EMBOLIZATION AB Pseudoaneurysms of the superficial temporal artery (STA) are rare vascular lesions of the external carotid artery system and are most often incurred after blunt head trauma. Diagnosis can be made on clinical grounds, and is confirmed by ultrasonography (US) or CT angiography. Surgical ligation and excision of the aneurysm remains a definitive treatment modality. Patients with STA pseudoaneurysms are often referred to a neurovascular specialist given the neurovascular origin and gross anatomic location of these lesions. Three patients presented to our neurovascular service several weeks following blunt head injury to the anterolateral skull surface with progressive, palpable, pulsatile masses. Each patient underwent CT angiography, which demonstrated a pseudoaneurysm of the frontal branch of the STA, followed by operative ligation and en bloc excision. The present series highlights the anatomical considerations relevant to STA injury and pseudoaneurysm formation following blunt head trauma and reviews the necessary diagnostic and treatment considerations. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Stapleton, Christopher J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Stapleton, Christopher J.; Fusco, Matthew R.; Thomas, Ajith J.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fusco, Matthew R.; Thomas, Ajith J.; Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Neurosurg, Boston, MA 02215 USA. [Levy, Elad I.] SUNY Buffalo, Toshiba Stroke Res Ctr, Buffalo, NY 14260 USA. [Levy, Elad I.] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14260 USA. [Levy, Elad I.] Kaleida Hlth, Millard Fillmore Gates Hosp, Buffalo, NY USA. [Levy, Elad I.] SUNY Buffalo, Dept Radiol, Buffalo, NY 14260 USA. RP Stapleton, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,ACC 745, Boston, MA 02114 USA. EM cstapleton@partners.org NR 14 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2014 VL 21 IS 9 BP 1529 EP 1532 DI 10.1016/j.jocn.2014.02.004 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7XZ UT WOS:000340815600011 PM 24631326 ER PT J AU Coumans, JVCE Neal, JB Grottkau, BE Nahed, BV Shin, JH Walcott, BP AF Coumans, Jean-Valery C. E. Neal, Jonathan B. Grottkau, Brian E. Nahed, Brian V. Shin, John H. Walcott, Brian P. TI Giant thoracic osteophyte: A distinct clinical entity SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Arthrodesis; Degenerative disease; Fusion; Myelopathy; Osteophyte; Spine; Thoracic ID IDIOPATHIC SKELETAL HYPEROSTOSIS; NEURAL AXIS; PSEUDOTUMOR; FEATURES; SPINE; DISH; CALCIFICATION AB Calcified lesions described within the neural axis are classified as either an ossification of the posterior longitudinal ligament, diffuse idiopathic skeletal hyperostosis, or ossification of the ligamentum flavum. We aim to describe a unique pathologic entity: the giant thoracic osteophyte. We identified four patients who were surgically treated at the Massachusetts General Hospital from 2006 to 2012 with unusual calcified lesions in the ventral aspect of the spinal canal. In order to differentiate giant thoracic osteophytes from calcified extruded disc material, disc volumetrics were performed on actual and simulated disc spaces. All patients underwent operative resection of the calcific lesion as they had signs and/or symptoms of spinal cord compression. The lesions were found to be isolated, large calcific masses that originated from the posterior aspect of adjacent thoracic vertebral bodies. Pathological examination was negative for tumor. Adjacent disc volumes were not significantly different from the index disc (p = 0.91). A simulated calculation hypothesizing that the calcific mass was extruded disc material demonstrated a significant difference (p = 0.01), making this scenario unlikely. In conclusion, giant thoracic osteophyte is a unique and rare entity that can be found in the thoracic spine. The central tenant of surgical treatment is resection to relieve spinal cord compression. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Coumans, Jean-Valery C. E.; Neal, Jonathan B.; Nahed, Brian V.; Shin, John H.; Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Coumans, Jean-Valery C. E.; Neal, Jonathan B.; Grottkau, Brian E.; Nahed, Brian V.; Shin, John H.; Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grottkau, Brian E.] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 14 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2014 VL 21 IS 9 BP 1599 EP 1602 DI 10.1016/j.jocn.2013.12.027 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7XZ UT WOS:000340815600025 PM 24836298 ER PT J AU Yanamadala, V Lin, N Zarzour, H Frerichs, KU Walcott, BP Thomas, AJ Puri, AS AF Yanamadala, Vijay Lin, Ning Zarzour, Hekmat Frerichs, Kai U. Walcott, Brian P. Thomas, Ajith J. Puri, Ajit S. TI Endovascular coiling of a ruptured basilar apex aneurysm with associated pseudoaneurysm SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Aneurysm; Endovascular coiling; Pseudoaneurysm; Subarachnoid hemorrhage ID INTERNAL CAROTID-ARTERY; MIDDLE CEREBRAL-ARTERY; OF-THE-LITERATURE; INTRACRANIAL PSEUDOANEURYSM; SURGERY; STENT; MANAGEMENT; SITE; ONYX AB Acute intracranial pseudoaneurysms secondary to aneurysmal rupture are a rare entity with no clear evidence-based guidelines for treatment to our knowledge. There are numerous examples of successful treatment of pseudoaneurysms both surgically and endovascularly, the latter mainly within the anterior circulation. Risk of pseudoaneurysm rupture in the acute state during endovascular procedures with subsequent difficulty in controlling the bleeding without sacrificing the feeder artery has led to some reservation in using endovascular treatments more broadly. We report a rare case of a 52-year-old-woman who presented with acute subarachnoid hemorrhage and was found to have a ruptured 5 mm x 8 mm bi-lobulated basilar apex aneurysm on CT angiography. Digital subtraction angiography demonstrated an associated anterior pseudoaneurysm that was formed secondary to the aneurysm rupture. The true aneurysm was successfully coiled with careful avoidance of the pseudoaneurysmal sac. Pseudoaneurysms are frequently identified for the first time during digital subtraction angiography. Recognizing their presence is essential for treatment planning. Acute pseudoaneurysms associated with true aneurysmal rupture can be safely and successfully treated by endovascular coiling of the true aneurysm. Care must be taken to avoid manipulation of the pseudoaneurysmal sac during the embolization. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Yanamadala, Vijay; Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Yanamadala, Vijay; Lin, Ning; Zarzour, Hekmat; Frerichs, Kai U.; Walcott, Brian P.; Thomas, Ajith J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lin, Ning; Zarzour, Hekmat; Frerichs, Kai U.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Frerichs, Kai U.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Thomas, Ajith J.] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA. [Puri, Ajit S.] Univ Massachusetts, Dept Radiol, New England Ctr Stroke Res, Worcester, MA 01605 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 22 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2014 VL 21 IS 9 BP 1637 EP 1640 DI 10.1016/j.jocn.2013.11.050 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7XZ UT WOS:000340815600034 PM 24768151 ER PT J AU Langevin, JP Srikandarajah, N Krahl, SE Gorgulho, A Behnke, E Malkasian, D DeSalles, AAF AF Langevin, Jean-Philippe Srikandarajah, Nisaharan Krahl, Scott E. Gorgulho, Alessandra Behnke, Eric Malkasian, Dennis DeSalles, Antonio A. F. TI Eyelid apraxia associated with deep brain stimulation of the periaqueductal gray area SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Deep brain stimulation; Eyelid apraxia; Periaqueductal gray area AB We report a patient with eyelid apraxia following deep brain stimulation of the periaqueductal gray area. Based on the position of our electrode, we argue that the phenomenon is linked to inhibition of the nearby central caudal nucleus of the oculomotor nucleus by high frequency stimulation. Published by Elsevier Ltd. C1 [Langevin, Jean-Philippe; Krahl, Scott E.; Gorgulho, Alessandra; Behnke, Eric; Malkasian, Dennis; DeSalles, Antonio A. F.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. [Langevin, Jean-Philippe] Greater Los Angeles VA Healthcare Syst, Neurosurg Serv, Los Angeles, CA 90073 USA. [Srikandarajah, Nisaharan] Walton Ctr, Liverpool, Merseyside, England. RP Langevin, JP (reprint author), Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. EM jlangevin@mednet.ucla.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2014 VL 21 IS 9 BP 1652 EP 1653 DI 10.1016/j.jocn.2014.03.002 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7XZ UT WOS:000340815600038 PM 24726237 ER PT J AU Woodward, WA Sneige, N Winter, K Kuerer, HM Hudis, C Rakovitch, E Smith, BL Pierce, LJ Germano, I Pu, AT Walker, EM Grisell, DL White, JR McCormick, B AF Woodward, Wendy A. Sneige, Nour Winter, Kathryn Kuerer, Henry Mark Hudis, Clifford Rakovitch, Eileen Smith, Barbara L. Pierce, Lori J. Germano, Isabelle Pu, Anthony T. Walker, Eleanor M. Grisell, David Lawrence White, Julia R. McCormick, Beryl CA RTOG TI Web based pathology assessment in RTOG 98-04 SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID CARCINOMA-IN-SITU; SURGICAL ADJUVANT BREAST; LOCAL RECURRENCE; CONSERVING TREATMENT; BOWEL PROJECT; EUROPEAN ORGANIZATION; RADIATION-THERAPY; SECTOR RESECTION; RANDOMIZED-TRIAL; RISK-FACTORS AB Aims Radiation Therapy Oncology Group 98-04 sought to identify women with 'good risk' ductal carcinoma in situ (DCIS) who receive no significant benefit from radiation. Enrolment criteria excluded close or positive margins and grade 3 disease. To ensure reproducibility in identifying good risk pathology, an optional web based teaching tool was developed and a random sampling of 10% of submitted slides were reviewed by a central pathologist. Methods Submitting pathologists were asked to use the web based teaching tool and submit an assessment of the tool along with the pathology specimen form and DCIS H&E stained slide. Per protocol pathology was centrally reviewed for 10% of the cases. Results Of the 55 DCIS cases reviewed, three had close or positive margins and three were assessed to include grade 3 DCIS, therefore 95% of DCIS cases reviewed were correctly graded, and 89% reviewed were pathologically appropriate for enrolment. Regarding the teaching tool, 13% of DCIS cases included forms that indicated the website was used. One of these seven who used the website submitted DCIS of grade 3. Conclusions Central review demonstrates high pathological concordance with enrolment eligibility, particularly with regard to accurate grading. The teaching tool appeared to be underused. C1 [Woodward, Wendy A.; Sneige, Nour; Kuerer, Henry Mark] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Winter, Kathryn] RTOG Stat Ctr, Philadelphia, PA USA. [Hudis, Clifford; McCormick, Beryl] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Rakovitch, Eileen] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pierce, Lori J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Germano, Isabelle] Mt Sinai Med Ctr, New York, NY 10029 USA. [Pu, Anthony T.] Radiol Associates Sacramento, Sacramento, CA USA. [Walker, Eleanor M.] Henry Ford Hosp, Detroit, MI 48202 USA. [Grisell, David Lawrence] Canc Ctr Carolinas Greenville CCOP, Greenville, SC USA. [White, Julia R.] Stephanie Spielman Comprehens Breast Ctr, Columbus, OH USA. RP McCormick, B (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM mccormib@mskcc.org FU RTOG [U10 CA21661]; CCOP from the National Cancer Institute (NCI) [U10 CA37422] FX This project was supported by RTOG grants U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). NR 23 TC 3 Z9 3 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 EI 1472-4146 J9 J CLIN PATHOL JI J. Clin. Pathol. PD SEP PY 2014 VL 67 IS 9 BP 777 EP 780 DI 10.1136/jclinpath-2014-202370 PG 4 WC Pathology SC Pathology GA AN8BR UT WOS:000340826800006 PM 24989024 ER PT J AU Maan, A Mansour, M Ruskin, JN Heist, EK AF Maan, Abhishek Mansour, Moussa Ruskin, Jeremy N. Heist, E. Kevin TI Impact of catheter ablation on P-wave parameters on 12-lead electrocardiogram in patients with atrial fibrillation SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Atrial fibrillation; Catheter ablation; Electrocardiogram ID PULMONARY VEIN ISOLATION; SIGNAL-AVERAGED ELECTROCARDIOGRAM; RADIOFREQUENCY ABLATION; ANATOMIC APPROACH; DURATION; EFFICACY; PREDICTION; INITIATION; MARKER; ADULTS AB Background: Catheter ablation has emerged as a widely used treatment modality for atrial fibrillation (AF). P-wave abnormalities have been described in the patients with AF, and catheter ablation may potentially further impact P-wave parameters due to ablation of atrial tissue. Methods: We reviewed data on P-wave parameters (P-wave duration, amplitude and P-wave duration and amplitude product) in leads V1 and aVF and changes in the P-terminal force (Ptf; product of duration and amplitude of terminal part of P-wave) in lead V1 from 12-lead electrocardiograms obtained prior to and after CA of a total of 46 (28 paroxysmal and 18 persistent) AF patients. Results: The median age of patients in our study was 63 (range: 30-77) years. We noticed a significant reduction in the P-wave duration (from 87.39 +/- 28.62 ms at baseline to 72.09 +/- 24.59 ms; p = 0.0072) and the product of P-wave duration and amplitude in lead V1 (12.16 +/- 5.54 mV ms at baseline to 8.30 +/- 5.78 mV ms, p = 0.0015) after CA. There was also a significant decrease in P-wave duration (from 92.57 +/- 19.67 ms at baseline to 76.48 +/- 16.32 ms after CA, p = 0.0001) and P-wave duration and amplitude product in lead aVF (12.61 +/- 4.05 mV ms at baseline to 9.77 +/- 3.86 m V ms after CA,p = 0.0001). CA also led to a significant decrease in Ptf (from 4.56 +/- 1.88 at baseline to 2.85 +/- 1.42 mV ms,p < 0.0001). Conclusion: Radiofrequency catheter ablation of AF leads to modification of P-wave parameters with substantial diminution in both the amplitude and duration of the P-wave in leads V1 and aVF. This likely represents reduction in electrically active atrial tissue after ablation, and may serve as a marker for the extent of ablated atrial tissue. (C) 2014 Elsevier Inc. All rights reserved. C1 [Maan, Abhishek; Mansour, Moussa; Ruskin, Jeremy N.; Heist, E. Kevin] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Heist, EK (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM kheist@mgh.harvard.edu FU Biosense-Webster; Boston Scientific; Cardiofocus; Endosense; MC10; St. Jude Medical; Voyage Medical; Biotronik FX A.M.: None. M.M.: Biosense-Webster (consultant, research grant), Boston Scientific (research grant), St. Jude (consultant), Cardiofocus (research grant), Endosense (research grant), MC10 (research grant), St. Jude Medical (consultant, research grant), Voyage Medical (research grant). J.N.R.: Astellas/Cardiome (consultant, significant); Biosense-Webster (consultant, modest) and Fellowship Support (significant); Boston Scientific (fellowship support, significant); CardioFocus-Clinical Oversight Committee (no compensation); CardioInsight-Scientific Advisory Board (modest); CryoCath-Scientific Steering Committee (no compensation); Medtronic-Consultant (modest) and fellowship support (significant); Med-IQ (honoraria, modest); Pfizer (consultant and scientific steering committee, modest); Portola (consultant and equity, modest); Sanofi (consultant, modest), St. Jude Medical (fellowship support, significant); Third Rock Ventures (consultant, significant). E.K.H. (all modest in amount): Biotronik (research grant, honoraria), Boston Scientific (research grant, consultant, honoraria), Medtronic (honoraria), Sanofi (consultant), Sorin (consultant, honoraria), St. Jude Medical (research grant, consultant, honoraria). NR 34 TC 5 Z9 6 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD SEP-OCT PY 2014 VL 47 IS 5 BP 725 EP 733 DI 10.1016/j.jelectrocard.2014.04.010 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO2DV UT WOS:000341126600025 PM 24850319 ER PT J AU Frank, JW Linder, JA Becker, WC Fiellin, DA Wang, EA AF Frank, Joseph W. Linder, Jeffrey A. Becker, William C. Fiellin, David A. Wang, Emily A. TI Increased Hospital and Emergency Department Utilization by Individuals with Recent Criminal Justice Involvement: Results of a National Survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE vulnerable populations; emergency medicine; hospital medicine; health care costs ID HEALTH-CARE; CORRECTIONAL FACILITIES; NICOTINE DEPENDENCE; FORMER INMATES; PUBLIC-HEALTH; HIGH-RISK; PRISON; RELEASE; PREVALENCE; SERVICES AB Individuals involved with the criminal justice system have increased health needs and poor access to primary care. To examine hospital and emergency department (ED) utilization and related costs by individuals with recent criminal justice involvement. Cross-sectional survey. Non-institutionalized, civilian U.S. adult participants (n = 154,356) of the National Survey on Drug Use and Health (2008-2011). Estimated proportion of adults who reported past year 1) hospitalization or 2) ED utilization according to past year criminal justice involvement, defined as 1) parole or probation, 2) arrest without subsequent correctional supervision, or 3) no criminal justice involvement; estimated annual expenditures using unlinked data from the Medical Expenditure Panel Survey. An estimated 5.7 million adults reported parole or probation and an additional 3.9 million adults reported an arrest in the past year. Adults with recent parole or probation and those with a recent arrest, compared with the general population, had higher rates of hospitalization (12.3 %, 14.3 %, 10.5 %; P < 0.001) and higher rates of ED utilization (39.3 %, 47.2 %, 26.9 %; P < 0.001). Recent parole or probation was an independent predictor of hospitalization (adjusted odds ratio [AOR], 1.21; 95 % confidence interval [CI], 1.02-1.44) and ED utilization (AOR, 1.35; 95 % CI, 1.12-1.63); Recent arrest was an independent predictor of hospitalization (AOR, 1.26; 95 % CI, 1.08-1.47) and ED utilization (AOR, 1.81; 95 % CI, 1.53-2.15). Individuals with recent criminal justice involvement make up 4.2 % of the U.S. adult population, yet account for an estimated 7.2 % of hospital expenditures and 8.5 % of ED expenditures. Recent criminal justice involvement is associated with increased hospital and ED utilization and costs. The criminal justice system may offer an important point of contact for efforts to improve the healthcare utilization patterns of a large and vulnerable population. C1 [Frank, Joseph W.] Univ Colorado, Sch Med, Div Gen Internal Med, Aurora, CO 80045 USA. [Frank, Joseph W.] Denver VA Med Ctr, Denver, CO USA. [Linder, Jeffrey A.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Linder, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Becker, William C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Becker, William C.; Fiellin, David A.; Wang, Emily A.] Yale Univ, Sch Med, Gen Internal Med Sect, New Haven, CT USA. RP Frank, JW (reprint author), Univ Colorado, Sch Med, Div Gen Internal Med, 8th Floor,Acad Off 1,12631 E 17th Ave, Aurora, CO 80045 USA. EM joseph.frank@ucdenver.edu OI Fiellin, David/0000-0002-4006-010X FU Health Resources and Services Administration [T32 HP10251]; Veterans Health Administration Health Services Research & Development Career Development Award [08-276]; National Heart, Lung and Blood Institute [K23 HL103720] FX Dr. Frank was supported by the Health Resources and Services Administration through an institutional National Research Service Award (T32 HP10251). Dr. Becker is supported by a Veterans Health Administration Health Services Research & Development Career Development Award (08-276). Dr. Wang is supported by the National Heart, Lung and Blood Institute (K23 HL103720). NR 38 TC 11 Z9 11 U1 1 U2 11 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 SEP PY 2014 VL 29 IS 9 BP 1226 EP 1233 DI 10.1007/s11606-014-2877-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600007 PM 24817280 ER PT J AU Sabbatini, AK Tilburt, JC Campbell, EG Sheeler, RD Egginton, JS Goold, SD AF Sabbatini, Amber K. Tilburt, Jon C. Campbell, Eric G. Sheeler, Robert D. Egginton, Jason S. Goold, Susan D. TI Controlling Health Costs: Physician Responses to Patient Expectations for Medical Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE physician stewardship; cost-conscious care; health care costs; physician decision-making ID INSURANCE DESIGN; DECISION-MAKING; NATIONAL-SURVEY; US; SERVICES; PROFESSIONALISM; COMMUNICATION; ONCOLOGISTS; ATTITUDES; REQUESTS AB Physicians have dual responsibilities to make medical decisions that serve their patients' best interests but also utilize health care resources wisely. Their ability to practice cost-consciously is particularly challenged when faced with patient expectations or requests for medical services that may be unnecessary. To understand how physicians consider health care resources and the strategies they use to exercise cost-consciousness in response to patient expectations and requests for medical care. Exploratory, qualitative focus groups of practicing physicians were conducted. Participants were encouraged to discuss their perceptions of resource constraints, and experiences with redundant, unnecessary and marginally beneficial services, and were asked about patient requests or expectations for particular services. Sixty-two physicians representing a variety of specialties and practice types participated in nine focus groups in Michigan, Ohio, and Minnesota in 2012 Iterative thematic content analysis of focus group transcripts Physicians reported making trade-offs between a variety of financial and nonfinancial resources, considering not only the relative cost of medical decisions and alternative services, but the time and convenience of patients, their own time constraints, as well as the logistics of maintaining a successful practice. They described strategies and techniques to educate patients, build trust, or substitute less costly alternatives when appropriate, often adapting their management to the individual patient and clinical environment. Physicians often make nuanced trade-offs in clinical practice aimed at efficient resource use within a complex flow of clinical work and patient expectations. Understanding the challenges faced by physicians and the strategies they use to exercise cost-consciousness provides insight into policy measures that will address physician's roles in health care resource use. C1 [Sabbatini, Amber K.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA. [Tilburt, Jon C.] Mayo Clin, Div Gen Internal Med, Rochester, MN USA. [Tilburt, Jon C.] Mayo Clin, Biomed Eth Res Unit, Rochester, MN USA. [Tilburt, Jon C.; Egginton, Jason S.] Mayo Clin, Ctr Sci Hlth Care Delivery, Rochester, MN USA. [Campbell, Eric G.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Sheeler, Robert D.] Mayo Clin, Dept Family Med, Rochester, MN USA. [Goold, Susan D.] Univ Michigan, Dept Med & Hlth Management & Policy, Ann Arbor, MI 48109 USA. [Goold, Susan D.] Ctr Bioeth & Social Sci Med, Ann Arbor, MI USA. RP Sabbatini, AK (reprint author), Univ Michigan, Dept Emergency Med, NCRC, 2800 Plymouth Rd,Bldg 10,Room G015, Ann Arbor, MI 48109 USA. EM asabbati@med.umich.edu OI Goold, Susan Dorr/0000-0002-0258-9774 FU Greenwall Foundation FX The authors would like to thank Greenwall Foundation for the support of this work. NR 33 TC 6 Z9 6 U1 0 U2 10 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 SEP PY 2014 VL 29 IS 9 BP 1234 EP 1241 DI 10.1007/s11606-014-2898-6 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600008 PM 24871228 ER PT J AU Dattalo, M Nothelle, S Tackett, S Larochelle, M Porto-Carreiro, F Yu, E Hanyok, LA AF Dattalo, Melissa Nothelle, Stephanie Tackett, Sean Larochelle, Marc Porto-Carreiro, Fernanda Yu, Eunice Hanyok, Laura A. TI Frontline Account: Targeting Hot Spotters in an Internal Medicine Residency Clinic SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE medical education graduate; primary care redesign; patient-centered care ID SATISFACTION C1 [Dattalo, Melissa; Nothelle, Stephanie; Tackett, Sean; Porto-Carreiro, Fernanda; Yu, Eunice; Hanyok, Laura A.] Johns Hopkins Bayview Med Ctr, Dept Internal Med, Baltimore, MD USA. [Dattalo, Melissa] Univ Wisconsin, Sch Med & Publ Hlth, Div Geriatr & Gerontol, Madison, WI USA. [Dattalo, Melissa] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. [Larochelle, Marc] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Larochelle, Marc] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Dattalo, M (reprint author), Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. EM mdattalo@uwhealth.org OI Tackett, Sean/0000-0001-5369-7225 FU NCATS NIH HHS [UL1 TR000427] NR 4 TC 4 Z9 4 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 SEP PY 2014 VL 29 IS 9 BP 1305 EP 1307 DI 10.1007/s11606-014-2861-6 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600021 PM 24830738 ER PT J AU Bischoff, K Shah, SM Dhaliwal, G Hollander, H AF Bischoff, Kara Shah, Shilpa M. Dhaliwal, Gurpreet Hollander, Harry TI A Heart-Breaking Case of Fever and Rash SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE clinical problem solving; rash; fever ID KAWASAKI-DISEASE; MEDICINE C1 [Bischoff, Kara; Shah, Shilpa M.; Dhaliwal, Gurpreet; Hollander, Harry] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Shah, SM (reprint author), Univ Calif San Francisco, Dept Med, 1545 Divisadero St, San Francisco, CA 94121 USA. EM shilpa.shah@ucsf.edu NR 13 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 SEP PY 2014 VL 29 IS 9 BP 1310 EP 1314 DI 10.1007/s11606-014-2775-3 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600024 PM 24687288 ER PT J AU Lowalekar, SK Cao, HY Lu, XG Treanor, PR Thatte, HS AF Lowalekar, Samar K. Cao, Haiyan Lu, Xiu-Gui Treanor, Patrick R. Thatte, Hemant S. TI Sub-normothermic preservation of donor hearts for transplantation using a novel solution, Somah: A comparative pre-clinical study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE organ preservation solutions; transplantation; organ edema; high energy phosphates; 2D echo; ex vivo cardiac function; in vitro cardiac animation ID ORGAN PRESERVATION; PERFUSION PRESERVATION; ISCHEMIA-REPERFUSION; COLD-STORAGE; CARDIOMYOCYTES; INJURY; FLOW AB BACKGROUND: Hearts preserved ex vivo at extreme hypothermia (4 degrees C) undergo time-dependent irreversible injury. Our studies using a novel solution, Somah, suggest that hearts are viably preserved at 21 degrees C. In this study we evaluate the relative efficacy of Somah for preservation of hearts at 21 degrees C when compared with the clinically used Celsior and University of Wisconsin (UWS) solutions. METHODS: Porcine hearts arrested by cardioplegia at 21 degrees C using Somali, Celsior or UWS solution were stored in the respective solutions at 21 degrees C (n = 5) for 5 hours and then reperfused ex vivo for functional assessment. We assessed development of edema, cardiac tissue high-energy phosphate (HEP; ATP + creatine phosphate) levels and release of cardiac enzymes. Alterations in left ventricular wall thicknesses and functional parameters were examined by 2-dimensional (2D) echocardiography. Changes in myocardial oxygen consumption (MVO2) and lactate utilization were assessed at reperfusion. RESULTS: Heart weights were unaltered during 5-hour storage in all groups. After storage, HEP levels were 28.33 +/- 5.51, 10.20 +/- 2.78 and 5.92 +/- 1.46 nmol/liter per milligram protein (p < 0.001) in the Somali, Celsior and UWS group hearts, respectively. Upon reanimation, 2D echocardiography showed edema in the Celsior and UWS hearts; prompt attainment of physiologic function was associated with rapid establishment of aerobic metabolism not requiring stimulatory interventions in the Somali hearts, but not in the Celsior/UWS hearts. Percent fractional area change, ejection fraction and stroke volume were significantly higher (p < 0.001) in Somali hearts than in Celsior and UWS group hearts. CONCLUSIONS: Increased synthesis of BEP, rapid metabolic switch and optimal function together provide evidence that hearts procured for transplantation are preserved in a superior viable condition at 21 degrees C with Somali, but not with other commonly used clinical preservation solutions. Published by Elsevier Inc. C1 [Lowalekar, Samar K.; Cao, Haiyan; Lu, Xiu-Gui; Thatte, Hemant S.] Harvard Univ, Sch Med, Dept Surg, Div Cardiothorac Surg, Boston, MA 02115 USA. [Lowalekar, Samar K.; Cao, Haiyan; Lu, Xiu-Gui; Thatte, Hemant S.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Lowalekar, Samar K.; Cao, Haiyan; Lu, Xiu-Gui; Treanor, Patrick R.; Thatte, Hemant S.] VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. RP Thatte, HS (reprint author), VA Boston Healthcare Syst, Dept Surg MC112, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM hemant_thatte@hms.harvard.edu FU VA Merit Grant FX This work was supported by a VA Merit Grant (to H.S.T.) and by an unrestricted research gift from Somahlution (Jupiter, FL) to the Boston VA Research Institute (to H.S.T.). NR 20 TC 4 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD SEP PY 2014 VL 33 IS 9 BP 963 EP 970 DI 10.1016/j.healun.2014.05.006 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AO2CY UT WOS:000341124300012 PM 25001113 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI REPORT OF THE NATIONAL INSTITUTES OF HEALTH TASK FORCE ON RESEARCH STANDARDS FOR CHRONIC LOW BACK PAIN SO JOURNAL OF MANIPULATIVE AND PHYSIOLOGICAL THERAPEUTICS LA English DT Article DE Low Back Pain; Chronic Pain; Patient Outcome Assessment; Research Design ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES; INTERVENTIONAL THERAPIES AB Objectives: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed nonspecific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. The purpose of this article is to disseminate the report of the National Institutes of Health (NIH) task force on research standards for cLBP. Methods: The NIH Pain Consortium charged a research task force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. Results: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the Patient Reported Outcomes Measurement Information System methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved these recommendations, which investigators should incorporate into NIH grant proposals. Conclusions: The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of cLBP. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will become a dynamic document and undergo continual improvement. C1 [Deyo, Richard A.] OHSU, Dept Family Med, Portland, OR 97239 USA. [Deyo, Richard A.; Chou, Roger] OHSU, Dept Med, Portland, OR 97239 USA. [Deyo, Richard A.] OHSU, Dept Publ Hlth & Community Med, Portland, OR 97239 USA. [Dworkin, Samuel F.] Univ Washington, Dept Psychiat & Behav Sci, Dept Oral Med, Seattle, WA 98195 USA. [Amtmann, Dagmar] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Dept Orthopaed Surg, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. [Carragee, Eugene] Stanford Univ, Dept Orthopaed Surg, Sch Med, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Chou, Roger] OHSU, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Cook, Karon] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [DeLitto, Anthony] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Palmer Ctr Chiropract Res, Davenport, IA USA. [Khalsa, Partap] NIH, Div Extramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Loeser, John] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Loeser, John; Turk, Dennis] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Mackey, Sean] Stanford Univ, Dept Anesthesia & Pain Management, Stanford, CA 94305 USA. [Panagis, James] NIAMSD, NIH, Orthopaed Res Program, Bethesda, MD 20892 USA. [Rainville, James] New England Baptist Hosp, Dept Phys Med & Rehabil, Roxbury Crossing, MA USA. [Tosteson, Tor] Geisel Sch Med Dartmouth, Dept Community & Family Med, Hanover, NH USA. [Tosteson, Tor] Geisel Sch Med Dartmouth, Dartmouth Inst, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Deyo, RA (reprint author), OHSU, Mail Code FM,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deyor@ohsu.edu FU NCCAM; National Institute for Arthritis, Musculoskeletal, and Skin Diseases, NIH FX This study was supported by the NCCAM and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases, NIH. No conflicts of interest were reported for this study. NR 125 TC 3 Z9 3 U1 8 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-4754 J9 J MANIP PHYSIOL THER JI J. Manip. Physiol. Ther. PD SEP PY 2014 VL 37 IS 7 BP 449 EP 467 DI 10.1016/j.jmpt.2014.07.006 PG 19 WC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation SC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation GA AO2XD UT WOS:000341189600001 PM 25127996 ER PT J AU Oklu, R Deipolyi, AR Wicky, S Ergul, E Deik, AA Chen, JW Hirsch, JA Wojtkiewicz, GR Clish, CB AF Oklu, Rahmi Deipolyi, Amy R. Wicky, Stephan Ergul, Emel Deik, Amy A. Chen, John W. Hirsch, Joshua A. Wojtkiewicz, Gregory R. Clish, Clary B. TI Identification of small compound biomarkers of pituitary adenoma: a bilateral inferior petrosal sinus sampling study SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; CUSHINGS-SYNDROME; HUMAN METABOLOME; PHYTANIC ACID; CANCER; RISK; SERUM; METABONOMICS; PROFILES; NETWORKS AB Evaluation of the pathogenic mechanisms underlying Cushing disease (CD) is limited partly by the inaccessibility of the pituitary gland for biopsy. We used bilateral inferior petrosal sinus sampling (BIPSS), the gold standard in diagnosing pituitary sources of CD, to obtain central blood samples for in vivo metabolomic analysis of pathways involved in pituitary adenomas. We evaluated 16 samples from eight patients who underwent BIPSS to measure adrenocorticotropic hormone (ACTH) levels in the inferior petrosal sinus (IPS) bilaterally. Seven patients had CD with concordant BIPSS, surgical, and pathologic findings. Samples from the IPS contralateral to histologically proven lesions were used as controls. BIPSS of the eighth patient revealed no central pituitary ACTH source, and these samples were also included as controls. Plasma samples were profiled using a combination of three liquid chromatography tandem mass spectrometry methods, which assessed 259 metabolites. Following Bonferroni correction for multiple comparisons, three small compound biomarkers of CD (pyridoxate, deoxycholic acid, and 3-methyladipate) were identified to be significantly altered in pituitary adenomas. The pathway most significantly impacted in CD samples is one previously shown to be upregulated in other cancers. Exploiting the BIPSS technique, we showed a complete metabolite and lipid profile of pituitary adenomas in CD. These potential biomarkers of CD may elucidate tumor biology and suggest possible diagnostic molecular imaging probes as well as therapeutic targets in patients with recurrent disease after surgery. C1 [Oklu, Rahmi; Deipolyi, Amy R.; Wicky, Stephan; Ergul, Emel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Deik, Amy A.; Clish, Clary B.] Broad Inst Massachusetts Inst Technol & Harvard U, Div Metabolite Profiling, Cambridge, MA USA. [Chen, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Neuroradiol, Boston, MA 02114 USA. [Chen, John W.; Wojtkiewicz, Gregory R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, 55 Fruit St,291 Gray Bigelow, Boston, MA 02114 USA. EM roklu@partners.org OI Deipolyi, Amy/0000-0003-3144-386X FU NIBIB NIH HHS [L30 EB012342] NR 31 TC 4 Z9 5 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2014 VL 6 IS 7 BP 541 EP 546 DI 10.1136/neurintsurg-2013-010821 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AO0IY UT WOS:000340993500012 PM 24005126 ER PT J AU Kanaly, CW Mehta, AI Ding, D Hoang, JK Kranz, PG Herndon, JE Coan, A Crocker, I Waller, AF Friedman, AH Reardon, DA Sampson, JH AF Kanaly, Charles W. Mehta, Ankit I. Ding, Dale Hoang, Jenny K. Kranz, Peter G. Herndon, James E., II Coan, April Crocker, Ian Waller, Anthony F. Friedman, Allan H. Reardon, David A. Sampson, John H. TI A novel, reproducible, and objective method for volumetric magnetic resonance imaging assessment of enhancing glioblastoma SO JOURNAL OF NEUROSURGERY LA English DT Article DE brain neoplasm; disease progression; glioma; magnetic resonance imaging; recurrence; oncology ID HIGH-GRADE GLIOMAS; CONTRAST ENHANCEMENT; RESPONSE ASSESSMENT; END-POINT; CRITERIA; BEVACIZUMAB; RECIST; CHEMOTHERAPY; METASTASES; BRAIN AB Object. Robust methodology that allows objective, automated, and observer-independent measurements of brain tumor volume, especially after resection, is lacking. Thus, determination of tumor response and progression in neurooncology is unreliable. The objective of this study was to determine if a semi-automated volumetric method for quantifying enhancing tissue would perform with high reproducibility and low interobserver variability. Methods. Fifty-seven MR images from 13 patients with glioblastoma were assessed using our method, by 2 neuroradiologists, 1 neurosurgeon, 1 neurosurgical resident, 1 nurse practitioner, and 1 medical student. The 2 neuroradiologists also performed traditional 1-dimensional (1D) and 2-dimensional (2D) measurements. Intraclass correlation coefficients (ICCs) assessed interobserver variability between measurements. Radiological response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) guidelines and Macdonald criteria. Kappa statistics described interobserver variability of volumetric radiological response determinations. Results. There was strong agreement for 1D (RECIST) and 2D (Macdonald) measurements between neuroradiologists (ICC = 0.42 and 0.61, respectively), but the agreement using the authors' novel automated approach was significantly stronger (ICC = 0.97). The volumetric method had the strongest agreement with regard to radiological response (k = 0.96) when compared with 2D (k = 0.54) or 1D (k = 0.46) methods. Despite diverse levels of experience of the users of the volumetric method, measurements using the volumetric program remained remarkably consistent in all users (0.94). Conclusions. Interobserver variability using this new semi-automated method is less than the variability with traditional methods of tumor measurement. This new method is objective, quick, and highly reproducible among operators with varying levels of expertise. This approach should be further evaluated as a potential standard for response assessment based on contrast enhancement in brain tumors. C1 [Kanaly, Charles W.; Mehta, Ankit I.; Friedman, Allan H.; Sampson, John H.] Duke Univ, Med Ctr, Div Neurosurg, Durham, NC USA. [Hoang, Jenny K.; Kranz, Peter G.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC USA. [Herndon, James E., II; Coan, April] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Sampson, John H.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC USA. [Ding, Dale] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. [Crocker, Ian; Waller, Anthony F.] Emory Univ, Dept Radiat Oncol, Atlanta, GA USA. [Reardon, David A.] Dana Farber Canc Inst, Boston, MA USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Div Neurosurg, POB 3050,Rm 220,Sands Bldg,Res Dr, Durham, NC 27710 USA. EM john.sampson@duke.edu RI Hoang, Jenny/B-7779-2016; Kranz, Peter/B-2471-2016; OI Hoang, Jenny/0000-0002-6715-0922; Kranz, Peter/0000-0001-5410-7135; Sykes, April/0000-0002-7667-8155 FU NIH [R25, 5R01-CA135272-03, 5R21-NS067975-02]; Goldhirsh Foundation; Pediatric Brain Tumor Foundation of the United States; Ben and Catherine Ivy Foundation FX Anthony F. Waller has a consulting relationship with Velocity Medical Solutions. Dr. Ian Crocker is a cofounder of Velocity Medical Solutions and is entitled to royalties on sales based on the intellectual property agreement between Velocity Medical Solutions and Emory University, but had no role in data collection and analysis. Dr. Crocker did provide technical support and design modifications to the software to adapt it to this novel use. This work was supported in part by NIH R25 grants to Drs. Mehta and Sampson, NIH grant no. 5R01-CA135272-03 to Dr. Sampson, the Goldhirsh Foundation, Pediatric Brain Tumor Foundation of the United States, NIH grant no. 5R21-NS067975-02, and The Ben and Catherine Ivy Foundation. NR 23 TC 5 Z9 5 U1 0 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2014 VL 121 IS 3 BP 536 EP 542 DI 10.3171/2014.4.JNS121952 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AN6EW UT WOS:000340688700005 PM 25036205 ER PT J AU Alter, RY Wamsley, CC Mullen, JT Haile, WZ Goldsmith, JD Kasper, EM AF Alter, Raanan Y. Wamsley, Christina C. Mullen, John T. Haile, Winta Z. Goldsmith, Jeffrey D. Kasper, Ekkehard M. TI Peripheral nerve fibromyxoid sarcoma SO JOURNAL OF NEUROSURGERY LA English DT Article DE peripheral nerve tumor; oncology; prognosis; fibromyxoid sarcoma; fluorescence in situ hybridization ID NEOPLASMS; IMPACT AB Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue neoplasm with metastatic potential and needs to be recognized as such, because it can be mistaken for other types of sarcoma due to its unremarkable appearance. This 49-year-old man presented with an approximately 5-cm mass on the anteromedial aspect of his left thigh that slowly increased over 10 years. Clinical symptoms were limited to local discomfort and intermittent distal numbness. Due to the location, imaging findings, and lack of serious symptoms, the initial differential diagnosis favored a schwannoma. An initial biopsy revealed histopathological findings consistent with a perineurioma, although with atypical features. The patient elected to have the mass excised, and the tumor, which arose from a branch of the saphenous nerve, could be separated well from the surrounding soft tissue. Histopathological investigation of the mass displayed characteristic features of a fibromyxoid sarcoma, which was confirmed by subsequent fluorescence in situ hybridization analysis. Due to concerns about infiltration beyond the margins, radical reexcision was advocated and performed, resulting in definite clear surgical margins. At follow-up, the patient had regained full strength with no residual neurological symptoms or any new deficits. He has since been healthy and disease free for a total of 4 years in follow-up. This case documents, to the authors' knowledge, the first observation of an LGFMS associated with a peripheral nerve. It also supports the use of fluorescence in situ hybridization analysis as an essential diagnostic method in establishing the diagnosis of LGFMS. C1 [Alter, Raanan Y.; Wamsley, Christina C.; Haile, Winta Z.; Kasper, Ekkehard M.] Beth Israel Deaconess Med Ctr, Div Neurosurg, Boston, MA 02215 USA. [Goldsmith, Jeffrey D.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Mullen, John T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Kasper, EM (reprint author), Beth Israel Deaconess Med Ctr, Div Neurosurg, West Campus Lowry Med Off Bldg Ste 3B, Boston, MA 02215 USA. EM ekasper@bidmc.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2014 VL 121 IS 3 BP 576 EP 579 DI 10.3171/2014.3.JNS13838 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AN6EW UT WOS:000340688700010 PM 24766104 ER PT J AU Peacock, ZS Tricomi, BJ Lawler, ME Faquin, WC Magill, JC Murphy, BA Kaban, LB Troulis, MJ AF Peacock, Zachary S. Tricomi, Brad J. Lawler, Matthew E. Faquin, William C. Magill, John C. Murphy, Brian A. Kaban, Leonard B. Troulis, Maria J. TI Skeletal and Soft Tissue Response to Automated, Continuous, Curvilinear Distraction Osteogenesis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID NERVE GROWTH-FACTOR; HISTOMORPHOMETRIC ANALYSIS; IMMUNOHISTOCHEMICAL CHANGES; MANDIBULAR DEFORMITIES; CLINICAL-APPLICATION; BONE DISTRACTION; RABBIT MODEL; DEVICE; MUSCLE; EXPRESSION AB Purpose: To document the bone formation and soft tissue changes in response to automated, continuous, curvilinear distraction osteogenesis (DO) at rates greater than 1 mm/day in a minipig model. Materials and Methods: Two groups of Yucatan minipigs underwent automated, continuous, curvilinear DO of the right mandible: group A, 1.5 mm/day (n = 5); and group B, 3.0 mm/day (n = 5). Each minipig underwent 12 mm of distraction followed by 24 days of fixation. The distracted and contralateral mandibles were harvested at the end of fixation. The percentage of surface area (PSA) of the regenerate occupied by bone, fibrous tissue, cartilage, and hematoma was determined using computerized histomorphometric analysis. The control groups consisted of DO wounds distracted discontinuously at 1 mm/day and the nonoperated contralateral mandible. The ipsilateral and contralateral digastric muscles were harvested and stained for proliferating cell nuclear antigen (PCNA), myogenic differentiation-1 (MyoD), and paired Box 7 protein (PAX7). Results: All 10 minipigs completed the distraction and fixation period. The PSA occupied by bone was similar for groups A (PSA 64.36% +/- 5.87%) and B (PSA 63.83% +/- 3.37%) and the control group (1 mm/day; PSA 64.89% +/- 0.56%) but was less than that on the nonoperated side (PSA 84.67% +/- 0.86%). The PSA occupied by cartilage and hematoma in all groups was minimal (<1.1%). The digastric muscles had no abnormal tissue or inflammation, and PAX7, MyoD, and PCNA expression had returned to the baseline levels. Conclusions: The results of the present study indicate that bone formation in response to automated, continuous, and curvilinear DO at a rate of 1.5 and 3.0 mm/day is nearly identical to that with discontinuous DO at 1 mm/day. In addition, no deleterious effects were found on the digastric muscles. (C) 2014 American Association of Oral and Maxillofacial Surgeons C1 [Peacock, Zachary S.; Lawler, Matthew E.; Kaban, Leonard B.; Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Tricomi, Brad J.] Univ Massachusetts, Boston, MA 02125 USA. [Tricomi, Brad J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Magill, John C.; Murphy, Brian A.] Phys Sci Inc, Andover, MA 01810 USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. EM zpeacock@partners.org FU National Institutes of Health/National Institute of Dental and Craniofacial Research [5R44DE014803-03]; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery; Hanson Foundation (Boston, MA) FX The present study was funded by a National Institutes of Health/National Institute of Dental and Craniofacial Research Small Business Innovation Research grant (grant 5R44DE014803-03), the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund, and the Hanson Foundation (Boston, MA). NR 64 TC 2 Z9 2 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2014 VL 72 IS 9 BP 1773 EP 1787 DI 10.1016/j.joms.2014.01.004 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AO5DC UT WOS:000341361400021 PM 24602810 ER PT J AU Ullrich, C Chen, K Orellana, L Kang, T Feudtner, C Geyer, R Dussel, V Wolfe, J AF Ullrich, Christina Chen, Kun Orellana, Liliana Kang, Tammy Feudtner, Chris Geyer, Russ Dussel, Veronica Wolfe, Joanne TI Fatigue Reported by Children with Cancer in the PediQUEST Study: Patterns, Correlates, and Potential Targets SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Ullrich, Christina; Chen, Kun; Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ullrich, Christina; Dussel, Veronica; Wolfe, Joanne] Boston Childrens Hosp, Boston, MA USA. [Ullrich, Christina; Wolfe, Joanne] Harvard Univ, Sch Med, Boston, MA USA. [Orellana, Liliana] Univ Buenos Aires, Inst Calculus, Buenos Aires, DF, Argentina. [Kang, Tammy] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kang, Tammy; Feudtner, Chris] Univ Penn, Philadelphia, PA 19104 USA. [Geyer, Russ] Seattle Childrens Hosp, Seattle, WA USA. [Geyer, Russ] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Geyer, Russ] Univ Washington, Seattle, WA 98195 USA. [Dussel, Veronica] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. RI Orellana, Liliana/S-3302-2016 OI Orellana, Liliana/0000-0003-3736-4337 NR 0 TC 0 Z9 0 U1 0 U2 4 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2014 VL 30 IS 3 MA S1.2-C BP 196 EP 196 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AO3IQ UT WOS:000341223300016 ER PT J AU Jerez, C Uzal, LG Bravo, A Brage, E Urtasun, M Bevilacqua, MS Wolfe, J Requena, ML Dussel, V AF Jerez, Celeste Gabriel Uzal, Luciano Bravo, Ariela Brage, Eugenia Urtasun, Maria Silvina Bevilacqua, Maria Wolfe, Joanne Laura Requena, Maria Dussel, Veronica TI Providing Pediatric Palliative Care to Children with Cancer in Argentina: Existing Resources, Barriers, and Facilitators. Results from A National Mapping Study SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Jerez, Celeste; Gabriel Uzal, Luciano; Bravo, Ariela; Brage, Eugenia; Urtasun, Maria; Silvina Bevilacqua, Maria; Laura Requena, Maria; Dussel, Veronica] Inst Efectividad Clin & Sanitaria, Buenos Aires, Argentina. [Wolfe, Joanne; Dussel, Veronica] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2014 VL 30 IS 3 MA B01-C BP 202 EP 202 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AO3IQ UT WOS:000341223300036 ER PT J AU Pantilat, S Bragg, A O'Riordan, D Ferrell, B Lindenauer, P Lorenz, K Stoneberg, J AF Pantilat, Steven Bragg, Ashley O'Riordan, David Ferrell, Betty Lindenauer, Peter Lorenz, Karl Stoneberg, Jeffrey TI Palliative Care Quality Network: Toward Quality Improvement in Palliative Care SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Pantilat, Steven; Bragg, Ashley; O'Riordan, David] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ferrell, Betty] City Hope Natl Med Ctr, Los Angeles, CA USA. [Lindenauer, Peter] Bay State Med Ctr, Springfield, MA USA. [Lorenz, Karl] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Stoneberg, Jeffrey] Alta Bates Summit Med Ctr, Oakland, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2014 VL 30 IS 3 MA B08-D BP 204 EP 205 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AO3IQ UT WOS:000341223300045 ER PT J AU Friedrichsdorf, S Foster, L Hauser, J Remke, S Roman, E Wolfe, J AF Friedrichsdorf, Stefan Foster, Laurie Hauser, Joshua Remke, Stacy Roman, Elisa Wolfe, Joanne TI Education in Palliative and End-of-Life Care for Pediatrics (EPEC-Pediatrics) SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Friedrichsdorf, Stefan; Foster, Laurie] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Friedrichsdorf, Stefan; Remke, Stacy] Univ Minnesota, Minneapolis, MN USA. [Wolfe, Joanne] Boston Childrens Hosp, Boston, MA USA. [Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hauser, Joshua; Roman, Elisa] Northwestern Feinberg Sch Med, Chicago, IL USA. [Roman, Elisa] Buehler Ctr Aging Hlth & Soc, Chicago, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2014 VL 30 IS 3 MA P058 BP 226 EP 226 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AO3IQ UT WOS:000341223300118 ER PT J AU Uzal, LG Jerez, C Bravo, A Brage, E Urtasun, M Silvinabevilacqua, M Wolfe, J Requena, ML Dussel, V AF Gabriel Uzal, Luciano Jerez, Celeste Bravo, Ariela Brage, Eugenia Urtasun, Maria Silvinabevilacqua, Maria Wolfe, Joanne Laura Requena, Maria Dussel, Veronica TI End of-Life Care in Children with Cancer in Argentina: Current Practices. Results from a National Mapping Study SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Gabriel Uzal, Luciano; Jerez, Celeste; Bravo, Ariela; Brage, Eugenia; Urtasun, Maria; Silvinabevilacqua, Maria; Laura Requena, Maria; Dussel, Veronica] Efectividad Clin & Sanitaria, Buenos Aires, DF, Argentina. [Wolfe, Joanne; Dussel, Veronica] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2014 VL 30 IS 3 MA P206 BP 240 EP 240 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AO3IQ UT WOS:000341223300168 ER PT J AU Chang, YP Banerjee, J Dowell, C Wu, J Gyanda, R Houghten, RA Toll, L McIntosh, JM Armishaw, CJ AF Chang, Y-P. Banerjee, J. Dowell, C. Wu, J. Gyanda, R. Houghten, R. A. Toll, L. McIntosh, J. M. Armishaw, C. J. TI DISCOVERY OF A POTENT AND SELECTIVE NICOTINIC ACETYLCHOLINE RECEPTOR ANTAGONIST FROM A CONOTOXIN COMBINATORIAL LIBRARY SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract DE alpha-conotoxin BuIA; nicotinic acetylcholine receptor; positional scanning synthetic combinatorial library C1 [Chang, Y-P.] Forsyth Inst, Cambridge, MA 02142 USA. [Banerjee, J.; Wu, J.; Gyanda, R.; Houghten, R. A.; Toll, L.; Armishaw, C. J.] Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA. [Dowell, C.; McIntosh, J. M.] George E Wahlen Vet Affairs Med Ctr, Salt Lake City, UT 84108 USA. [Dowell, C.; McIntosh, J. M.] Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA. [Dowell, C.; McIntosh, J. M.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. NR 3 TC 0 Z9 0 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-2617 EI 1099-1387 J9 J PEPT SCI JI J. Pept. Sci. PD SEP PY 2014 VL 20 SU 1 MA P206 BP S238 EP S239 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AN8TD UT WOS:000340876400351 ER PT J AU Chang, YP Muckeen, M Alonzi, DS Sagar, R Dickens, A Chapman, TM Butters, TD Anthony, DC Davis, BG AF Chang, Y-P Muckeen, M. Alonzi, D. S. Sagar, R. Dickens, A. Chapman, T. M. Butters, T. D. Anthony, D. C. Davis, B. G. TI DISCOVERY OF A SELECTIVE LYSOSOMAL ALPHA-MANNOSIDASE INHIBITOR FROM AN IMINO-SUGAR LIBRARY SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract DE free oligosaccharide; iminosugar; alpha-mannosidase; protein N-glycosylation C1 [Chang, Y-P] Forsyth Inst, Cambridge, MA 02142 USA. [Muckeen, M.; Alonzi, D. S.; Butters, T. D.] Univ Oxford, Oxford Glycobiol Inst, Oxford OX1 3QU, England. [Sagar, R.; Dickens, A.; Chapman, T. M.; Davis, B. G.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England. [Anthony, D. C.] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. RI Davis, Benjamin/C-5281-2011 OI Davis, Benjamin/0000-0002-5056-407X FU Biotechnology and Biological Sciences Research Council [BB/C510824/1, BB/E004350/1, BB/J009725/1, EGA17763]; Engineering and Physical Sciences Research Council [EP/D023335/1, EP/D023343/1, EP/E000614/1, EP/G026688/1, EP/I500200/1, GR/T26542/01] NR 3 TC 0 Z9 0 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-2617 EI 1099-1387 J9 J PEPT SCI JI J. Pept. Sci. PD SEP PY 2014 VL 20 SU 1 MA O22 BP S52 EP S53 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AN8TD UT WOS:000340876400046 ER PT J AU Oliveira, B Morais, M Mendes, F Raposinho, P Santos, I Correia, JDG AF Oliveira, B. Morais, M. Mendes, F. Raposinho, P. Santos, I. Correia, J. D. G. TI RADIOMETALATTED L-ARGININE DERIVATIVES FOR IMAGING NITRIC OXIDE SYNTHASE IN VIVO SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract DE cancer; imaging; nitric oxide synthase; rhenium; technetium-99m ID COMPLEXES C1 [Oliveira, B.; Morais, M.; Mendes, F.; Raposinho, P.; Santos, I.; Correia, J. D. G.] Univ Tecn Lisboa, Inst Super Tecn, Ctr Ciencias & Tecnol Nucl, CTN, P-2695066 Bobadela Lrs, Portugal. [Oliveira, B.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Oliveira, B.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RI Santos, Isabel /J-6036-2013; Morais, Mauricio/A-2354-2010 OI Santos, Isabel /0000-0001-7362-0022; Morais, Mauricio/0000-0001-7718-1629 NR 6 TC 0 Z9 0 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-2617 EI 1099-1387 J9 J PEPT SCI JI J. Pept. Sci. PD SEP PY 2014 VL 20 SU 1 MA P306 BP S301 EP S301 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AN8TD UT WOS:000340876400451 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI Does the timing of surgery for proximal humeral fracture affect inpatient outcomes? SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Surgery; delay; proximal humeral fracture; perioperative; mortality; outcomes; risk factors; discharge; epidemiology ID HIP FRACTURE; PRIMARY HEMIARTHROPLASTY; PERIOPERATIVE-OUTCOMES; ADMINISTRATIVE DATA; METABOLIC SYNDROME; OPERATIVE DELAY; MORTALITY; ARTHROPLASTY; COMORBIDITY; EPIDEMIOLOGY AB Background: Delayed surgical treatment of hip fractures is associated with adverse medical outcomes, but it is unclear whether the same is true for proximal humeral fractures. The purpose of this study was to evaluate the relationship between surgical delay for proximal humeral fracture and inpatient adverse events, in-hospital death, prolonged postoperative stay, and nonroutine discharge. Methods: Of the more than 70,000 patients with an operatively treated proximal humeral fracture identified in the Nationwide Inpatient Sample between 2008 and 2011, 87% underwent surgery within 2 days of admission and 13% underwent surgery 3 days or more after admission. Multivariable logistic regression analyses were performed to evaluate the effect of surgical delay on inpatient outcomes and to identify risk factors associated with late surgery. Results: Surgery 3 days or more after admission for fracture of the proximal humerus had no influence on in-hospital death but was independently associated with inpatient adverse events (odds ratio [OR], 2.1; 95% confidence interval [CI], 2.0-2.2), prolonged postoperative stay (OR, 1.7; 95% CI, 1.7-1.9), and increased nonroutine discharge (OR, 2.7; 95% CI, 2.6-2.9). Risk factors for surgery 3 days or more after admission included advanced age, male sex, Elixhauser comorbidity score, polytrauma, Hispanic race or black race, no insurance coverage, low household income, and weekend admission. Conclusions: Even when comorbidities and complexity are controlled for, delaying surgery for proximal humeral fracture is likely to increase inpatient morbidity, postoperative length of stay, and nonroutine discharge. It appears that avoiding nonmedical delays is advantageous. Level of evidence: Level II, Retrospective Design, Prognosis Study. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St,Ste 2100, Boston, MA 02114 USA. EM dring@mgh.harvard.edu NR 41 TC 12 Z9 12 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP PY 2014 VL 23 IS 9 BP 1257 EP 1262 DI 10.1016/j.jse.2014.03.010 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AO2GW UT WOS:000341137200011 PM 24925700 ER PT J AU Onur, T Dang, A AF Onur, Tarik Dang, Alexis TI Reduction of Environmental Temperature Mitigates Local Anesthetic Cytotoxicity in Bovine Articular Chondrocytes SO JOURNAL OF SPORTS SCIENCE AND MEDICINE LA English DT Article DE Clinical hypothermia; local anesthetics; articular cartilage; osteoarthritis; chondrolysis ID IN-VITRO; BUPIVACAINE; CARTILAGE; CHONDROTOXICITY; HYPOTHERMIA; CHONDROLYSIS; ROPIVACAINE; CRYOTHERAPY; EPINEPHRINE; EXPOSURE AB The purpose of this study was to assess whether reducing environmental temperature will lead to increased chondrocyte viability following injury from a single-dose of local anesthetic treatment. Bovine articular chondrocytes from weight bearing portion s of femoral condyles were harvested and cultured. 96-well plates were seeded with 15,000 chondrocytes per well. Chondrocytes were treated with one of the following conditions: ITS Media, 1x PBS, 2% lidocaine, 0.5% bupivacaine, or 0.5% ropivacaine. Each plate was then incubated at 37 degrees C, 23 degrees C, or 4 degrees C for one hour and then returned to media at 37 degrees C. Chondrocyte viability was assessed 24 hours after treatment. Chondrocyte viability is presented as a ratio of the fluorescence of the treatment group over the average of the media group at that temperature (ratio +/- SEM). At 37 degrees C, lidocaine (0.35 +/- 0.04) and bupivacaine (0.30 +/- 0.05) treated chondrocytes show low cell viability when compared to the media (1.00 +/- 0.03) control group (p < 0.001). Lidocaine treated chondrocytes were significantly more viable at 23 degrees C (0.84 +/- 0.08) and 4 degrees C (0.86 +/- 0.085) than at 37 degrees C (p < 0.001). Bupivacaine treated chondrocytes were significantly more viable at 4 degrees C (0.660 +/- 0.073) than at 37 degrees C or 23 degrees C (0.330 +/- 0.069) (p < 0.001 and p = 0.002 respectively). Reducing the temperature from 37 degrees C to 23 degrees C during treatment with lidocaine increases chondrocyte viability following injury. Chondrocytes treated with bupivacaine can be rescued by reducing the temperature to 4 degrees C. C1 [Onur, Tarik; Dang, Alexis] San Francisco VA Med Ctr, Dept Orthopaed Surg, San Francisco, CA 91458 USA. RP Onur, T (reprint author), San Francisco VA Med Ctr, Dept Orthopaed Surg, 1700 Owens St,366, San Francisco, CA 91458 USA. EM t.s.onur17@gmail.com; alexis.dang@gmail.com NR 25 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL SPORTS SCIENCE & MEDICINE PI BURSA PA MEDICAL FACULTY ULUDAG UNIV, DEPT SPORTS MEDICINE, BURSA, 16059, TURKEY SN 1303-2968 J9 J SPORT SCI MED JI J. Sport. Sci. Med. PD SEP PY 2014 VL 13 IS 3 BP 516 EP 521 PG 6 WC Sport Sciences SC Sport Sciences GA AN7BL UT WOS:000340753400008 PM 25177176 ER PT J AU Fallon, EM Nazarian, A Nehra, D Pan, AH O'Loughlin, AA Nose, V Puder, M AF Fallon, Erica M. Nazarian, Ara Nehra, Deepika Pan, Amy H. O'Loughlin, Alison A. Nose, Vania Puder, Mark TI The effect of docosahexaenoic acid on bone microstructure in young mice and bone fracture in neonates SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Bone; Bone microstructure; Omega-3 polyunsaturated fatty acids; Fish oil; Docosahexaenoic acid; Murine; Neonate; Fracture ID N-3 FATTY-ACIDS; FISH-OIL; MINERAL DENSITY; ARACHIDONIC-ACID; GROWING RATS; DEFICIENCY; OSTEOPOROSIS; METABOLISM; PREVENT; FEMUR AB Background: As low bone mineral density is a risk factor for fracture in childhood, optimizing age appropriate bone mass is recommended and might lower the impact of bone loss related to age. Consumption of omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic and docosahexaenoic (DHA) acids have been shown to beneficially modulate bone metabolism. The objective of this study was to determine the incidence of fracture in neonates receiving a fish compared with soybean oil-based intravenous lipid emulsion and evaluate the effect of varying dietary omega-3 PUFA consumption on growing bone in young mice. Materials and methods: Eligibility criteria for the clinical study included gestational age <= 37 wk and parenteral nutrition-dependence for >= 4 wk. Radiographs were reviewed after lipid initiation to identify radiologic bone fracture. The animal study evaluated female C57/Bl6 mice randomized into one of five groups from age 3-12 wk, at which time femurs were harvested for micro-computed tomography and light microscopy analysis. Results: A lower incidence of bone fracture was found in neonates maintained on fish compared with soybean oil. In the animal study, findings suggest the DHA diet provides the best protection against trabecular bone loss as evidenced by increased bone volume fraction, increased trabecular number, and decreased trabecular separation on micro- computed tomography. These protective effects appeared to affect the bone microstructure alone. Conclusions: The lower fracture risk observed in fish oil fed neonates in combination with the protective effects of DHA observed in the femurs of young C57/BL6 mice suggest an important role for omega-3 PUFAs on bone growth. (C) 2014 Elsevier Inc. All rights reserved. C1 [Fallon, Erica M.; Nehra, Deepika; Pan, Amy H.; O'Loughlin, Alison A.; Puder, Mark] Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Fallon, Erica M.; Nehra, Deepika; Pan, Amy H.; O'Loughlin, Alison A.; Puder, Mark] Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Fallon, Erica M.; Nazarian, Ara; Nehra, Deepika; Pan, Amy H.; O'Loughlin, Alison A.; Nose, Vania; Puder, Mark] Harvard Univ, Sch Med, Boston, MA USA. [Nazarian, Ara] Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. [Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Puder, M (reprint author), Boston Childrens Hosp, Dept Surg, 300 Longwood Ave,Fegan 3, Boston, MA 02115 USA. EM mark.puder@childrens.harvard.edu FU Children's Hospital Surgical Foundation; Vascular Biology Program within Boston Children's Hospital; Joshua Ryan Rappaport Fellowship; National Institutes of Health [T32DK007754-12] FX This work was funded by the Children's Hospital Surgical Foundation and the Vascular Biology Program within Boston Children's Hospital (E. M. F., D.N., A. H. P., A.A.O., and M. P.), the Joshua Ryan Rappaport Fellowship (E. M. F.), and the National Institutes of Health Grant T32DK007754-12 (DN). NR 27 TC 3 Z9 3 U1 1 U2 7 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 SEP PY 2014 VL 191 IS 1 BP 148 EP 155 DI 10.1016/j.jss.2014.04.005 PG 8 WC Surgery SC Surgery GA AO0TA UT WOS:000341023700021 PM 24793452 ER PT J AU Dodgion, CM Neville, BA Lipsitz, SR Schrag, D Breen, E Zinner, MJ Greenberg, CC AF Dodgion, Christopher M. Neville, Bridget A. Lipsitz, Stuart R. Schrag, Deborah Breen, Elizabeth Zinner, Michael J. Greenberg, Caprice C. TI Hospital variation in sphincter preservation for elderly rectal cancer patients SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Hospital variation; Sphincter sparing surgery; Rectal cancer; Elderly ID LOW ANTERIOR RESECTION; TRANSANAL ENDOSCOPIC MICROSURGERY; COMORBIDITY INDEX; PROCEDURE VOLUME; SPARING SURGERY; UNITED-STATES; MEDICARE DATA; RISK-FACTORS; CLAIMS DATA; DATA-BASE AB Background: The primary goal of an operation for rectal cancer is to cure cancer and, where possible, preserve continence. A wide range of sphincter preservation rates have been reported. This study evaluated hospital variation in the use of low anterior resection (LAR), local excision (LE), and abdominoperineal resection (APR) in the treatment of elderly rectal cancer patients. Methods: Using Surveillance, Epidemiology, and End Results-Medicare linked data, we identified 4959 patients older than 65 y with stage I-III rectal cancer diagnosed from 2000-2005 who underwent operative intervention at one of 370 hospitals. We evaluated the distribution of hospital-specific procedure rates and used generalized mixed models with random hospital effects to examine the influence of patient characteristics and hospital on operation type, using APR as a reference. Results: The median hospital performed APR on 33% of elderly patients with rectal cancer. Hospital was a stronger predictor of LAR receipt than any patient characteristic, explaining 32% of procedure choice, but not a strong predictor of LE, explaining only 3.8%. Receipt of LE was primarily related to tumor size and tumor stage, which combined explained 31% of procedure variation. Conclusions: Receipt of LE is primarily determined by patient characteristics. In contrast, the hospital where surgery is performed significantly influences whether a patient undergoes an LAR or APR. Understanding the factors that cause this institutional variation is crucial to ensuring equitable availability of sphincter preservation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Dodgion, Christopher M.; Greenberg, Caprice C.] Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program, Madison, WI 53792 USA. [Neville, Bridget A.; Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Lipsitz, Stuart R.; Breen, Elizabeth; Zinner, Michael J.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Greenberg, CC (reprint author), Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program, 600 Highland Ave,BX7375 Clin Sci Ctr, Madison, WI 53792 USA. EM greenberg@surgery.wisc.edu RI Dodgion, Chris/A-2877-2016 OI Dodgion, Chris/0000-0002-5789-7731 FU American Surgical Association Foundation Fellowship; NIH/NCI [T32 CA009535-23]; Brigham and Women's Hospital Center for Surgery and Public Health Postdoctoral Cabot Fellowship FX American Surgical Association Foundation Fellowship (C. C. G.); NIH/NCI T32 CA009535-23 (C. M. D.); and Brigham and Women's Hospital Center for Surgery and Public Health Postdoctoral Cabot Fellowship (C. M. D.). NR 58 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2014 VL 191 IS 1 BP 161 EP 168 DI 10.1016/j.jss.2014.03.047 PG 8 WC Surgery SC Surgery GA AO0TA UT WOS:000341023700023 PM 24750983 ER PT J AU Wrzosek, MI MacMillan, CM AF Wrzosek, Marika I. MacMillan, Carlene M. TI The Book of Woe: The DSM and the Unmaking of Psychiatry SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Wrzosek, Marika I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wrzosek, MI (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM miwrzosek@partners.org; cmacmillan@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2014 VL 53 IS 9 BP 1031 EP 1032 DI 10.1016/j.jaac.2014.07.002 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AO3HW UT WOS:000341221300013 ER PT J AU Baughn, E Petersen, TD Kimball, AB AF Baughn, Eubee Petersen, Tyler Daniel Kimball, Alexandra Boer TI Meta-analysis comparing efficacy of antibiotics versus oral contraceptives in acne vulgaris SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE acne vulgaris; birth control; meta-analysis; oral antibiotics; oral contraceptive; tetracyclines ID PLACEBO-CONTROLLED TRIAL; 20 MU-G; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; ETHINYL ESTRADIOL; CYPROTERONE-ACETATE; MODERATE ACNE; PROPIONIBACTERIUM-ACNES; CLINICAL-IMPLICATIONS; TOPICAL CLINDAMYCIN AB Background: Both antibiotics and oral contraceptive pills (OCPs) have been found to be effective in managing acne vulgaris. Despite widespread use, few direct comparisons of efficacy between the 2 modalities have been published. Objective: We compared the efficacy of antibiotics and OCPs in managing acne. Methods: A meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane collaboration guidelines. Results: A review of 226 publications yielded 32 randomized controlled trials that met our inclusion criteria. At 3 and 6 months, compared with placebo, both antibiotics and OCPs effected greater percent reduction in inflammatory, noninflammatory, and total lesions; the 2 modalities at each time point demonstrated statistical parity, except that antibiotics were superior to OCPs in percent reduction of total lesions at 3 months (weighted mean inflammatory lesion reduction: 3-month course of oral antibiotic treatment = 53.2%, 3-month course of OCPs = 35.6%, 3-month course of placebo treatment = 26.4%, 6-month course of oral antibiotic treatment = 57.9%, 6-month course of OCPs = 61.9%, 6-month course of placebo treatment = 34.2%; weighted mean noninflammatory lesion reduction: 3-month course of oral antibiotic treatment = 41.9%, 3-month course of OCPs = 32.6%, 3-month course of placebo treatment = 17.1%, 6-month course of oral antibiotic treatment = 56.4%, 6-month course of OCPs = 49.1%, 6-month course of placebo treatment = 23.4%; weighted mean total lesion reduction: 3-month course of oral antibiotic treatment = 48.0%, 3-month course of OCPs = 37.3%, 3-month course of placebo treatment = 24.5%, 6-month course of oral antibiotic treatment = 52.8%, 6-month course of OCPs = 55.0%, 6-month course of placebo treatment = 28.6%). Limitations: Investigative treatment heterogeneity and publication bias are limitations. Conclusions: Although antibiotics may be superior at 3 months, OCPs are equivalent to antibiotics at 6 months in reducing acne lesions and, thus, may be a better first-line alternative to systemic antibiotics for long-term acne management in women. C1 [Baughn, Eubee; Kimball, Alexandra Boer] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Petersen, Tyler Daniel] Western Univ Hlth Sci, Coll Osteopath Med Pacific, Lebanon, NH USA. [Kimball, Alexandra Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 57 TC 0 Z9 0 U1 2 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2014 VL 71 IS 3 BP 450 EP 459 DI 10.1016/j.jaad.2014.03.051 PG 10 WC Dermatology SC Dermatology GA AO2JH UT WOS:000341146700033 ER PT J AU Semkova, K Lott, JP Lazova, R AF Semkova, Kristina Lott, Jason P. Lazova, Rossitza TI Clinicopathologic features and survival in Spitzoid malignant melanoma and conventional malignant melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE conventional melanoma; melanoma; metastasis; prognosis; sentinel lymph node; sentinel lymph node biopsy; Spitzoid malignant melanoma; survival ID MELANOCYTIC TUMORS; BRAF; NRAS; DIAGNOSIS; MUTATION; NEVUS AB Background: Although recent advances in genetics have revealed distinct mutational profiles and molecular signaling pathways associated with Spitzoid malignant melanoma (SMM), less is known about the clinicopathologic characteristics and behavior of SMM compared with conventional melanoma. Objective: We sought to determine the clinicopathologic characteristics and mortality risk associated with SMM and conventional malignant melanoma. Methods: We conducted a retrospective study of 30 patients with SMM and 30 patients with conventional melanoma. The two groups were matched by age, gender, and depth of tumor invasion. Additional patient- and tumor-level characteristics were compared between groups and regression modeling was used to assess relative mortality risk. Results: Unadjusted analyses of SMM and conventional malignant melanoma revealed no significant differences in clinical impression, anatomic location, mitotic rate, and presence of ulceration. Sentinel lymph node biopsy, completion lymphadenectomy, and visceral metastases did not differ between groups. Cox proportional hazards regression showed no differences in mortality between Spitzoid and conventional melanoma. Limitations: Small sample size, short follow-up duration, and residual confounding may limit the accuracy and generalizability of our results. Conclusions: SMM and conventional malignant melanoma differ in some clinicopathologic features. We did not find a statistically significant difference in mortality between the two. C1 [Semkova, Kristina] Med Univ Sofia, Dept Dermatol & Venereol, Sofia, Bulgaria. [Lott, Jason P.; Lazova, Rossitza] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Lott, Jason P.] Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT USA. [Lott, Jason P.] US Dept Vet Affairs, West Haven, CT USA. [Lazova, Rossitza] Yale Canc Ctr, New Haven, CT USA. RP Lazova, R (reprint author), Dermatopathol Lab, 15 York St,POB 208059, New Haven, CT 06520 USA. EM rossitza.lazova@yale.edu OI Lott, Jason/0000-0002-4097-7225 NR 14 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2014 VL 71 IS 3 BP 516 EP 520 DI 10.1016/j.jaad.2014.04.012 PG 5 WC Dermatology SC Dermatology GA AO2JH UT WOS:000341146700042 PM 24836544 ER PT J AU Luo, Y Sohani, AR Hochberg, EP Szolovits, P AF Luo, Yuan Sohani, Aliyah R. Hochberg, Ephraim P. Szolovits, Peter TI Automatic lymphoma classification with sentence subgraph mining from pathology reports SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PREDOMINANT HODGKIN LYMPHOMA; B-CELL LYMPHOMA; EXTRACTION SYSTEM; BIOMEDICAL TEXT; SMOKING STATUS; IDENTIFICATION; POPULATION; KNOWLEDGE; RECORDS AB Objective Pathology reports are rich in narrative statements that encode a complex web of relations among medical concepts. These relations are routinely used by doctors to reason on diagnoses, but often require hand-crafted rules or supervised learning to extract into prespecified forms for computational disease modeling. We aim to automatically capture relations from narrative text without supervision. Methods We design a novel framework that translates sentences into graph representations, automatically mines sentence subgraphs, reduces redundancy in mined subgraphs, and automatically generates subgraph features for subsequent classification tasks. To ensure meaningful interpretations over the sentence graphs, we use the Unified Medical Language System Metathesaurus to map token subsequences to concepts, and in turn sentence graph nodes. We test our system with multiple lymphoma classification tasks that together mimic the differential diagnosis by a pathologist. To this end, we prevent our classifiers from looking at explicit mentions or synonyms of lymphomas in the text. Results and Conclusions We compare our system with three baseline classifiers using standard n-grams, full Meta Map concepts, and filtered Meta Map concepts. Our system achieves high F-measures on multiple binary classifications of lymphoma (Burkitt lymphoma, 0.8; diffuse large B-cell lymphoma, 0.909; follicular lymphoma, 0.84; Hodgkin lymphoma, 0.912). Significance tests show that our system outperforms all three baselines. Moreover, feature analysis identifies subgraph features that contribute to improved performance; these features agree with the state-of-the-art knowledge about lymphoma classification. We also highlight how these unsupervised relation features may provide meaningful insights into lymphoma classification. C1 [Luo, Yuan; Szolovits, Peter] MIT, Cambridge, MA 02139 USA. [Luo, Yuan; Szolovits, Peter] MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Cambridge, MA USA. [Sohani, Aliyah R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Lymphoma, Cambridge, MA USA. [Hochberg, Ephraim P.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Luo, Y (reprint author), MIT, R252,32 Vassar St, Cambridge, MA 02139 USA. EM yuanluo@mit.edu OI Szolovits, Peter/0000-0001-8411-6403 FU National Library of Medicine [U54LM008748]; Scullen Center for Cancer Data Analysis FX The work described was supported in part by Grant Number U54LM008748 from the National Library of Medicine and by the Scullen Center for Cancer Data Analysis. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Library of Medicine or the National Institutes of Health. NR 50 TC 7 Z9 7 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2014 VL 21 IS 5 BP 824 EP 832 DI 10.1136/amiajnl-2013-002443 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA AN4TM UT WOS:000340581400010 PM 24431333 ER PT J AU Hsiao, LL Wu, JS Yeh, AC Shieh, EC Cui, C Li, A Polding, LC Ahmed, R Lim, K Lu, TS Rhee, CM Bonventre, JV AF Hsiao, Li-Li Wu, Jingshing Yeh, Albert C. Shieh, Eric C. Cui, Cheryl Li, Ang Polding, Laura C. Ahmed, Rayhnuma Lim, Kenneth Lu, Tzong-Shi Rhee, Connie M. Bonventre, Joseph V. TI The Kidney Disease Screening and Awareness Program (KDSAP): A Novel Translatable Model for Increasing Interest in Nephrology Careers SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID UNITED-STATES; PREVALENCE; HEALTH AB Despite the increasing prevalence of CKD in the United States, there is a declining interest among United States medical graduates in nephrology as a career choice. Effective programs are needed to generate interest at early educational stages when career choices can be influenced. The Kidney Disease Screening and Awareness Program (KDSAP) is a novel program initiated at Harvard College that increases student knowledge of and interest in kidney health and disease, interest in nephrology career paths, and participation in kidney disease research. This model, built on physician mentoring, kidney screening of underserved populations, direct interactions with kidney patients, and opportunities to participate in kidney research, can be reproduced and translated to other workforce-challenged subspecialties. C1 [Hsiao, Li-Li; Lim, Kenneth; Lu, Tzong-Shi; Bonventre, Joseph V.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Hsiao, Li-Li; Shieh, Eric C.; Lu, Tzong-Shi; Bonventre, Joseph V.] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Jingshing] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Wu, Jingshing] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Yeh, Albert C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA. [Cui, Cheryl; Bonventre, Joseph V.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA. [Li, Ang] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Polding, Laura C.; Ahmed, Rayhnuma] Harvard Univ, Harvard Coll, Cambridge, MA 02138 USA. [Rhee, Connie M.] Univ Calif Irvine, Med Ctr, Div Nephrol & Hypertens, Orange, CA USA. RP Hsiao, LL (reprint author), Brigham & Womens Hosp, Room 120,41 Ave Louis Pasteur, Boston, MA 02115 USA. EM lhsiao@partners.org FU SDSC Global Foundation; Rotary Club-DaAn; Genzyme; Renal Division of the Brigham and Women's Hospital; Harvard University's Undergraduate Council; Public Service Network FX KDSAP has been supported by the SDSC Global Foundation, Rotary Club-DaAn, a Genzyme grant, and the Renal Division of the Brigham and Women's Hospital. This support provides for the equipment, materials, supplies, and other expenses incurred by the health screening events. In addition, KDSAP receives funding from Harvard University's Undergraduate Council and Public Service Network for KDSAP's general day-to-day operational activities as well as transportation vouchers for student volunteers and participants at community health screenings. NR 16 TC 2 Z9 2 U1 1 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2014 VL 25 IS 9 BP 1909 EP 1915 DI 10.1681/ASN.2013090928 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AO1FY UT WOS:000341059200007 PM 24876120 ER PT J AU Li, XZ Dai, Y Chuang, PY He, JC AF Li, Xuezhu Dai, Yan Chuang, Peter Y. He, John Cijiang TI Induction of Retinol Dehydrogenase 9 Expression in Podocytes Attenuates Kidney Injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; VITAMIN-A; TRANSGENIC MICE; KEY REGULATOR; ACID; DIFFERENTIATION; NEPHROPATHY; RECEPTOR; PROTEIN; NEF AB The intracellular concentration of retinoic acid is determined by two sequential oxidation reactions that convert retinol to retinoic acid. We recently demonstrated that retinoic acid synthesis is significantly impaired in glomeruli of HIV-1 transgenic mice (Tg26), a murine model of HIV-associated nephropathy. This impaired retinoic acid synthesis correlates with reduced renal expression of retinol dehydrogenase 9, which catalyzes the rate-limiting step of retinoic acid synthesis by converting retinol to retinal. Because retinoic acid has renal protective effects and can induce podocyte differentiation, we hypothesized that restoration of retinoic acid synthesis could slow the progression of renal disease. Herein, we demonstrate that overexpression of retinol dehydrogenase 9 in cultured podocytes induces the expression of podocyte differentiation markers. Furthermore, we confirm that podocyte-specific overexpression of retinol dehydrogenase 9 in mice with established kidney disease due to either HIV-associated nephropathy or adriamycin-induced nephropathy decreases proteinuria, attenuates kidney injury, and restores podocyte differentiation markers. Our data suggest that restoration of retinoic acid synthesis could be a new approach to treat kidney disease. C1 [Li, Xuezhu; Dai, Yan; Chuang, Peter Y.; He, John Cijiang] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA. [Li, Xuezhu] Tongji Univ, Sch Med, Shanghai East Hosp, Dept Nephrol, Shanghai 200092, Peoples R China. [Dai, Yan; He, John Cijiang] James J Peters Vet Affairs Med Ctr, Renal Sect, Bronx, NY USA. RP He, JC (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [1R01-DK078897, 1R01-DK088541, P01-DK56492, 5K08-DK082760]; Chinese 973 fund [2012CB517601] FX J.C.H. and P.Y.C. are supported by grants from the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (1R01-DK078897, 1R01-DK088541, and P01-DK56492 to J.C.H.; 5K08-DK082760 to P.Y.C.). J.C.H. is also supported by the Chinese 973 fund (2012CB517601). NR 39 TC 1 Z9 1 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2014 VL 25 IS 9 BP 1933 EP 1941 DI 10.1681/ASN.2013111150 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AO1FY UT WOS:000341059200010 PM 24652806 ER PT J AU Bakaeen, FG Shroyer, ALW Gammie, JS Sabik, JF Cornwell, LD Coselli, JS Rosengart, TK O'Brien, SM Wallace, A Shahian, DM Grover, FL Puskas, JD AF Bakaeen, Faisal G. Shroyer, A. Laurie W. Gammie, James S. Sabik, Joseph F. Cornwell, Lorraine D. Coselli, Joseph S. Rosengart, Todd K. O'Brien, Sean M. Wallace, Amelia Shahian, David M. Grover, Frederick L. Puskas, John D. TI Trends in use of off-pump coronary artery bypass grafting: Results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ON-PUMP; REDUCE MORBIDITY; RANDOMIZED-TRIAL; MORTALITY; OUTCOMES; METAANALYSIS; REVASCULARIZATION; SURVIVAL; PATENCY; VOLUME AB Objectives: Recent national trends in off-pump versus on-pump coronary artery bypass grafting have not been reported. Methods: We analyzed data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database regarding isolated primary coronary artery bypass grafting operations (N = 2,137,841; 1997-2012). The off-pump percentages were calculated in aggregate, by center, and by surgeon. On the basis of the 2007/2008 yearly off-pump volume, the analysis subgroups were ''high'' (center n > 200, surgeon n > 100), "intermediate'' (center n = 50-200, surgeon n = 20-100), and "low'' (center n = 1-49, surgeon n = 1-19). Results: The use of off-pump procedures peaked in 2002 (23%) and again in 2008 (21%), followed by a progressive decline in off-pump frequency to 17% by 2012. After 2008, off-pump rates declined among both high-volume and intermediate-volume centers and surgeons; little change was observed for low-volume centers or surgeons (off-pump rates 10% since 2008). By the end of the study period, 84% of centers performed fewer than 50 off-pump cases per year, 34% of surgeons performed no off-pump operations, and 86% of surgeons performed fewer than 20 off-pump cases per year. Except for a higher (7.8%) conversion rate in 2003, the rate for conversions fluctuated approximately 6%. Conclusions: Enthusiasm for off-pump coronary artery bypass grafting has been tempered. The percentage of coronary artery bypass grafting operations performed off-pump has steadily declined over the last 5 years, and currently this technique is used in fewer than 1 in 5 patients who undergo surgical coronary revascularization. A minority of surgeons and centers continue to perform off-pump coronary artery bypass grafting in most of their patients. C1 [Bakaeen, Faisal G.; Cornwell, Lorraine D.; Coselli, Joseph S.; Rosengart, Todd K.] Baylor Coll Med, Div Cardiovasc Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Bakaeen, Faisal G.; Coselli, Joseph S.; Rosengart, Todd K.] Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX 77025 USA. [Shroyer, A. Laurie W.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Gammie, James S.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Sabik, Joseph F.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [O'Brien, Sean M.; Wallace, Amelia] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Grover, Frederick L.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Puskas, John D.] Emory Univ, Atlanta, GA 30322 USA. RP Bakaeen, FG (reprint author), One Baylor Plaza, Houston, TX 77030 USA. EM fbakaeen@bcm.edu RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 31 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD SEP PY 2014 VL 148 IS 3 BP 856 EP 863 DI 10.1016/j.jtcvs.2013.12.047 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AN9PF UT WOS:000340938700020 PM 25043865 ER PT J AU Cutz, JC Craddock, KJ Torlakovic, E Brandao, G Carter, RF Bigras, G Deschenes, J Izevbaye, I Xu, ZL Greer, W Yatabe, Y Ionescu, D Karsan, A Jung, SM Fraser, RS Blumenkrantz, M Lavoie, J Fortin, F Bojarski, A Cote, GB van den Berghe, JA Rashid-Kolvear, F Trotter, M Sekhon, HS Albadine, R Danh, TT Gorska, I Knoll, JHM Xu, J Blencowe, B Iafrate, AJ Hwang, DM Pintilie, M Gaspo, R Couture, C Tsao, MS AF Cutz, Jean-Claude Craddock, Kenneth J. Torlakovic, Emina Brandao, Guilherme Carter, Ronald F. Bigras, Gilbert Deschenes, Jean Izevbaye, Iyare Xu, Zhaolin Greer, Wenda Yatabe, Yasushi Ionescu, Diana Karsan, Aly Jung, Sungmi Fraser, Richard S. Blumenkrantz, Miriam Lavoie, Josee Fortin, Flechere Bojarski, Anna Cote, Gilbert B. van den Berghe, Janette A. Rashid-Kolvear, Fariborz Trotter, Martin Sekhon, Harmanjatinder S. Albadine, Roula Danh Tran-Thanh Gorska, Isabelle Knoll, Joan H. M. Xu, Jie Blencowe, Ben Iafrate, A. John Hwang, David M. Pintilie, Melania Gaspo, Rania Couture, Christian Tsao, Ming-Sound TI Canadian Anaplastic Lymphoma Kinase Study A Model for Multicenter Standardization and Optimization of ALK Testing in Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE ALK testing; Immunohistochemistry; Standardization; Fluorescence in situ hybridization; reverse-transcriptase polymerase chain reaction ID CANCER PATIENTS; IMMUNOHISTOCHEMISTRY; ADENOCARCINOMAS; REARRANGEMENTS; FISH; GENE; CRIZOTINIB; EGFR; IHC AB Introduction: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals. Methods: Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study samples. Thirteen laboratories performed IHC using locally developed staining protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score. Twelve centers conducted FISH using protocols based on Vysis' ALK break-apart FISH kit. Initial IHC results were used to -optimize local IHC protocols, followed by a repeat IHC study to assess the results of standardization. Three laboratories conducted a prospective parallel IHC and FISH analysis on 411 consecutive clinical samples using post-validation optimized assays. Results: Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68, respectively. IHC optimization improved the intraclass correlation coefficients to 0.94. Factors affecting FISH scoring and outliers were identified. Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100% sensitivity and specificity for IHC versus FISH. Conclusions: Multicenter standardization study may accelerate the implementation of ALK testing protocols across a country/region. Our data support the use of an appropriately validated IHC assay to screen for ALK+ lung cancers. C1 [Cutz, Jean-Claude; Carter, Ronald F.] McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Cutz, Jean-Claude; Carter, Ronald F.] McMaster Univ, Hamilton, ON, Canada. [Craddock, Kenneth J.; Torlakovic, Emina; Hwang, David M.; Pintilie, Melania; Tsao, Ming-Sound] Princess Margaret Canc Ctr, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada. [Craddock, Kenneth J.; Torlakovic, Emina; Hwang, David M.; Pintilie, Melania; Tsao, Ming-Sound] Univ Toronto, Toronto, ON, Canada. [Brandao, Guilherme] McGill Univ, Jewish Gen Hosp, Dept Pathol, Montreal, PQ H3T 1E2, Canada. [Brandao, Guilherme] McGill Univ, Lady David Inst, Montreal, PQ, Canada. [Bigras, Gilbert; Deschenes, Jean; Xu, Jie] Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. [Bigras, Gilbert; Deschenes, Jean; Xu, Jie] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Izevbaye, Iyare] Univ Alberta Hosp, Dept Mol Pathol, Edmonton, AB T6G 2B7, Canada. [Xu, Zhaolin; Greer, Wenda] Queen Elizabeth 2 Hlth Sci Ctr, Dept Pathol, Halifax, NS, Canada. [Xu, Zhaolin; Greer, Wenda] Dalhousie Univ, Halifax, NS, Canada. [Yatabe, Yasushi] Aichi Canc Ctr Hosp, Dept Pathol, Nagoya, Aichi 464, Japan. [Ionescu, Diana; Karsan, Aly] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. [Ionescu, Diana; Karsan, Aly] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Jung, Sungmi; Fraser, Richard S.; Blumenkrantz, Miriam; Lavoie, Josee] McGill Univ, Ctr Hlth, Dept Pathol, Montreal, PQ, Canada. [Fortin, Flechere] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Bojarski, Anna; Cote, Gilbert B.] Hlth Sci North, Dept Pathol, Sudbury, ON, Canada. [van den Berghe, Janette A.; Rashid-Kolvear, Fariborz; Trotter, Martin] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada. [Sekhon, Harmanjatinder S.] Ottawa Hosp, Dept Pathol, Ottawa, ON, Canada. [Sekhon, Harmanjatinder S.] Univ Ottawa, Ottawa, ON, Canada. [Albadine, Roula; Danh Tran-Thanh; Gorska, Isabelle] Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. [Knoll, Joan H. M.] London Hlth Sci Ctr, Dept Pathol, London, ON, Canada. [Blencowe, Ben] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Iafrate, A. John] Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp, Boston, MA USA. [Gaspo, Rania] Pfizer Oncol Canada, Kirkland, PQ, Canada. [Couture, Christian] Univ Laval, Inst Univ Cardiol & Pneumol Quebec Hop Laval, Quebec City, PQ, Canada. RP Tsao, MS (reprint author), 200 Elizabeth St, Toronto, ON M5G 2C4, Canada. EM ming.tsao@uhn.ca RI Karsan, Aly/K-2067-2015 FU Pfizer Canada FX The authors thank the technical assistance of Olga Ludvoski, Cherry Have, James Ho, Diana Munavish Joschko, Mark Ballantyne, Christy Dixon, Melissa Duong, Diane Grant, Rachid Iarouline, Melody Montgomery, Jocelyn O'Toole, Jennifer Puddicombe Kim Fomenti, Debra Spence, Fran Williams, Elizabeth Cullen, Jill Simpson, Lynne Faist, Noemie Riendeau, Gina Poirier, Shahira Clemens, and Sarah Canil. This work was supported by a research grant from Pfizer Canada. Authors wish to thank Abbott Molecular for providing free probes and FISH training using the Vysis ALK break-apart probes. We also thank Nichirei Biosciences for providing N-Histofine ALK Detection Kit for this study. NR 23 TC 30 Z9 31 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2014 VL 9 IS 9 BP 1255 EP 1263 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AO0TR UT WOS:000341025800010 PM 25122422 ER PT J AU Drilon, A Sugita, H Sima, CS Zauderer, M Rudin, CM Kris, MG Rusch, VW Azzoli, CG AF Drilon, Alexander Sugita, Hirofumi Sima, Camelia S. Zauderer, Marjorie Rudin, Charles M. Kris, Mark G. Rusch, Valerie W. Azzoli, Christopher G. TI A Prospective Study of Tumor Suppressor Gene Methylation as a Prognostic Biomarker in Surgically Resected Stage I to IIIA Non-Small-Cell Lung Cancers SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small-cell lung cancer; Resected; Promoter methylation; Epigenetics; Tumor suppressor gene ID PROMOTER HYPERMETHYLATION; DNA METHYLATION; CLINICAL-IMPLICATIONS; TRANSFERASE-PI; RASSF1A; ADENOCARCINOMA; EXPRESSION; MARKERS; DAPK AB Introduction: While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene promoter methylation in early-stage non-small-cell lung cancers (NSCLCs), few studies have investigated this question prospectively. Methods: Primary tumor tissue from patients with resected pathologic stage I to IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual tumor suppressor genes (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. Results: A total of 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (62%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p = 0.03). The total number of genes with methylated promoters did not correlate with RFS (p = 0.89) or OS (p = 0.55). Conclusion: Contrary to data established by previous retrospective series, tumor suppressor gene promoter methylation (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs. C1 [Drilon, Alexander; Sima, Camelia S.; Zauderer, Marjorie; Rudin, Charles M.; Kris, Mark G.; Rusch, Valerie W.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Sugita, Hirofumi] Tokyo Med & Dent Univ, Tokyo, Japan. [Azzoli, Christopher G.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Drilon, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, 300 East 66th St, New York, NY 10065 USA. EM drilona@mskcc.org FU National Cancer Institute [RO1CA092315] FX The project described was supported by grant number RO1CA092315 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 29 TC 9 Z9 9 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2014 VL 9 IS 9 BP 1272 EP 1277 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AO0TR UT WOS:000341025800012 PM 25122424 ER PT J AU Izar, B Zhou, HY Heist, RS Azzoli, CG Muzikansky, A Scribner, EEF Bernardo, LA Dias-Santagata, D Iafrate, AJ Lanuti, M AF Izar, Benjamin Zhou, Haiyu Heist, Rebecca S. Azzoli, Christopher G. Muzikansky, Alona Scribner, Emily E. F. Bernardo, Lindsay A. Dias-Santagata, Dora Iafrate, Anthony J. Lanuti, Michael TI The Prognostic Impact of KRAS, Its Codon and Amino Acid Specific Mutations, on Survival in Resected Stage I Lung Adenocarcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; KRAS; Survival; lobectomy ID ADJUVANT CHEMOTHERAPY; RAS ONCOGENE; CANCER; EGFR; REARRANGEMENTS; CARCINOMAS; GEFITINIB AB Background: Despite complete surgical resection, patients with stage I non-small-cell lung cancer (NSCLC) are at risk for disease recurrence. The impact of common oncogenic driver mutations on prognosis in stage I NSCLC is limited. The pure prognostic value of KRAS mutational status was explored in resected stage I lung adenocarcinoma. Methods: Mutation status was tested in patients who had complete resection of stage I lung adenocarcinoma without any adjuvant therapy, using a multiplex polymerase chain reaction)-based assay. Disease-free survival (DFS) and overall survival (OS) were compared between patients with KRAS-mutant (KRAS-MUT), KRAS-MUT subtypes, and KRAS wild-type (KRAS-WT) tumors. Results: A total of 312 patients were included in this analysis; 127 harbored KRAS mutations and 185 had KRAS-WT tumors. When compared with KRAS-WT, KRAS-MUT was associated with significantly shorter OS (hazard ratio 4.36, 95% confidence interval 2.09-9.07; p < 0.0001) and DFS (hazard ratio 3.62, 95% confidence interval 2.11-6.22; p < 0.0001). When stratifying KRAS-WT patients based on EGFR status, KRAS-MUT patients had worse OS (p = 0.0001) and DFS (p < 0.0001) than patients with EGFR-MUT and EGFR-WT/KRAS-WT (WT/WT). Patients with codon 12 mutations had superior DFS (p = 0.0314), but there were no differences in OS compared with mutations found in codons 13 and 61 (p = 0.1772). We observed better DFS associated with G12C/G12V mutations compared with other amino acid specific KRAS mutations (p = 0.0271) with a trend towards improved OS (p = 0.0636). Multivariate analysis identified KRAS mutation as independent predictor of worse OS (p = 0.001) and DFS (p < 0.0001). Conclusion: KRAS is an independent prognostic marker in resected stage I lung adenocarcinoma. Differential outcomes are associated with codon and amino acid specific KRAS mutations. C1 [Izar, Benjamin; Heist, Rebecca S.; Azzoli, Christopher G.; Scribner, Emily E. F.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. [Zhou, Haiyu; Lanuti, Michael] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Bernardo, Lindsay A.; Dias-Santagata, Dora; Iafrate, Anthony J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lanuti, Michael] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zhou, Haiyu] Southern Med Univ, Guangdong Gen Hosp, Dept Thorac Surg, Guangzhou, Guangdong, Peoples R China. RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM MLanuti@partners.org FU Division of Thoracic Surgery at the Massachusetts General Hospital FX Financial support for this study was provided by the Division of Thoracic Surgery at the Massachusetts General Hospital. NR 23 TC 16 Z9 16 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2014 VL 9 IS 9 BP 1363 EP 1369 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AO0TR UT WOS:000341025800023 PM 25122432 ER PT J AU Kabbinavar, F Fehrenbacher, L Hainsworth, J Kasubhai, S Kressel, B Marsland, T Patel, T Rubin, M White, L Yang, JCH Klughammer, B Colburn, D Miller, V Johnson, BE AF Kabbinavar, Fairooz Fehrenbacher, Louis Hainsworth, John Kasubhai, Saifuddin Kressel, Bruce Marsland, Thomas Patel, Taral Rubin, Mark White, Leonard Yang, James Chih-Hsin Klughammer, Barbara Colburn, Dawn Miller, Vincent Johnson, Bruce E. TI Biomarker Analyses from a Randomized, Placebo-Controlled, Phase IIIb Trial Comparing Bevacizumab with or without Erlotinib as Maintenance Therapy for the Treatment of Advanced Non-Small-Cell Lung Cancer (ATLAS) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Erlotinib; Bevacizumab; Non-small-cell lung cancer; Biomarkers; Maintenance ID 1ST-LINE TREATMENT; PROGRESSION-FREE; OPEN-LABEL; EGFR; KRAS; CHEMOTHERAPY; MULTICENTER; IMPACT; SURVIVAL AB Introduction: ATLAS compared bevacizumab plus erlotinib (B+E) with bevacizumab plus placebo (B+P) as maintenance therapy after first-line bevacizumab plus chemotherapy (B+C) for advanced non-small-cell lung cancer (NSCLC). Prespecified biomarkers were prospectively evaluated. Methods: Tumor samples were analyzed for: epidermal growth factor receptor (EGFR) expression (immunohistochemistry [IHC]); EGFR gene copy number (fluorescence in-situ hybridization [FISH]); EGFR mutations (exon 19 deletions/L858R mutations); and KRAS mutations (exons 2/3). Progression-free survival (PFS) and overall survival (OS) were estimated. Results: Of 743 patients randomized to receive maintenance treatment (after four cycles of B+C without progression), 190 (B+E) and 177 (B+P) were evaluable for biomarker status. Median PFS (from randomization) was 4.4 months (B+E) versus 3.7 months (B+P; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.99), which was numerically similar to the intent-to-treat PFS. PFS benefit of B+E was observed across most biomarker subgroups. EGFR IHC, EGFR FISH, and EGFR/KRAS mutation status were not predictive of outcome. B+E-treated patients with EGFR mutation-positive NSCLC had longer PFS compared with B+P-treated patients (HR, 0.44; 95% CI, 0.22-0.86; p = 0.0139). Patients with KRAS wild-type disease had significant PFS improvements with B+E, compared with B+P (HR, 0.66; 95% CI, 0.485-0.914; p = 0.0105). No OS benefit of B+E was observed. Conclusions: Patients with KRAS wild-type or EGFR mutation-positive NSCLC derived PFS benefits from B+E. However, EGFR IHC, EGFR FISH, and EGFR or KRAS mutation status were not strongly predictive of survival. A larger sample size would be needed to confirm the initial trends observed in this study. C1 [Kabbinavar, Fairooz] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Fehrenbacher, Louis] Kaiser Permanente Northern CA, Antioch, CA USA. [Hainsworth, John] Sarah Cannon Res Inst, Nashville, TN USA. [Kasubhai, Saifuddin] Northwest Med Specialties, Tacoma, WA USA. [Kressel, Bruce] Sibley Mem Hosp, Washington, DC USA. [Marsland, Thomas] Integrated Community Oncol Network, Jacksonville, FL USA. [Patel, Taral] Mark H Zangmeister Ctr, Columbus, OH USA. [Rubin, Mark] Florida Canc Specialists, Bonita Springs, FL USA. [White, Leonard] Arch Med Serv Inc, Ctr Canc Care & Res, St Louis, MO USA. [Yang, James Chih-Hsin] Natl Taiwan Univ, Taipei 10764, Taiwan. [Klughammer, Barbara] F Hoffmann La Roche Ltd, Basel, Switzerland. [Colburn, Dawn] Genentech Inc, San Francisco, CA 94080 USA. [Miller, Vincent] Weill Cornell Med Coll, New York, NY USA. [Miller, Vincent] Thorac Oncol Serv, New York, NY USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kabbinavar, F (reprint author), Univ Calif Los Angeles, Translat Res Oncol US, 924 Westwood Blvd,Suite 1050, Los Angeles, CA 90095 USA. EM FKabbina@mednet.ucla.edu OI Yang, James Chih-Hsin/0000-0002-5586-5138 FU F. Hoffmann-La Roche Ltd. FX Support for third-party writing assistance for this manuscript was funded by F. Hoffmann-La Roche Ltd. NR 15 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2014 VL 9 IS 9 BP 1411 EP 1417 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AO0TR UT WOS:000341025800030 PM 25122437 ER PT J AU Millham, FH Burke, P Gates, J Gupta, A Mooney, D Rabinovici, R Yaffe, MB Velmahos, GC AF Millham, Frederick Heaton Burke, Peter Gates, Jonathan Gupta, Alok Mooney, David Rabinovici, Reuven Yaffe, Michael B. Velmahos, George C. CA Boston Trauma Ctr Chiefs TI Boston Marathon bombings: An after-action review SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Review C1 [Millham, Frederick Heaton] South Shore Hosp, Dept Surg, Weymouth, MA USA. [Burke, Peter] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Burke, Peter] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Gates, Jonathan] Brigham & Womens Hosp, Trauma Serv, Boston, MA 02115 USA. [Gupta, Alok] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mooney, David] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Rabinovici, Reuven] Tufts Univ, Sch Med, Dept Surg, Boston, MA 02111 USA. [Yaffe, Michael B.] MIT, Dept Biol, Boston, MA USA. [Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Millham, FH (reprint author), South Shore Hosp, Weymouth, MA 02190 USA. EM fmillham@partners.org NR 10 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2014 VL 77 IS 3 BP 501 EP 503 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AO2BJ UT WOS:000341120200019 ER PT J AU Rago, AP Duggan, MJ Beagle, J Peev, MP Marini, J Hwabejire, JO Hannett, P Zugates, G Busold, R Helmick, M Velmahos, G Demoya, MA Yeh, DD Fagenholz, PJ Sharma, U King, DR AF Rago, Adam P. Duggan, Michael J. Beagle, John Peev, Miroslav P. Marini, John Hwabejire, John O. Hannett, Patricia Zugates, Greg Busold, Rany Helmick, Marc Velmahos, George Demoya, Marc A. Yeh, Daniel Dante Fagenholz, Peter J. Sharma, Upma King, David R. TI Self-expanding foam for prehospital treatment of intra-abdominal hemorrhage: 28-day survival and safety SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Noncompressible; abdominal hemorrhage; survival; safety; swine ID OPERATION-ENDURING-FREEDOM; SEVERE SPLENIC INJURY; COMBAT CASUALTY CARE; FIBRIN SEALANT FOAM; ABDOMINAL INSUFFLATION; PRIMARY ANASTOMOSIS; HEMOSTATIC AGENT; COLON INJURIES; PRIMARY REPAIR; IRAQI-FREEDOM AB BACKGROUND: Intracavitary noncompressible hemorrhage remains a significant cause of preventable death on the battlefield and in the homeland. We previously demonstrated the hemostatic efficacy of an in situ self-expanding poly(urea) urethane foam in a severe, closed-cavity, hepatoportal exsanguination model in swine. We hypothesized that treatment with, and subsequent explantation of, foam would not adversely impact 28-day survival in swine. METHODS: Following a closed-cavity splenic transection, animals received either fluid resuscitation alone (control group, n = 6) or resuscitation plus foam treatment at doses of 100 mL (n = 6), 120 mL (n = 6), and 150 mL (n = 2). Foam was allowed to polymerize in situ and was explanted after 3 hours. The animals were recovered and monitored for 28 days. RESULTS: All 18 animals in the 100-mL, 120-mL, and control groups survived to the 28-day endpoint without complications. The 150-mL group was terminated after the acute phase (n = 2). En bloc explantation of the foam took less than 2 minutes and was associated with millimeter-sized remnant particles. All foam animals required some level of enteric repair (imbrication or resection). Excluding the aborted 150-mL group, all animals survived, with no differences in renal or hepatic function, serum chemistries, or semiquantitative abdominal adhesion scores. Histologic analysis demonstrated that remnant particles were associated with a fibrotic capsule and mild inflammation, similar to that of standard suture reaction. In addition, safety testing(including genotoxicity, pyrogenicity, and cytotoxicity) was performed consistent with the ISO-10993 standard, and the materials passed all tests. CONCLUSION: For a distinct dose range, 28-day recovery after foam treatment and explantation for noncompressible, intra-abdominal hemorrhage is not associated with significant physiologic or biochemical evidence of end-organ dysfunction. A foam volume exceeding the maximum tolerable dose was identified. Bowel repair is required to ensure survival. (Copyright (C) 2014 by Lippincott Williams & Wilkins) C1 [Rago, Adam P.; Marini, John; Hannett, Patricia; Zugates, Greg; Busold, Rany; Helmick, Marc; Sharma, Upma] Arsenal Med Inc, Watertown, MA USA. [Duggan, Michael J.; Beagle, John; Peev, Miroslav P.; Hwabejire, John O.; Velmahos, George; Demoya, Marc A.; Yeh, Daniel Dante; Fagenholz, Peter J.; King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02141 USA. Harvard Univ, Sch Med, Boston, MA USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, USAR, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@mgh.harvard.edu OI King, David/0000-0003-1028-1478 FU DARPA; ARO [W911NF-10-C-0089, W911NF-12-C-0066] FX This study was supported by DARPA and ARO contracts W911NF-10-C-0089 and W911NF-12-C-0066. NR 27 TC 8 Z9 9 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2014 VL 77 SU 2 BP S127 EP S133 DI 10.1097/TA.0000000000000380 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AO2BL UT WOS:000341120400013 PM 25159345 ER PT J AU Voscopoulos, CJ MacNabb, CM Freeman, J Galvagno, SM Ladd, D George, E AF Voscopoulos, Christopher J. MacNabb, Colin Marshall Freeman, Jenny Galvagno, Samuel M., Jr. Ladd, Diane George, Edward TI Continuous noninvasive respiratory volume monitoring for the identification of patients at risk for opioid-induced respiratory depression and obstructive breathing patterns SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Noninvasive respiratory volume monitoring; opioid-induced respiratory; depression; postoperative apnea; identification ID SLEEP-APNEA; CONTROLLED ANALGESIA; MINUTE VENTILATION; PAIN MANAGEMENT; SAFETY; COMPLICATIONS; BATTLEFIELD; BUPIVACAINE; RECOVERY; SURGERY AB BACKGROUND: Opioid-induced respiratory depression (OIRD) and postoperative apnea (POA) can lead to complications after surgery or traumatic injury. Previously, real-time monitoring of respiratory insufficiency and identification of apneic events have been difficult. A noninvasive respiratory volume monitor (RVM) that reports minute ventilation (MV), tidal volume, and respiratory rate is now available. The RVM was used to report the effect of opioids on respiratory status as well as demonstrate apneic breathing patterns in a hospital postanesthesia care unit. METHODS: RVM traces were collected from 132 patients. Predicted MV (MVPRED) for each patient was used to calculate and the "percent predicted" MV (MVMEASURED /MVPRED x 100%) before opioid administration. Patients were stratified patients into two categories: "at risk," MV of less than 80% MVPRED, and "not at risk," MV of 80% MVPRED or greater. After opioid dosing, patients with MV of less than 40% MVPRED were categorized as "unsafe." POA was defined as more than five apneic or hypopneic events per hour. RESULTS: Of the 132 patients, 50 received opioids. Baseline MV was 7.2 +/- 0.5 L/min. The MV-based protocol classified 18 of 50 patients as at risk before opioid administration. After the first opioid dose administration, at-risk patients experienced an average MV decrease (36.7% +/- 8.5% MVPRED) and 13 of 18 decreased into unsafe; the 32 not at-risk patients experienced a lesser average MV decrease (76.9% +/- 6.3% MVPRED). Only 1 of 32 not at-risk patients had a decrease in MV to unsafe. The proposed protocol had a sensitivity of 93% and a specificity of 86%. Of the 132 patients, 26 displayed POA. Of the 26 patients, 12 experienced POA without receiving opioids. Of the 26 patients with POA, 14 also received opioids, and of those, 6 were classified as unsafe. CONCLUSION: This investigation indicates that at risk and unsafe respiratory patterns occur frequently after procedure. RVM provides continuous noninvasive objective measurements of OIRD and POA. The RVM may prove a useful tool in opioid dosing and in recognition and management of POA and strong potential value in the rapid detection of OIRD and apnea in the contemporary combat casualty environment. (Copyright (C) 2014 by Lippincott Williams & Wilkins) C1 [George, Edward] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA USA. [Voscopoulos, Christopher J.] Brigham & Womens Hosp, Dept Anesthesiol Pain & Perioperat Med, Boston, MA 02115 USA. [MacNabb, Colin Marshall; Freeman, Jenny; Ladd, Diane] Resp Mot Inc, Waltham, MA 02452 USA. [Galvagno, Samuel M., Jr.] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. [Ladd, Diane] W Virginia Univ, Sch Nursing, Morgantown, WV 26506 USA. RP Freeman, J (reprint author), Resp Mot Inc, 411 Waverley Oaks Rd,Bldg 1,Suite 150, Waltham, MA 02452 USA. EM jfreeman@respiratorymotion.com FU Respiratory Motion, Inc. FX This study was supported by Respiratory Motion, Inc. NR 43 TC 9 Z9 9 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2014 VL 77 SU 2 BP S208 EP S215 DI 10.1097/TA.0000000000000400 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AO2BL UT WOS:000341120400027 PM 25159358 ER PT J AU Vedantham, S Sista, AK Klein, SJ Nayak, L Razavi, MK Kalva, SP Saad, WE Dariushnia, SR Caplin, DM Chao, CP Ganguli, S Walker, TG Nikolic, B AF Vedantham, Suresh Sista, Akhilesh K. Klein, Seth J. Nayak, Lina Razavi, Mahmood K. Kalva, Sanjeeva P. Saad, Wael E. Dariushnia, Sean R. Caplin, Drew M. Chao, Christine P. Ganguli, Suvranu Walker, T. Gregory Nikolic, Boris CA Europe Stand Practice Comm TI Quality Improvement Guidelines for the Treatment of Lower-Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CATHETER-DIRECTED THROMBOLYSIS; PHLEGMASIA-CERULEA-DOLENS; SPRAY PHARMACOMECHANICAL THROMBOLYSIS; PERCUTANEOUS MECHANICAL THROMBECTOMY; VENOUS THROMBOSIS; POSTTHROMBOTIC SYNDROME; RANDOMIZED-TRIAL; OF-LIFE; COMPRESSION STOCKINGS; PULMONARY-EMBOLISM C1 [Vedantham, Suresh; Klein, Seth J.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO 63110 USA. [Sista, Akhilesh K.] Weill Cornell Med Coll, Dept Radiol, Div Intervent Radiol, New York, NY USA. [Caplin, Drew M.] Northshore Univ Hosp, Dept Radiol, Manhasset, NY USA. [Nikolic, Boris] Stratton Med Ctr, Dept Radiol, Albany, NY USA. [Nayak, Lina] Stanford Univ, Med Ctr, Dept Radiol, Stanford, CA 94305 USA. [Razavi, Mahmood K.] St Joseph Vasc Inst, Ctr Clin Trials, Orange, CA USA. [Chao, Christine P.] Sutter Hlth, Dept Radiol, Sacramento, CA USA. [Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Dept Intervent Radiol, Dallas, TX 75390 USA. [Saad, Wael E.] Univ Michigan, Med Ctr, Dept Radiol, Ann Arbor, MI 48109 USA. [Dariushnia, Sean R.] Emory Univ, Dept Intervent Radiol & Image Guided Med, Atlanta, GA 30322 USA. [Ganguli, Suvranu; Walker, T. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Vedantham, S (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO 63110 USA. EM vedanthams@mir.wustl.edu OI Sista, Akhilesh/0000-0001-5582-796X FU Covidien (Mansfield, Massachusetts); Bayer (Leverkusen, Germany); BSN Medical (Hamburg, Germany); Genentech (South San Francisco, California); Abbott Vascular (Abbott Park, Illinois); Bard (Covington, Georgia); Boston Scientific (Natick, Massachusetts); Covidien; Veniti (St. Louis, Missouri); TriVascular (Santa Rosa, California); Celonova Biosciences (San Antonio, Texas); Siemens; Merit Medical (South Jordan, Utah); Boston Scientific FX S.V.'s employer Washington University receives research grant support from Covidien (Mansfield, Massachusetts), Bayer (Leverkusen, Germany), BSN Medical (Hamburg, Germany), and Genentech (South San Francisco, California) for a study that S.V. conducts as principal investigator; M.R. is a paid consultant for Abbott Vascular (Abbott Park, Illinois), Bard (Covington, Georgia), Boston Scientific (Natick, Massachusetts), Covidien, Veniti (St. Louis, Missouri), and TriVascular (Santa Rosa, California); S.K. is a paid consultant for Celonova Biosciences (San Antonio, Texas) and has royalty agreements with Amirsys (Salt Lake City, Utah) and Elsevier (Amsterdam, The Netherlands); and W.S. is a paid consultant for Siemens, Merit Medical (South Jordan, Utah), and Boston Scientific. None of the other authors have identified a conflict of interest. NR 65 TC 19 Z9 22 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2014 VL 25 IS 9 BP 1317 EP 1325 DI 10.1016/j.jvir.2014.04.019 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AO1JI UT WOS:000341068000001 PM 25000825 ER PT J AU Buzon, MJ Martin-Gayo, E Pereyra, F Ouyang, ZY Sun, H Li, JZ Piovoso, M Shaw, A Dalmau, J Zangger, N Martinez-Picado, J Zurakowski, R Yu, XG Telenti, A Walker, BD Rosenberg, ES Lichterfeld, M AF Buzon, Maria J. Martin-Gayo, Enrique Pereyra, Florencia Ouyang, Zhengyu Sun, Hong Li, Jonathan Z. Piovoso, Michael Shaw, Amy Dalmau, Judith Zangger, Nadine Martinez-Picado, Javier Zurakowski, Ryan Yu, Xu G. Telenti, Amalio Walker, Bruce D. Rosenberg, Eric S. Lichterfeld, Mathias TI Long-Term Antiretroviral Treatment Initiated at Primary HIV-1 Infection Affects the Size, Composition, and Decay Kinetics of the Reservoir of HIV-1-Infected CD4 T Cells SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; STEM-CELL; IMMUNE-RESPONSES; CENTRAL MEMORY; THERAPY; INDIVIDUALS; REPLICATION; PERSISTENCE; DIVERSITY; IMMEDIATE AB Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy at primary HIV-1 infection and remained on suppressive treatment for > 10 years; patients with similar treatment duration but initiation of suppressive therapy during chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed primarily during the initial 3 to 4 years of treatment. However, in patients who started antiretroviral therapy in early infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. HIV-1-specific T cell responses remained continuously detectable during antiretroviral therapy, independently of the timing of treatment initiation. Together, these data suggest that early HIV-1 treatment initiation, even when continued for > 10 years, is unlikely to lead to viral eradication, but the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients good candidates for future interventional studies aiming at HIV-1 eradication and cure. IMPORTANCE Antiretroviral therapy can effectively suppress HIV-1 replication to undetectable levels; however, HIV-1 can persist despite treatment, and viral replication rapidly rebounds when treatment is discontinued. This is mainly due to the presence of latently infected CD4 T cells, which are not susceptible to antiretroviral drugs. Starting treatment in the earliest stages of HIV-1 infection can limit the number of these latently infected cells, raising the possibility that these viral reservoirs are naturally eliminated if suppressive antiretroviral treatment is continued for extremely long periods of time. Here, we analyzed nine patients who started on antiretroviral therapy within the earliest weeks of the disease and continued treatment for more than 10 years. Our data show that early treatment accelerated the decay of infected CD4 T cells and led to very low residual levels of detectable HIV-1 after long-term therapy, levels that were otherwise detectable in patients who are able to maintain a spontaneous, drug-free control of HIV-1 replication. Thus, long-term antiretroviral treatment started during early infection cannot eliminate HIV-1, but the reduced reservoirs of HIV-1 infected cells in such patients may increase their chances to respond to clinical interventions aiming at inducing a drug-free remission of HIV-1 infection. C1 [Buzon, Maria J.; Pereyra, Florencia; Rosenberg, Eric S.; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Buzon, Maria J.; Martin-Gayo, Enrique; Pereyra, Florencia; Ouyang, Zhengyu; Sun, Hong; Shaw, Amy; Yu, Xu G.; Walker, Bruce D.; Lichterfeld, Mathias] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Li, Jonathan Z.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Sun, Hong] China Med Univ, Affiliated Hosp 1, AIDS Res Ctr, Shenyang, Liaoning, Peoples R China. [Piovoso, Michael] Penn State Univ, Dept Elect Engn, Malvern, PA USA. [Dalmau, Judith; Martinez-Picado, Javier] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Inst Recerca SIDA IrsiCaixa, Badalona, Spain. [Zangger, Nadine; Telenti, Amalio] CHU Vaudois, Inst Microbiol, CH-1011 Lausanne, Switzerland. [Martinez-Picado, Javier] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain. [Zurakowski, Ryan] Univ Delaware, Dept Elect & Comp Engn, Newark, DE 19716 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Lichterfeld, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM mlichterfeld@partners.org RI Ouyang, Zhengyu/P-3576-2014; Buzon, Maria J/G-8286-2015; Martinez-Picado, Javier/G-5507-2012; Dalmau, Judith/I-7065-2016 OI Buzon, Maria J/0000-0003-4427-9413; Martinez-Picado, Javier/0000-0002-4916-2129; Dalmau, Judith/0000-0001-7513-3711 FU National Institutes of Health [AI098487, AI106468, AI089339, AI078799, AI098484, AI100699, AI074415]; American Foundation for AIDS Research [108302-51-RGRL]; Doris Duke Charitable Foundation [2009034]; Massachusetts General Hospital; HU CFAR NIH/NIAID fund [5P30AI060354-10]; Spanish Ministry of Science and Innovation [SAF2013-49042-R]; HIVACAT program FX This work was supported by the National Institutes of Health (grants AI098487 and AI106468 to M. L.; AI089339, AI078799, and AI098484 to X. G. Y.; AI100699 to J.Z.L.) and by the American Foundation for AIDS Research (grant 108302-51-RGRL). M. L. is a recipient of the Clinical Scientist Development Award from the Doris Duke Charitable Foundation (grant 2009034). M.J.B. is supported by the Tosteson postdoctoral fellowship award from Massachusetts General Hospital. M.J.B. and E. G. are recipients of the Scholar Award from HU CFAR NIH/NIAID fund 5P30AI060354-10. J.M-P. is supported by the Spanish Ministry of Science and Innovation (SAF2013-49042-R) and the HIVACAT program. Patient blood sample collection was supported by the National Institutes of Health (grant AI074415), by the Mark and Lisa Schwartz Foundation, and by the Bill & Melinda Gates Foundation. NR 45 TC 59 Z9 60 U1 2 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 2014 VL 88 IS 17 BP 10056 EP 10065 DI 10.1128/JVI.01046-14 PG 10 WC Virology SC Virology GA AO3LW UT WOS:000341232300047 PM 24965451 ER PT J AU Kuang, XMT Li, XG Anmole, G Mwimanzi, P Shahid, A Le, AQ Chong, L Qian, H Miura, T Markle, T Baraki, B Connick, E Daar, ES Jessen, H Kelleher, AD Little, S Markowitz, M Pereyra, F Rosenberg, ES Walker, BD Ueno, T Brumme, ZL Brockman, MA AF Kuang, Xiaomei T. Li, Xiaoguang Anmole, Gursev Mwimanzi, Philip Shahid, Aniqa Le, Anh Q. Chong, Louise Qian, Hua Miura, Toshiyuki Markle, Tristan Baraki, Bemuluyigza Connick, Elizabeth Daar, Eric S. Jessen, Heiko Kelleher, Anthony D. Little, Susan Markowitz, Martin Pereyra, Florencia Rosenberg, Eric S. Walker, Bruce D. Ueno, Takamasa Brumme, Zabrina L. Brockman, Mark A. TI Impaired Nef Function Is Associated with Early Control of HIV-1 Viremia SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; I DOWN-REGULATION; HUMAN-LEUKOCYTE ANTIGEN; T-CELL RESPONSES; ELITE CONTROLLERS; REPLICATION CAPACITY; ANTIRETROVIRAL THERAPY; MAXIMUM-LIKELIHOOD; ESCAPE MUTATIONS; DRUG-RESISTANCE AB Host and viral factors influence the HIV-1 infection course. Reduced Nef function has been observed in HIV-1 controllers during the chronic phase, but the kinetics and mechanisms of Nef attenuation in such individuals remain unclear. We examined plasma RNA-derived Nef clones from 10 recently infected individuals who subsequently suppressed viremia to less than 2,000 RNA copies/ml within 1 year postinfection (acute controllers) and 50 recently infected individuals who did not control viremia (acute progressors). Nef clones from acute controllers displayed a lesser ability to downregulate CD4 and HLA class I from the cell surface and a reduced ability to enhance virion infectivity compared to those from acute progressors (all P < 0.01). HLA class I downregulation activity correlated inversely with days postinfection (Spearman's R = -0.85, P = 0.004) and positively with baseline plasma viral load (Spearman's R = 0.81, P = 0.007) in acute controllers but not in acute progressors. Nef polymorphisms associated with functional changes over time were identified in follow-up samples from six controllers. For one such individual, mutational analyses indicated that four polymorphisms selected by HLA-A*31 and B*37 acted in combination to reduce Nef steady-state protein levels and HLA class I downregulation activity. Our results demonstrate that relative control of initial HIV-1 viremia is associated with Nef clones that display reduced function, which in turn may influence the course of HIV-1 infection. Transmission of impaired Nef sequences likely contributed in part to this observation; however, accumulation of HLA-associated polymorphisms in Nef that impair function also suggests that CD8(+) T-cell pressures play a role in this phenomenon. IMPORTANCE Rare individuals can spontaneously control HIV-1 viremia in the absence of antiretroviral treatment. Understanding the host and viral factors that contribute to the controller phenotype may identify new strategies to design effective vaccines or therapeutics. The HIV-1 Nef protein enhances viral pathogenesis through multiple mechanisms. We examined the function of plasma HIV-1 RNA-derived Nef clones isolated from 10 recently infected individuals who subsequently controlled HIV viremia compared to the function of those from 50 individuals who failed to control viremia. Our results demonstrate that early Nef clones from HIV controllers displayed lower HLA class I and CD4 downregulation activity, as well as a reduced ability to enhance virion infectivity. The accumulation of HLA-associated polymorphisms in Nef during the first year postinfection was associated with impaired protein function in some controllers. This report highlights the potential for host immune responses to modulate HIV pathogenicity and disease outcome by targeting cytotoxic T lymphocyte (CTL) epitopes in Nef. C1 [Kuang, Xiaomei T.; Anmole, Gursev; Mwimanzi, Philip; Chong, Louise; Markle, Tristan; Baraki, Bemuluyigza; Brockman, Mark A.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. [Kuang, Xiaomei T.; Qian, Hua; Ueno, Takamasa] Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan. [Mwimanzi, Philip; Shahid, Aniqa; Le, Anh Q.; Baraki, Bemuluyigza; Brumme, Zabrina L.; Brockman, Mark A.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Miura, Toshiyuki; Pereyra, Florencia; Walker, Bruce D.] Harvard Univ, MIT, Ragon Inst MGH, Cambridge, MA 02139 USA. [Connick, Elizabeth] Univ Colorado, Dept Med, Denver, CO USA. [Daar, Eric S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Jessen, Heiko] Jessen Jessen Praxis, Berlin, Germany. [Kelleher, Anthony D.] Univ New S Wales, Kirby Inst Infect & Immun Soc, Sydney, NSW, Australia. [Little, Susan] Univ Calif San Diego, Div Infect Dis, San Diego, CA 92103 USA. [Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Pereyra, Florencia; Rosenberg, Eric S.; Walker, Bruce D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Bethesda, MD USA. [Ueno, Takamasa] Kumamoto Univ, IRCMS, Kumamoto, Japan. [Brumme, Zabrina L.; Brockman, Mark A.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. RP Brockman, MA (reprint author), Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. EM mark_brockman@sfu.ca RI Ueno, Takamasa/F-5788-2013; OI Ueno, Takamasa/0000-0003-4852-4236; Brockman, Mark/0000-0001-6432-1426 FU Canadian Institutes for Health Research (CIHR) [MOP-93536, THA-118569]; Ministry of Health, Labor, and Welfare of Japan; Canadian Association for HIV Research; Bristol-Myers Squibb Canada; ViiV Healthcare; Michael Smith Foundation for Health Research (MSFHR); CIHR Frederick Banting and Charles Best Masters Award; MSFHR FX This study was supported by the Canadian Institutes for Health Research (CIHR), operating grants MOP-93536 (to Z.L.B.) and THA-118569 (to M. A. B.), and by grants-in-aid from the Global COE Program (Ministry of Education, Science, Sports, and Culture of Japan) and the Ministry of Health, Labor, and Welfare of Japan (to T. U.). X. T. K. is supported by a Master's Scholarship from the Canadian Association for HIV Research in partnership with Bristol-Myers Squibb Canada and ViiV Healthcare. P. M. is supported by Postdoctoral Fellowships from the Michael Smith Foundation for Health Research (MSFHR) and CIHR. A. Q. L. is supported by a CIHR Frederick Banting and Charles Best Masters Award. Z.L.B. is the recipient of a CIHR New Investigator Award and a Scholar Award from MSFHR. M. A. B. holds a Canada Research Chair (Tier 2) in Viral Pathogenesis and Immunity from the Canada Research Chairs Program. NR 82 TC 14 Z9 14 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 2014 VL 88 IS 17 BP 10200 EP 10213 DI 10.1128/JVI.01334-14 PG 14 WC Virology SC Virology GA AO3LW UT WOS:000341232300059 PM 24965469 ER PT J AU Tipper, C Sodroski, JG AF Tipper, Christopher Sodroski, Joseph G. TI Contribution of Glutamine Residues in the Helix 4-5 Loop to Capsid-Capsid Interactions in Simian Immunodeficiency Virus of Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID CYCLOPHILIN-A; REVERSE TRANSCRIPTION; RETROVIRUS INFECTION; FUNCTIONAL-ANALYSIS; TERMINAL DOMAIN; HIV-1; PROTEIN; TYPE-1; RESTRICTION; CELLS AB Following retrovirus entry, the viral capsid (CA) disassembles into its component capsid proteins. The rate of this uncoating process, which is regulated by CA-CA interactions and by the association of the capsid with host cell factors like cyclophilin A (CypA), can influence the efficiency of reverse transcription. Inspection of the CA sequences of lentiviruses reveals that several species of simian immunodeficiency viruses (SIVs) have lost the glycine-proline motif in the helix 4-5 loop important for CypA binding; instead, the helix 4-5 loop in these SIVs exhibits an increase in the number of glutamine residues. In this study, we investigated the role of these glutamine residues in SIVmac239 replication. Changes in these residues, particularly glutamine 89 and glutamine 92, resulted in a decreased efficiency of core condensation, decreased stability of the capsids in infected cells, and blocks to reverse transcription. In some cases, coexpression of two different CA mutants produced chimeric virions that exhibited higher infectivity than either parental mutant virus. For this complementation of infectivity, glutamine 89 was apparently required on one of the complementing pair of mutants and glutamine 92 on the other. Modeling suggests that glutamines 89 and 92 are located on the distal face of hexameric capsid spokes and thus are well positioned to contribute to interhexamer interactions. Requirements to evade host restriction factors like TRIMCyp may drive some SIV lineages to evolve means other than CypA binding to stabilize the capsid. One solution used by several SIV strains consists of glutamine-based bonding. IMPORTANCE The retroviral capsid is an assembly of individual capsid proteins that surrounds the viral RNA. After a retrovirus enters a cell, the capsid must disassemble, or uncoat, at a proper rate. The interactions among capsid proteins contribute to this rate of uncoating. We found that some simian immunodeficiency viruses use arrays of glutamine residues, which can form hydrogen bonds efficiently, to keep their capsids stable. This strategy may allow these viruses to forego the use of capsid-stabilizing factors from the host cell, some of which have antiviral activity. C1 [Tipper, Christopher; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sodroski, Joseph G.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Sodroski, Joseph G.] Harvard Univ, Cambridge, MA 02138 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU National Institutes of Health [AI063987, AI06354, T32 AI07245, P41 RR-01081]; International AIDS Vaccine Initiative; late William F. McCarty-Cooper FX This work was supported by the National Institutes of Health (grant AI063987 and Center for AIDS Research Award AI06354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper. C.T. was supported by a training grant from the National Institutes of Health (T32 AI07245). The Computer Graphics Laboratory, University of California, San Francisco, which is the source of the UCSF Chimera package used in this study, is supported by NIH grant P41 RR-01081. NR 53 TC 1 Z9 1 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 2014 VL 88 IS 18 BP 10289 EP 10302 DI 10.1128/JVI.01388-14 PG 14 WC Virology SC Virology GA AO3MQ UT WOS:000341234900004 PM 24991000 ER PT J AU Utermark, T Schmit, F Lee, SH Gao, XL Schaffhausen, BS Roberts, TM AF Utermark, Tamara Schmit, Fabienne Lee, Sang Hyun Gao, Xueliang Schaffhausen, Brian S. Roberts, Thomas M. TI The Phosphatidylinositol 3-Kinase (PI3K) Isoform Dependence of Tumor Formation Is Determined by the Genetic Mode of PI3K Pathway Activation Rather than by Tissue Type SO JOURNAL OF VIROLOGY LA English DT Article ID MIDDLE T-ANTIGEN; P110-ALPHA ISOFORM; TUMORIGENESIS; PTEN; PROSTATE; GROWTH; CANCER; TRANSFORMATION; METABOLISM; THERAPY AB Previous work has shown that prostate cancer in a Pten-null murine model is dependent on the p110 beta isoform of phosphatidylinositol 3-kinase (PI3K), while breast cancer driven by either polyoma middle T antigen (MT) or HER2 is p110 alpha dependent. Whether these differences in isoform dependence arise from tissue specificity or from the nature of the oncogenic signal activating the PI3K pathway is important, given increasing interest in using isoform-specific PI3K inhibitors in cancer therapy. To approach this question, we studied the PI3K isoform dependence of our recently constructed prostate cancer model driven by MT. Since MT activates a number of signaling pathways, we first confirmed that the MT-driven prostate cancer model was actually dependent on PI3K. A newly generated transgenic prostate line expressing an MT allele (Y315F) known to be defective for PI3K binding displayed a markedly reduced ability to drive tumor formation. We next selectively ablated expression of either p110 alpha or p110 beta in mice in which wild-type MT was expressed in the prostate. We found that tumor formation driven by MT was significantly delayed by the loss of p110 alpha expression, while ablation of p110 beta had no effect. Since the tumor formation driven by MT is p110 alpha dependent in the prostate as well as in the mammary gland, our data suggest that PI3K isoform dependence is driven by the mode of PI3K pathway activation rather than by tissue type. IMPORTANCE Middle T antigen (MT), the oncogene of polyomavirus, can drive tumor formation in a variety of cell types and tissues. Interestingly, MT has no intrinsic enzymatic activity but instead functions by binding and activating cellular signaling proteins. One of the most important of these is the lipid kinase PI3K, which was first studied in MT immunoprecipitates. Ubiquitously expressed PI3K comes in two major isoforms: p110 alpha and p110 beta. Previous work in animal models showed that p110 alpha was the key isoform in breast tumors driven by oncogenes, including MT and HER2, while p110 beta was key in prostate tumors driven by Pten loss. We asked the simple question of whether a prostate tumor driven by MT depends on p110 alpha, which would suggest that the mode of activation determines p110 isoform dependence, or p110 beta, which would suggest that tissue type determines isoform dependence. The clear answer is that MT depends on p110 alpha in both the prostate and breast. C1 [Utermark, Tamara; Schmit, Fabienne; Lee, Sang Hyun; Gao, Xueliang; Roberts, Thomas M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Utermark, Tamara; Schmit, Fabienne; Lee, Sang Hyun; Gao, Xueliang; Roberts, Thomas M.] Harvard Univ, Sch Med, Dept Biochem & Mol Pharmacol, Boston, MA USA. [Schaffhausen, Brian S.] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM Thomas_Roberts@dfci.harvard.edu FU NIH [CA30002, CA34722, CA50661] FX This work was supported by NIH grants CA30002 (to T.M.R.), CA34722 (to B.S.S.), and CA50661 (to T.M.R. and B.S.S.). NR 23 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 2014 VL 88 IS 18 BP 10673 EP 10679 DI 10.1128/JVI.01409-14 PG 7 WC Virology SC Virology GA AO3MQ UT WOS:000341234900035 PM 24991009 ER PT J AU Frank, RM Provencher, MT Romeo, AA AF Frank, Rachel M. Provencher, Matthew T. Romeo, Anthony A. TI Comment on "Reconstruction of posterior glenoid deficiency using distal tibial osteoarticular allograft" SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Letter C1 [Frank, Rachel M.; Romeo, Anthony A.] Rush Univ, Dept Orthopaed Surg, Med Ctr, Chicago, IL 60612 USA. [Provencher, Matthew T.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Frank, RM (reprint author), Rush Univ, Dept Orthopaed Surg, Med Ctr, 1611 West Harrison St,Suite 300, Chicago, IL 60612 USA. EM rmfrank3@gmail.com; mattprovencher@gmail.com; ShoulderElbowDoc@gmail.com OI Romeo, Anthony/0000-0003-4848-3411 NR 6 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-2056 EI 1433-7347 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD SEP PY 2014 VL 22 IS 9 BP 2257 EP 2258 DI 10.1007/s00167-013-2722-6 PG 2 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AO1RK UT WOS:000341091100042 PM 24146053 ER PT J AU Viana, LM Bahmad, F Rauch, SD AF Viana, Lucas M. Bahmad, Fayez, Jr. Rauch, Steven D. TI Intratympanic Gentamicin as a Treatment for Drop Attacks in Patients With Meniere's Disease SO LARYNGOSCOPE LA English DT Article DE Meniere's disease; drop attack; intratympanic gentamicin AB ObjectivesHypothesis: Vertigo attacks in most cases of Meniere's disease (MD) are successfully treated with lifestyle changes and medication. However, approximately 6% of patients with MD develop drop attacks (DAs), a potentially life-threatening condition. Traditional treatment for DAs has been surgical labyrinthectomy. The objective of this study was to assess the effectiveness of intratympanic gentamicin for DAs in patients with MD. Study Design: Retrospective charts review. Methods: All charts were reviewed from Meniere DA patients at our hospital during the 10-year period from 2002 to 2012 who had been treated with intratympanic gentamicin and had been followed for at least 1 year afterward. Results: Twenty-four ears fulfilled inclusion criteria. The time for manifestation of DAs varied from 1 to 20 years after diagnosis (mean 10 years). A total of 83.3% of ears with intractable MD and DA achieved complete symptom control of DAs after the first intratympanic gentamicin cycle and 95.8% after the further injections. Among patients with no DA recurrence by the end of the study follow-up, the symptom-free interval varied from 12 to 120 months (mean: 43.5 months). All 15 patients with >= 24 months follow-up were still free of DAs. Elevated or absent vestibular evoked myogenic potential thresholds were more common in DA than in contralateral ears, and hearing loss was not a major complication of the treatment. Conclusion: Intratympanic gentamicin treatment appears to be a long-lasting and effective treatment for MD with DAs. C1 [Viana, Lucas M.; Rauch, Steven D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Viana, Lucas M.; Bahmad, Fayez, Jr.] Univ Brasilia, Fac Hlth Sci, Brasilia, DF, Brazil. RP Viana, LM (reprint author), Ed Dr Crispim SMHN Quadra 2 Bloco C Sala 515 ASA, BR-70710149 Brasilia, DF, Brazil. EM lucasmvianaorl@gmail.com NR 17 TC 4 Z9 4 U1 4 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2014 VL 124 IS 9 BP 2151 EP 2154 DI 10.1002/lary.24716 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AO1UM UT WOS:000341100500044 PM 24729095 ER PT J AU Leonardis, RL Duvvuri, U Mehta, D AF Leonardis, Rachel L. Duvvuri, Umamaheswar Mehta, Deepak TI Transoral Robotic-Assisted Laryngeal Cleft Repair in the Pediatric Patient SO LARYNGOSCOPE LA English DT Article DE Robotic; pediatric robotics; transoral robotics; laryngeal cleft repair ID SURGERY; SAFETY AB Objectives/Hypothesis: To assess the feasibility of performing robotic-assisted laryngeal cleft repair in the pediatric population. Study Design: Retrospective chart review at a tertiary academic children's hospital. Methods: All patients underwent transoral robotic-assisted laryngeal cleft repair from March 2011 to June 2013. Demographics, robotic docking time, operative time, and postoperative course and swallowing function were collected and analyzed. Results: Five children, three male and two female, underwent successful transoral robotic-assisted laryngeal cleft repair for closure of a type I laryngeal cleft. Mean age at time of surgery was 21.6 months (standard deviation 6.1 months; range, 15-29 months). From case 1 to case 5, robotic docking time (18-10 minutes), robotic operative time (102-36 minutes), and total operating room time (173-105 minutes) decreased. There were no complications with time until extubation (range, 2-3 days), length of intensive care unit stay (range, 3-4 days), and total hospital stay (range, 3-5 days) within acceptable range following laryngeal cleft repair. Modified barium swallow (two patients) or fiberoptic endoscopic evaluation of swallowing (three patients) was performed postoperatively, with all patients showing complete resolution of penetration and aspiration. In addition, all patients experienced subjective resolution of dysphagia and/or choking with feeds postoperatively. Conclusions: Transoral robotic-assisted laryngeal cleft repair may offer specific advantages over a traditional endoscopic approach. In our experience, the procedure was well tolerated and associated with definitive surgical cure in all patients. The scope of robotic technology continually expands and should be considered a feasible tool at an institution-based level. C1 [Leonardis, Rachel L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Dept Otolaryngol, Med Ctr, Pittsburgh, PA 15260 USA. [Mehta, Deepak] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Inst Eye & Ear, Suite 300,203 Lothrop St, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu FU Department of Veterans Affairs; PNC foundation FX This work was funded in part by the Department of Veterans Affairs, and the PNC foundation (U.D.). NR 9 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2014 VL 124 IS 9 BP 2167 EP 2169 DI 10.1002/lary.24680 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AO1UM UT WOS:000341100500047 PM 24648210 ER PT J AU Guo, P Yuan, YS Chi, FL AF Guo, Peng Yuan, Yasheng Chi, Fanglu TI Biomimetic alginate/polyacrylamide porous scaffold supports human mesenchymal stem cell proliferation and chondrogenesis SO MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS LA English DT Article DE Polyacrylamide; Alginate; Hydrogel; Mesenchymal stem cell; Proliferation; Chondrogenesis ID POLYMER NETWORK HYDROGELS; ARTICULAR-CARTILAGE REPAIR; ALGINATE GEL SYSTEM; SODIUM ALGINATE; ALKALINE-PHOSPHATASE; TISSUE; BONE; DIFFERENTIATION; CHONDROCYTES; UTILITY AB We describe the development of alginate/polyacrylamide (ALG/PAAm) porous hydrogels based on interpenetrating polymer network structure for human mesenchymal stem cell proliferation and chondrogenesis. Three ALG/PAAm hydrogels at molar ratios of 10/90,20/80, and 30/70 were prepared and characterized with enhanced elastic and rubbery mechanical properties, which are similar to native human cartilage tissues. Their elasticity and swelling properties were also studied under different physiological pH conditions. Finally, in vitro tests demonstrated that human mesenchymal stem cells could proliferate on the as-synthesized hydrogels with improved alkaline phosphatase activities. These results suggest that ALG/PAAm hydrogels may be a promising biomaterial for cartilage tissue engineering. (C) 2014 Elsevier B.V. All rights reserved. C1 [Guo, Peng; Yuan, Yasheng; Chi, Fanglu] EENT Hosp, Dept ENT Head & Neck Surg, Shanghai 200031, Peoples R China. [Guo, Peng; Yuan, Yasheng; Chi, Fanglu] Fudan Univ, Shanghai Med Sch, Shanghai 210029, Peoples R China. [Yuan, Yasheng] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab, Boston, MA 02114 USA. RP Yuan, YS (reprint author), EENT Hosp, Dept ENT Head & Neck Surg, Shanghai 200031, Peoples R China. EM yuanyasheng@163.com FU National Institute on Deafness and other Communicative Disorders (from the NSFC grant) [81028003/H1305, 30973303]; National Institute on Deafness and other Communicative Disorders (from the Key Basic Research Project of Shanghai Committee of Science and Technology) [10JC1402500]; National Institute on Deafness and other Communicative Disorders (from the Ministry of Education grant) [20090071120072]; National Institute on Deafness and other Communicative Disorders (from the Innovation Program of Shanghai Committee of Science and Technology) [11411952300] FX This work was supported by grants from the National Institute on Deafness and other Communicative Disorders (Award Number 81028003/H1305 from the NSFC grant; 30973303 from the NSFC grant; 10JC1402500 from the Key Basic Research Project of Shanghai Committee of Science and Technology; 20090071120072 from the Ministry of Education grant, and 11411952300 from the Innovation Program of Shanghai Committee of Science and Technology). NR 41 TC 13 Z9 13 U1 5 U2 48 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-4931 EI 1873-0191 J9 MAT SCI ENG C-MATER JI Mater. Sci. Eng. C-Mater. Biol. Appl. PD SEP 1 PY 2014 VL 42 BP 622 EP 628 DI 10.1016/j.msec.2014.06.013 PG 7 WC Materials Science, Biomaterials SC Materials Science GA AN6EJ UT WOS:000340687400079 PM 25063162 ER PT J AU Lamont, EB Zaslavsky, AM Subramanian, SV Meilleur, AE He, YL Landrum, MB AF Lamont, Elizabeth B. Zaslavsky, Alan M. Subramanian, Subu V. Meilleur, Ashley E. He, Yulei Landrum, Mary B. TI Elderly Breast and Colorectal Cancer Patients' Clinical Course Patient and Contextual Influences SO MEDICAL CARE LA English DT Article DE cancer; elderly; neighborhoods and health; small area variation ID HEALTH-CARE; UNITED-STATES; MEDICARE; DISPARITIES; MORTALITY; BENEFICIARIES; AREA; US; GENERALIZABILITY; SEGREGATION AB Background: The social and medical environments that surround people are each independently associated with their cancer course. The extent to which these characteristics may together mediate patients' cancer care and outcomes is not known. Methods: Using multilevel methods and data, we studied elderly breast and colorectal cancer patients (level I) within urban social (level II: ZIP code tabulation area) and health care (level III: hospital service area) contexts. We sought to determine (1) which, if any, observable social and medical contextual attributes were associated with patient cancer outcomes after controlling for observable patient attributes, and (2) the magnitude of residual variation in patient cancer outcomes at each level. Results: Numerous patient attributes and social area attributes, including poverty, were associated with unfavorable patient cancer outcomes across the full clinical cancer continuum for both cancers. Health care area attributes were not associated with patient cancer outcomes. After controlling for observable covariates at all 3 levels, there was substantial residual variation in patient cancer outcomes at all levels. Conclusions: After controlling for patient attributes known to confer risk of poor cancer outcomes, we find that neighborhood socioeconomic disadvantage exerts an independent and deleterious effect on residents' cancer outcomes, but the area supply of the specific types of health care studied do not. Multilevel interventions targeted at cancer patients and their social areas may be useful. We also show substantial residual variation in patient outcomes across social and health care areas, a finding potentially relevant to traditional small area variation research methods. C1 [Lamont, Elizabeth B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Lamont, Elizabeth B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lamont, Elizabeth B.; Zaslavsky, Alan M.; Meilleur, Ashley E.; He, Yulei; Landrum, Mary B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Subramanian, Subu V.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Lamont, EB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180A Longwood Ave, Boston, MA 02115 USA. EM lamont@hcp.med.harvard.edu FU [P01 AG031093]; [R21 AG030607] FX Supported by P01 AG031093 and R21 AG030607. NR 42 TC 1 Z9 1 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD SEP PY 2014 VL 52 IS 9 BP 809 EP 817 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AO0SA UT WOS:000341020900009 PM 25119954 ER PT J AU Rutter, MK Sullivan, LM Fox, CS Wilson, PWF Nathan, DM Vasan, RS D'Agostino, RB Meigs, JB AF Rutter, Martin K. Sullivan, Lisa M. Fox, Caroline S. Wilson, Peter W. F. Nathan, David M. Vasan, Ramachandran S. D'Agostino, Ralph B. Meigs, James B. TI Baseline Levels, and Changes Over Time in Body Mass Index and Fasting Insulin, and Their Relationship to Change in Metabolic Trait Clustering SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; CORONARY-HEART-DISEASE; SYNDROME SYNDROME-X; RESISTANCE SYNDROME; CARDIOVASCULAR-DISEASE; WAIST CIRCUMFERENCE; OBESITY; RISK; ADULTS; HYPERINSULINEMIA AB Background: Multiple abnormal metabolic traits are found together or "cluster'' within individuals more often than is predicted by chance. The individual and combined role of adiposity and insulin resistance (IR) on metabolic trait clustering is uncertain. We tested the hypothesis that change in trait clustering is a function of both baseline level and change in these measures. Methods: In 2616 nondiabetic Framingham Offspring Study participants, body mass index (BMI) and fasting insulin were related to a within-person 7-year change in a trait score of 0-4 Adult Treatment Panel III metabolic syndrome traits (hypertension, high triglycerides, low high-density lipoprotein cholesterol, hyperglycemia). Results: At baseline assessment, mean trait score was 1.4 traits, and 7-year mean (SEM) change in trait score was +0.25 (0.02) traits, P < 0.0001. In models with BMI predictors only, for every quintile difference in baseline BMI, the 7-year trait score increase was 0.14 traits, and for every quintile increase in BMI during 7-year follow-up, the trait score increased by 0.3 traits. Baseline level and change in fasting insulin were similarly related to trait score change. In models adjusted for age-sex-baseline cluster score, 7-year change in trait score was significantly related to both a 1-quintile difference in baseline BMI (0.07 traits) and fasting insulin (0.18 traits), and to both a 1-quintile 7-year increase in BMI (0.21 traits) and fasting insulin (0.18 traits). Conclusions: Change in metabolic trait clustering was significantly associated with baseline levels and changes in both BMI and fasting insulin, highlighting the importance of both obesity and IR in the clustering of metabolic traits. C1 [Rutter, Martin K.] Univ Manchester, Fac Med & Human Sci, Inst Human Dev, Endocrinol & Diabet Res Grp, Manchester M13 9PT, Lancs, England. [Rutter, Martin K.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester Diabet Ctr, Manchester, Lancs, England. [Sullivan, Lisa M.] Boston Univ, Dept Biostat, Boston, MA USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Consulting Unit, Boston, MA USA. [Fox, Caroline S.; Nathan, David M.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Caroline S.; Vasan, Ramachandran S.] NHLBI, Framingham, MA USA. [Fox, Caroline S.; Vasan, Ramachandran S.] Framingham Mass Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol & Metab, Boston, MA 02115 USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Atlanta, GA USA. [Nathan, David M.; Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Rutter, MK (reprint author), Univ Manchester, Fac Med & Human Sci, Inst Human Dev, Endocrinol & Diabet Res Grp, Manchester M13 9PT, Lancs, England. EM martin.rutter@manchester.ac.uk OI Rutter, Martin/0000-0001-6380-539X; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute (NHLBI); Boston University [N01-HC-25195]; National Institute for Diabetes and Digestive and Kidney Diseases [K24 DK080140]; Higher Education Funding Council for England FX This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (contract no. N01-HC-25195), and the National Institute for Diabetes and Digestive and Kidney Diseases (K24 DK080140) (J.B.M.). M. K. R. is supported by the Higher Education Funding Council for England (Clinical Senior Lecturer Award). The research was facilitated by the Manchester Biomedical Research Centre and the NIHR Greater Manchester Clinical Research Network. NR 48 TC 5 Z9 5 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 EI 1557-8518 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD SEP PY 2014 VL 12 IS 7 BP 372 EP 380 DI 10.1089/met.2013.0148 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO2UK UT WOS:000341181300004 PM 25007010 ER PT J AU Korn, LL Thomas, HL Hubbeling, HG Spencer, SP Sinha, R Simkins, HMA Salzman, NH Bushman, FD Laufer, TM AF Korn, L. L. Thomas, H. L. Hubbeling, H. G. Spencer, S. P. Sinha, R. Simkins, H. M. A. Salzman, N. H. Bushman, F. D. Laufer, T. M. TI Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells SO MUCOSAL IMMUNOLOGY LA English DT Article ID COMMENSAL BACTERIA; MICROBIAL COMMUNITIES; NKP46(+) CELLS; DEFICIENT MICE; HOMEOSTASIS; IMMUNITY; INFLAMMATION; HOST; MICROFLORA; INFECTION AB The innate and adaptive immune systems in the intestine cooperate to maintain the integrity of the intestinal barrier and to regulate the composition of the resident microbiota. However, little is known about the crosstalk between the innate and adaptive immune systems that contribute to this homeostasis. We find that CD4 + Tcells regulate the number and function of barrier-protective innate lymphoid cells (ILCs), as well as production of antimicrobial peptides (AMPs), Reg3 gamma and Reg3 beta. RAG1 - / - mice lacking T and B cells had elevated ILC numbers, interleukin-22 (IL-22) production, and AMP expression, which were corrected by replacement of CD4 + Tcells. Major histocompatibility class II - / - (MHCII - / -) mice lacking CD4 + T cells also had increased ILCs, IL- 22, and AMPs, suggesting that negative regulation by CD4 + T cells occurs at steady state. We utilized transfers and genetically modified mice to show that reduction of IL- 22 is mediated by conventional CD4 + Tcells and is T- cell receptor dependent. The IL-22-AMP axis responds to commensal bacteria; however, neither the bacterial repertoire nor the gross localization of commensal bacteria differed between MHCII + / - and MHCII - / - littermates. These data define a novel ability of CD4 + T cells to regulate intestinal IL-22-producing ILCs and AMPs. C1 [Korn, L. L.; Thomas, H. L.; Hubbeling, H. G.; Spencer, S. P.; Simkins, H. M. A.; Laufer, T. M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Hubbeling, H. G.; Laufer, T. M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Sinha, R.; Bushman, F. D.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Salzman, N. H.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Laufer, TM (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. EM tlaufer@mail.med.upenn.edu OI Salzman, Nita/0000-0003-0939-6139; Bushman, Frederic/0000-0003-4740-4056 FU Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine [P30-DK050306]; Penn Genome Frontiers Institute; University of Pennsylvania Center for AIDS Research (CFAR) [P30 AI 045008, R01-AI57757]; Training Program in Rheumatic Disease [5T32AR007442-25] FX This work was supported by a pilot grant from the Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine P30-DK050306, the Penn Genome Frontiers Institute, and the University of Pennsylvania Center for AIDS Research (CFAR) P30 AI 045008, and R01-AI57757 (NHS). LLK was supported by the Training Program in Rheumatic Disease 5T32AR007442-25. NR 45 TC 19 Z9 19 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2014 VL 7 IS 5 BP 1045 EP 1057 DI 10.1038/mi.2013.121 PG 13 WC Immunology SC Immunology GA AO3FW UT WOS:000341215600003 PM 24448096 ER PT J AU Vilardaga, JP Jean-Alphonse, FG Gardella, TJ AF Vilardaga, Jean-Pierre Jean-Alphonse, Frederic G. Gardella, Thomas J. TI Endosomal generation of cAMP in GPCR signaling SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; PARATHYROID-HORMONE RECEPTOR; BETA-ADRENERGIC-RECEPTOR; LIVING CELLS; BETA(2)-ADRENERGIC RECEPTORS; PROPARATHYROID HORMONE; DISTINCT CONFORMATIONS; ENDOCYTIC PATHWAY; MOLECULAR-BASIS; ARRESTIN FOLD AB It has been widely assumed that the production of the ubiquitous second messenger cyclic AMP, which is mediated by cell surface G protein-coupled receptors (GPCRs), and its termination take place exclusively at the plasma membrane. Recent studies reveal that diverse GPCRs do not always follow this conventional paradigm. In the new model, GPCRs mediate G-protein signaling not only from the plasma membrane but also from endosomal membranes. This model proposes that following ligand binding and activation, cell surface GPCRs internalize and redistribute into early endosomes, where trimeric G protein signaling can be maintained for an extended period of time. This Perspective discusses the molecular and cellular mechanistic subtleties as well as the physiological consequences of this unexpected process, which is considerably changing how we think about GPCR signaling and regulation and how we study drugs that target this receptor family. C1 [Vilardaga, Jean-Pierre; Jean-Alphonse, Frederic G.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15260 USA. [Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Gardella, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. RP Vilardaga, JP (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15260 USA. EM jpv@pitt.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01 DK087688, R01 DK102495, P01 DK11794] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers R01 DK087688 and DK102495 (to J.-P.V.) and P01 DK11794 (project I to T.J.G.). NR 65 TC 28 Z9 28 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD SEP PY 2014 VL 10 IS 9 BP 700 EP 706 DI 10.1038/NCHEMBIO.1611 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO2DX UT WOS:000341126800004 PM 25271346 ER PT J AU Gidon, A Al-Bataineh, MM Jean-Alphonse, FG Stevenson, HP Watanabe, T Louet, C Khatri, A Calero, G Pastor-Soler, NM Gardella, TJ Vilardaga, JP AF Gidon, Alexandre Al-Bataineh, Mohammad M. Jean-Alphonse, Frederic G. Stevenson, Hilary P. Watanabe, Tomoyuki Louet, Claire Khatri, Ashok Calero, Guillermo Pastor-Soler, Nuria M. Gardella, Thomas J. Vilardaga, Jean-Pierre TI Endosomal GPCR signaling turned off by negative feedback actions of PKA and v-ATPase SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PARATHYROID-HORMONE RECEPTOR; HUMAN-FIBROBLASTS; PTH RECEPTOR; ENDOCYTOSIS; ACIDIFICATION; RETROMER; ARRESTIN; PROTEINS; CAMP AB The PTH receptor is to our knowledge one of the first G protein-coupled receptor (GPCR) found to sustain cAMP signaling after internalization of the ligand-receptor complex in endosomes. This unexpected model is adding a new dimension on how we think about GPCR signaling, but its mechanism is incompletely understood. We report here that endosomal acidification mediated by the PKA action on the v-ATPase provides a negative feedback mechanism by which endosomal receptor signaling is turned off. C1 [Gidon, Alexandre; Jean-Alphonse, Frederic G.; Louet, Claire; Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15260 USA. [Al-Bataineh, Mohammad M.; Pastor-Soler, Nuria M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Stevenson, Hilary P.; Calero, Guillermo] Univ Pittsburgh, Sch Med, Dept Med, Dept Biol Struct, Pittsburgh, PA 15213 USA. [Watanabe, Tomoyuki; Khatri, Ashok; Gardella, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. RP Gidon, A (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15260 USA. EM jpv@pitt.edu OI Gidon, Alexandre/0000-0001-9722-1253 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the US National Institutes of Health (NIH) [R01 DK087688, R01 DK102495, P01 DK11794, R01 DK08184, F32 DK097889]; Cellular Physiology Core of the 'Pittsburgh Kidney Research Center' [P30 DK079307] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the US National Institutes of Health (NIH) under Award numbers R01 DK087688 and R01 DK102495 (to J.-P.V.), P01 DK11794 (project I to T.J.G.), R01 DK08184 (to N.M.P.-S.) and F32 DK097889 (to M.M.A.-B.) as well as the Cellular Physiology Core of the P30 DK079307 'Pittsburgh Kidney Research Center'. The authors thank K.R. Hallows for his suggestions on the v-ATPase phosphorylation assay. NR 18 TC 22 Z9 22 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD SEP PY 2014 VL 10 IS 9 BP 707 EP 709 DI 10.1038/NCHEMBIO.1589 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO2DX UT WOS:000341126800005 PM 25064832 ER PT J AU De Jager, PL Srivastava, G Lunnon, K Burgess, J Schalkwyk, LC Yu, L Eaton, ML Keenan, BT Ernst, J McCabe, C Tang, AN Raj, T Replogle, J Brodeur, W Gabriel, S Chai, HS Younkin, C Younkin, SG Zou, FG Szyf, M Epstein, CB Schneider, JA Bernstein, BE Meissner, A Ertekin-Taner, N Chibnik, LB Kellis, M Mill, J Bennett, DA AF De Jager, Philip L. Srivastava, Gyan Lunnon, Katie Burgess, Jeremy Schalkwyk, Leonard C. Yu, Lei Eaton, Matthew L. Keenan, Brendan T. Ernst, Jason McCabe, Cristin Tang, Anna Raj, Towfique Replogle, Joseph Brodeur, Wendy Gabriel, Stacey Chai, High S. Younkin, Curtis Younkin, Steven G. Zou, Fanggeng Szyf, Moshe Epstein, Charles B. Schneider, Julie A. Bernstein, Bradley E. Meissner, Alex Ertekin-Taner, Nilufer Chibnik, Lori B. Kellis, Manolis Mill, Jonathan Bennett, David A. TI Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci SO NATURE NEUROSCIENCE LA English DT Article ID COGNITIVE IMPAIRMENT; SUSCEPTIBILITY LOCI; RELIGIOUS ORDERS; WIDE ASSOCIATION; COMMON VARIANTS; AGING PROJECT; GENETIC RISK; RUSH MEMORY; GENOME; NEUROPATHOLOGY AB We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network. C1 [De Jager, Philip L.; Srivastava, Gyan; Keenan, Brendan T.; Tang, Anna; Raj, Towfique; Replogle, Joseph; Chibnik, Lori B.] Brigham & Womens Hosp, Dept Neurol, Inst Neurosci, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [De Jager, Philip L.; Srivastava, Gyan; Keenan, Brendan T.; Tang, Anna; Raj, Towfique; Replogle, Joseph; Chibnik, Lori B.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [De Jager, Philip L.; Srivastava, Gyan; Raj, Towfique; Replogle, Joseph; Bernstein, Bradley E.; Chibnik, Lori B.] Harvard Univ, Sch Med, Boston, MA USA. [De Jager, Philip L.; Srivastava, Gyan; Eaton, Matthew L.; Keenan, Brendan T.; Ernst, Jason; McCabe, Cristin; Raj, Towfique; Replogle, Joseph; Chibnik, Lori B.; Kellis, Manolis] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Lunnon, Katie; Schalkwyk, Leonard C.; Mill, Jonathan] Univ Exeter, Sch Med, Exeter, Devon, England. [Lunnon, Katie; Schalkwyk, Leonard C.; Mill, Jonathan] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Burgess, Jeremy; Chai, High S.; Younkin, Curtis; Younkin, Steven G.; Zou, Fanggeng; Ertekin-Taner, Nilufer] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Burgess, Jeremy; Chai, High S.; Ertekin-Taner, Nilufer] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Yu, Lei; Schneider, Julie A.; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Eaton, Matthew L.; Ernst, Jason; Meissner, Alex; Kellis, Manolis] MIT, CSAIL, Cambridge, MA 02139 USA. [Brodeur, Wendy; Gabriel, Stacey] Broad Inst, Genet Anal Platform, Cambridge, MA USA. [Szyf, Moshe] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. [Epstein, Charles B.; Bernstein, Bradley E.; Meissner, Alex] Broad Inst, Epigen Program, Cambridge, MA USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Meissner, Alex] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP De Jager, PL (reprint author), Brigham & Womens Hosp, Dept Neurol, Inst Neurosci, Program Translat NeuroPsychiat Genom, 75 Francis St, Boston, MA 02115 USA. EM pdejager@partners.org; david_a_bennett@rush.edu RI Schalkwyk, Leonard/A-2150-2010; Mill, Jonathan/B-3276-2010; Lunnon, Katie/C-4638-2012; OI Schalkwyk, Leonard/0000-0001-7030-5756; Mill, Jonathan/0000-0003-1115-3224; Lunnon, Katie/0000-0001-7570-6065; Replogle, Joseph/0000-0003-1832-919X FU US National Institutes of Health [R01 AG036042, R01AG036836, R01 AG17917, R01AG15819, R01 AG032990, R01 AG18023, RC2 AG036547, P30 AG10161, P50 AG016574, U01 ES017155, KL2 RR024151, K25 AG041906-01, AG036039]; Siragusa Foundation; Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program; Alzheimer's Research UK FX We thank the National Institute for Health (NIHR) Biomedical Research Unit in Dementia in the South London and Maudsley NHS Foundation Trust (SLaM), Brains for Dementia Research (Alzheimer Brain Bank UK) and the donors and families who made this research possible. We also would like to thank the participants of the ROS and MAP studies for their participation in these studies. Support for this research was provided by grants from the US National Institutes of Health (R01 AG036042, R01AG036836, R01 AG17917,R01AG15819, R01 AG032990, R01 AG18023, RC2 AG036547, P30 AG10161, P50 AG016574, U01 ES017155, KL2 RR024151, K25 AG041906-01). Support was also provided by the Siragusa Foundation to N.E.-T., and the Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program to N.E.-T., S.G.Y. and F.Z. This work was funded by US National Institutes of Health grant AG036039 to J.M. and an Equipment Grant from Alzheimer's Research UK. NR 41 TC 124 Z9 124 U1 7 U2 57 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2014 VL 17 IS 9 BP 1156 EP 1163 DI 10.1038/nn.3786 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AO2DJ UT WOS:000341125400008 PM 25129075 ER PT J AU Samuel, MA Voinescu, PE Lilley, BN de Cabo, R Foretz, M Viollet, B Pawlyk, B Sandberg, MA Vavvas, DG Sanes, JR AF Samuel, Melanie A. Voinescu, P. Emanuela Lilley, Brendan N. de Cabo, Rafa Foretz, Marc Viollet, Benoit Pawlyk, Basil Sandberg, Michael A. Vavvas, Demetrios G. Sanes, Joshua R. TI LKB1 and AMPK regulate synaptic remodeling in old age SO NATURE NEUROSCIENCE LA English DT Article ID PROTEIN-KINASE AMPK; NEURONAL POLARIZATION; MOUSE RETINA; SAD KINASES; CALORIC RESTRICTION; MAMMALIAN RETINA; BIPOLAR CELLS; LIFE-SPAN; ROD; PHOSPHORYLATION AB Age-related decreases in neural function result in part from alterations in synapses. To identify molecular defects that lead to such changes, we focused on the outer retina, in which synapses are markedly altered in old rodents and humans. We found that the serine/threonine kinase LKB1 and one of its substrates, AMPK, regulate this process. In old mice, synaptic remodeling was accompanied by specific decreases in the levels of total LKB1 and active (phosphorylated) AMPK. In the absence of either kinase, young adult mice developed retinal defects similar to those that occurred in old wild-type animals. LKB1 and AMPK function in rod photoreceptors where their loss leads to aberrant axonal retraction, the extension of postsynaptic dendrites and the formation of ectopic synapses. Conversely, increasing AMPK activity genetically or pharmacologically attenuates and may reverse age-related synaptic alterations. Together, these results identify molecular determinants of age-related synaptic remodeling and suggest strategies for attenuating these changes. C1 [Samuel, Melanie A.; Voinescu, P. Emanuela; Lilley, Brendan N.; Sanes, Joshua R.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Samuel, Melanie A.; Voinescu, P. Emanuela; Lilley, Brendan N.; Sanes, Joshua R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [de Cabo, Rafa] NIA, Lab Expt Gerontol, Translat Gerontol Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Foretz, Marc; Viollet, Benoit] INSERM, Inst Cochin, U1016, Paris, France. [Foretz, Marc; Viollet, Benoit] CNRS, UMR8104, Paris, France. [Foretz, Marc; Viollet, Benoit] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Pawlyk, Basil; Sandberg, Michael A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat,Dept Opht, Boston, MA USA. [Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab,Dept Ophthalmol, Boston, MA USA. RP Sanes, JR (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM sanesj@mcb.harvard.edu RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693; Vavvas, Demetrios/0000-0002-8622-6478 FU US National Institutes of Health [AG32322, 5K99AG044444]; Damon Runyon Cancer Research Foundation; Research to Prevent Blindness; Foundation Fighting Blindness; Intramural Research Program of the National Institute on Aging FX We thank members of our laboratory for scientific discussions and advice, and A. Thanos for help with the AMPK animals. This work was funded by the US National Institutes of Health (AG32322 to J.R.S. and 5K99AG044444 to M.A. Samuel), the Damon Runyon Cancer Research Foundation (M.A. Samuel), Research to Prevent Blindness (J.R.S. and D.G.V.), the Foundation Fighting Blindness (B.P.), and the Intramural Research Program of the National Institute on Aging (R.d.C.). NR 48 TC 17 Z9 17 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2014 VL 17 IS 9 BP 1190 EP 1197 DI 10.1038/nn.3772 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AO2DJ UT WOS:000341125400012 PM 25086610 ER PT J AU Bethoux, F Rogers, HL Nolan, KJ Abrams, GM Annaswamy, TM Brandstater, M Browne, B Burnfield, JM Feng, WW Freed, MJ Geis, C Greenberg, J Gudesblatt, M Ikramuddin, F Jayaraman, A Kautz, SA Lutsep, HL Madhavan, S Meilahn, J Pease, WS Rao, N Seetharama, S Sethi, P Turk, MA Wallis, RA Kufta, C AF Bethoux, Francois Rogers, Helen L. Nolan, Karen J. Abrams, Gary M. Annaswamy, Thiru M. Brandstater, Murray Browne, Barbara Burnfield, Judith M. Feng, Wuwei Freed, Mitchell J. Geis, Carolyn Greenberg, Jason Gudesblatt, Mark Ikramuddin, Farha Jayaraman, Arun Kautz, Steven A. Lutsep, Helmi L. Madhavan, Sangeetha Meilahn, Jill Pease, William S. Rao, Noel Seetharama, Subramani Sethi, Pramod Turk, Margaret A. Wallis, Roi Ann Kufta, Conrad TI The Effects of Peroneal Nerve Functional Electrical Stimulation Versus Ankle-Foot Orthosis in Patients With Chronic Stroke: A Randomized Controlled Trial SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE functional electrical stimulation; stroke rehabilitation; foot drop; gait speed; quality of life; ankle-foot orthosis ID AMERICAN-HEART-ASSOCIATION; PERFORMANCE-MEASURES; WALKING PERFORMANCE; CHRONIC HEMIPARESIS; DROP STIMULATOR; GAIT; RELIABILITY; NEUROPROSTHESIS; SCALE; REHABILITATION AB Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. Objective. To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. Methods. In a multicenter randomized controlled trial (ClinicalTrials.gov#NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. Results. A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. Conclusions. Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance. C1 [Bethoux, Francois] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Rogers, Helen L.; Kufta, Conrad] Innovat Neurotron, Austin, TX USA. [Nolan, Karen J.] Kessler Fdn, Res Ctr, W Orange, NJ USA. [Nolan, Karen J.] Rutgers New Jersey Med Sch, Newark, NJ USA. [Abrams, Gary M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Annaswamy, Thiru M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Annaswamy, Thiru M.] UT Southwestern Med Ctr, Dallas, TX USA. [Brandstater, Murray] Loma Linda Univ, Med Ctr, Loma Linda, CA USA. [Browne, Barbara] Magee Mem Rehabilitat Ctr, Philadelphia, PA USA. [Burnfield, Judith M.] Madonna Rehabil Hosp, Lincoln, NE USA. [Feng, Wuwei] Med Univ S Carolina, Charleston, SC 29425 USA. [Freed, Mitchell J.] Florida Hosp, Neurosci & Orthoped Res Inst, Orlando, FL USA. [Geis, Carolyn] Halifax Hlth Ctr Neurosci, Daytona Beach, FL USA. [Greenberg, Jason] Helen Hayes Hosp, New York, NY USA. [Gudesblatt, Mark] South Shore Neurol Associates, Patchogue, NY USA. [Ikramuddin, Farha] Univ Minnesota Fairview, Minneapolis, MN USA. [Jayaraman, Arun] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lutsep, Helmi L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Madhavan, Sangeetha] Univ Illinois, Chicago, IL USA. [Meilahn, Jill] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA. [Pease, William S.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Rao, Noel] Marianjoy Rehabil Hosp, Wheaton, IL USA. [Seetharama, Subramani] Hartford Hosp, Hartford, CT 06115 USA. [Sethi, Pramod] Guilford Neurol Associates, Greensboro, NC USA. [Turk, Margaret A.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Wallis, Roi Ann] West Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Bethoux, F (reprint author), Cleveland Clin Fdn, Desk U10,9500 Euclid Ave, Cleveland, OH 44195 USA. EM bethouf@ccf.org OI Nolan, PhD, Karen J/0000-0002-4667-0873 FU Innovative Neurotronics FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Innovative Neurotronics. NR 38 TC 16 Z9 19 U1 7 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 EI 1552-6844 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD SEP PY 2014 VL 28 IS 7 BP 688 EP 697 DI 10.1177/1545968314521007 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AN6ST UT WOS:000340728100008 PM 24526708 ER PT J AU Cohen, SL Einarsson, JI Wang, KC Brown, D Boruta, D Scheib, SA Fader, AN Shibley, T AF Cohen, Sarah L. Einarsson, Jon I. Wang, Karen C. Brown, Douglas Boruta, David Scheib, Stacey A. Fader, Amanda N. Shibley, Tony TI Contained Power Morcellation Within an Insufflated Isolation Bag SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LAPAROSCOPIC SUPRACERVICAL HYSTERECTOMY; UTERINE MORCELLATION; MANUAL MORCELLATION; IN-VITRO; SURGERY; TISSUE; NEPHRECTOMY; MYOMECTOMY; SARCOMA AB OBJECTIVE: To describe a technique for contained power morcellation within an insufflated isolation bag at the time of uterine specimen removal during minimally invasive gynecologic procedures. METHODS: Over the study period of January 2013 to April 2014, 73 patients underwent morcellation of the uterus or myomas within an insufflated isolation bag at the time of minimally invasive hysterectomy or myomectomy. This technique involves placing the specimen into a large plastic bag within the abdomen, exteriorizing the opening of the bag, insufflating the bag within the peritoneal cavity, and then using a power morcellator within the bag to remove the specimen in a contained fashion. Procedures were performed at four institutions and included multiport laparoscopy, single-site laparoscopy, multiport robot-assisted laparoscopy, or single-site robot-assisted laparoscopy. Demographic and perioperative characteristics were collected for the cases. RESULTS: Surgical specimen morcellation within an insufflated isolation bag was successfully used in all cases. The median operative time was 114 minutes (range 32380 minutes), median estimated blood loss was 50 mL (range 10-500 mL), and the median specimen weight was 257 g (range 53-1,481 g). There were no complications related to the contained morcellation technique nor was there visual evidence of tissue dissemination outside of the isolation bag. CONCLUSION: Morcellation within an insufflated isolation bag is a feasible technique. Methods for morcellating uterine tissue in a contained manner may provide an option to minimize the risks of open power morcellation while preserving the benefits of minimally invasive surgery. C1 Brigham & Womens Hosp, Div Minimally Invas Gynecol Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Minimally Invas Gynecol Surg, Boston, MA 02114 USA. Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Div Gynecol Specialties, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Kelly Gynecol Oncol Serv, Baltimore, MD 21287 USA. Fairview Ridges Hosp, Burnsville, MN USA. RP Cohen, SL (reprint author), 75 Francis St, Boston, MA 02115 USA. EM scohen20@partners.org NR 22 TC 46 Z9 48 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2014 VL 124 IS 3 BP 491 EP 497 DI 10.1097/AOG.0000000000000421 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AO4OV UT WOS:000341320800003 PM 25162248 ER PT J AU Nicklas, JM Zera, CA England, LJ Rosner, BA Horton, E Levkoff, SE Seely, EW AF Nicklas, Jacinda M. Zera, Chloe A. England, Lucinda J. Rosner, Bernard A. Horton, Edward Levkoff, Sue E. Seely, Ellen W. TI A Web-Based Lifestyle Intervention for Women With Recent Gestational Diabetes Mellitus A Randomized Controlled Trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PHYSICAL-ACTIVITY; HEALTH BEHAVIORS; RISK-FACTORS; PREGNANCY; OBESITY; WEIGHT; HISTORY; TERM; QUESTIONNAIRE; METAANALYSIS AB OBJECTIVE: To test the feasibility and effectiveness of a Web-based lifestyle intervention based on the Diabetes Prevention Program modified for women with recent gestational diabetes mellitus to reduce postpartum weight retention. METHODS: We randomly allocated 75 women with recent gestational diabetes mellitus to either a Web-based lifestyle program (Balance after Baby) delivered over the first postpartum year or to a control group. Primary outcomes were change in body weight at 12 months from 1) first postpartum measured weight; and 2) self-reported prepregnancy weight. RESULTS: There were no significant differences in baseline characteristics between groups including age, body mass index, race, and income status. Women assigned to the Balance after Baby program (n=36, three lost to follow-up) lost a mean of 2.8 kg (95% confidence interval -4.8 to -0.7) from 6 weeks to 12 months postpartum, whereas the control group (n=39, one lost to follow-up) gained a mean of 0.5 kg (-1.4 to +2.4) (P=.022). Women in the intervention were closer to prepregnancy weight at 12 months postpartum (mean change 20.7 kg; -3.5 to +2.2) compared with women in the control arm (+4.0 kg; +1.3 to +6.8) (P=.035). CONCLUSION: A Web-based lifestyle modification program for women with recent gestational diabetes mellitus decreased postpartum weight retention. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Dept Med, Div Gen Med & Primary Care,Channing Div Network M, Boston, MA 02215 USA. Harvard Univ, Dept Global Hlth & Social Med, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. [Nicklas, Jacinda M.] Univ Colorado, Sch Med, Div Gen Internal Med, Aurora, CO 80045 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Univ S Carolina, Coll Social Work, Columbia, SC 29208 USA. RP Nicklas, JM (reprint author), Univ Colorado, Sch Med, Div Gen Internal Med, 12348 E Montview Blvd,C263, Aurora, CO 80045 USA. EM Jacinda.Nicklas@ucdenver.edu FU Intramural CDC HHS [CC999999]; NCCIH NIH HHS [T32 AT000051, T32AT000051]; NHLBI NIH HHS [9K24HL096141, K24 HL096141]; NICHD NIH HHS [K12 HD057022]; PHS HHS [MM-1094-09/09] NR 28 TC 17 Z9 17 U1 3 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2014 VL 124 IS 3 BP 563 EP 570 DI 10.1097/AOG.0000000000000420 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AO4OV UT WOS:000341320800013 PM 25162257 ER PT J AU Desai, RJ Hernandez-Diaz, S Bateman, BT Huybrechts, KF AF Desai, Rishi J. Hernandez-Diaz, Sonia Bateman, Brian T. Huybrechts, Krista F. TI Increase in Prescription Opioid Use During Pregnancy Among Medicaid-Enrolled Women Reply SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 [Desai, Rishi J.; Bateman, Brian T.; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Desai, Rishi J.; Bateman, Brian T.; Huybrechts, Krista F.] Harvard Univ, Sch Med, Boston, MA USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Desai, RJ (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2014 VL 124 IS 3 BP 638 EP 638 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AO4OV UT WOS:000341320800033 PM 25162278 ER PT J AU Bramlett, HM Dietrich, WD Marcillo, A Mawhinney, LJ Furones-Alonso, O Bregy, A Peng, Y Wu, Y Pan, J Wang, J Guo, XE Bauman, WA Cardozo, C Qin, W AF Bramlett, H. M. Dietrich, W. D. Marcillo, A. Mawhinney, L. J. Furones-Alonso, O. Bregy, A. Peng, Y. Wu, Y. Pan, J. Wang, J. Guo, X. E. Bauman, W. A. Cardozo, C. Qin, W. TI Effects of low intensity vibration on bone and muscle in rats with spinal cord injury SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone loss; Bone marrow cells; Low intensity vibration; Spinal cord injury ID WHOLE-BODY VIBRATION; LEVEL MECHANICAL VIBRATIONS; MINERAL DENSITY; LOW-MAGNITUDE; SKELETAL-MUSCLE; HIGH-FREQUENCY; GROWING RATS; RISK-FACTORS; SOST GENE; STIMULATION AB Spinal cord injury (SCI) causes rapid and marked bone loss. The present study demonstrates that low-intensity vibration (LIV) improves selected biomarkers of bone turnover and gene expression and reduces osteoclastogenesis, suggesting that LIV may be expected to benefit to bone mass, resorption, and formation after SCI. Sublesional bone is rapidly and extensively lost following spinal cord injury (SCI). Low-intensity vibration (LIV) has been suggested to reduce loss of bone in children with disabilities and osteoporotic women, but its efficacy in SCI-related bone loss has not been tested. The purpose of this study was to characterize effects of LIV on bone and bone cells in an animal model of SCI. The effects of LIV initiated 28 days after SCI and provided for 15 min twice daily 5 days each week for 35 days were examined in female rats with moderate severity contusion injury of the mid-thoracic spinal cord. Bone mineral density (BMD) of the distal femur and proximal tibia declined by 5 % and was not altered by LIV. Serum osteocalcin was reduced after SCI by 20 % and was increased by LIV to a level similar to that of control animals. The osteoclastogenic potential of bone marrow precursors was increased after SCI by twofold and associated with 30 % elevation in serum CTX. LIV reduced the osteoclastogenic potential of marrow precursors by 70 % but did not alter serum CTX. LIV completely reversed the twofold elevation in messenger RNA (mRNA) levels for SOST and the 40 % reduction in Runx2 mRNA in bone marrow stromal cells resulting from SCI. The findings demonstrate an ability of LIV to improve selected biomarkers of bone turnover and gene expression and to reduce osteoclastogenesis. The study indicates a possibility that LIV initiated earlier after SCI and/or continued for a longer duration would increase bone mass. C1 [Bramlett, H. M.; Dietrich, W. D.; Marcillo, A.; Mawhinney, L. J.; Furones-Alonso, O.; Bregy, A.] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Dept Neurol Surg, Miami, FL 33136 USA. [Bramlett, H. M.] Bruce W Carter Miami VA Med Ctr, Miami, FL USA. [Peng, Y.; Wu, Y.; Pan, J.; Bauman, W. A.; Cardozo, C.; Qin, W.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY 10468 USA. [Wang, J.; Guo, X. E.] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Bauman, W. A.; Cardozo, C.; Qin, W.] Mt Sinai Sch Med, New York, NY USA. RP Qin, W (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Weiping.Qin@mssm.edu FU Veterans Health Administration; Biomedical Laboratory Research and Development Service [BX000521]; Department of Defense [SC090504]; Miami Project to Cure Paralysis; Rehabilitation Research and Development Service [B9212-C, B0687-R] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (B9212-C and B0687-R), Biomedical Laboratory Research and Development Service (BX000521), the Department of Defense (#SC090504), and The Miami Project to Cure Paralysis. We wish to thank Drs. Edelle Field-Fote and Mark Nash for critical reading of the manuscript. NR 59 TC 5 Z9 6 U1 0 U2 7 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD SEP PY 2014 VL 25 IS 9 BP 2209 EP 2219 DI 10.1007/s00198-014-2748-8 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN6AK UT WOS:000340675200006 PM 24861907 ER PT J AU Seyyedi, M Viana, LM Nadol, JB AF Seyyedi, Mohammad Viana, Lucas M. Nadol, Joseph B., Jr. TI Within-Subject Comparison of Word Recognition and Spiral Ganglion Cell Count in Bilateral Cochlear Implant Recipients SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Cochlear implantation; Correlation, Performance; Spiral ganglion cell; Word recognition ID ELECTRODE INSERTION; AUDITORY NEURONS; HISTOPATHOLOGY; PERFORMANCE; SURVIVAL; STIMULATION; DEAFNESS; OUTCOMES; MONKEYS; DEPTH AB Objectives: Although published reports have not demonstrated a positive correlation between the number of residual spiral ganglion cells (SGCs) and word recognition scores in patients with unilateral multichannel cochlear implants, this study was designed to retest this hypothesis in patients with bilateral multichannel cochlear implants. Materials and Methods: From a pool of 133 temporal bones, all subjects with bilateral multichannel cochlear implants who were deafened bilaterally by the same etiology were studied. A total of 12 temporal bones from 6 subjects were identified and processed after death for histology. The SGCs were counted using standard techniques. The differences between left and right SGC counts as well as the differences in word recognition scores were calculated for each subject. Correlation analysis was performed between the differences of SGC counts and the differences of word recognition scores. Results: Differences in SGC counts were highly correlated with the differences in word recognition scores (R = 0.934, p = 0.006). Conclusion: This study suggests higher residual SGCs predicted better performance after implantation in a given patient. The results also support attempts to identify factors which may promote survival of SGCs. C1 [Seyyedi, Mohammad; Viana, Lucas M.; Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Seyyedi, Mohammad; Viana, Lucas M.; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Viana, Lucas M.] Univ Brasilia, Fac Hlth Sci, Brasilia, DF, Brazil. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.harvard.edu FU National Institute of Deafness and Other Communication Disorders [R01-DC000152] FX This work was supported by grant R01-DC000152 from the National Institute of Deafness and Other Communication Disorders. NR 22 TC 20 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2014 VL 35 IS 8 BP 1446 EP 1450 PG 5 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AO0RR UT WOS:000341019900026 PM 25120196 ER PT J AU van Tilburg, MJ Herrmann, BS Guinan, JJ Rauch, SD AF van Tilburg, Mark J. Herrmann, Barbara S. Guinan, John J., Jr. Rauch, Steven D. TI Normalization Reduces Intersubject Variability in Cervical Vestibular Evoked Myogenic Potentials SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Cervical vestibular evoked myogenic potential; Intersubject variability; Normalization ID TEST-RETEST RELIABILITY; STERNOCLEIDOMASTOID MUSCLE; VALUES AB Objective: Cervical vestibular evoked myogenic potentials are used to assess saccular and inferior vestibular nerve function. Normalization of the VEMP waveform has been proposed to reduce the variability in vestibular evoked myogenic potentials by correcting for muscle activation. In this study, we test the hypothesis that normalization of the raw cervical VEMP waveform causes a significant decrease in the intersubject variability. Study Design: Prospective cohort study. Setting: Large specialty hospital, department of otolaryngology. Subjects: Twenty healthy subjects were used in this study. Intervention: All subjects underwent cervical vestibular evoked myogenic potential testing using short tone bursts at 250, 500, 750, and 1,000 Hz. Both intersubject and intrasubject variability was assessed. Main Outcome Measures: Variability between raw and normalized peak-to-peak amplitudes was compared using the coefficient of variation. Intrasubject variability was assessed using the intraclass correlation coefficient and interaural asymmetry ratio. Results: cVEMPs were present in most ears. Highest peak-to-peak amplitudes were recorded at 750 Hz. Normalization did not alter cVEMP tuning characteristics. Normalization of the cVEMP response caused a significant reduction in intersubject variability of the peak-to-peak amplitude. No significant change was seen in the intrasubject variability. Conclusion: Normalization significantly reduces cVEMP intersubject variability in healthy subjects without altering cVEMP characteristics. By reducing cVEMP amplitude variation due to nonsaccular, muscle-related factors, cVEMP normalization is expected to improve the ability to distinguish between healthy and pathologic responses in the clinical application of cVEMP testing. C1 [van Tilburg, Mark J.; Rauch, Steven D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Herrmann, Barbara S.; Guinan, John J., Jr.; Rauch, Steven D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM steven_rauch@meei.harvard.edu NR 15 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2014 VL 35 IS 8 BP E222 EP E227 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AO0RR UT WOS:000341019900002 PM 24836595 ER PT J AU Tsai, A McDonald, AG Rosenberg, AE Gupta, R Kleinman, PK AF Tsai, Andy McDonald, Anna G. Rosenberg, Andrew E. Gupta, Rajiv Kleinman, Paul K. TI High-resolution CT with histopathological correlates of the classic metaphyseal lesion of infant abuse (vol 44, pg 124, 2014) SO PEDIATRIC RADIOLOGY LA English DT Correction C1 [Tsai, Andy; Kleinman, Paul K.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [McDonald, Anna G.] Off Chief Med Examiner, Boston, MA USA. [Rosenberg, Andrew E.] Univ Miami Hosp, Dept Pathol, Miami, FL USA. [Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Tsai, A (reprint author), Boston Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM andy.tsai@childrens.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 2014 VL 44 IS 9 BP 1190 EP 1190 DI 10.1007/s00247-014-3111-0 PG 1 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AN8RA UT WOS:000340870400020 ER PT J AU Doumit, G Abouhassan, W Yaremchuk, MJ AF Doumit, Gaby Abouhassan, William Yaremchuk, Michael J. TI Aesthetic Refinements in the Treatment of Graves Ophthalmopathy SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID TRANSPALPEBRAL DECOMPRESSION; ENDOCRINE OPHTHALMOPATHY; INTRAORBITAL FAT; ORBITOPATHY; EXPERIENCE; OPERATIONS; REMOVAL; DISEASE AB Background: Graves ophthalmopathy is a chronic, multisystem, autoimmune disorder characterized by increased volume of intraorbital fat and hypertrophic extraocular muscles. Proptosis, impaired ocular motility, diplopia, lid retraction, and impaired visual acuity are treated with orbit decompression and fat reduction. The authors present the addition of skeletal augmentation to further improve periorbital aesthetics. Methods: Through a transconjunctival with lateral canthotomy incision, a balanced orbital decompression was executed, removing medial and lateral walls and medial floor. Intraorbital fat was excised. All patients underwent placement of porous polyethylene infraorbital rim implants and midface soft-tissue elevation, increasing inferior orbital rim projection and improving the globe-cheek relationship. From 2009 to 2012, 13 patients (11 female and two male; 26 eyes) with Graves ophthalmopathy underwent surgery at two institutions. Outcomes were evaluated for improvements of proptosis, diplopia, dry eye symptoms, and cosmetic satisfaction. Results: Postoperative follow-up ranged from 0.5 to 3 years (median, 1.5 years). The mean improvement on Hertel exophthalmometry was 5.4 mm. Diplopia resolved in three patients (23 percent). No patients had worsening diplopia, and 12 (92 percent) discontinued use of eye lubricants. All patients had cosmetic satisfaction. One patient suffered temporary inferior orbital nerve paresthesia. There were no infections, hematomas, or ocular complications. Conclusions: Skeletal augmentation is a useful adjunct to orbital decompression and fat excision for treating Graves ophthalmopathy. Balanced orbital decompression with infraorbital rim implants is reliable, effective, and safe, with good, lasting results. Resolution of ocular symptoms is improved, as are the patient's personal well-being and social life, with a high-benefit to low-risk. C1 Cleveland Clin, Dept Plast Surg, Inst Dermatol & Plast Surg, Cleveland, OH USA. Univ Cincinnati, Sch Med, Dept Surg, Div Plast Reconstruct & Hand Burn Surg, Cincinnati, OH 45267 USA. Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Abouhassan, W (reprint author), Univ Cincinnati, Coll Med, Dept Surg, Div Plast Reconstruct & Hand Burn Surg, 231 Albert Sabin Way,POB 670558, Cincinnati, OH 45267 USA. EM william.abouhassn@uc.edu NR 9 TC 0 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 2014 VL 134 IS 3 BP 519 EP 526 DI 10.1097/PRS.0000000000000453 PG 8 WC Surgery SC Surgery GA AO1JU UT WOS:000341069200015 PM 24804641 ER PT J AU Inslicht, SS Richards, A Madden, E Rao, MN O'Donovan, A Talbot, LS Rucker, E Metzler, TJ Hauger, RL Neylan, TC AF Inslicht, Sabra S. Richards, Anne Madden, Erin Rao, Madhu N. O'Donovan, Aoife Talbot, Lisa S. Rucker, Evelyn Metzler, Thomas J. Hauger, Richard L. Neylan, Thomas C. TI Sex differences in neurosteroid and hormonal responses to metyrapone in posttraumatic stress disorder SO PSYCHOPHARMACOLOGY LA English DT Article DE Sex differences; Posttraumatic stress disorder; Progesterone; Allopregnanolone; ACTH; Metyrapone ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; GABA(A) RECEPTOR FUNCTION; DEXAMETHASONE-SUPPRESSION; PARAVENTRICULAR NUCLEUS; GLUCOCORTICOID-RECEPTOR; GENDER-DIFFERENCES; RAT HYPOTHALAMUS; COMBAT VETERANS; MESSENGER-RNA AB Mechanisms contributing to sex differences in the regulation of acute stress responsivity and their effect on the increased incidence of posttraumatic stress disorder (PTSD) in women are poorly understood. The reproductive hormone, progesterone, through conversion to allopregnanolone (ALLO), suppresses the hypothalamic pituitary adrenal (HPA) axis and has potent anxiolytic effects. The potential that progesterone and allopregnanolone reactivity modulate HPA axis responses and account for sex differences in PTSD has not been previously examined. The present study examined the effects of sex and PTSD on adrenocorticotropic hormone (ACTH), progesterone, and allopregnanolone responses to metyrapone and whether progesterone and allopregnanolone reactivity could affect the ACTH response in PTSD. Healthy medication-free male and premenopausal follicular phase female participants with chronic PTSD (n = 43; 49 % female) and controls (n = 42; 50 % female) completed an overnight metyrapone challenge and ACTH, progesterone, and allopregnanolone were obtained by repeated blood sampling. The increase in ACTH response to metyrapone was higher in PTSD subjects compared to controls and in women compared to men. Contrary to our initial prediction of an inverse relationship, progesterone and allopregnanolone were positively associated with ACTH. Progesterone and allopregnanolone partially mediated the relationship between PTSD and ACTH. Our findings of increased ACTH to metyrapone in PTSD and in women may reflect heightened hypothalamic CRF hypersecretion. Progesterone and allopregnanolone partially mediated the ACTH response in PTSD. Further characterizing sex differences in these processes will advance our understanding of the pathophysiology of PTSD, and may ultimately lead to better-targeted, more effective treatment. C1 [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; Rao, Madhu N.; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] San Francisco VA Med Ctr, Stress & Hlth Res Program, San Francisco, CA 94121 USA. [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; Rao, Madhu N.; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] Vet Hlth Res Inst, NCIRE, San Francisco, CA 94121 USA. [Rao, Madhu N.] Univ Calif San Francisco, Dept Med, Div Endocrinol, San Francisco, CA 94143 USA. [Hauger, Richard L.] San Diego VA Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA 92161 USA. [Hauger, Richard L.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. RP Inslicht, SS (reprint author), San Francisco VA Med Ctr, Stress & Hlth Res Program, 4150 Clement St 116P, San Francisco, CA 94121 USA. EM sabra.inslicht@ucsf.edu FU National Institute for Mental Health [5R01MH073978-04, 5R34MH077667-03]; Veterans Health Research Institute; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration; Clinical Research Center of the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 RR024131]; BLR&D Merit Review grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; VA Center of Excellence for Stress and Mental Health (CESAMH); NIH/NIMH [MH074697] FX This research and development project was conducted by the Stress and Health Research Program at the San Francisco VA Medical Center and is made possible by a research grant that was awarded and administered by the US Army Medical Research and Materiel Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD (SI: W81XWH-05-2-0094). This study was also supported by the National Institute for Mental Health (TCN: 5R01MH073978-04, 5R34MH077667-03), the Veterans Health Research Institute, the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration, and the Clinical Research Center of the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. RLH was supported by a BLR&D Merit Review grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, the VA Center of Excellence for Stress and Mental Health (CESAMH), and a NIH/NIMH (MH074697) RO1 grant. NR 106 TC 3 Z9 3 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2014 VL 231 IS 17 BP 3581 EP 3595 DI 10.1007/s00213-014-3621-3 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AN6DN UT WOS:000340684300030 PM 24952092 ER PT J AU Montgomery, AE Fargo, JD Kane, V Culhane, DP AF Montgomery, Ann Elizabeth Fargo, Jamison D. Kane, Vincent Culhane, Dennis P. TI Development and Validation of an Instrument to Assess Imminent Risk of Homelessness Among Veterans SO PUBLIC HEALTH REPORTS LA English DT Article ID PREVENTION; ASSISTANCE AB Objectives. Veterans are overrepresented within the homeless population compared with their non-veteran counterparts, particularly when controlling for poverty. The U.S. Department of Veterans Affairs (VA) aims to prevent new episodes of homelessness by targeting households at greatest risk; however, there are no instruments that systematically assess veterans' risk of homelessness. We developed and tested a brief screening instrument to identify imminent risk of homelessness among veterans accessing VA health care. Methods. The study team developed initial assessment items, conducted cognitive interviews with veterans experiencing homelessness, refined pilot items based on veterans' and experts' feedback and results of psychometric analyses, and assigned weights to items in the final instrument to indicate a measure of homelessness risk. Results. One-third of veterans who responded to the field instrument reported imminent risk of homelessness (i.e., housing instability in the previous 90 days or expected in the next 90 days). The reliability coefficient for the instrument was 0.85, indicating good internal consistency. Veterans who had a recent change in income, had unpaid housing expenses, were living temporarily with family and friends, needed help to get or keep housing, and had poor rental and credit histories were more likely to report a risk of homelessness than those who did not: Conclusion. This study provides the field with an instrument to identify individuals and households at risk of or experiencing homelessness, which is necessary to prevent and end homelessness. In addition, it supports VA's investment in homelessness prevention and rapid rehousing services for veterans who are experiencing or are at risk for homelessness. C1 [Montgomery, Ann Elizabeth; Fargo, Jamison D.; Kane, Vincent; Culhane, Dennis P.] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA 19104 USA. [Fargo, Jamison D.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Montgomery, AE (reprint author), US Dept Vet Affairs, Natl Ctr Homelessness Vet, 4100 Chester Ave,Ste 201, Philadelphia, PA 19104 USA. EM ann.montgomery2@va.gov NR 16 TC 2 Z9 2 U1 0 U2 9 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2014 VL 129 IS 5 BP 428 EP 436 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO2DC UT WOS:000341124700005 PM 25177054 ER PT J AU Sprangers, MAG Thong, MSY Bartels, M Barsevick, A Ordonana, J Shi, QL Wang, XS Klepstad, P Wierenga, EA Singh, JA Sloan, JA AF Sprangers, Mirjam A. G. Thong, Melissa S. Y. Bartels, Meike Barsevick, Andrea Ordonana, Juan Shi, Qiuling Wang, Xin Shelley Klepstad, Pal Wierenga, Eddy A. Singh, Jasvinder A. Sloan, Jeff A. TI Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update SO QUALITY OF LIFE RESEARCH LA English DT Review DE Biological pathways; Genes; Molecular markers; Quality of life; Patient-reported outcomes (PROs) ID GENOME-WIDE ASSOCIATION; BREAST-CANCER SURVIVORS; METHYLTRANSFERASE GENOTYPE VAL158MET; SINGLE NUCLEOTIDE POLYMORPHISMS; MAJOR DEPRESSIVE DISORDER; FUNCTIONAL POLYMORPHISM; PERSONALITY DIMENSIONS; SLEEP DISTURBANCE; SYMPTOM CLUSTER; MENTAL-HEALTH AB There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL. C1 [Sprangers, Mirjam A. G.; Thong, Melissa S. Y.] Univ Amsterdam, Acad Med Ctr, Dept Med Psychol J3 211, NL-1105 AZ Amsterdam, Netherlands. [Thong, Melissa S. Y.] Tilburg Univ, Ctr Res Psychol Somat Dis CoRPS, NL-5000 LE Tilburg, Netherlands. [Bartels, Meike] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Barsevick, Andrea] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Ordonana, Juan] Univ Murcia, Dept Human Anat & Psychobiol, Murcia, Spain. [Shi, Qiuling; Wang, Xin Shelley] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Klepstad, Pal] St Olavs Univ Hosp, Chair Dept Intens Care Med, Trondheim, Norway. [Wierenga, Eddy A.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Rochester, MN USA. [Sloan, Jeff A.] Mayo Clin, Sect Canc Ctr Stat, Dept Hlth Sci, Div Biomed Stat & Informat, Rochester, MN USA. RP Sprangers, MAG (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Med Psychol J3 211, Meibergdreef 15, NL-1105 AZ Amsterdam, Netherlands. EM m.a.sprangers@amc.uva.nl RI Ordonana, Juan/M-1196-2014; Bartels, Meike/D-4492-2014; OI Ordonana, Juan/0000-0001-7779-6017; Bartels, Meike/0000-0002-9667-7555; Barsevick, Andrea/0000-0003-1829-6826 FU Social Psychology Fellowship from the Dutch Cancer Society [UVT2011-4960] FX The present research is supported in part by a Social Psychology Fellowship from the Dutch Cancer Society to Melissa Thong (#UVT2011-4960). NR 66 TC 15 Z9 15 U1 3 U2 21 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD SEP PY 2014 VL 23 IS 7 BP 1997 EP 2013 DI 10.1007/s11136-014-0656-1 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AN4ZF UT WOS:000340597900009 PM 24604075 ER PT J AU Dekker, SE Sillesen, M Bambakidis, T Jin, G Liu, BL Boer, C Johansson, PI Halaweish, I Maxwell, J Alam, HB AF Dekker, Simone E. Sillesen, Martin Bambakidis, Ted Jin, Guang Liu, Baoling Boer, Christa Johansson, Par I. Halaweish, Ihab Maxwell, Jake Alam, Hasan B. TI Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs SO SURGERY LA English DT Article ID FRESH-FROZEN PLASMA; LARGE-ANIMAL-MODEL; PREHOSPITAL MANAGEMENT; INTRACRANIAL-PRESSURE; MASSIVE TRANSFUSION; E-SELECTIN; RESUSCITATION; BLOOD; COAGULOPATHY; NEUTROPHILS AB Background. Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related deaths. These insults disrupt coagulation and endothelial systems. This study investigated whether previously reported differences in lesion size and brain swelling during normal saline (NS), colloids (Hextend [HEX]), and fresh frozen plasma (HP) resuscitation are associated with differential effects on coagulation and endothelial systems. Methods. We subjected 15 Yorkshire swine to TBI and HS (40% blood volume), and kept in HS for 2 hours before resuscitation with NS, HEX, or REP Markers of endothelial activation (E-selectin, Intercellular adhesion molecule [ICAM]-1), coagulation activation (prothrombin fragment 1 + 2), and natural anticoagulation (activated protein C (aPC]) were determined in serum and brain whole cell lysates. Results. Serum levels of aPC were greater in the NS group (203 +/- 30 pg/mL) compared with HEX (77 +/- 28 pg/mL; P = .02) and HP (110 +/- 28 pg/mL; P = .09), as was PF 1 + 2 in the brain when compared with FFP (PF 1 + 2, 89 +/- 46 vs 37 +/- 14 ng/mL; P = .035). Brain E-selectin was greater in the NS group compared with FFP (3.36 +/- 0.02 vs 3.31 +/- 0.01 ng/mL; P = .029). Circulating ICAM-1 levels were increased in the NS group (151 +/- 9 ng/mL) compared with the HEX (100 +/- 9 ng/mL; P < .01) and REP (108 +/- 9 ng/mL; P = .01). Conclusion. In this clinically realistic large animal model of TBI + HS, NS resuscitation was associated with an early activation of coagulation, natural anticoagulation, and endothelial systems, compared with HEX and FFP. C1 [Dekker, Simone E.; Bambakidis, Ted; Jin, Guang; Liu, Baoling; Halaweish, Ihab; Maxwell, Jake; Alam, Hasan B.] Univ Michigan Hosp, Dept Surg, Ann Arbor, MI 48109 USA. [Dekker, Simone E.; Boer, Christa] Vrije Univ Amsterdam, Med Ctr, Inst Cardiovasc Res, Dept Anesthesiol, Amsterdam, Netherlands. [Sillesen, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care,Dept S, Boston, MA USA. [Sillesen, Martin] Copenhagen Univ Hosp, Dept Surg, Hillerod, Denmark. [Johansson, Par I.] Univ Copenhagen, Rigshosp, Capital Reg Blood Bank, DK-2100 Copenhagen, Denmark. [Johansson, Par I.] Univ Texas Houston, Sch Med, Dept Surg, Ctr Translat Injury Res CeTIR, Houston, TX USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu RI Johansson, Par/P-9283-2015 OI Johansson, Par/0000-0001-9778-5964 FU US Army Medical Research Material Command [00521959]; Lundbeck Foundation [R134-A12630] FX Funded by a grant from the US Army Medical Research Material Command GRANTT00521959 (to H.B.A.) and a grant from the Lundbeck Foundation R134-A12630 (to M.S and P.I.J). NR 41 TC 9 Z9 9 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2014 VL 156 IS 3 BP 556 EP 563 DI 10.1016/j.surg.2014.04.016 PG 8 WC Surgery SC Surgery GA AO3KN UT WOS:000341228200009 PM 24953275 ER PT J AU Tol, JAMG Gouma, DJ Bassi, C Dervenis, C Montorsi, M Adham, M Andren-Sandberg, A Asbun, HJ Bockhorn, M Buchler, MW Conlon, KC Fernandez-Cruz, L Fingerhut, A Friess, H Hartwig, W Izbicki, JR Lillemoe, KD Milicevic, MN Neoptolemos, JP Shrikhande, SV Vollmer, CM Yeo, CJ Charnley, RM AF Tol, Johanna A. M. G. Gouma, Dirk J. Bassi, Claudio Dervenis, Christos Montorsi, Marco Adham, Mustapha Andren-Sandberg, Ake Asbun, Horacio J. Bockhorn, Maximilian Buechler, Markus W. Conlon, Kevin C. Fernandez-Cruz, Laureano Fingerhut, Abe Friess, Helmut Hartwig, Werner Izbicki, Jakob R. Lillemoe, Keith D. Milicevic, Miroslav N. Neoptolemos, John P. Shrikhande, Shailesh V. Vollmer, Charles M. Yeo, Charles J. Charnley, Richard M. CA Int Study Grp Pancreatic Surg TI Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: A consensus statement by the International Study Group on Pancreatic Surgery (ISGPS) SO SURGERY LA English DT Article ID LYMPH-NODE METASTASIS; EXTENDED RETROPERITONEAL LYMPHADENECTOMY; ANTEGRADE MODULAR PANCREATOSPLENECTOMY; CELIAC AXIS RESECTION; PERIAMPULLARY ADENOCARCINOMA; RADICAL PANCREATECTOMY; DISTAL PANCREATECTOMY; PROGNOSTIC-FACTOR; BODY CANCER; PANCREATICODUODENECTOMY AB Background. The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy. Methods. During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience. Results. The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the left side of the;superior mesenteric artery (SMA) and around the celiac trunk, splenie artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Ln's. Consensus was reached on selectively removing suspected Ln's outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive. Conclusion. Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Ln's outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies. C1 [Tol, Johanna A. M. G.; Gouma, Dirk J.] Univ Amsterdam, Acad Med Ctr, Dept Surg, NL-1105 AZ Amsterdam, Netherlands. [Bassi, Claudio] Univ Verona, Pancreas Inst, Dept Surg & Oncol, I-37100 Verona, Italy. [Dervenis, Christos] Agia Olga Hosp, Dept Surg 1, Athens, Greece. [Montorsi, Marco] Univ Milan, IRCCS, Inst Clin Humanitas, Dept Gen Surg, Milan, Italy. [Adham, Mustapha] Hop Edouard Herriot, Dept HPB Surg, Lyon, France. [Andren-Sandberg, Ake] Karolinska Univ Hosp, Karolinska Inst, Dept Surg, Stockholm, Sweden. [Asbun, Horacio J.] Mayo Clin, Dept Gen Surg, Jacksonville, FL 32224 USA. [Bockhorn, Maximilian; Izbicki, Jakob R.] Univ Hosp Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Hamburg, Germany. [Buechler, Markus W.; Hartwig, Werner] Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany. [Conlon, Kevin C.] Univ Dublin, Trinity Coll, Professorial Surg Unit, Dublin, Ireland. [Fernandez-Cruz, Laureano] Univ Barcelona, Hosp Clin Barcelona, Dept Surg, Barcelona, Spain. [Fingerhut, Abe] Univ Athens, Hippokrateon Hosp, Dept Digest Surg 1, Athens, Greece. [Fingerhut, Abe] Med Univ Graz, Dept Surg, Sect Surg Res, Graz, Austria. [Friess, Helmut] Tech Univ Munich, Klinikum Rechts Isar, Dept Surg, D-80290 Munich, Germany. [Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Milicevic, Miroslav N.] Univ Belgrade, Clin Ctr Serbia, Surg Clin 1, Belgrade, Serbia. [Neoptolemos, John P.] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool Canc Res UK Ctr, Liverpool L69 3BX, Merseyside, England. [Shrikhande, Shailesh V.] Tata Mem Hosp, Dept Gastrointestinal & HPB Surg Oncol, Bombay 400012, Maharashtra, India. [Vollmer, Charles M.] Univ Penn, Dept Surg, Penn Med, Philadelphia, PA 19104 USA. [Yeo, Charles J.] Thomas Jefferson Univ, Dept Surg, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA. [Charnley, Richard M.] Freeman Rd Hosp, Dept HPB & Transplant Surg, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England. RP Gouma, DJ (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM D.J.Gouma@amc.nl RI Adham, Mustapha/A-1270-2017 NR 46 TC 68 Z9 82 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2014 VL 156 IS 3 BP 591 EP 600 DI 10.1016/j.surg.2014.06.016 PG 10 WC Surgery SC Surgery GA AO3KN UT WOS:000341228200014 PM 25061003 ER PT J AU Sahora, K Fernandez-del Castillo, C Dong, F Marchegiani, G Thayer, SP Ferrone, CR Sahani, DV Brugge, WR Warshaw, AL Lillemoe, KD Mino-Kenudson, M AF Sahora, Klaus Fernandez-del Castillo, Carlos Dong, Fei Marchegiani, Giovanni Thayer, Sarah P. Ferrone, Cristina R. Sahani, Dushyant V. Brugge, William R. Warshaw, Andrew L. Lillemoe, Keith D. Mino-Kenudson, Mari TI Not all mixed-type intraductal papillary mucinous neoplasms behave like main-duct lesions: Implications of minimal involvement of the main pancreatic duct SO SURGERY LA English DT Article ID INTERNATIONAL CONSENSUS GUIDELINES; MALIGNANCY; MANAGEMENT; PREDICTORS; PROGNOSIS; RESECTION; TUMORS; CYSTS AB Background. The malignant potential of intraductal mucinous neoplasm of the pancreas (IPMN) is associated closely with main pancreatic duct (MPD) involvement. Because mixed-type IPMN is thought to have the same malignant potential as that of main-duct (MD)-IPMN, resection is recommended; however, the biological nature of mixed-type IPMN with only minimal involvement of MPD (min-mix-IPMN) may be different. Methods. A prospective database of 404 resected IPMNs was re-reviewed to subclassify mixed-type IPMNs. We defined min-mix-IPMN as absence of gross abnormalities (except for dilatation) of MPD and noncircumferential microscopic involvement of MPD limited to few sections. Results. We identified 46 min-mix-IPMNs, 163 IPMNs with extensive involvement of MPD (ex-mix-IPMN), 175 branch-duct (BD)-IPMNs, and 20 MD-IPMNs. The majority of min-mix-IPMNs were found incidentally and increased cyst size on surveillance was the leading operative indication. The median diameter of MPD was 2 mm in min-mix-IPMN versus 9 mm in ex-mix-IPMN (P < .0001), and cysts 10 mm were present in 62% of ex-mix-IPMNs versus 93% of min-mix-IPMNs (P < .0001). Most importantly, the vast majority of min-mix-IPMNs exhibited gastric-type epithelium, similar to BD-IPMNs, whereas intestinal-type epithelium was present in half of ex-mix-IPMNs, similar to MD-IPMNs. The prevalence of high-grade lesions was less in min-mix-1PMN than ex-mix-IPMN (P < .0001). These differences were reflected in better disease-specific outcomes of min-mix-IPMN compared with ex-mix-IPMN (P = .046). Conclusion. Min-mix-IPMN often presents with no MPD dilation and is an incidental finding by microscopic examination. min-mix-IPMN shares the pathologic features and less aggressive biology with BD-IPMN. We propose that min-mix-IPMN be categorized differently than ex-mix-IPMN. C1 [Sahora, Klaus; Fernandez-del Castillo, Carlos; Marchegiani, Giovanni; Thayer, Sarah P.; Ferrone, Cristina R.; Warshaw, Andrew L.; Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dong, Fei; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Brugge, William R.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Sahora, Klaus; Fernandez-del Castillo, Carlos; Marchegiani, Giovanni; Thayer, Sarah P.; Ferrone, Cristina R.; Warshaw, Andrew L.; Lillemoe, Keith D.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Sahani, Dushyant V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Brugge, William R.] Harvard Univ, Sch Med, Dept Internal Med, Boston, MA USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org FU National Cancer Institute [P01 CA117969, R01 CA169086, P50 CA127003] FX S.P.T. was supported by National Cancer Institute grants P01 CA117969 and R01 CA169086. M.M.-K. was supported by National Cancer Institute grants P50 CA127003 and R01 CA169086. NR 26 TC 22 Z9 22 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2014 VL 156 IS 3 BP 611 EP 621 DI 10.1016/j.surg.2014.04.023 PG 11 WC Surgery SC Surgery GA AO3KN UT WOS:000341228200016 PM 25081232 ER PT J AU Hutter, MM AF Hutter, Matthew M. TI Commentary on: "Association between quality of care and complications following abdominal surgery" SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. EM mhutter@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2014 VL 156 IS 3 BP 640 EP 641 DI 10.1016/j.surg.2014.05.019 PG 2 WC Surgery SC Surgery GA AO3KN UT WOS:000341228200019 PM 25175504 ER PT J AU Sheridan, RL AF Sheridan, Robert L. TI Commentary on: Surgical skills needed for humanitarian missions in resource-limited settings: Common operative procedures performed at Medecins Sans Frontieres facilities SO SURGERY LA English DT Editorial Material C1 [Sheridan, Robert L.] Massachusetts Gen Hosp, Boston Shriners Hosp Children, Dept Surg, Boston, MA 02114 USA. [Sheridan, Robert L.] Harvard Univ, Sch Med, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Hosp Children, Dept Surg, 51 Blossom St, Boston, MA 02114 USA. EM rsheridan@mgh.harvard.edu 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 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2014 VL 156 IS 3 BP 650 EP 650 DI 10.1016/j.surg.2014.05.001 PG 1 WC Surgery SC Surgery GA AO3KN UT WOS:000341228200021 PM 24984803 ER PT J AU Goldstein, AM AF Goldstein, Allan M. TI Commentary on: Why was there no mention of informed consent and ethics committee approval in a prospective trial? SO SURGERY LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02138 USA. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02138 USA. EM agoldstein@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2014 VL 156 IS 3 BP 735 EP 736 DI 10.1016/j.surg.2014.02.024 PG 2 WC Surgery SC Surgery GA AO3KN UT WOS:000341228200034 PM 24792509 ER PT J AU Jakobiec, FA Rai, R Lefebvre, DR AF Jakobiec, Frederick A. Rai, Ruju Lefebvre, Daniel R. TI Papillary hidradenoma of the eyelid margin: clinical and immunohistochemical observations further supporting an apocrine rather than an eccrine origin SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE eyelid; apocrine gland; eccrine gland; apocrine adenoma; papillary hidradenoma; syringocystadenoma papilliferum; immunohistochemistry; gross cystic disease fluid protein-15; cytokeratin 7; myoepithelium; androgen receptor ID SWEAT GLAND CARCINOMA; ANDROGEN RECEPTOR; SYRINGOCYSTADENOMA PAPILLIFERUM; DIFFERENTIAL-DIAGNOSIS; CHONDROID SYRINGOMA; SEBACEOUS GLANDS; TUMORS; CYSTADENOMA; NEOPLASMS; ADENOMA AB A 46-year-old woman was evaluated for a "recurring papilloma" of the left medial upper eyelid margin. Beneath the papillary lesion medial to the punctum was a 5-mm diameter cutaneous mass thought to be cystic. After excisional biopsy, histopathologic analysis documented the presence of an epidermal keratinizing squamous papilloma surmounting a circumscribed dermal papillary hidradenoma composed of deeply eosinophilic columnar cells. Additionally, there was intraductal proliferation of tumor extending toward a subclinical poral opening through the epidermis. Immunohistochemistry proved the apocrine nature of the benign, non-cystic lesion by virtue of its nuclear androgen receptor and cytoplasmic gross-cystic disease fluid protein-15 positivity, along with its smooth muscle actin-positive myoepithelial layer. This and prior cases establish that apocrine tumors, both benign and malignant, are strictly localized at or near the eyelid margin where only apocrine glands are found. These tumors are more often papillary than solid adenomas, and most exceptionally can be malignant. We review the differential diagnosis of simulating eccrine eyelid tumors. We recommend wide local excision for benign lesions, in view of possible intraductal extension that can be eccentric to the main tumor and the miniscule potential for malignant transformation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Jakobiec, Frederick A.; Rai, Ruju] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, Boston, MA 02114 USA. [Lefebvre, Daniel R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Rai, Ruju; Lefebvre, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St Suite 328, Boston, MA 02114 USA. EM Fred_jakobiec@meei.harvard.edu NR 41 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD SEP-OCT PY 2014 VL 59 IS 5 BP 540 EP 547 DI 10.1016/j.survophthal.2014.01.002 PG 8 WC Ophthalmology SC Ophthalmology GA AN6WO UT WOS:000340739300006 PM 24661803 ER PT J AU Kaiser, J Dietrich, J AF Kaiser, Jochen Dietrich, Joerg TI Challenges in research on the neural basis of aEurochemobrain" SO TRANSLATIONAL NEUROSCIENCE LA English DT Editorial Material DE Chemotherapy; Cognitive impairment; Brain imaging ID BREAST-CANCER SURVIVORS; ADJUVANT CHEMOTHERAPY; COGNITIVE IMPAIRMENT; DOCETAXEL CHEMOTHERAPY; BRAIN STRUCTURE; WORKING-MEMORY; WHITE-MATTER; CHEMOBRAIN; DYSFUNCTION; NEUROGENESIS AB Cancer survivors treated with chemotherapy frequently complain about impairment of cognitive functions including attention and memory. While the contribution of factors like psychological distress, anxiety or fatigue to this "chemobrain" syndrome has been discussed, studies in rodents have demonstrated the toxicity of various chemotherapeutic substances to the adult central nervous system. In humans, structural brain imaging has revealed both reduced gray and white matter volume and decreased white matter integrity related to chemotherapeutic treatment. Studies of brain function have found alterations in brain activation patterns during different types of tasks. Nevertheless, further clinical research using prospective designs in larger samples is required to better understand the relationship between chemotherapy and cognitive deficits. Variables that need to be considered more systematically include drug dose, genetic variations, and psychological factors. Assessing both electroencephalographic and hemodynamic responses during tasks at different stages of the processing hierarchy and at different difficulty levels should help in pinpointing the cortical processes affected by chemotherapy. C1 [Kaiser, Jochen] Goethe Univ Frankfurt, Inst Med Psychol, Fac Med, D-60528 Frankfurt, Germany. [Dietrich, Joerg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MGH Canc Ctr, Boston, MA 02114 USA. [Dietrich, Joerg] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. RP Kaiser, J (reprint author), Goethe Univ Frankfurt, Inst Med Psychol, Fac Med, D-60528 Frankfurt, Germany. EM j.kaiser@med.uni-frankfurt.de NR 47 TC 2 Z9 2 U1 0 U2 10 PU DE GRUYTER OPEN LTD PI WARSAW PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND SN 2081-3856 EI 2081-6936 J9 TRANSL NEUROSCI JI Transl. Neurosci. PD SEP PY 2014 VL 5 IS 3 BP 222 EP 225 DI 10.2478/s13380-014-0223-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA AN5WP UT WOS:000340663000008 ER PT J AU Biello, KB Rosenberger, JG Novak, DS Robertson, AM Mayer, KH Mimiaga, MJ AF Biello, Katie B. Rosenberger, Joshua G. Novak, David S. Robertson, Angela M. Mayer, Kenneth H. Mimiaga, Matthew J. TI Epidemiology of Sexual Health in the Virtual Environment: A Multinational Online Survey of Spanish- and Portuguese-Speaking Men who use an Internet Sexual Networking Site SO AIDS AND BEHAVIOR LA English DT Article DE Sexual risk behaviors; HIV; Sexually transmitted infections; Men who have sex with men; Internet sexual networking websites; International surveillance; Latin America ID UNITED-STATES; SENTINEL SURVEILLANCE; LATIN-AMERICA; HIV RISK; INFECTION; BEHAVIORS; MSM; PREVALENCE; COUNTRIES; TRENDS AB There is limited data on the sexual health of users of sexual networking websites for men who have sex with men (MSM) in Latin America. Members of a MSM-targeted social/sexual networking website in Latin America, Spain, and Portugal participated in an online sexual health survey. Among 36,063 respondents, nearly 90 % reported having anal or vaginal intercourse in the past 3 months. Among sexually active men, 53.2 % used condoms inconsistently. In the past year, 54 % of respondents reported undergoing sexually transmitted infections (STI) testing and 67 % reported testing yearly or more often for HIV. Self-reported HIV prevalence was 9.1 %. Differences were seen by geographic region. Unprotected intercourse with partners of different or unknown HIV status was associated with recent STI diagnosis (OR = 1.83, t = 13.15, d.f. = 21, p < .001) and HIV diagnosis (OR = 2.20, t = 14.00, d.f. = 21, p < .001). Online surveys are a promising tool for HIV/STI surveillance and prevention internationally to reach an important subset of MSM. C1 [Biello, Katie B.; Robertson, Angela M.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Biello, Katie B.; Robertson, Angela M.; Mayer, Kenneth H.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Rosenberger, Joshua G.] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA. [Novak, David S.] Online Buddies Inc, OLB Res Inst, Cambridge, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Biello, KB (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM kbiello@fenwayhealth.org OI Bazzi, Angela/0000-0001-6828-1919 NR 31 TC 9 Z9 9 U1 0 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD SEP PY 2014 VL 18 IS 9 BP 1675 EP 1685 DI 10.1007/s10461-014-0844-6 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AN3HD UT WOS:000340476000006 PM 24980249 ER PT J AU McMahon, JM Myers, JE Kurth, AE Cohen, SE Mannheimer, SB Simmons, J Pouget, ER Trabold, N Haberer, JE AF McMahon, James M. Myers, Julie E. Kurth, Ann E. Cohen, Stephanie E. Mannheimer, Sharon B. Simmons, Janie Pouget, Enrique R. Trabold, Nicole Haberer, Jessica E. TI Oral Pre-Exposure Prophylaxis (PrEP) for Prevention of HIV in Serodiscordant Heterosexual Couples in the United States: Opportunities and Challenges SO AIDS PATIENT CARE AND STDS LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; TENOFOVIR DISOPROXIL FUMARATE; ACTIVE ANTIRETROVIRAL THERAPY; BONE-MINERAL DENSITY; COST-EFFECTIVENESS; CONDOM-USE; RISK BEHAVIORS; CARE PROVIDERS; HEALTH-CARE; VIRAL LOAD AB Oral HIV pre-exposure prophylaxis (PrEP) is a promising new biomedical prevention approach in which HIV-negative individuals are provided with daily oral antiretroviral medication for the primary prevention of HIV-1. Several clinical trials have demonstrated efficacy of oral PrEP for HIV prevention among groups at high risk for HIV, with adherence closely associated with level of risk reduction. In the United States (US), three groups have been prioritized for initial implementation of PrEP-injection drug users, men who have sex with men at substantial risk for HIV, and HIV-negative partners within serodiscordant heterosexual couples. Numerous demonstration projects involving PrEP implementation among MSM are underway, but relatively little research has been devoted to study PrEP implementation in HIV-serodiscordant heterosexual couples in the US. Such couples face a unique set of challenges to PrEP implementation at the individual, couple, and provider level with regard to PrEP uptake and maintenance, adherence, safety and toxicity, clinical monitoring, and sexual risk behavior. Oral PrEP also provides new opportunities for serodiscordant couples and healthcare providers for primary prevention and reproductive health. This article provides a review of the critical issues, challenges, and opportunities involved in the implementation of oral PrEP among HIV-serodiscordant heterosexual couples in the US. C1 [McMahon, James M.; Trabold, Nicole] Univ Rochester, Med Ctr, Sch Nursing, Rochester, NY 14624 USA. [Myers, Julie E.] New York City Dept Hlth & Mental Hyg, Bur HIV AIDS Prevent & Control, New York, NY USA. [Myers, Julie E.] Columbia Univ, Dept Med, Div Infect Dis, New York, NY USA. [Kurth, Ann E.] NYU, Coll Nursing, New York, NY USA. [Cohen, Stephanie E.] San Francisco Dept Publ Hlth STD Prevent & Contro, San Francisco, CA USA. [Mannheimer, Sharon B.] Columbia Univ Coll Phys & Surg, Dept Med, Harlem Hosp, New York, NY 10032 USA. [Simmons, Janie; Pouget, Enrique R.] Natl Dev & Res Inst Inc, New York, NY USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.] Harvard Univ, Sch Med, Boston, MA USA. RP McMahon, JM (reprint author), Univ Rochester, Med Ctr, Sch Nursing, 601 Elmwood Ave,Box SON, Rochester, NY 14624 USA. EM james_mcmahon@urmc.rochester.edu FU University of Rochester Center for AIDS Research [NIH P30AI078498]; National Institute on Mental Health [K23MH087228] FX Support for this work was provided to Dr. McMahon by the University of Rochester Center for AIDS Research (NIH P30AI078498). Dr. Haberer received support from the National Institute on Mental Health (K23MH087228). NR 160 TC 15 Z9 15 U1 4 U2 14 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 2014 VL 28 IS 9 BP 462 EP 474 DI 10.1089/apc.2013.0302 PG 13 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AN4GC UT WOS:000340544600002 PM 25045996 ER PT J AU Gonzalez, S Camarillo, C Rodriguez, M Ramirez, M Zavala, J Armas, R Contreras, SA Contreras, J Dassori, A Almasy, L Flores, D Jerez, A Raventos, H Ontiveros, A Nicolini, H Escamilla, M AF Gonzalez, Suzanne Camarillo, Cynthia Rodriguez, Marco Ramirez, Mercedes Zavala, Juan Armas, Regina Contreras, Salvador A. Contreras, Javier Dassori, Albana Almasy, Laura Flores, Deborah Jerez, Alvaro Raventos, Henriette Ontiveros, Alfonso Nicolini, Humberto Escamilla, Michael TI A Genome-Wide Linkage Scan of Bipolar Disorder in Latino Families Identifies Susceptibility loci at 8q24 and 14q32 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetics; family studies; Mexican; Mexican-American; Central-American; bipolar disorder ID AFFECTIVE PUERPERAL PSYCHOSIS; DNA-BINDING ACTIVITY; ASSOCIATION ANALYSIS; SLEEP DISTURBANCE; CHROMOSOME 8Q24; I DISORDER; SCHIZOAFFECTIVE DISORDER; GENETIC-HETEROGENEITY; TRANSCRIPTION FACTOR; FRONTAL-CORTEX AB A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with S-all statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 x 10(-5)) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population. (C) 2014 Wiley Periodicals, Inc. C1 [Gonzalez, Suzanne; Camarillo, Cynthia; Rodriguez, Marco; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Ctr Excellence Neurosci, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Gonzalez, Suzanne; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Armas, Regina] Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA USA. [Contreras, Salvador A.; Dassori, Albana] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Contreras, Javier; Raventos, Henriette] Univ Costa Rica, Ctr Invest Biol Celular & Mol & Escuela Biol, San Jose, Costa Rica. [Dassori, Albana] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Almasy, Laura] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Flores, Deborah] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Ctr Harbor, Torrance, CA 90509 USA. [Jerez, Alvaro] Ctr Int Trastornos Afect & Conducta Adict, Guatemala City, Guatemala. [Ontiveros, Alfonso] Inst Informac & Invest Salud Mental AC, Monterrey, Nuevo Leon, Mexico. [Nicolini, Humberto] Grp Estudios Med & Familiares Carracci SC, Mexico City, DF, Mexico. [Nicolini, Humberto] Inst Nacl Med Genom, Mexico City, DF, Mexico. RP Escamilla, M (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, Paul L Foster Sch Med, 4800 Alberta, El Paso, TX 79905 USA. EM m.escamilla@ttuhsc.edu OI Nicolini, Humberto/0000-0003-2494-0067; Raventos, Henriette/0000-0001-9423-8308; Jerez Magana, Alvaro Antonio/0000-0002-1208-3769 FU NIMH Genetics Initiative study: Genetics of Bipolar Disorder in Latino Populations [5RO1MH069856] FX Grant sponsor: NIMH Genetics Initiative study: Genetics of Bipolar Disorder in Latino Populations; Grant number: 5RO1MH069856. NR 130 TC 4 Z9 5 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP PY 2014 VL 165 IS 6 BP 479 EP 491 DI 10.1002/ajmg.b.32251 PG 13 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AN3OF UT WOS:000340497100004 PM 25044503 ER PT J AU Wilens, TE Yule, A Martelon, M Zulauf, C Faraone, SV AF Wilens, Timothy E. Yule, Amy Martelon, MaryKate Zulauf, Courtney Faraone, Stephen V. TI Parental History of Substance Use Disorders (SUD) and SUD in Offspring: A Controlled Family Study of Bipolar Disorder SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SPECTRUM DISORDERS; FOLLOW-UP; ADOLESCENTS; CHILDREN; ALCOHOLISM; TEACHER; TRANSMISSION; COOCCURRENCE; ASSOCIATION; PREDICTORS AB Background and Objectives: Adolescents with bipolar disorder (BPD) have been previously shown to be at very high risk for substance use disorders (SUD). We now examine the influence of a parental history of substance use disorders on SUD risk in offspring with and without BPD. Methods: We studied 190 parents ascertained through 104 adolescent BPD probands and 189 parents ascertained through 98 control probands using structured interviews. We compared the prevalence of SUD using logistic regression. Results: While adjusting for BPD in our combined sample, probands with a parental history of SUD were more likely to have an alcohol use disorder compared to probands without a parental history. Probands with a parental history of SUD were not more likely to have a drug use disorder or overall SUD compared to probands without a parental history. BPD in the offspring did not pose any additional risk between parental history of SUD and offspring SUD. Conclusion: Alcohol use disorders were more common in the offspring of parents with a SUD history compared to parents without SUD and the risk was not influenced by offspring BPD. Scientific Significance: Clarifying the mechanisms linking parental SUD to offspring SUD, particularly in children and adolescents with BPD, would help clinicians to educate and monitor high-risk families, which would facilitate strategies to mitigate risks associated with parental substance abuse. C1 [Wilens, Timothy E.; Yule, Amy; Martelon, MaryKate; Zulauf, Courtney] Adult ADHD Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol, Boston, MA USA. [Wilens, Timothy E.; Yule, Amy; Martelon, MaryKate; Zulauf, Courtney] Adult ADHD Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol, Boston, MA USA. [Wilens, Timothy E.] 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 Wilens, TE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [R01 DA012945, R01 DA12945] NR 33 TC 1 Z9 1 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2014 VL 23 IS 5 BP 440 EP 446 DI 10.1111/j.1521-0391.2014.12125.x PG 7 WC Substance Abuse SC Substance Abuse GA AN4BR UT WOS:000340533100005 PM 24628811 ER PT J AU Van Horn, DHA Rennert, L Lynch, KG McKay, JR AF Van Horn, Deborah H. A. Rennert, Lior Lynch, Kevin G. McKay, James R. TI Social Network Correlates of Participation in Telephone Continuing Care for Alcohol Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DRINKING OUTCOMES; SUBSTANCE-ABUSE; USE DISORDERS; SUPPORT; AFTERCARE; COCAINE; PREDICTORS AB Background and Objectives: Research on face-to-face treatment for substance misuse suggests that patients' social networks may impact treatment entry and participation, but there has been no similar research on entry and participation in telephone-based continuing care. We examined whether alcohol-specific social support predicted engagement and participation in telephone continuing care for alcohol dependence, and whether treatment participation resulted in beneficial changes in participants' social networks. Methods: Participants were 252 adults (162 male) enrolled in a randomized clinical trial testing the effectiveness of telephone continuing care for alcohol dependence. Participants who completed 3 weeks of intensive outpatient treatment were randomly assigned to treatment as usual, telephone monitoring (TM; N = 83), or telephone monitoring and brief counseling (TMC; N = 83). TM and TMC included 18 months of telephone treatment. Alcohol-specific social support was measured with the Important People Inventory at baseline and 6, 12, 18, and 24-month follow-up. Results: Alcohol-specific social support did not predict entry into TM or TMC. Among those who entered telephone treatment (N = 127), participants with higher network percentage of daily drinkers, higher percentage of network members who accept drinking, and lower percentage of network members who do not accept drinking completed more continuing care calls. There was no effect of continuing care participation on alcohol-specific social support over 24 months of follow-up. Conclusion: Participants with more problematic social networks may self-select additional support in the form of telephone continuing care. Telephone continuing care does not appear to result in social network change. C1 [Van Horn, Deborah H. A.; Rennert, Lior; Lynch, Kevin G.; McKay, James R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [McKay, James R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Van Horn, DHA (reprint author), Univ Penn, Ctr Continuum Care Addict, Perelman Sch Med, Dept Psychiat, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM dvh@mail.med.upenn.edu FU NIAAA NIH HHS [R01 AA14850, R01 AA014850]; NIDA NIH HHS [K24 DA029062] NR 27 TC 0 Z9 0 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2014 VL 23 IS 5 BP 447 EP 452 DI 10.1111/j.1521-0391.2014.12128.x PG 6 WC Substance Abuse SC Substance Abuse GA AN4BR UT WOS:000340533100006 PM 24628884 ER PT J AU Irons, JG Babson, KA Bergeria, CL Bonn-Miller, MO AF Irons, Jessica G. Babson, Kimberly A. Bergeria, Cecilia L. Bonn-Miller, Marcel O. TI Physical Activity and Cannabis Cessation SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MODERATE-INTENSITY EXERCISE; MARIJUANA USE; ACTIVITY QUESTIONNAIRE; SUBSTANCE USE; DEPENDENCE; VALIDITY; ABSTINENCE; MOTIVES; METAANALYSIS; ADOLESCENTS AB Background and Objectives: Based on recent empirical and theoretical work suggesting that physical activity (PA) activates many of the same physiological systems as cannabis, the present study sought to investigate the impact of PA level (ie, low [including none] vs. moderate/high) on a cannabis cessation attempt during the first 7 days post-quit. Methods: The present study was a 2 time-point prospective study of 84 cannabis dependent military veterans (3 female) who responded to study flyers, within a Veterans Affairs Medical Center, seeking individuals interested in engaging in a self-guided cessation attempt. All study measures were self-report. Results: Though no baseline differences between those with low and those with moderate/high levels of physical activity were observed, results revealed that participants who reported low levels of physical activity, versus moderate/high levels, were significantly more likely to report a cannabis lapse during the week following a quit attempt, particularly within the first 4 days of the cessation period. Further, individuals with low levels of PA were also more likely to report greater mean cannabis use during the first 4 days of the cessation period. Conclusions and Scientific Significance: Findings suggest that early interventions aimed at increasing physical activity may be useful among individuals with cannabis dependence who are engaged in a cessation attempt. C1 [Irons, Jessica G.] James Madison Univ, Dept Psychol, Harrisonburg, VA 22807 USA. [Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Babson, Kimberly A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Menlo Pk, CA USA. [Bergeria, Cecilia L.] Univ Vermont, Burlington, VT USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. [Bonn-Miller, Marcel O.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Irons, JG (reprint author), James Madison Univ, Dept Psychol, MSC 7704, Harrisonburg, VA 22807 USA. EM ironsjg@jmu.edu OI Babson, Kimberly/0000-0002-9233-8230 NR 45 TC 6 Z9 6 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2014 VL 23 IS 5 BP 485 EP 492 DI 10.1111/j.1521-0391.2014.12135.x PG 8 WC Substance Abuse SC Substance Abuse GA AN4BR UT WOS:000340533100012 PM 24629045 ER PT J AU Smith, TB Cortez-Retamozo, V Grigoryeva, LS Hill, E Pittet, MJ Da Silva, N AF Smith, T. B. Cortez-Retamozo, V. Grigoryeva, L. S. Hill, E. Pittet, M. J. Da Silva, N. TI Mononuclear phagocytes rapidly clear apoptotic epithelial cells in the proximal epididymis SO ANDROLOGY LA English DT Article DE animal models; apoptosis; epididymis; immunology; mouse; reproductive tract ID DIFFERENTIAL GENE-EXPRESSION; EFFERENT DUCT LIGATION; RAT EPIDIDYMIS; INITIAL SEGMENT; IN-VIVO; PROTEIN; MICE; SED1/MFG-E8; MATURATION; INTEGRITY AB We have shown previously that a network of mononuclear phagocytes (MPs) expressing macrophage and dendritic cell markers such as CD11c, F4/80 and CX3CR1, lines the base of the epididymal tubule. However, in the initial segment (IS) and only in that particular segment, epididymal MPs establish extremely close interactions with the epithelium by projecting slender dendrites between most epithelial cells. We undertook the present study to determine how epididymal phagocytes respond to the transient wave of apoptosis initiated by unilateral efferent duct ligation (EDL) in the epididymal epithelium. We show profound morphological and phenotypical changes restricted to the MPs populating the proximal epididymis following EDL. Within 48 h, a large subset of IS epithelial cells had entered an apoptotic state, visualized by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and CD11c(+) and CX3CR1(+) MPs readily engulfed TUNEL-positive cells and other debris. Despite the high levels of apoptosis and the rapid clearance of apoptotic cells occurring after EDL, the epithelium preserved its overall architecture and maintained tight junctions of the blood-epididymis barrier (BEB). The discovery of a functional population of MPs in the epididymal epithelium responsible for maintaining the integrity of the BEB raises further questions regarding the role of these cells in clearing defective epithelial cells in the steady-state epididymis, as well as pathogens and abnormal spermatozoa in the lumen. C1 [Smith, T. B.; Cortez-Retamozo, V.; Grigoryeva, L. S.; Hill, E.; Da Silva, N.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Smith, T. B.; Cortez-Retamozo, V.; Grigoryeva, L. S.; Hill, E.; Pittet, M. J.; Da Silva, N.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Da Silva, N (reprint author), Massachusetts Gen Hosp, Div Nephrol, 185 Cambridge St,CPZN 8-218, Boston, MA 02114 USA. EM dasilva.nicolas@mgh.harvard.edu FU National Institutes of Health [R01HD069623, R01AI084880]; Boston Area Diabetes and Endocrinology Research Center [DK057521]; MGH Center for the Study of Inflammatory Bowel Disease [DK043351] FX This study was supported by National Institutes of Health grants R01HD069623 (NDS) and R01AI084880 (MJP). The Microscopy Core facility of the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK057521) and the MGH Center for the Study of Inflammatory Bowel Disease (DK043351). NR 44 TC 7 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD SEP PY 2014 VL 2 IS 5 BP 755 EP 762 DI 10.1111/j.2047-2927.2014.00251.x PG 8 WC Andrology SC Endocrinology & Metabolism GA AN4QH UT WOS:000340572200016 PM 25082073 ER PT J AU Wu, GC Chan, ED Chou, YC Yu, CY Hsieh, TY Hsieh, CB Chian, CF Ke, FC Dai, YL Su, WL AF Wu, Geng-Chin Chan, Edward D. Chou, Yu-Ching Yu, Chih-Yung Hsieh, Tsai-Yuan Hsieh, Chung-Bao Chian, Chih-Feng Ke, Fu-Chang Dai, Yu-Ling Su, Wen-Lin TI Risk factors for the development of pulmonary oil embolism after transcatheter arterial chemoembolization of hepatic tumors SO ANTI-CANCER DRUGS LA English DT Article DE hepatocellular carcinoma; pulmonary oil embolism; transcatheter arterial chemoembolization ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; RESPIRATORY-DISTRESS-SYNDROME; TRANSARTERIAL CHEMOEMBOLIZATION; LIPIODOL EMBOLISM; EMBOLIZATION; COMPLICATIONS; DOXORUBICIN; INFUSION; FAILURE; SHUNT AB Pulmonary oil embolism (POE) is a rare fatal complication after transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE). As risk factors have not been clearly delineated, the aim of the present study was to identify the risk factors for development of POE after TACE. A retrospective analysis was carried out on patients with unresectable hepatocellular carcinoma who received TAE or TACE at the Tri-Service General Hospital (Taiwan) between January 2005 and December 2008. The diagnosis of TAE-induced or TACE-induced POE was based on development of respiratory signs and symptoms relatively soon after the procedure, as well as based on characteristic radiographic findings. Of the 219 enrolled patients in this study, 20 were diagnosed with POE after TAE or TACE. On univariate logistic regression analysis, patients developing POE were found to be older (67.95+/-15.95 vs. 61.44+/-12.59 years, P=0.033), with a lower serum albumin level (3.25+/-0.58 vs. 3.62+/-0.57 g/dl, P=0.009), a higher grade of liver cirrhosis as classified on the basis of Child's criteria (P<0.006), a larger tumor size (8.55+/-4.52 vs. 4.78+/-3.97 cm in diameter, P<0.001), a higher lipioidol dose (22.35+/-11.01 vs. 13.69+/-7.66 ml, P=0.003), and a higher doxorubicin dose (50.27+/-7.05 vs. 40.75+/-13.61 mg, P<0.001). Following multivariate logistic regression analysis, only lipiodol dose was found to be a significant risk factor for POE (odds ratio=1.133, 95% confidence interval: 1.004, 1.279; P=0.044). The receiver operator characteristic curve cutoff point for lipiodol dose level was 14.5 ml, with a sensitivity of 80% and a specificity of 66.3%. In conclusion, the lipiodol dose could be considered as a predictive factor for POE after TAE or TACE in hepatic malignant tumor patients. On the basis of this retrospective study, the safe lipiodol dose to minimize the risk for POE is 14.5 ml or lower; however, larger, prospective studies are needed to determine the optimally safe and yet efficacious dose. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Wu, Geng-Chin; Ke, Fu-Chang] Taoyuan Armed Forces Gen Hosp, Div Pulm Med, Dept Internal Med, Taoyuan, Taiwan. [Chou, Yu-Ching; Su, Wen-Lin] Natl Def Med Ctr, Sch Publ Hlth, Taipei, Taiwan. [Yu, Chih-Yung] Triserv Gen Hosp, Dept Radiol, Taipei, Taiwan. [Hsieh, Tsai-Yuan] Triserv Gen Hosp, Div Gastroenterol, Dept Internal Med, Taipei, Taiwan. [Hsieh, Chung-Bao] Triserv Gen Hosp, Div Organ Transplantat, Dept Surg, Taipei, Taiwan. [Chian, Chih-Feng; Dai, Yu-Ling; Su, Wen-Lin] Triserv Gen Hosp, Div Pulm & Crit Care Med, Dept Med, Taipei, Taiwan. [Su, Wen-Lin] Buddhist Tzu Chi Med Fdn, Taipei Tzu Chi Hosp, Div Pulm & Crit Care Med, Dept Med, New Taipei City 231, Taiwan. [Chan, Edward D.] Univ Colorado, Anschutz Med Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Chan, Edward D.] Natl Jewish Hlth, Div Mycobacterial & Resp Infect, Dept Med, Denver, CO USA. RP Su, WL (reprint author), Buddhist Tzu Chi Med Fdn, Taipei Tzu Chi Hosp, Div Pulm & Crit Care Med, Dept Med, 289 Jianguo Rd, New Taipei City 231, Taiwan. EM williamsu2007@gmail.com NR 32 TC 0 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 EI 1473-5741 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD SEP PY 2014 VL 25 IS 8 BP 976 EP 981 DI 10.1097/CAD.0000000000000113 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AN4LD UT WOS:000340558400014 PM 24736105 ER PT J AU Chen, L Kim, IK Lane, AM Gauthier, D Munzenrider, JE Gragoudas, ES Miller, JW AF Chen, Ling Kim, Ivana K. Lane, Anne M. Gauthier, Danny Munzenrider, John E. Gragoudas, Evangelos S. Miller, Joan W. TI Proton beam irradiation for non-AMD CNV: 2-year results of a randomised clinical trial SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; INTRAVITREAL BEVACIZUMAB AVASTIN; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; PATHOLOGICAL MYOPIA; ANGIOID STREAKS; MULTIFOCAL CHOROIDITIS; RADIATION-THERAPY; VERTEPORFIN; SECONDARY AB Aims To evaluate safety and visual outcomes after proton beam irradiation (PBI) therapy for subfoveal choroidal neovascularisation (CNV) secondary to causes other than age-related macular degeneration (AMD). Methods This study is a prospective, unmasked and randomised clinical trial using two dosage regimens, conducted in the Massachusetts Eye and Ear Infirmary. The study included 46 patients with CNV secondary to non-AMD and best-corrected visual acuity of 20/320 or better. Patients were randomly assigned to receive 16 or 24 cobalt gray equivalents (CGE) of PBI in two equal fractions. Complete ophthalmological examinations, fundus photography and fluorescein angiography were performed at baseline and 6, 12, 18 and 24 months after treatment. Results At 1 year after treatment, 82% and 72% lost fewer than 1.5 lines of vision in the 16 CGE and in 24 CGE groups, respectively. At 2 years after therapy, 77% in the lower dose group and 64% in the higher dose group lost fewer than 1.5 lines of vision. Mild radiation complications such as radiation vasculopathy developed in 17.6% of patients. Conclusions PBI is a safe and efficacious treatment for subfoveal CNV not due to AMD. The data with respect to visual outcomes and radiation complications trend in favour of the 16 CGE group, although differences do not reach statistical significance. PBI may be considered as an alternative to current therapies. C1 [Chen, Ling; Kim, Ivana K.; Lane, Anne M.; Gragoudas, Evangelos S.; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA. [Chen, Ling] Univ Hong Kong, Dept Ophthalmol, Hong Kong, Hong Kong, Peoples R China. [Chen, Ling] Fudan Univ, Shanghai Med Sch, Eye & ENT Hosp, Dept Ophthalmol & Vis Sci, Shanghai 200433, Peoples R China. [Gauthier, Danny] Univ Montreal, Hop Notre Dame, Dept Ophthalmol, Retina Serv, Montreal, PQ, Canada. [Munzenrider, John E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Miller, JW (reprint author), Massachusetts Eye & Ear Infirm, Chair Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM joan_miller@meei.harvard.edu FU National Natural Science Foundation of China [81000381, 81371042]; major programme of the Natural Science Foundation of China [2013CB967503]; Scientific Research Starting Foundation for the Returned Overseas Chinese Scholars, Ministry of Education; Retina Research Fund of Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Melanoma Research Fund of Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Neovascular Research Fund of Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Macula Foundation, New York, New York FX LC is sponsored by the National Natural Science Foundation of China (grant no. 81000381, 81371042), the major programme of the Natural Science Foundation of China (grant no. 2013CB967503) and the Scientific Research Starting Foundation for the Returned Overseas Chinese Scholars, Ministry of Education. The study was supported by the Retina Research Fund, Melanoma Research Fund, and Neovascular Research Fund of Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; and the Macula Foundation, New York, New York. NR 30 TC 1 Z9 1 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD SEP PY 2014 VL 98 IS 9 BP 1212 EP 1217 DI 10.1136/bjophthalmol-2013-304761 PG 6 WC Ophthalmology SC Ophthalmology GA AN3QW UT WOS:000340504400013 PM 24820046 ER PT J AU Yee, CC Papakostas, TD Vavvas, DG AF Yee, Chan Chee Papakostas, Thanos D. Vavvas, Demetrios G. TI Quantitative assessment of central retinal thickness in recurrent neovascular age-related macular degeneration SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Letter ID OPTICAL COHERENCE TOMOGRAPHY; INSTRUMENTS; EYES C1 [Yee, Chan Chee; Papakostas, Thanos D.; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02134 USA. RP Yee, CC (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 7 Islington St, Boston, MA 02134 USA. EM drchenziyi100@gmail.com OI Vavvas, Demetrios/0000-0002-8622-6478 NR 5 TC 0 Z9 0 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD SEP PY 2014 VL 98 IS 9 DI 10.1136/bjophthalmol-2014-305673 PG 1 WC Ophthalmology SC Ophthalmology GA AN3QW UT WOS:000340504400032 ER PT J AU Bulson, R Jun, W AF Bulson, Ryan Jun, Weon TI Metastatic disease producing internuclear ophthalmolplegia: a case report SO CLINICAL AND EXPERIMENTAL OPTOMETRY LA English DT Editorial Material ID OPHTHALMOPLEGIA C1 [Bulson, Ryan] Portland VA Med Ctr, Portland, OR 97239 USA. Univ Pacific, Coll Optometry, Portland, OR USA. RP Bulson, R (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM ryan.bulson@pacificu.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0816-4622 EI 1444-0938 J9 CLIN EXP OPTOM JI Clin. Exp. Optom. PD SEP PY 2014 VL 97 IS 5 BP 468 EP 470 DI 10.1111/cxo.12176 PG 3 WC Ophthalmology SC Ophthalmology GA AN4EU UT WOS:000340541200016 PM 24989875 ER PT J AU Northcut, TB Kienow, A AF Northcut, Terry B. Kienow, Amy TI The Trauma Trifecta of Military Sexual Trauma: A Case Study Illustrating the Integration of Mind and Body in Clinical Work with Survivors of MST SO CLINICAL SOCIAL WORK JOURNAL LA English DT Article DE Military sexual trauma; Posttraumatic stress disorder; Mindfulness; Cognitive behavioral; Self harm; Integrative psychotherapy ID DELIBERATE SELF-HARM; POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; FEMALE VETERANS; NEGATIVE AFFECT; WOMEN VETERANS; RISK-FACTORS; LIFE-COURSE; SERVICE; VICTIMIZATION AB Military sexual trauma (MST) has recently received much attention from the media in contemporary society. With the ever-increasing population of United States service members returning from the Iraq and Afghanistan wars, it is vital for any mental health practitioner to be aware of the epidemic that is sexual assault in the military, the unique trauma experiences of the MST survivor, and treatment implications incorporating multiple psychological theories. This article explores three factors, referred to as the trauma trifecta, in which the effects of MST are exacerbated: the loss of professional and personal identity, the regulatory functions of self harm behaviors, and the retraumatization that many service members endure as a result of the distinctive characteristics of the military culture and its service to veterans. A case study with clinical interventions will be utilized to demonstrate this concept of "the trauma trifecta" and the unique challenges in treating the PTSD symptoms that can result from MST in clinical therapy. Drawing from multiple theories in clinical treatment, this paper illustrates the strengths and limitations of cognitive-behavioral techniques, highlights the integration of feminist theory to illustrate the obstacles of power structures, and mind-body interventions, bridging the gap between talk therapy and body therapy. Through this unique integration of multiple therapies, the case study illustrates the veteran's reengagement with her body and the reformulation of her identity post MST. C1 [Northcut, Terry B.] Loyola Univ Chicago, Sch Social Work, Chicago, IL 60611 USA. [Kienow, Amy] US Dept Vet Affairs, Orland Pk Vet Ctr, Orland Pk, IL 60462 USA. RP Northcut, TB (reprint author), Loyola Univ Chicago, Sch Social Work, 820 N Michigan Ave, Chicago, IL 60611 USA. EM tnorthc@luc.edu; kienow.amy@gmail.com NR 78 TC 0 Z9 0 U1 1 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0091-1674 EI 1573-3343 J9 CLIN SOC WORK J JI Clin. Soc. Work J. PD SEP PY 2014 VL 42 IS 3 SI SI BP 247 EP 259 DI 10.1007/s10615-014-0479-0 PG 13 WC Social Work SC Social Work GA AN3SB UT WOS:000340507800006 ER PT J AU Horan, W Pineda, J Wynn, J Iacoboni, M Green, M AF Horan, William P. Pineda, Jaime A. Wynn, Jonathan K. Iacoboni, Marco Green, Michael F. TI Some markers of mirroring appear intact in schizophrenia: evidence from mu suppression SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE mu suppression; Schizophrenia; Mirror neuron system; Empathy ID AUTISM SPECTRUM DISORDERS; PSYCHIATRIC RATING-SCALE; BORDERLINE PERSONALITY-DISORDER; SOCIAL COGNITION; NEURON DYSFUNCTION; EMPATHIC ACCURACY; IMITATION; NEUROSCIENCE; MECHANISMS; PSYCHOSIS AB Although schizophrenia is associated with impairments in social cognition, the scope and neural correlates of these disturbances are largely unknown. In this study, we investigated whether schizophrenia patients show impaired functioning of the mirror neuron system (MNS), as indexed by electroencephalographic (EEG) mu (8-13 Hz) suppression, a hypothesized biomarker of MNS activity that is sensitive to the degree of social interaction depicted in visual stimuli. A total of 32 outpatients and 26 healthy controls completed an EEG paradigm that included six action observation or execution conditions that differed in their degrees of social interaction. Participants also completed a validated empathy questionnaire. Across both groups, we found a significant linear increase in mu suppression across the conditions involving greater levels of social engagement and interaction, but no significant group or interaction effects. Patients self-reported diminished empathic concern and perspective taking, which showed some moderate relations to mu suppression levels. Thus, the schizophrenia group showed generally intact modulation of MNS functioning at the electrophysiological level, despite self-reporting empathic disturbances. The disturbances commonly seen on self-report, performance, and neuroimaging measures of mentalizing in schizophrenia may largely reflect difficulties with higher-level inferential processes about others' emotions, rather than a basic incapacity to share in these experiences. C1 [Horan, William P.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Pineda, Jaime A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Iacoboni, Marco] Univ Calif Los Angeles, Los Angeles, CA USA. RP Horan, W (reprint author), Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu OI Wynn, Jonathan/0000-0002-1763-8540 FU Abbott Laboratories; Amgen; Cypress; Lundbeck; Teva; Otsuka; Sunovion; VA Career Development Award; NIMH [MH065707, MH43292] FX M.F.G. reports having received consulting fees from Abbott Laboratories, Amgen, Cypress, Lundbeck, and Teva. He has received speaking fees from Otsuka and Sunovion. The rest of the authors report no biomedical financial interests or potential conflicts of interest. Support for this study came from a VA Career Development Award (to W. P. H.) and from NIMH Grant Nos. MH065707 and MH43292 (M. F. G.). The authors thank Amanda Bender, Michelle Dolinsky, Crystal Gibson, Cory Tripp, and Katherine Weiner for assistance in the data collection. NR 68 TC 14 Z9 15 U1 5 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2014 VL 14 IS 3 BP 1049 EP 1060 DI 10.3758/s13415-013-0245-8 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AN3FT UT WOS:000340471500013 PM 24415272 ER PT J AU Uthman, OA Magidson, JF Safren, SA Nachega, JB AF Uthman, Olalekan A. Magidson, Jessica F. Safren, Steven A. Nachega, Jean B. TI Depression and Adherence to Antiretroviral Therapy in Low-, Middle- and High-Income Countries: A Systematic Review and Meta-Analysis SO CURRENT HIV/AIDS REPORTS LA English DT Article DE HIV; ART; Depression; Adherence; Co-infections and comorbidity ID HIV-INFECTED PATIENTS; HUMAN-IMMUNODEFICIENCY-VIRUS; POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; MULTICENTER AIDS COHORT; INJECTION-DRUG USERS; QUALITY-OF-LIFE; MEDICATION ADHERENCE; SUBSTANCE-ABUSE AB We investigated the associations between depressive symptoms and adherence to antiretroviral therapy (ART) among people living with HIV (PLHIV). We searched the PubMed, EMBASE and Cochrane CENTRAL databases for studies that reported an association between depression and adherence to ART as a primary or secondary outcome. We used a random-effect model to pool the risk estimates from the individual studies. The odds ratio (OR) with their 95 % CIs were used as summary estimates. Of 2861 citations, 111 studies that recruited 42,366 PLHIV met our inclusion criteria. When reported, the rate of PLHIV with depressive symptoms ranged from 12.8 to 78 % and the proportion of PLHIV who achieved good adherence (>= 80 %) ranged from 20 to 98 %. There were no significant differences in rate of depressive symptoms in PLHIV by country income group; however, the proportion of PLHIV who achieved good adherence was significantly higher in lower-income countries (as defined in the 2012 World Bank Country Income Groups) (pooled rate = 86 %) compared to higher-income countries (pooled rate = 67.5 %; p < .05). We found that the likelihood of achieving good ART adherence was 42 % lower among those with depressive symptoms compared to those without (pooled OR = 0.58, 95 % CI 0.55 to 0.62). The relationship between depressive symptoms and adherence to ART was consistent across the country's income group, study design and adherence rates. We found that the magnitude of the association significantly decreases with more recent publications and increasing study sample size. The higher the prevalence of depressive symptoms of PLHIV recruited in the studies, the lower the likelihood of achieving good adherence to ART. In conclusion, the likelihood of achieving good adherence was lower among those with depressive symptoms compared to those without. C1 [Uthman, Olalekan A.] Univ Warwick, Warwick Ctr Appl Hlth Res & Delivery WCARHD, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England. [Uthman, Olalekan A.] Univ Liverpool, Liverpool Sch Trop Med, Int Hlth Grp, Liverpool L3 5QA, Merseyside, England. [Magidson, Jessica F.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Behav Med Serv, Boston, MA USA. [Magidson, Jessica F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Chester M Pierce MD Div Global Psyc, Boston, MA USA. [Nachega, Jean B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Infect Dis Epidemiol Res Program, Pittsburgh, PA 15261 USA. [Nachega, Jean B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Nachega, Jean B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Nachega, Jean B.] Univ Stellenbosch, Fac Med & Hlth Sci, Dept Med, Cape Town, South Africa. [Nachega, Jean B.] Univ Stellenbosch, Fac Med & Hlth Sci, Ctr Infect Dis, Cape Town, South Africa. RP Nachega, JB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Infect Dis Epidemiol Res Program, 130 DeSoto St,503 Parran Hall, Pittsburgh, PA 15261 USA. EM JBN16@PITT.EDU OI Uthman, Olalekan/0000-0002-8567-3081 FU US National Institutes for Allergy and Infectious Disease-National Institutes of Health (NIAID-NIH), AIDS Clinical Trial Group (ACTG), Stellenbosch University (SU)-Clinical Trial Unit (CTU) [2UM1AI069521-08]; US NIH-Fogarty International Center (FIC)/Health Resources and Services Administration (HRSA)/US President Emergency Plan for AIDS Relief (PEPFAR) Grant [T84HA21652-01-00]; European Developing Countries Clinical Trial Partnership (EDCTP) Senior Fellowship [TA-08-40200-021]; NIH [T32MH093310, K24MH094214] FX The US National Institutes for Allergy and Infectious Disease-National Institutes of Health (NIAID-NIH), AIDS Clinical Trial Group (ACTG), Stellenbosch University (SU)-Clinical Trial Unit (CTU) Award: 2UM1AI069521-08 (J. B. N.); the US NIH-Fogarty International Center (FIC)/Health Resources and Services Administration (HRSA)/US President Emergency Plan for AIDS Relief (PEPFAR) Grant Award, T84HA21652-01-00 for Medical Education Partnership Initiative (MEPI) (J. B. N.); the European Developing Countries Clinical Trial Partnership (EDCTP) Senior Fellowship Award: TA-08-40200-021 (J. B. N.); the Wellcome Trust Southern Africa Consortium for Research Excellence (SACORE): WT087537MA (J. B. N.); FAS Marie Curie International Post Doc: 2012-0064 (O. A. U.); The MGH Global Psychiatric Clinical Research Training Program: NIH T32MH093310 (J. F. M); K24MH094214 (S. A. S.). NR 138 TC 31 Z9 32 U1 5 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD SEP PY 2014 VL 11 IS 3 BP 291 EP 307 DI 10.1007/s11904-014-0220-1 PG 17 WC Infectious Diseases SC Infectious Diseases GA AN1UF UT WOS:000340368500011 PM 25038748 ER PT J AU Chen, SS Seliger, SL Fried, LF AF Chen, Shan Shan Seliger, Stephen L. Fried, Linda F. TI Complete inhibition of the renin-angiotensin-aldosterone system; where do we stand? SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE angiotensin receptor blocker; angiotensin-converting enzyme; cardiovascular disease; diabetic nephropathy; mineralocorticoid receptor blocker ID CONVERTING-ENZYME-INHIBITOR; CHRONIC HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; PRESERVED EJECTION FRACTION; RANDOMIZED CONTROLLED-TRIAL; CHRONIC RENAL-INSUFFICIENCY; TYPE-2 DIABETIC-PATIENTS; MYOCARDIAL-INFARCTION; ADDING SPIRONOLACTONE; RECEPTOR BLOCKER AB Purpose of review This review presents the role of combination therapy of renin-angiotensin-aldosterone system blockade on cardiovascular and kidney disease. Recent findings Three large randomized controlled trials comparing combination therapy of renin-angiotensin-aldosterone system blockade to monotherapy in individuals with increased cardiovascular risk, chronic kidney disease, or diabetic nephropathy have been reported. These trials - ONTARGET, ALTITUDE, and VA NEPHRON-D - demonstrated an excess risk of adverse effects [ especially acute kidney injury (AKI) and hyperkalemia] with combination therapy, without significant benefit in reducing cardiovascular and renal morbidity. Summary Current evidence supports avoiding dual renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. Subsequent studies of dual renin-angiotensin-aldosterone system blockade should examine adverse event risks and renal progression endpoints. C1 [Chen, Shan Shan; Fried, Linda F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Seliger, Stephen L.] VA Maryland Healthcare Syst, Baltimore, MD USA. [Seliger, Stephen L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Chen, SS (reprint author), Univ Pittsburgh, Sch Med, Presbyterian Univ Hosp C1100, Renal Electrolyte Div, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM Chens4@upmc.edu NR 61 TC 3 Z9 3 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 EI 1473-6543 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2014 VL 23 IS 5 BP 449 EP 455 DI 10.1097/MNH.0000000000000043 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA AN4OG UT WOS:000340566800003 PM 25014549 ER PT J AU LeVarge, BL Channick, RN AF LeVarge, Barbara L. Channick, Richard N. TI Chronic thromboembolic pulmonary hypertension: evolution in management SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Review DE chronic thromboembolic pulmonary hypertension; pulmonary embolism; pulmonary thromboendarterectomy ID INTERNATIONAL PROSPECTIVE REGISTRY; THROMBOTIC RISK-FACTORS; LONG-TERM TREATMENT; CIRCULATORY ARREST; HIGH PREVALENCE; ENDARTERECTOMY; ANGIOPLASTY; PERFUSION; EMBOLISM; THROMBOENDARTERECTOMY AB Purpose of review Chronic thromboembolic pulmonary hypertension (CTEPH) is an important cause of pulmonary hypertension. Although surgery is potentially curative, some patients present with inoperable disease. In these patients, medical therapies for pulmonary arterial hypertension are increasingly being used. Recent findings The pathobiology of CTEPH development remains incompletely understood; however, evidence supports both large and small vessel disorder in patients with the disease. Surgical thromboendarterectomy is an increasingly well tolerated and often curative procedure and is the management strategy of choice for most patients. Although excellent outcomes in surgical management have been noted, the role of medical management in selected patients with inoperable or recurrent or persistent disease after surgery is increasing. A recent large, randomized controlled clinical trial of riociguat in CTEPH demonstrated improvements in exercise capacity, functional class, and hemodynamics. A safe, effective angioplasty approach to CTEPH is being pursued in addition. Summary The approach to CTEPH management in the operable patient remains surgical, without clear benefit to preoperative pulmonary arterial hypertension-specific therapy at this time. Patients with inoperable disease or pulmonary hypertension following thromboendarterectomy, however, should be considered for medical management, with riociguat currently having the strongest evidence specific to CTEPH. C1 [LeVarge, Barbara L.] Beth Israel Deaconess Med Ctr, Dept Pulm & Crit Care Med, Boston, MA 02215 USA. [Channick, Richard N.] Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. RP LeVarge, BL (reprint author), Beth Israel Deaconess Med Ctr, Dept Pulm & Crit Care Med, 330 Brookline Ave, Boston, MA 02215 USA. EM blevarge@bidmc.harvard.edu NR 64 TC 2 Z9 2 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-5287 EI 1531-6971 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD SEP PY 2014 VL 20 IS 5 BP 400 EP 408 DI 10.1097/MCP.0000000000000088 PG 9 WC Respiratory System SC Respiratory System GA AN3TY UT WOS:000340512800002 PM 25093673 ER PT J AU Hauer, JM Wolfe, J AF Hauer, Julie M. Wolfe, Joanne TI Supportive and palliative care of children with metabolic and neurological diseases SO CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE LA English DT Review DE decision-making; metabolic disease; neurological impairment; pediatric palliative care ID LIFE-THREATENING CONDITIONS; LIMITING CONDITIONS; HOSPICE CARE; FAMILIES; RECOMMENDATIONS; LESSONS AB Purpose of review To review the role of pediatric palliative care (PPC) for children with metabolic and neurological diseases. Recent findings There is a growing body of literature in PPC, though it remains limited for children with metabolic and neurological diseases. Evidence indicates the benefit of PPC. Utilization of PPC programmes can facilitate communication, ensure that families are better informed, improve certainty with decisions, enhance positive emotions, result in fewer invasive interventions at the end of life, and have an impact on location of death. Barriers to utilization of PPC include concern about taking away hope and uncertainty about prognosis. Challenging areas for children with metabolic and neurological diseases include the identification of distressing symptoms and prognostic uncertainty. This article aims to review literature relevant to this group of children, as well as provide a framework when considering specific palliative care needs. Summary PPC for children with metabolic and neurological diseases can lessen a child's physical discomfort and enhance parental certainty with decision-making. These areas along with other needs throughout the illness trajectory and bereavement are being increasingly met by the growing availability of PPC programmes. C1 [Hauer, Julie M.] Boston Childrens Hosp, Div Gen Pediat, Boston, MA USA. [Wolfe, Joanne] Boston Childrens Hosp, Div Oncol, Boston, MA USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Pediat Palliat Care, Boston, MA 02115 USA. RP Hauer, JM (reprint author), Seven Hills Pediat Ctr, 22 Hillside, Groton, MA 01450 USA. EM julie.hauer@childrens.harvard.edu NR 26 TC 3 Z9 3 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1751-4258 EI 1751-4266 J9 CURR OPIN SUPPORT PA JI Curr. Opin Support Palliat. Car. PD SEP PY 2014 VL 8 IS 3 BP 296 EP 302 DI 10.1097/SPC.0000000000000063 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AN3TT UT WOS:000340512300018 PM 25004174 ER PT J AU Kaplan, D Sun, ZX Tallman, MS Flinn, IW Xiao, WB Caimi, PF Kaye, NM Lazarus, HM AF Kaplan, David Sun, Zhuoxin Tallman, Martin S. Flinn, Ian W. Xiao, Wenbin Caimi, Paolo F. Kaye, Nicholas M. Lazarus, Hillard M. TI Prognostic Information and Biological Insights in Chronic Lymphocytic Leukemia by High-Resolution Immunophenotypic Analysis of ZAP70 SO CYTOMETRY PART A LA English DT Article DE chronic lymphocytic leukemia; ZAP70; phospho-ZAP70; prognosis ID FLOW-CYTOMETRIC ANALYSIS; PHASE-III TRIAL; GENOMIC ABERRATIONS; ZAP-70 EXPRESSION; CD38 EXPRESSION; MUTATION STATUS; D-CYCLINS; DISEASE; MARKERS; CELLS AB The E2997 Phase III trial included preservation of valuable chronic lymphocytic leukemia (CLL) patient specimens and relevant clinical outcome data. Using a novel high-resolution technology on a flow cytometry platform, we assessed 79 E2997 samples for the expression of 27 analytes that reflected the activity of signaling pathways and apoptosis. We found that the expression levels of ZAP70 segregated the samples into two subpopulations with the distribution showing a peak-trough-peak configuration. Although prior assessment of ZAP70 by standard procedures did not reveal any prognostic information, we found by using the trough in the distribution as a cutpoint that ZAP70 expression levels were significantly correlated with both progression-free survival and overall survival. Additionally, the cells expressing high versus low levels of ZAP70 demonstrated distinct molecular organization as indicated by the other analytes assessed. Our analysis demonstrates the value of ZAP70 expression as a prognostic indicator and suggests that the different clinical results may be due to the distinct molecular biology of the ZAP70-low versus the ZAP70-high CLL samples. (C) 2014 International Society for Advancement of Cytometry C1 [Kaplan, David; Kaye, Nicholas M.] Pathfinder Biotech, Cleveland, OH USA. [Kaplan, David; Xiao, Wenbin] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH 44106 USA. [Kaplan, David; Xiao, Wenbin; Caimi, Paolo F.; Lazarus, Hillard M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sun, Zhuoxin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Flinn, Ian W.] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. [Caimi, Paolo F.; Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH 44106 USA. RP Kaplan, D (reprint author), Univ Hosp Case Med Ctr, Dept Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. EM david.kaplan@case.edu FU Public Health Service from the National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA14548, CA16116, CA17145, CA014548-38, CA043703-20]; Department of Health and Human Services; American Cancer Society [IRG-91-022-18] FX We gratefully thank Drs. Robert Peter Gale, Nate Berger, Mitchell Smith, Omar Abdel-Wahab, and Brian Hill for their helpful reviews of the manuscript. We acknowledge the technical assistance of Ms. Victoria Vachon and Ms. Fangfang Liu. We also appreciate Dr. Michael Grever and Dr. John Byrd who organized the collection of the E2997 samples, and the ECOG core laboratory that processed, stored, and sent the samples. The E2997 study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA14548, CA16116, CA17145, CA014548-38, and CA043703-20 from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Supported in part by grant #IRG-91-022-18 to the Case Comprehensive Cancer Center from the American Cancer Society. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 27 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 EI 1552-4930 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2014 VL 85A IS 9 BP 798 EP 808 DI 10.1002/cyto.22485 PG 11 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AN4CR UT WOS:000340535700009 PM 24845539 ER PT J AU Pirie, CG Alario, AF Barysauskas, CM Gradil, C Uricchio, CK AF Pirie, C. G. Alario, A. F. Barysauskas, C. M. Gradil, C. Uricchio, C. K. TI Manual corneal thickness measurements of healthy equine eyes using a portable spectral-domain optical coherence tomography device SO EQUINE VETERINARY JOURNAL LA English DT Article DE horse; optical coherence tomography; cornea; thickness; pachymetry ID EPITHELIAL THICKNESS; INTRAOCULAR-PRESSURE; HORSES; DIAMETER AB Reasons for performing study: Corneal thickness measurements of the equine globe using spectral-domain optical coherence tomography (SD-OCT) have not been reported. Objectives: To determine corneal thickness measurements and the intra- and interoperator reliability of a portable SD-OCT device in equine eyes. Study design: Prospective observational study. Methods: Horses free of ocular disease were used for this study. Gentle manual restraint, in combination with detomidine hydrochloride and a head stand, were employed to ensure proper animal positioning. Corneal pachymetry measurements were obtained from both eyes of each animal 3 times by 2 operators in succession. A 6 mm corneal pachymetry protocol was performed using a portable SD-OCT device. All measurements were obtained manually by one operator (C.G.P.) using the integrated calliper function. Measurements included epithelial thickness, stromal thickness, Descemet's membrane thickness and total corneal thickness. All recorded measurements were analysed to determine both intra- and interoperator reliability. Results: Thirty horses with a mean age of 10.6 +/- 6.4 years were examined. Mean epithelial, stromal, Descemet's membrane and total corneal thickness values obtained were, respectively, 174.7 +/- 13.6, 599.2 +/- 45.4, 38.4 +/- 15.3 and 812.0 +/- 44.1 mu m for operator A and 175.9 +/- 12.9, 599.2 +/- 44.9, 38.4 +/- 15.0 and 812.9 +/- 42.9 mu m for operator B. A positive correlation was found between Descemet's membrane thickness and age, whereby Descemet's membrane thickness increased by 2 mu m/year (P<0.0001). The coefficients of variation for both operators were <4% for all measurements. Intraclass correlations ranged from 0.92 to 0.98. Conclusions: Manual corneal thickness measurement using a portable SD-OCT device provides epithelial, stromal, Descemet's membrane and total corneal thickness measurements with clinically acceptable intra- and interoperator reliability in healthy equine eyes. C1 [Pirie, C. G.; Alario, A. F.] TCSVM, Dept Clin Sci, North Grafton, MA 01536 USA. [Barysauskas, C. M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gradil, C.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. [Uricchio, C. K.] Univ Massachusetts, Stockbridge Sch Agr, Amherst, MA 01003 USA. RP Pirie, CG (reprint author), TCSVM, Dept Clin Sci, North Grafton, MA 01536 USA. EM chris.pirie@tufts.edu NR 18 TC 6 Z9 6 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0425-1644 EI 2042-3306 J9 EQUINE VET J JI Equine Vet. J. PD SEP PY 2014 VL 46 IS 5 BP 631 EP 634 DI 10.1111/evj.12198 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA AN3YX UT WOS:000340525900019 PM 24131285 ER PT J AU de Guillory, CD Schoolfield, JD Johnson, D Yeh, CK Chen, S Cappelli, DP Bober-Moken, IG Dang, H AF de Guillory, Carolina Diaz Schoolfield, John D. Johnson, Dorthea Yeh, Chih-Ko Chen, Shuo Cappelli, David P. Bober-Moken, Irene G. Dang, Howard TI Co-Relationships between glandular salivary flow rates and dental caries SO GERODONTOLOGY LA English DT Article DE caries; saliva; ageing; ethnicity ID DIFFERENT AGE-GROUPS; ROOT CARIES; HEALTH; IMPACT AB Objective: This study was designed to evaluate the relationship of age, gender, ethnicity and salivary flow rates on dental caries in an adult population using data collected from the Oral Health San Antonio Longitudinal Study of Aging (OH: SALSA). Background: Saliva is essential to maintain a healthy oral environment and diminished output can result in dental caries. Although gender and age play a role in the quantity of saliva, little is known about the interaction of age, gender and ethnicity on dental caries and salivary flow rates. Materials and methods: Data from the 1147 participants in the OH: SALSA were analysed. The dependent variables were the number of teeth with untreated coronal caries, number of teeth with root caries and the number of coronal and root surfaces with untreated caries. The independent variables were stimulated and unstimulated glandular salivary flow rates along with the age, sex and ethnicity (e. g. European or Mexican ancestry) of the participants. Results: Coronal caries experience was greater in younger participants while root surface caries experience was greater in the older participants. Coronal caries was lower in the older age groups while the root caries experience increased. Men had a statistically significant (p < 0.02) higher experience of root caries than women. Values for unstimulated and stimulated parotid salivary flow rates showed no age difference and remained constant with age, whereas the age differences in the unstimulated and stimulated submandibular/sublingual salivary flow rates were significant. The mean number of teeth with coronal and root caries was higher in Mexican-Americans than in European-Americans. Conclusions: Over one-fourth of the adults between the ages of 60 and 79 have untreated root caries over one-third having untreated coronal caries. Lower salivary flow rates play a significant role in both the number of teeth and the number of surfaces developing caries in these adults. Women and individuals of European-American ancestry experience less caries. C1 [de Guillory, Carolina Diaz; Yeh, Chih-Ko; Cappelli, David P.; Bober-Moken, Irene G.; Dang, Howard] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Schoolfield, John D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Johnson, Dorthea] Univ Texas Hlth Sci Ctr San Antonio, Dept Community Dent, San Antonio, TX 78229 USA. [Chen, Shuo] Univ Texas Hlth Sci Ctr San Antonio, Dept Dev Dent, San Antonio, TX 78229 USA. [Yeh, Chih-Ko] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Dang, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM dang@uthscsa.edu FU HRSA [D13HP30016]; NIH [DE019892] FX This work was supported by grants from HRSA (D13HP30016 to DPC) and NIH (DE019892 to SC). NR 29 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0734-0664 EI 1741-2358 J9 GERODONTOLOGY JI Gerodontology PD SEP PY 2014 VL 31 IS 3 BP 210 EP 219 DI 10.1111/ger.12028 PG 10 WC Dentistry, Oral Surgery & Medicine; Geriatrics & Gerontology SC Dentistry, Oral Surgery & Medicine; Geriatrics & Gerontology GA AN3ZP UT WOS:000340527700007 ER PT J AU Bhatt, AB AF Bhatt, Ami B. TI Survival in Eisenmenger syndrome: a paradigm shift in outcomes research for adult congenital heart disease? SO HEART LA English DT Editorial Material ID HYPERTENSION C1 Massachusetts Gen Hosp, Dept Cardiol, Adult Congenital Heart Dis Program, Boston, MA 02114 USA. RP Bhatt, AB (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Adult Congenital Heart Dis Program, Boston, MA 02114 USA. EM ABHATT@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD SEP PY 2014 VL 100 IS 17 BP 1308 EP 1310 DI 10.1136/heartjnl-2014-306211 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AN3OO UT WOS:000340498000003 PM 25099648 ER PT J AU Jaffer, FA Verjans, JW AF Jaffer, Farouc A. Verjans, Johan W. TI Molecular imaging of atherosclerosis: clinical state-of-the-art SO HEART LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PLAQUE INFLAMMATION; CORONARY-ARTERIES; FEASIBILITY; REDUCTION; DISEASE C1 [Jaffer, Farouc A.; Verjans, Johan W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Verjans, Johan W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. RP Jaffer, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,Simches Bldg,Room 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL108229] NR 20 TC 12 Z9 12 U1 0 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD SEP PY 2014 VL 100 IS 18 BP 1469 EP 1477 DI 10.1136/heartjnl-2011-301370 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AN3PJ UT WOS:000340500100015 PM 24365664 ER PT J AU Dondoni, L Scarparo, RK Kantarci, A Van Dyke, TE Figueiredo, JAP Batista, EL AF Dondoni, L. Scarparo, R. K. Kantarci, A. Van Dyke, T. E. Figueiredo, J. A. P. Batista, E. L., Jr. TI Effect of the pro-resolution lipid mediator Resolvin E1 (RvE1) on pulp tissues exposed to the oral environment SO INTERNATIONAL ENDODONTIC JOURNAL LA English DT Article DE dental pulp; inflammation; resolution; Resolvin E1 ID MINERAL TRIOXIDE AGGREGATE; INTRACANAL MEDICATION; AIRWAY INFLAMMATION; REPARATIVE DENTIN; IMMATURE TEETH; RAT MOLARS; PERIODONTITIS; MANAGEMENT; NECROSIS; CEMENT AB Aim To evaluate the effects of topical Resolvin E1 (RvE1) application on infected dental pulps. Methodology Forty-two male Wistar rats (n = 6 per three groups/and two time periods) were used. To induce inflammation, pulps in mandibular right first molars were accessed and then left exposed to the oral environment for 24 h. After this period, topical medication with a corticosteroid/antibiotic blend, or RvE1, or its vehicle (Ethanol 0.1%) was directly applied onto the pulp tissue and teeth were restored with silver amalgam. The effects of the protocols were evaluated histologically and compared with control pulps not exposed to the oral environment. The inflammatory changes after 24 and 72 h were assessed through a scoring method and analysed using the Kruskal-Wallis test followed by Dunn's. Differences were considered significant if P < 0.05 (CI = 95%). Results Ethanol and corticosteroid/antibiotic treatment were not effective in arresting severe inflammatory alterations of exposed pulps at 24 and 72 h (P < 0.05, CI = 95%). At both time periods, RvE1 treatment led to a reduction of tissue cellularity and extent of inflammation, whose changes were not different from control pulps (P > 0.05, CI = 95%). Conclusions A protective role for RvE1 in pulp inflammation was observed even in the presence of contamination, suggesting that it may be a candidate for a novel therapeutic strategy for conservative dental pulp treatment. C1 [Dondoni, L.; Scarparo, R. K.; Figueiredo, J. A. P.] Pontificia Univ Catolica Rio Grande Sul PUCRS, Porto Alegre, RS, Brazil. [Kantarci, A.; Van Dyke, T. E.] Forsyth Inst, Dept Periodontol & Translat Biol Res, Cambridge, MA USA. [Batista, E. L., Jr.] Univ Manitoba, Fac Dent, Dept Diagnost & Surg Sci, Winnipeg, MB, Canada. [Batista, E. L., Jr.] Univ Manitoba, Dept Oral Biol, Winnipeg, MB, Canada. RP Batista, EL (reprint author), Univ Manitoba, Fac Dent, D342D-790 Bannatyne Ave, Winnipeg, MB R3E 0W2, Canada. EM eraldo.batistajunior@umanitoba.ca RI Figueiredo, Jose Antonio/I-4805-2012 OI Figueiredo, Jose Antonio/0000-0002-8876-5993 FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, Brazil FX The other authors have no financial affiliation(e.g. employment, direct: payment, stock holdings, retainers, consultantships, patent licensing arrangements or honoraria), or involvement with any commercial organization with direct financial interest in the subject or materials discussed in this manuscript, nor have any such arrangements existed in the past 3 years. This study was in part supported by grants from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, Brazil. NR 31 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0143-2885 EI 1365-2591 J9 INT ENDOD J JI Int. Endod. J. PD SEP PY 2014 VL 47 IS 9 BP 827 EP 834 DI 10.1111/iej.12224 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AN3SK UT WOS:000340508800003 PM 24298979 ER PT J AU Conti, CL Moscon, JA Fregni, F Nitsche, MA Nakamura-Palacios, EM AF Conti, Catarine Lima Moscon, Janine Andrade Fregni, Felipe Nitsche, Michael Andreas Nakamura-Palacios, Ester Miyuki TI Cognitive related electrophysiological changes induced by non-invasive cortical electrical stimulation in crack-cocaine addiction SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Crack-cocaine; cue-reactivity; event-related potential; prefrontal cortex; tDCS ID ELECTROMAGNETIC TOMOGRAPHY LORETA; EVENT-RELATED POTENTIALS; HUMAN MOTOR CORTEX; PREFRONTAL CORTEX; MOTIVATIONAL RELEVANCE; EXECUTIVE FUNCTIONS; INTEGRATIVE THEORY; BRAIN-STIMULATION; ATTENTIONAL BIAS; NEURAL RESPONSE AB Prefrontal dysfunction is a hallmark in drug addiction, yet interventions exploring modulation of prefrontal cortex function in drug addiction have not been fully investigated with regard to physiological alterations. We tested the hypothesis that non-invasive prefrontal stimulation would change neural activity in crack-cocaine addiction, investigating the effects of transcranial Direct Current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex (DLPFC) induced cortical excitability modulation on the visual P3 Event Related Potentials (ERP) component under neutral and drug cue exposition in crack-cocaine addicts. Thirteen crack-cocaine users were randomly distributed to receive five applications (once a day, every other day) of bilateral (left cathodal/right anodal) tDCS (20 min, 2 mA, 35 cm(2)) or sham tDCS over the DLPFC. Brain activity was measured under crack-related or neutral visual-cued ERPs. There were significant differences in P3-related parameters when comparing group of stimulation (active vs. sham tDCS) and number of sessions (single vs. repetitive tDCS). After a single session of tDCS, P3 current intensity in the left DLPFC increased during neutral cues and decreased during crack-related cues. This effect was opposite to what was observed in the sham-tDCS group. In contrast, repetitive tDCS increased current density not only in the DLPFC, but also in a wider array of prefrontal areas, including presumably the frontopolar cortex (FPC) orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), when subjects were visualizing crack-related cues. Thus, single and repetitive application of tDCS can impact cognitive processing of neutral and especially crack-related visual cues in prefrontal areas, which may be of importance for treatment of crack-cocaine addiction. C1 [Conti, Catarine Lima; Moscon, Janine Andrade; Nakamura-Palacios, Ester Miyuki] Univ Fed Espirito Santo, Lab Cognit Sci & Neuropsychopharmacol, Program Postgrad Physiol Sci, Vitoria, ES, Brazil. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Lab Neuromodulat,Spauding Rehabil Hosp, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spauding Rehabil Hosp, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat,Dept N, Boston, MA 02215 USA. [Nitsche, Michael Andreas] Univ Gottingen, Clin Clin Neurophysiol, Univ Med Ctr, Lab Neuroplast, D-37073 Gottingen, Germany. RP Nakamura-Palacios, EM (reprint author), Univ Fed Espirito Santo, Ctr Ciencias Saude, Programa Posgrad Ciencias Fisiol, Av Marechal Campos 1468, BR-29047105 Vitoria, ES, Brazil. EM emnpalacios@gmail.com FU governmental institution (CAPES) FX We are grateful to the patients and their families for their great effort in participating in this study. We also thank the students Henrique Mineiro Calvacante and Pollyane Rodrigues for their help in the database and craving questionnaire application, respectively, due to their participation in this trial as trainees. CLC and JAM received a student scholarship from a governmental institution (CAPES) during the period of this study. NR 65 TC 12 Z9 12 U1 5 U2 20 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD SEP PY 2014 VL 17 IS 9 BP 1465 EP 1475 DI 10.1017/S1461145714000522 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AN2IU UT WOS:000340409100012 PM 24776374 ER PT J AU Heppt, MV Wang, JX Hristova, DM Wei, Z Berking, C Besch, R Rauscher, FJ Fisher, DE Herlyn, M Fukunaga-Kalabis, M AF Heppt, M. V. Wang, J. X. Hristova, D. M. Wei, Z. Berking, C. Besch, R. Rauscher, F. J. Fisher, D. E. Herlyn, M. Fukunaga-Kalabis, M. TI MSX1 reprograms melanocytes towards a neural crest-like state and promotes the progression of melanoma SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Heppt, M. V.; Berking, C.; Besch, R.] Klinikum Univ Munchen, Klin & Poliklin Dermatol & Allergol, Munich, Germany. [Heppt, M. V.; Wang, J. X.; Hristova, D. M.; Herlyn, M.; Fukunaga-Kalabis, M.] Wistar Inst Anat & Biol, Melanoma Res Ctr, Philadelphia, PA 19104 USA. [Wei, Z.] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA. [Rauscher, F. J.] Wistar Inst Anat & Biol, Ctr Canc, Philadelphia, PA 19104 USA. [Fisher, D. E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1610-0379 EI 1610-0387 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD SEP PY 2014 VL 12 SU 3 SI SI MA FV18 BP 7 EP 7 PG 1 WC Dermatology SC Dermatology GA AN4BL UT WOS:000340532500019 ER PT J AU Park, LG Howie-Esquivel, J Dracup, K AF Park, Linda G. Howie-Esquivel, Jill Dracup, Kathleen TI A quantitative systematic review of the efficacy of mobile phone interventions to improve medication adherence SO JOURNAL OF ADVANCED NURSING LA English DT Review DE medication adherence; mobile phone; nursing; short message service (SMS); text messaging ID RANDOMIZED-CONTROLLED-TRIAL; SHORT-MESSAGE SERVICE; ANTIRETROVIRAL THERAPY; TEXT MESSAGES; PROGRAM; SMS; REMINDERS; SCHIZOPHRENIA; HIV/AIDS; MHEALTH AB Aims. To evaluate the characteristics and efficacy of mobile phone interventions to improve medication adherence. Secondary aims are to explore participants' acceptability and satisfaction with mobile phone interventions and to evaluate the selected studies in terms of study rigour, impact, cost and resource feasibility, generalizability and implications for nursing practice and research. Background. Medication non-adherence is a major global challenge. Mobile phones are the most commonly used form of technology worldwide and have the potential to promote medication adherence. Design. Guidelines from the Centre for Reviews and Dissemination were followed for this systematic review. Data Sources. A comprehensive search of databases (PubMed, Web of Science, CINAHL, PsycInfo, Google Chrome and Cochrane) and bibliographies from related articles was performed from January 2002-January 2013 to identify the included studies. Review Methods. A quantitative systematic review without meta-analysis was conducted and the selected studies were critically evaluated to extract and summarize pertinent characteristics and outcomes. Results. The literature search produced 29 quantitative research studies related to mobile phones and medication adherence. The studies were conducted for prevention purposes as well as management of acute and chronic illnesses. All of the studies used text messaging. Eighteen studies found significant improvement in medication adherence. Conclusion. While the majority of investigators found improvement in medication adherence, long-term studies characterized by rigorous research methodologies, appropriate statistical and economic analyses and the test of theory-based interventions are needed to determine the efficacy of mobile phones to influence medication adherence. C1 [Park, Linda G.] Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA USA. [Howie-Esquivel, Jill; Dracup, Kathleen] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Park, LG (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA USA. EM linda.park@ucsf.edu RI Emchi, Karma/Q-1952-2016 NR 49 TC 21 Z9 21 U1 7 U2 47 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-2402 EI 1365-2648 J9 J ADV NURS JI J. Adv. Nurs. PD SEP PY 2014 VL 70 IS 9 BP 1932 EP 1953 DI 10.1111/jan.12400 PG 22 WC Nursing SC Nursing GA AN2CJ UT WOS:000340390700002 PM 24689978 ER PT J AU Joshi, G Faraone, SV Wozniak, J Petty, C Fried, R Galdo, M Furtak, SL McDermott, K Epstien, C Walker, R Caron, A Feinberg, L Biederman, J AF Joshi, Gagan Faraone, Stephen V. Wozniak, Janet Petty, Carter Fried, Ronna Galdo, Maribel Furtak, Stephannie L. McDermott, Katie Epstien, Cecily Walker, Rosemary Caron, Ashley Feinberg, Leah Biederman, Joseph TI Examining the Clinical Correlates of Autism Spectrum Disorder in Youth by Ascertainment Source SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Psychiatric comorbidity; Youth ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ASPERGER-SYNDROME; PSYCHIATRIC COMORBIDITY; REFERRED POPULATION; GLOBAL ASSESSMENT; BIPOLAR DISORDER; ANXIETY SYMPTOMS; YOUNG-ADULTS AB To examine whether presentation of autism spectrum disorder (ASD) and associated patterns of psychiatric comorbidity and dysfunction vary by referral source. ASD youth referred to a specialized ambulatory program for ASD (N = 143) were compared to ASD youth referred to a general child psychiatry clinic (N = 217). More ASD clinic youth met criteria for a more robust form of ASD (autistic disorder); more youth referred to the psychiatry clinic met criteria for broader spectrum ASD (pervasive developmental disorder not otherwise specified). General psychiatry clinic youth with ASD suffered from a greater burden of psychopathologies and higher levels of dysfunction. The presentation of ASD in psychiatrically referred youth differs between general and ASD-specialized clinics, though both referral populations have high levels of comorbidity and dysfunction. C1 [Joshi, Gagan; Wozniak, Janet; Petty, Carter; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L.; McDermott, Katie; Epstien, Cecily; Walker, Rosemary; Caron, Ashley; Feinberg, Leah; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Joshi, Gagan; Wozniak, Janet; Fried, Ronna; 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 Joshi, G (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM joshi.gagan@mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K23 MH100450] NR 54 TC 6 Z9 6 U1 3 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2117 EP 2126 DI 10.1007/s10803-014-2063-4 PG 10 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400003 PM 24566937 ER PT J AU Johnson, CR Turner, K Stewart, PA Schmidt, B Shui, A Macklin, E Reynolds, A James, J Johnson, SL Courtney, PM Hyman, SL AF Johnson, Cynthia R. Turner, Kylan Stewart, Patricia A. Schmidt, Brianne Shui, Amy Macklin, Eric Reynolds, Anne James, Jill Johnson, Susan L. Courtney, Patty Manning Hyman, Susan L. TI Relationships Between Feeding Problems, Behavioral Characteristics and Nutritional Quality in Children with ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Feeding problems; Mealtime behaviors; Nutrition ID AUTISM SPECTRUM DISORDERS; TYPICALLY DEVELOPING-CHILDREN; PERVASIVE DEVELOPMENTAL DISORDERS; FOOD SELECTIVITY; YOUNG-CHILDREN; MEALTIME BEHAVIORS; REPETITIVE BEHAVIORS; SENSORY SENSITIVITY; ASPERGERS-DISORDER; TREATMENT OUTCOMES AB Many children with autism spectrum disorders (ASD) have co-occurring feeding problems. However, there is limited knowledge about how these feeding habits are related to other behavioral characteristics ubiqitious in ASD. In a relatively large sample of 256 children with ASD, ages 2-11, we examined the relationships between feeding and mealtime behaviors and social, communication, and cognitive levels as well repetitive and ritualistic behaviors, sensory behaviors, and externalizing and internalizing behaviors. Finally, we examined whether feeding habits were predictive of nutritional adequacy. In this sample, we found strong associations between parent reported feeding habits and (1) repetitive and ritualistic behaviors, (2) sensory features, and (3) externalizing and internalizing behavior. There was a lack of association between feeding behaviors and the social and communication deficits of ASD and cognitive levels. Increases in the degree of problematic feeding behaviors predicted decrements in nutritional adequacy. C1 [Johnson, Cynthia R.; Turner, Kylan] Univ Pittsburgh, Autism Ctr, Sch Med, Pittsburgh, PA 15213 USA. [Stewart, Patricia A.; Schmidt, Brianne; Hyman, Susan L.] Univ Rochester, Dept Pediat, Sch Med, Rochester, NY 14642 USA. [Stewart, Patricia A.] Univ Rochester, Clin & Translat Sci Inst, Sch Med, Rochester, NY 14642 USA. [Shui, Amy; Macklin, Eric] Massachusetts Gen Hosp, MGH Biostat, Boston, MA 02114 USA. [Reynolds, Anne; Johnson, Susan L.] Univ Colorado, Aurora, CO 80045 USA. [James, Jill] Univ Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Courtney, Patty Manning] Cincinnati Childrens Hosp, Cincinnati, OH 45229 USA. RP Johnson, CR (reprint author), Univ Pittsburgh, Autism Ctr, Sch Med, 3420 Fifth Ave, Pittsburgh, PA 15213 USA. EM Cynthia.johnson@chp.edu OI Reynolds, Ann/0000-0002-0836-746X; Macklin, Eric/0000-0003-1618-3502 FU NCRR NIH HHS [UL1 RR 024160]; PHS HHS [UA3 MC 11054] NR 79 TC 18 Z9 18 U1 8 U2 37 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2175 EP 2184 DI 10.1007/s10803-014-2095-9 PG 10 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400008 PM 24664635 ER PT J AU Blanch-Hartigan, D Blake, KD Viswanath, K AF Blanch-Hartigan, Danielle Blake, Kelly D. Viswanath, Kasisomayajula TI Cancer Survivors' Use of Numerous Information Sources for Cancer-Related Information: Does More Matter? SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Health information-seeking behavior; Cancer survivors; Cancer; Numerous source seekers; Patient-provider communication ID NATIONAL TRENDS SURVEY; HEALTH PRIORITIES; UNITED-STATES; SEEKING; BEHAVIORS; CARE; PERCEPTIONS; PREVENTION; AVOIDANCE; BELIEFS AB A large proportion of the 14 million cancer survivors in the USA are actively seeking health information. This study builds on the informed- and shared-decision making literature, examining cancer survivors' health information seeking behaviors to (1) quantify the number of health information sources used; (2) create a demographic profile of patients who report seeking cancer information from numerous sources versus fewer sources in five areas: cancer information overall, disease/treatment, self-care/management, health services, and work/finances; and (3) examine whether seeking cancer information from numerous sources is associated with self-efficacy, fear of recurrence, perceptions of information seeking difficulty, and resultant patient-provider communication. Data came from a survey of post-treatment cancer survivors (N = 501) who responded to a mailed questionnaire about health information seeking. Participants were divided into two groups using a median split: those who sought health information from more than five sources (numerous source seekers) and those that sought information from less than five sources (fewer source seekers). Multivariable logistic regression was used to model differential information seeking behaviors and outcomes for numerous versus fewer source seekers. On average, survivors sought cancer-related information from five different sources. Numerous source seekers were more likely to be women, have higher levels of education, and report fewer problems with cancer information-seeking. Overall, numerous source seekers were no more or less likely to discuss information with their providers or bring conflicting information to their providers. Understanding the characteristics, behaviors, and experiences of survivors who seek cancer-related information from numerous sources can contribute to informed decision making and patient-centered care. C1 [Blanch-Hartigan, Danielle] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Blake, Kelly D.] NCI, Behav Res Program, Hlth Commun & Informat Res Branch, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. RP Blanch-Hartigan, D (reprint author), NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,MSC 9764, Rockville, MD 20850 USA. EM danielleblanch@gmail.com NR 26 TC 6 Z9 6 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 EI 1543-0154 J9 J CANCER EDUC JI J. Cancer Educ. PD SEP PY 2014 VL 29 IS 3 BP 488 EP 496 DI 10.1007/s13187-014-0642-x PG 9 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA AN4AK UT WOS:000340529800016 PM 24699921 ER PT J AU Adams, ZW Sumner, JA Danielson, CK McCauley, JL Resnick, HS Gros, K Paul, LA Welsh, KE Ruggiero, KJ AF Adams, Zachary W. Sumner, Jennifer A. Danielson, Carla Kmett McCauley, Jenna L. Resnick, Heidi S. Groes, Kirstin Paul, Lisa A. Welsh, Kyleen E. Ruggiero, Kenneth J. TI Prevalence and predictors of PTSD and depression among adolescent victims of the Spring 2011 tornado outbreak SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Disaster; adolescents; PTSD; depression; tornadoes ID POSTTRAUMATIC STRESS SYMPTOMS; MENTAL-HEALTH RESEARCH; NEW-YORK-CITY; NATURAL DISASTER; NATIONAL SAMPLE; RISK-FACTORS; COMORBIDITY; CHILDREN; ATTACKS AB Background: Relatively few studies have examined prevalence and predictors of posttraumatic stress disorder (PTSD) or major depressive episode (MDE) in disaster-affected adolescents. Fewer still have administered diagnostic measures or studied samples exposed to tornadoes, a common type of disaster. Further, methodologic problems limit the generalizability of previous findings. This study addressed prevalence estimates and risk factors for PTSD and MDE among adolescents exposed to the Spring 2011 tornado outbreak in Alabama and Joplin, Missouri. Methods: A large (N = 2000), population-based sample of adolescents and caregivers, recruited randomly from tornado-affected communities, participated in structured telephone interviews. PTSD and MDE prevalence were estimated for the overall sample, by gender, and by age. Hierarchical logistic regression was used to identify risk factors for PTSD and MDE. Results: Overall, 6.7% of adolescents met diagnostic criteria for PTSD and 7.5% of adolescents met diagnostic criteria for MDE since the tornado. Girls were significantly more likely than boys to meet diagnostic criteria for MDE, and older adolescents were more likely than younger adolescents to report MDE since the tornado. Female gender, prior trauma exposure, and an injured family member were associated with greater risk for PTSD and MDE. Specific incident characteristics (loss of services, concern about others' safety) were associated with greater PTSD risk; prior disaster exposure was associated with lower MDE risk. Conclusions: However, most adolescents were resilient following tornado exposure, roughly 1 in 15 developed PTSD, 1 in 13 developed MDE, and many more endorsed subclinical mental health problems. Information regarding specific risk factors can guide early screening, prevention, and intervention efforts in disaster-affected communities. C1 [Adams, Zachary W.; Sumner, Jennifer A.; Danielson, Carla Kmett; McCauley, Jenna L.; Resnick, Heidi S.; Groes, Kirstin; Welsh, Kyleen E.; Ruggiero, Kenneth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Groes, Kirstin; Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Paul, Lisa A.] No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. RP Adams, ZW (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. EM adamsz@musc.edu FU National Institutes of Health [R01-MH081056]; [R21-MH086313]; [R01-DA031285]; [K12-DA031794]; [T32-MH018869] FX The National Institutes of Health (Grants R01-MH081056 to KJR) supported this study and the team of collaborators (R21-MH086313 and R01-DA031285 to C. K. D, K12-DA031794 sponsoring J.L.M, and T32-MH018869 sponsoring Z.W.A and J.A.S). All the authors declare that they have no potential or competing conflicts of interest. The authors thank the families for participating in this study. NR 33 TC 17 Z9 17 U1 8 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD SEP PY 2014 VL 55 IS 9 BP 1047 EP 1055 DI 10.1111/jcpp.12220 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AN2JD UT WOS:000340410000012 PM 24580551 ER PT J AU Mdala, I Olsen, I Haffajee, AD Socransky, SS Thoresen, M de Blasio, BF AF Mdala, Ibrahimu Olsen, Ingar Haffajee, Anne D. Socransky, Sigmund S. Thoresen, Magne de Blasio, Birgitte Freiesleben TI Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE antibiotics; chronic periodontitis; multi-state Markov models; periodontal therapy ID PANEL-DATA; DEFINITIONS; INDICATORS; SURVIVAL AB Aim: To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Material and Methods: Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. Results: In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87-97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4-5 months and sites recovered with a high probability (96-98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Conclusion: Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. C1 [Mdala, Ibrahimu; Olsen, Ingar] Univ Oslo, Fac Dent, Dept Oral Biol, N-0316 Oslo, Norway. [Haffajee, Anne D.; Socransky, Sigmund S.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. [Thoresen, Magne; de Blasio, Birgitte Freiesleben] Univ Oslo, Fac Med, Dept Biostat, N-0316 Oslo, Norway. [de Blasio, Birgitte Freiesleben] Norwegian Inst Publ Hlth, Dept Infect Dis Epidemiol, Div Infect Dis Surveillance, Oslo, Norway. RP Mdala, I (reprint author), Univ Oslo, Fac Dent, Dept Oral Biol, POB 1052 Blindern, N-0316 Oslo, Norway. EM ibrahimu.mdala@odont.uio.no FU University of Oslo; National Institute of Dental and Craniofacial Research [DE 12861]; European Commission [FP7-HEALTH-306029] FX The authors declare that they have no conflict of interests. Funding was from the University of Oslo, from the National Institute of Dental and Craniofacial Research (grant DE 12861) and from the European Commission FP7-HEALTH-306029 ["TRIGGER"] (IO). NR 27 TC 7 Z9 7 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 EI 1600-051X J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 2014 VL 41 IS 9 BP 837 EP 845 DI 10.1111/jcpe.12278 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AN4FN UT WOS:000340543100001 PM 24888705 ER PT J AU Lee, CT Chiu, TS Chuang, SK Tarnow, D Stoupel, J AF Lee, Chun-Teh Chiu, Tzu-Shan Chuang, Sung-Kiang Tarnow, Dennis Stoupel, Janet TI Alterations of the bone dimension following immediate implant placement into extraction socket: systematic review and meta-analysis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Review DE bone dimension; immediate implant; meta-analysis; systematic review ID BEAM COMPUTED-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; HARD-TISSUE ALTERATIONS; SINGLE-TOOTH IMPLANTS; ALVEOLAR RIDGE; MAXILLARY ANTERIOR; PROSPECTIVE COHORT; FLAP ELEVATION; CLINICAL-TRIAL; BUCCAL BONE AB Aim: This systematic review was aimed at analysing bone dimensional alterations within the first year following immediate implant placement. Materials and Methods: The electronic search was conducted using MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE from January 1980 to October 2013. Quality assessment of selected articles was performed using Cochrane Collaboration's tool or Newcastle-Ottawa scale according to the design of each study. A meta-analysis was performed to estimate bone dimensional reduction. Weighted mean differences in bone dimension between baseline and follow-up measurement were calculated. Subgroup analysis and mete-regression were conducted to evaluate the effects of different variables. Results: A total of 1348 articles were identified following the search process. Six studies were included in the present review. The weighted mean buccal horizontal bone dimensional reduction (BHDr) was 1.07 mm and buccal vertical bone dimensional reduction (BVDr) was 0.78 mm. The weighted mean palatal bone dimensional reduction was 0.62 mm horizontally (PHDr) and 0.50 mm vertically (PVDr). The initial thickness of the buccal alveolar plate (TB) of the socket was the only variable significantly correlated with BHDr and BVDr in meta-regression analysis. Conclusions: The bone dimensions of immediate implant sites demonstrated approximately 0.5-1.0 mm reduction in vertical and horizontal aspects 4-12 months following surgery. The results should be interpreted with care because of the data heterogeneity. The correlation of the socket buccal wall thickness, and other variables, with dimensional changes of the bony ridge should be investigated further in controlled clinical trials. C1 [Lee, Chun-Teh] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Div Periodontol, Boston, MA 02115 USA. [Chiu, Tzu-Shan; Tarnow, Dennis; Stoupel, Janet] Columbia Univ, Coll Dent Med, Sect Oral & Diagnost Sci, Div Periodont, New York, NY 10032 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Stoupel, J (reprint author), Columbia Univ, Coll Dent Med, Sect Oral & Diagnost Sci, Div Periodont, 630 W 168th St, New York, NY 10032 USA. EM js108@columbia.edu NR 72 TC 12 Z9 12 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 EI 1600-051X J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 2014 VL 41 IS 9 BP 914 EP 926 DI 10.1111/jcpe.12276 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AN4FN UT WOS:000340543100011 PM 24894299 ER PT J AU Paczynski, M Jackendoff, R Kuperberg, G AF Paczynski, Martin Jackendoff, Ray Kuperberg, Gina TI When Events Change Their Nature: The Neurocognitive Mechanisms Underlying Aspectual Coercion SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID LANGUAGE COMPREHENSION; SYNTAX; ERPS; SENTENCES; AMBIGUITY; KNOWLEDGE; MEMORY; MEG AB The verb "pounce" describes a single, near-instantaneous event. Yet, we easily understand that, "For several minutes the cat pounced." describes a situation in which multiple pounces occurred, although this interpretation is not overtly specified by the sentence's syntactic structure or by any of its individual words-a phenomenon known as "aspectual coercion." Previous psycholinguistic studies have reported processing costs in association with aspectual coercion, but the neurocognitive mechanisms giving rise to these costs remain contentious. Additionally, there is some controversy about whether readers commit to a full interpretation of the event when the aspectual information becomes available, or whether they leave it temporarily underspecified until later in the sentence. Using ERPs, we addressed these questions in a design that fully crossed context type (punctive, durative, frequentative) with verb type (punctive, durative). We found a late, sustained negativity to punctive verbs in durative contexts, but not in frequentative (e.g., explicitly iterative) contexts. This effect was distinct from the N400 in both its time course and scalp distribution, suggesting that it reflected a different underlying neurocognitive mechanism. We also found that ERPs to durative verbs were unaffected by context type. Together, our results provide strong evidence that neural activity associated with aspectual coercion is driven by the engagement of a morphosyntactically unrealized semantic operator rather than by violations of real-world knowledge, more general shifts in event representation, or event iterativity itself. More generally, our results add to a growing body of evidence that a set of late-onset sustained negativities reflect elaborative semantic processing that goes beyond simply combining the meaning of individual words with syntactic structure to arrive at a final representation of meaning. C1 [Paczynski, Martin; Jackendoff, Ray; Kuperberg, Gina] Tufts Univ, Medford, MA USA. [Kuperberg, Gina] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Paczynski, M (reprint author), Univ Miami, Dept Psychol, 5665 Ponce De Leon Blvd, Coral Gables, FL 33146 USA. EM m.paczynski@miami.edu FU NIMH NIH HHS [R01 MH071635] NR 44 TC 6 Z9 6 U1 0 U2 6 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2014 VL 26 IS 9 BP 1905 EP 1917 DI 10.1162/jocn_a_00638 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AN4GI UT WOS:000340545300003 PM 24702457 ER PT J AU Kleffel, S Lee, N Lezcano, C Sobolewski, K Mueller, H DoRosario, A Wang, L Frank, MH Murphy, GF Schatton, T AF Kleffel, S. Lee, N. Lezcano, C. Sobolewski, K. Mueller, H. DoRosario, A. Wang, L. Frank, M. H. Murphy, G. F. Schatton, T. TI ABCB5 inhibition sensitizes Merkel cell carcinoma cells to chemotherapy-induced apoptosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the European-Society-for-Dermatological-Research (ESDR) CY SEP 10-13, 2014 CL Copenhagen, DENMARK SP European Soc Dermatol Res C1 [Kleffel, S.; Lee, N.; Sobolewski, K.; Mueller, H.; Frank, M. H.; Schatton, T.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [DoRosario, A.; Wang, L.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Lezcano, C.; Murphy, G. F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2014 VL 134 SU 2 MA 105 BP S18 EP S18 PG 1 WC Dermatology SC Dermatology GA AN1OB UT WOS:000340352100105 ER PT J AU Eichner, C Jafari-Khouzani, K Cauley, S Bhat, H Polaskova, P Andronesi, OC Rapalino, O Turner, R Wald, LL Stufflebeam, S Setsompop, K AF Eichner, Cornelius Jafari-Khouzani, Kourosh Cauley, Stephen Bhat, Himanshu Polaskova, Pavlina Andronesi, Ovidiu C. Rapalino, Otto Turner, Robert Wald, Lawrence L. Stufflebeam, Steven Setsompop, Kawin TI Slice Accelerated Gradient-Echo Spin-Echo Dynamic Susceptibility Contrast Imaging with Blipped CAIPI for Increased Slice Coverage SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE DSC; GESE; CAIPIRINHA; blipped CAIPI; SMS; brain tumor ID CEREBRAL BLOOD-VOLUME; SELECTIVE EXCITATION; BRAIN; ACQUISITIONS; MAPS; MRI AB Purpose: To improve slice coverage of gradient echo spin echo (GESE) sequences for dynamic susceptibility contrast (DSC) MRI using a simultaneous-multiple-slice (SMS) method. Methods: Data were acquired on 3 Tesla (T) MR scanners with a 32-channel head coil. To evaluate use of SMS for DSC, an SMS GESE sequence with two-fold slice coverage and same temporal sampling was compared with a standard GESE sequence, both with 2 x in-plane acceleration. A signal to noise ratio (SNR) comparison was performed on one healthy subject. Additionally, data with Gadolinium injection were collected on three patients with glioblastoma using both sequences, and perfusion analysis was performed on healthy tissues as well as on tumor. Results: Retained SNR of SMS DSC is 90% for a gradient echo (GE) and 99% for a spin echo (SE) acquisition, compared with a standard acquisition without slice acceleration. Comparing cerebral blood volume maps, it was observed that the results of standard and SMS acquisitions are comparable for both GE and SE images. Conclusion: Two-fold slice accelerated DSC MRI achieves similar SNR and perfusion metrics as a standard acquisition, while allowing a significant increase in slice coverage of the brain. The results also point to a possibility to improve temporal sampling rate, while retaining the same slice coverage. (C) 2013 Wiley Periodicals, Inc. C1 [Eichner, Cornelius; Jafari-Khouzani, Kourosh; Cauley, Stephen; Polaskova, Pavlina; Andronesi, Ovidiu C.; Rapalino, Otto; Wald, Lawrence L.; Stufflebeam, Steven; Setsompop, Kawin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Eichner, Cornelius; Turner, Robert] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany. [Bhat, Himanshu] Siemens Healthcare Sect, Charlestown, MA USA. RP Eichner, C (reprint author), Athinoula A Martinos Ctr, 149 13th St, Charlestown, MA 02129 USA. EM ceichner@nmr.mgh.harvard.edu RI Cauley, Stephen/P-1386-2014; Setsompop, Kawin/P-1464-2014; Wald, Lawrence/D-4151-2009 OI Setsompop, Kawin/0000-0003-0455-7634; FU NIH Human Connectome Project [NIH U01MH093765, NIBIB R00EB012107] FX Grant sponsor: the NIH Human Connectome Project; Grant numbers: NIH U01MH093765; NIBIB R00EB012107. NR 30 TC 6 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD SEP PY 2014 VL 72 IS 3 BP 770 EP 778 DI 10.1002/mrm.24960 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AN4JB UT WOS:000340552700019 PM 24285593 ER PT J AU Benedek, G Zhu, WB Libal, N Casper, A Yu, XL Meza-Romero, R Vandenbark, AA Alkayed, NJ Offner, H AF Benedek, Gil Zhu, Wenbin Libal, Nicole Casper, Amanda Yu, Xiaolin Meza-Romero, Roberto Vandenbark, Arthur A. Alkayed, Nabil J. Offner, Halina TI A novel HLA-DR alpha 1-MOG-35-55 construct treats experimental stroke (vol 29, pg 37, 2014) SO METABOLIC BRAIN DISEASE LA English DT Correction C1 [Benedek, Gil; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Zhu, Wenbin; Libal, Nicole; Casper, Amanda; Alkayed, Nabil J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Benedek, Gil; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD SEP PY 2014 VL 29 IS 3 BP 885 EP 885 DI 10.1007/s11011-014-9518-3 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AN3MP UT WOS:000340492600036 ER PT J AU Samocha-Bonet, D Dixit, VD Kahn, CR Leibel, RL Lin, X Nieuwdorp, M Pietilainen, KH Rabasa-Lhoret, R Roden, M Scherer, PE Klein, S Ravussin, E AF Samocha-Bonet, D. Dixit, V. D. Kahn, C. R. Leibel, R. L. Lin, X. Nieuwdorp, M. Pietilainen, K. H. Rabasa-Lhoret, R. Roden, M. Scherer, P. E. Klein, S. Ravussin, E. TI Metabolically healthy and unhealthy obese - the 2013 Stock Conference report SO OBESITY REVIEWS LA English DT Article DE Insulin sensitive; metabolic syndrome; metabolically healthy; obesity ID ADIPOSE-TISSUE INFLAMMATION; MUSCLE ATP SYNTHESIS; FATTY LIVER-DISEASE; BETA-CELL FUNCTION; INSULIN-RESISTANCE; OLDER CHINESE; NLRP3 INFLAMMASOME; MONOZYGOTIC TWINS; ACQUIRED OBESITY; BARIATRIC SURGERY AB Obesity is closely associated with cardiovascular diseases and type 2 diabetes, but some obese individuals, despite having excessive body fat, exhibit metabolic health that is comparable with that of lean individuals. The 'healthy obese' phenotype was described in the 1980s, but major advancements in its characterization were only made in the past five years. During this time, several new mechanisms that may be involved in health preservation in obesity were proposed through the use of transgenic animal models, use of sophisticated imaging techniques and in vivo measurements of insulin sensitivity. However, the main obstacle in advancing our understanding of the metabolically healthy obese phenotype and its related long-term health risks is the lack of a standardized definition. Here, we summarize the proceedings of the 13th Stock Conference of the International Association of the Study of Obesity. We describe the current research and highlight the unanswered questions and gaps in the field. Better understanding of metabolic health in obesity will assist in therapeutic decision-making and help identify therapeutic targets to improve metabolic health in obesity. C1 [Samocha-Bonet, D.] Univ New S Wales, Garvan Inst Med Res, Sydney, NSW, Australia. [Dixit, V. D.] Yale Univ, Sch Med, Comparat Med Sect, New Haven, CT 06510 USA. [Dixit, V. D.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Kahn, C. R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Leibel, R. L.] Columbia Univ, Div Mol Genet, New York, NY USA. [Leibel, R. L.] Columbia Univ, Inst Human Nutr, Naomi Berrie Diabet Ctr, New York, NY 10032 USA. [Lin, X.] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China. [Lin, X.] Chinese Acad Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. [Nieuwdorp, M.] Amsterdam Med Ctr, Dept Internal Med, Amsterdam, Netherlands. [Nieuwdorp, M.] Amsterdam Med Ctr, Dept Vasc Med, Amsterdam, Netherlands. [Pietilainen, K. H.] Univ Helsinki, Cent Hosp, Div Endocrinol, Obes Res Unit,Res Programs Unit,Dept Med, Helsinki, Finland. [Pietilainen, K. H.] Univ Helsinki, Inst Mol Med Finland, FIMM, Helsinki, Finland. [Rabasa-Lhoret, R.] Univ Montreal, IRCM, Fac Med, Nutr Dept, Quebec City, PQ, Canada. [Roden, M.] Univ Dusseldorf, Inst Clin Diabetol, German Diabet Ctr, Dept Endocrinol & Diabetol,German Ctr Diabet Res, Dusseldorf, Germany. [Scherer, P. E.] Univ Texas SW Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 USA. [Klein, S.] Washington Univ, Sch Med, Ctr Human Nutr, St Louis, MO USA. [Ravussin, E.] Pennington Biomed Res Ctr, Div Hlth & Performance Enhancement, Baton Rouge, LA 70808 USA. RP Ravussin, E (reprint author), Pennington Biomed Res Ctr, Div Hlth & Performance Enhancement, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM Ravusse@pbrc.edu OI Samocha-Bonet, Dorit/0000-0001-9422-7852 FU Amway FX The authors would like to thank Dr David York who has coordinated the Stock Conferences for many years. In addition, we would like to thank the sponsor Amway for its partial support thus making this meeting possible. We also thank our speakers and all of the participants attending the 2013 Stock Conference for their intellectual contributions and thoughtful discussions during the meeting. NR 117 TC 37 Z9 38 U1 1 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1467-7881 EI 1467-789X J9 OBES REV JI Obes. Rev. PD SEP PY 2014 VL 15 IS 9 BP 697 EP 708 DI 10.1111/obr.12199 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN4VM UT WOS:000340586700001 PM 25059108 ER PT J AU Middelbeek, RJW James-Todd, T Patti, ME Brown, FM AF Middelbeek, Roeland J. W. James-Todd, Tamarra Patti, Mary-Elizabeth Brown, Florence M. TI Short-Term Insulin Requirements Following Gastric Bypass Surgery in Severely Obese Women with Type 1 Diabetes SO OBESITY SURGERY LA English DT Article DE Gastric bypass surgery; Type 1 diabetes; Insulin requirements ID BARIATRIC SURGERY; MEDICAL THERAPY; MELLITUS; WEIGHT AB In severely obese type 2 diabetes patients, gastric bypass surgery (GB) reduces body mass index (BMI) and hemoglobin A1c (HbA1c) and allows reduced doses of insulin and other medications. Data regarding the effects of GB on severely obese patients with type 1 diabetes are limited. Severely obese women with type 1 diabetes (n = 9) were studied immediately before and after GB (7.7 +/- 5.8 weeks, mean +/- SD). On average, GB reduced mean BMI by 11 % and mean HbA1c by 0.9 % (from 8.0 to 7.1 %), with a parallel 38 % decrease in basal insulin requirements (expressed per kilogram of body weight). GB rapidly decreased BMI, HbA1c, and insulin requirements in severely obese women with type 1 diabetes. However, physiologic insulin replacement remains necessary in patients with type 1 diabetes. C1 [Middelbeek, Roeland J. W.; Patti, Mary-Elizabeth; Brown, Florence M.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [James-Todd, Tamarra] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02120 USA. [Patti, Mary-Elizabeth; Brown, Florence M.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Middelbeek, Roeland J. W.; James-Todd, Tamarra; Patti, Mary-Elizabeth; Brown, Florence M.] Harvard Univ, Sch Med, Boston, MA USA. RP Brown, FM (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM rmiddelb@bidmc.harvard.edu; tjames-todd@partners.org; maryelizabeth.patti@joslin.harvard.edu; florence.brown@joslin.harvard.edu FU NIDDK NIH HHS [T32 DK007260] NR 18 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD SEP PY 2014 VL 24 IS 9 BP 1442 EP 1446 DI 10.1007/s11695-014-1228-8 PG 5 WC Surgery SC Surgery GA AN1YK UT WOS:000340379700006 PM 24668543 ER PT J AU Mai, CL Firth, PG Ahmed, Z Rodriguez, S Yaster, M AF Mai, Christine L. Firth, Paul G. Ahmed, Zulfiqar Rodriguez, Samuel Yaster, Myron TI The development of a specialty: an interview with Dr. Mark C. Rogers, a pioneering pediatric intensivist SO PEDIATRIC ANESTHESIA LA English DT Editorial Material DE Mark C. Rogers; pediatric anesthesiology; pediatric critical care medicine; pediatric intensive care unit AB Dr. Mark C. Rogers (1942-), Professor of Anesthesiology, Critical Care Medicine, and Pediatrics at the Johns Hopkins University, was recruited by the Department of Pediatrics at Johns Hopkins Hospital in 1977 to become the first director of its pediatric intensive care unit. After the dean of the medical school appointed him to chair the Department of Anesthesia in 1979, Rogers changed the course and culture of the department. He renamed it the Department of Anesthesiology and Critical Care Medicine, and developed a long-term strategy of excellence in clinical care, research, and education. However, throughout this period, he never lost his connection to pediatric intensive care. He has made numerous contributions to pediatric critical care medicine through research and his authoritative textbook, Rogers' Textbook of Pediatric Intensive Care. He established a training programme that has produced a plethora of leaders, helped develop the pediatric critical care board examination, and initiated the first World Congress of Pediatric Intensive Care. Based on a series of interviews with Dr. Rogers, this article reviews his influential career and the impact he made on developing pediatric critical care as a specialty. C1 [Mai, Christine L.; Firth, Paul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care Med & Pain Med, Boston, MA USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Univ, Dept Anesthesiol, Baltimore, MD USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Univ, Dept Crit Care Med, Baltimore, MD USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. [Mai, Christine L.; Firth, Paul G.] Massachusetts Eye & Ear Infirm, Dept Anesthesia, Boston, MA 02114 USA. [Ahmed, Zulfiqar] Anesthesia Associates Ann Arbor, Ann Arbor, MI USA. [Ahmed, Zulfiqar] Wayne State Univ, Detroit, MI USA. [Rodriguez, Samuel] Boston Childrens Hosp, Dept Anesthesiol, Boston, MA USA. RP Mai, CL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care Med & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM cmai1@partners.org NR 5 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD SEP PY 2014 VL 24 IS 9 BP 912 EP 918 DI 10.1111/pan.12497 PG 7 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA AN4BU UT WOS:000340533400004 PM 25065470 ER PT J AU Ramesh, AS Krishna, SG Denman, WT Tobias, JD AF Ramesh, Archana S. Krishna, Senthil G. Denman, William T. Tobias, Joseph D. TI An in vitro and in vivo validation of a novel monitor for intracuff pressure in cuffed endotracheal tubes SO PEDIATRIC ANESTHESIA LA English DT Article DE intracuff pressure; cuffed endotracheal tube; pediatric anesthesia ID CHILDREN; INFANTS AB Background: The clinical practice of pediatric anesthesiology has changed with increasing use of cuffed endotracheal tubes (cETTs) in infants and children. To limit the risk of tracheal mucosal damage, regular monitoring of intracuff pressure (CP) is necessary. This study evaluates the efficacy and accuracy of a novel syringe device that provides a digital readout of the CP. Methods: The study was conducted in two phases. In phase 1, an in vitro study, cETTs of sizes 4.0, 5.0, and 6.0 mm ID were placed into polyvinylchloride tubing of appropriate sizes. The cuffs were then inflated, and the CP was measured simultaneously using the syringe device and a manometer. In phase 2, an in vivo study on 200 pediatric patients, the syringe device and the manometer were simultaneously attached to the pilot balloon to measure the CP following endotracheal intubation. Statistical analysis included linear regression analysis and Bland-Altman comparison. Results: Linear regression analysis of the in vitro study demonstrated an R-2 value of 0.9989. Bias and precision were -1.92 +/- 0.62 with 95% level of agreement (LOA) ranging from -3.13 to -0.72. For the in vivo study, the linear regression analysis demonstrated an R-2 value of 0.9943. The bias and precision were -0.53 +/- 0.68 with 95% LOA ranging from -1.86 to 0.81. Conclusion: The study has demonstrated clinically acceptable correlation between the CPs obtained from the standard manometer and the syringe device both in vitro and in vivo. This device is a simple, reliable, portable, and affordable method to monitor CP. C1 [Ramesh, Archana S.; Krishna, Senthil G.; Tobias, Joseph D.] Nationwide Childrens Hosp, Dept Anesthesiol & Pain Med, Columbus, OH 43205 USA. [Krishna, Senthil G.; Tobias, Joseph D.] Ohio State Univ, Dept Anesthesiol & Pain Med, Columbus, OH 43210 USA. [Denman, William T.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Tobias, Joseph D.] Ohio State Univ, Dept Pediat, Nationwide Childrens Hosp, Columbus, OH 43210 USA. RP Tobias, JD (reprint author), Nationwide Childrens Hosp, Dept Anesthesiol & Pain Med, 700 Childrens Dr, Columbus, OH 43205 USA. EM Joseph.Tobias@Nationwidechildrens.org NR 9 TC 3 Z9 3 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD SEP PY 2014 VL 24 IS 9 BP 1005 EP 1008 DI 10.1111/pan.12498 PG 4 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA AN4BU UT WOS:000340533400018 PM 25059837 ER PT J AU Spencer, RJ Chang, PH Guimaraes, AR Firth, PG AF Spencer, Rebecca J. Chang, Philip H. Guimaraes, Alexander R. Firth, Paul G. TI The use of Google Glass for airway assessment and management SO PEDIATRIC ANESTHESIA LA English DT Article DE Google Glass; difficult airway; intubation; innovation; anesthesia; video recording ID DIFFICULT TRACHEAL INTUBATION AB Currently, information about airway assessment and tracheal intubation is communicated verbally or in writing. Google Glass can record this information in real time with minimal disruption to work flow, using standard operating room lighting. C1 [Spencer, Rebecca J.; Firth, Paul G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Chang, Philip H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Firth, PG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM pfirth@partners.org NR 5 TC 6 Z9 6 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD SEP PY 2014 VL 24 IS 9 BP 1009 EP 1011 DI 10.1111/pan.12496 PG 3 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA AN4BU UT WOS:000340533400019 PM 25039494 ER PT J AU Duncan, CN AF Duncan, Christine N. TI Bleomycin and Pulmonary Screening: Many Questions, Few Answers SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material ID CHILDHOOD-CANCER SURVIVOR; ADOLESCENT CANCER C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Duncan, CN (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 320, Boston, MA 02115 USA. EM christine_duncan@dfci.harvard.edu NR 8 TC 0 Z9 0 U1 1 U2 2 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 SEP PY 2014 VL 61 IS 9 BP 1527 EP 1528 DI 10.1002/pbc.25083 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AN4EO UT WOS:000340540600001 PM 24810221 ER PT J AU Gorlick, S Barkauskas, DA Krailo, M Piperdi, S Sowers, R Gill, J Geller, D Randall, RL Janeway, K Schwartz, C Grier, H Meyers, PA Gorlick, R Bernstein, M Marina, N AF Gorlick, Sarah Barkauskas, Donald A. Krailo, Mark Piperdi, Sajida Sowers, Rebecca Gill, Jonathan Geller, David Randall, R. Lor Janeway, Katherine Schwartz, Cindy Grier, Holcombe Meyers, Paul A. Gorlick, Richard Bernstein, Mark Marina, Neyssa TI HER-2 Expression is Not Prognostic in Osteosarcoma; A Children's Oncology Group Prospective Biology Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE Her-2; human epidermal growth factor receptor; immunohistochemistry; osteosarcoma ID SITU HYBRIDIZATION ANALYSIS; HIGH-GRADE OSTEOSARCOMAS; GROWTH-FACTOR RECEPTOR; BREAST-CANCER; GENE AMPLIFICATION; ERBB2 EXPRESSION; P-GLYCOPROTEIN; EWINGS-SARCOMA; SURVIVAL; OVEREXPRESSION AB Background. Since the initial reports of human epidermal growth factor receptor 2 (HER-2) expression as being prognostic in osteosarcoma, numerous small studies varying in the interpretation of the immunohistochemical (IHC) staining patterns have produced conflicting results. The Children's Oncology Group therefore embarked on a prospective biology study in a larger sample of patients to define in osteosarcoma the prognostic value of HER-2 expression using the methodology employed in the initial North American study describing an association between HER-2 expression and outcome. Procedure. The analytic patient population was comprised of 149 patients with newly diagnosed osteosarcoma, 135 with localized disease and 14 with metastatic disease, all of whom had follow up clinical data. Paraffin embedded material from the diagnostic biopsy was stained with CB11 antibody and scored by two independent observers. Correlation of HER-2 IHC score and demographic variables was analyzed using a Fisher's exact test and correlation with survival using a Kaplan-Meier analysis. Results. No association was found with HER-2 status and any of the demographic variables tested including the presence or absence of metastatic disease at diagnosis. No association was found between HER-2 status and either event free survival or overall survival in the patients with localized disease. Conclusion. HER-2 expression is not prognostic in osteosarcoma in the context of this large prospective study. HER-2 expression cannot be used as a basis for stratification of therapy. Identification of potential prognostic factors should occur in the context of large multi-institutional biology studies. (c) 2014 Wiley Periodicals, Inc. C1 [Gorlick, Sarah; Piperdi, Sajida; Sowers, Rebecca; Gill, Jonathan; Gorlick, Richard] Childrens Hosp Montefiore, Dept Pediat, Bronx, NY 10467 USA. [Gorlick, Sarah; Piperdi, Sajida; Sowers, Rebecca; Gill, Jonathan; Gorlick, Richard] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Barkauskas, Donald A.; Krailo, Mark] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Geller, David] Montefiore Med Ctr, Dept Orthopaed Surg, Bronx, NY 10467 USA. [Geller, David] Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Randall, R. Lor] Univ Utah, Huntsman Canc Inst, Sarcoma Serv, Salt Lake City, UT USA. [Randall, R. Lor] Univ Utah, Primary Childrens Hosp, Salt Lake City, UT USA. [Janeway, Katherine; Grier, Holcombe] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Janeway, Katherine; Grier, Holcombe] Childrens Hosp, Boston, MA 02115 USA. [Schwartz, Cindy] Brown Univ, Warren Alpert Med Sch, Hasbro Childrens Hosp, Div Pediat Hematol Oncol, Providence, RI 02912 USA. [Meyers, Paul A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gorlick, Richard] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA. [Bernstein, Mark] IWK Hlth Ctr, Div Hematol Oncol, Halifax, NS, Canada. [Marina, Neyssa] Stanford Univ, Med Ctr, Div Hematol Oncol, Stanford, CA 94305 USA. [Marina, Neyssa] Lucile Packard Childrens Hosp, Stanford, CA USA. RP Gorlick, R (reprint author), Childrens Hosp Montefiore, Dept Pediat, 3415 Bainbridge Ave,Rosenthal Room 300, Bronx, NY 10467 USA. EM rgorlick@montefiore.org OI Meyers, Paul/0000-0001-6146-6101 FU Children's Oncology Group [U10 CA98543]; Human Specimen Banking [U24 CA114766] FX Grant sponsor: Children's Oncology Group; Grant number: U10 CA98543; Grant sponsor: Human Specimen Banking; Grant number: U24 CA114766 NR 35 TC 6 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2014 VL 61 IS 9 BP 1558 EP 1564 DI 10.1002/pbc.25074 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AN4EO UT WOS:000340540600007 PM 24753182 ER PT J AU Moreno, F Sinaki, B Fandino, A Dussel, V Orellana, L Chantada, G AF Moreno, Florencia Sinaki, Banafsheh Fandino, Adriana Dussel, Veronica Orellana, Liliana Chantada, Guillermo TI A Population-Based Study of Retinoblastoma Incidence and Survival in Argentine Children SO PEDIATRIC BLOOD & CANCER LA English DT Article DE cancer; children; retinoblastoma; survival ID CHILDHOOD-CANCER; TRILATERAL RETINOBLASTOMA; UNITED-STATES; COUNTRIES; BIRTH; AGE AB Background. An increased incidence of retinoblastoma in some developing countries has been reported but no conclusive data are available from population-based studies at national level. Purpose. To report the incidence and survival of retinoblastoma in Argentina from the National Pediatric Cancer Registry (ROHA) and the influence of socio-economical indicators on outcome. Procedure. Cases reported to the ROHA (2000-2009) were analyzed. Incidence rates were calculated using National Vital Statistics and survival was estimated. The extended human development index (EHDI) was used as a socio-economical indicator. Results. With 438 patients reported, an incidence of 5.0 cases per million children 0-14 years old (95% CI 3.5-6.4) was calculated. Median age at diagnosis was significantly higher for children from provinces with lower EHDI; (24 vs. 35 months for unilateral, (P = 0.003) and 9 versus 11.5 months for bilateral retinoblastoma (P = 0.027). The 3-year probability of survival was 0.87 and 0.94 for unilateral and bilateral retinoblastoma, respectively. Residents in provinces with higher EHDI had a better 3-year survival (0.93 vs. 0.77 for lower EHDI, P < 0.0001). Probability of survival was higher for patients treated at tertiary level institutions (P = 0.0015). The combination of low EHDI residence province with no treatment at a tertiary institution was associated with the worst survival outcome. For both, unilateral and bilateral disease, children who died were in average diagnosed at older age. Conclusions. The incidence of retinoblastoma in Argentina is comparable to that of developed countries. Retinoblastoma is diagnosed later and survival is lower in the less developed areas of the country. (c) 2014 Wiley Periodicals, Inc. C1 [Moreno, Florencia; Dussel, Veronica] Registro Oncopediat Hosp Argentino, ROHA, Hosp Based Pediat Canc Registry Argentina, Inst Nacl Canc, Buenos Aires, DF, Argentina. [Sinaki, Banafsheh] New York Med Coll, Dept Pediat, New York, NY USA. [Fandino, Adriana] Hosp JP Garrahan, Ophthalmol Serv, Buenos Aires, DF, Argentina. [Dussel, Veronica] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Dussel, Veronica] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Orellana, Liliana] Univ Buenos Aires, Inst Calculo, Buenos Aires, DF, Argentina. [Chantada, Guillermo] Hosp JP Garrahan, Hematol Oncol Serv, Buenos Aires, DF, Argentina. RP Moreno, F (reprint author), Registro Oncopediat Hosp Argentino, ROHA, Hosp Based Pediat Canc Registry Argentina, Inst Nacl Canc, Av Julio A Roca 781 Piso 11,C1067 ABC, Buenos Aires, DF, Argentina. EM roha@roha.org.ar RI Orellana, Liliana/I-5249-2013; Orellana, Liliana/S-3302-2016 OI Orellana, Liliana/0000-0003-3736-4337; Orellana, Liliana/0000-0003-3736-4337 NR 39 TC 8 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2014 VL 61 IS 9 BP 1610 EP 1615 DI 10.1002/pbc.25048 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AN4EO UT WOS:000340540600016 PM 24729462 ER PT J AU Maguire, LH Shellito, PC AF Maguire, Lillias H. Shellito, Paul C. TI Endoscopic piecemeal resection of large colorectal polyps with long-term followup SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Polypectomy; Piecemeal polypectomy; Endoscopy; Colorectal adenomas; Colorectal cancer ID LARGE COLONIC POLYPS; SUBMUCOSAL DISSECTION; ADENOMAS; REMOVAL; EXCISION; SURVEILLANCE; POLYPECTOMY AB Colonoscopic removal of large colorectal polyps is challenging and requires advanced endoscopic technique. Successful endoscopic management not only avoids the morbidity of surgery but also risks perforation, hemorrhage, and recurrence. This study is a retrospective review of a prospectively maintained database of all patients undergoing cautery snare piecemeal polypectomy for large colorectal polyps by a single operator over 20 years with long-term followup. 231 patients underwent 269 piecemeal polypectomies over a 20 year period. The complication rate was 4.3 %. Malignancy was identified in 25 (10.8 %) of patients. Local recurrences occurred in 24 % of patients with benign adenomas. The vast majority of these were managed with repeat endoscopy. Overall, benign large polyps were managed successfully endoscopically in 94.4 % of patients. Piecemeal polypectomy is effective and safe for the management of large colorectal polyps. With long-term followup, the recurrence rate is appreciable, but most recurrences can be successfully managed with further endoscopic intervention. More complex techniques such as endoscopic submucosal dissection are usually unnecessary. C1 [Maguire, Lillias H.; Shellito, Paul C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Maguire, LH (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM LHMaguire@partners.org NR 22 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD SEP PY 2014 VL 28 IS 9 BP 2641 EP 2648 DI 10.1007/s00464-014-3516-8 PG 8 WC Surgery SC Surgery GA AN2MA UT WOS:000340418200018 PM 24695984 ER PT J AU Swain, JD Pugliese, DN Mucumbitsi, J Rusingiza, EK Ruhamya, N Kagame, A Ganza, G Come, PC Breakey, S Greenwood, B Muehlschlegel, JD Patton-Bolman, C Binagwaho, A Bolman, RM AF Swain, JaBaris D. Pugliese, Daniel N. Mucumbitsi, Joseph Rusingiza, Emmanuel K. Ruhamya, Nathan Kagame, Abel Ganza, Gapira Come, Patricia C. Breakey, Suellen Greenwood, Bonnie Muehlschlegel, Jochen D. Patton-Bolman, Cecilia Binagwaho, Agnes Bolman, R. Morton TI Partnership for Sustainability in Cardiac Surgery to Address Critical Rheumatic Heart Disease in Sub-Saharan Africa: The Experience from Rwanda SO WORLD JOURNAL OF SURGERY LA English DT Article ID COST-EFFECTIVENESS-ANALYSIS; PRIMARY PREVENTION; CHILDREN; FEVER; PHARYNGITIS; COUNTRIES AB Rheumatic heart disease (RHD) in the developing world results in critical disability among children, adolescents, and young adults-marginalizing a key population at its peak age of productivity. Few regions in sub-Saharan Africa have independently created an effective strategy to detect and treat streptococcal infection and mitigate its progression to RHD. We describe a unique collaboration, where the Rwanda Ministry of Health, the Rwanda Heart Foundation, and an expatriate humanitarian cardiac surgery program have together leveraged an innovative partnership as a means to expand Rwanda's current capacity to address screening and primary prevention, as well as provide life-saving cardiac surgery for patients with critical RHD. Interviews with key personnel and review of administrative records were conducted to obtain qualitative and quantitative data on the recruitment of clinical personnel, procurement of equipment, and program finances. The number of surgical cases completed and the resultant clinical outcomes are reviewed. From 2008 to 2013, six annual visits were completed. A total of 128 prosthetic valves have been implanted in 86 complex patients in New York Heart Association (NYHA) class III or IV heart failure, with excellent clinical outcomes (5 % 30-day mortality). Postoperative complications included a cerebrovascular accident (n = 1) and hemorrhage, requiring reoperation (n = 2). All procedures were performed with participation of local personnel. This strategy provides a reliable and consistent model of sophisticated specialty care delivery; inclusive of patient-centered cardiac surgery, mentorship, didactics, skill transfer, and investment in a sustainable cardiac program to address critical RHD in sub-Saharan Africa. C1 [Swain, JaBaris D.; Pugliese, Daniel N.; Bolman, R. Morton] Harvard Univ, Sch Med, Dept Surg, Div Cardiac Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. [Swain, JaBaris D.; Pugliese, Daniel N.; Come, Patricia C.; Breakey, Suellen; Greenwood, Bonnie; Muehlschlegel, Jochen D.; Patton-Bolman, Cecilia; Bolman, R. Morton] Team Heart Inc, Boston, MA USA. [Mucumbitsi, Joseph; Rusingiza, Emmanuel K.; Ruhamya, Nathan; Kagame, Abel; Ganza, Gapira] Rwanda Heart Fdn, Kigali, Rwanda. [Mucumbitsi, Joseph; Ruhamya, Nathan] King Faisal Hosp, Kigali, Rwanda. [Rusingiza, Emmanuel K.; Kagame, Abel] Kigali Univ Teaching Hosp CHUK, Kigali, Rwanda. [Ganza, Gapira] Kanombe Mil Hosp, Kigali, Rwanda. [Come, Patricia C.] Harvard Vanguard Med Associates, Boston, MA USA. [Breakey, Suellen] Massachusetts Gen Hosp, Inst Hlth Profess, Charlestown, MA USA. [Greenwood, Bonnie] Harvard Univ, Brigham & Womens Hosp, Dept Pharm, Sch Med, Boston, MA 02115 USA. [Muehlschlegel, Jochen D.] Harvard Univ, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Sch Med, Boston, MA 02115 USA. [Binagwaho, Agnes] Rwanda Minist Hlth, Kigali, Rwanda. RP Swain, JD (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Cardiac Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. EM jdswain@partners.org OI Greenwood, Bonnie/0000-0002-7472-9043 FU Team Heart, Inc.; Medtronic Foundation; Sorin Group; St. Jude Medical, Inc.; Segal Family Foundation; Center for Surgery and Public Health at Brigham; Women's Hospital Department of Surgery; National Heart, Lung and Blood Institute (NHLBI) [T32 HL007734] FX Funding acknowledgement for these efforts include the generous donations from friends and family members of Team Heart, Inc. In-kind donations, various corporate sponsorships-including the Medtronic Foundation, the Sorin Group, St. Jude Medical, Inc., the Segal Family Foundation, the Arthur Tracy Cabot Fellowship at the Center for Surgery and Public Health at Brigham and Women's Hospital Department of Surgery, and the National Heart, Lung and Blood Institute (NHLBI) Harvard-Longwood Research Training Program in Vascular Surgery (Beth Israel Deaconess-Frank LoGerfo; PI) grant #T32 HL007734. NR 28 TC 5 Z9 5 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD SEP PY 2014 VL 38 IS 9 BP 2205 EP 2211 DI 10.1007/s00268-014-2559-2 PG 7 WC Surgery SC Surgery GA AN2NE UT WOS:000340421700003 PM 24728579 ER PT J AU Wang, CC Maciejewski, ML Rao, JK Sheitman, BB Sleath, BL Farley, JF AF Wang, Chi-Chuan Maciejewski, Matthew L. Rao, Jaya K. Sheitman, Brian B. Sleath, Betsy L. Farley, Joel F. TI Examining the Relationship Between Adjunctive Psychotherapy Use and Antipsychotic Persistence and Hospitalization SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Medicaid; Schizophrenia; Adjunctive psychotherapy; Adherence; Hospitalization ID IMPROVE MEDICATION ADHERENCE; RESEARCH-TEAM PORT; OUTCOMES-RESEARCH; TREATMENT RECOMMENDATIONS; PSYCHOSOCIAL TREATMENTS; NATIONAL TRENDS; CLAIMS DATA; FOLLOW-UP; SCHIZOPHRENIA; PATTERNS AB This study assessed whether the addition of adjunctive psychotherapy to antipsychotic pharmacotherapy improved antipsychotic persistence and reduced the risk of hospitalization among patients with schizophrenia using 2001-2003 Medicaid claims data from four states: Illinois, Kansas, Minnesota, and North Carolina. New antipsychotic users aged 18 or older were included. Our study showed that adjunctive psychotherapy use was associated with increased antipsychotic persistence during the first two months of treatment but was not associated with risk of hospitalization. Further research is needed to understand how to optimize the benefits of psychotherapy in terms of frequency of appointments, duration, and type. C1 [Wang, Chi-Chuan] Natl Taiwan Univ, Sch Pharm, Taipei 10051, Taiwan. [Maciejewski, Matthew L.] US Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Rao, Jaya K.; Sleath, Betsy L.; Farley, Joel F.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. [Sheitman, Brian B.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. RP Wang, CC (reprint author), Natl Taiwan Univ, Sch Pharm, 1 Jen Ai Rd,Sect 1, Taipei 10051, Taiwan. EM chicwang@ntu.edu.tw; matthew.maciejewski@va.gov; jayarao@unc.edu; brian_sheitman@med.unc.edu; betsy_sleath@unc.edu; jffarley@unc.edu NR 48 TC 1 Z9 1 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD SEP PY 2014 VL 41 IS 5 BP 598 EP 607 DI 10.1007/s10488-013-0503-7 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AM6IC UT WOS:000339966800004 PM 23733044 ER PT J AU Wiggins, BS Nappi, J Fortier, CR Taber, DJ AF Wiggins, Barbara S. Nappi, Jean Fortier, Christopher R. Taber, David J. TI Cardiovascular Drug Shortages: Predominant Etiologies, Clinical Implications, and Management Strategies SO ANNALS OF PHARMACOTHERAPY LA English DT Review DE drug shortages; cardiovascular; antiarrhythmics; vasoactive agents; diuretics; electrolytes; inotropes ID INDUCED NEPHROPATHY; SODIUM-BICARBONATE; HEART-FAILURE; SEVERE SEPSIS; PREVENTION; TRIAL AB Objective: To review the literature surrounding the incidence, significance, and management of cardiovascular (CV) drug shortages. Data Sources: A literature search was conducted using all available indexing databases from January 1996 to August 2013, coupled with assessments of the ASHP (American Society of Health System Pharmacists) and Food and Drug Administration Web sites designated to drug shortages. Data were also gathered through a review of listservs discussing this topic. Data Synthesis: CV drug shortages are among the top 5 national drug class shortages that are posing a threat to patient care and public health. When a drug shortage occurs, it requires modifications to prescribing and the method medications are processed by the pharmacy. These necessary yet cumbersome changes can potentially result in less-than-desirable prescribing options and increases in personnel time because of administrative and dispensing obstacles. Any one of these has the potential to increase costs and/or lead to worse outcomes. Several factors have been shown to contribute to these shortages, including manufacturing delays, increased demand, medication discontinuations, and lack of raw materials. In this article, we review 13 of the critical CV drug shortages, describe their role in therapy, discuss the reasons for the shortage, define their impact on patient care, and recommend alternative therapies. Conclusions:, CV drug shortages are common and can potentially lead to deleterious patient outcomes. Institutions should develop plans for early identification, management, and resolution to minimize the clinical sequelae associated with drug shortages. C1 [Wiggins, Barbara S.; Taber, David J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Wiggins, Barbara S.; Nappi, Jean] South Carolina Coll Pharm, Charleston, SC USA. [Fortier, Christopher R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taber, DJ (reprint author), Med Univ S Carolina, Div Transplant Surg, 96 Jonathan Lucas St,CSB 409, Charleston, SC 29425 USA. EM taberd@musc.edu NR 28 TC 4 Z9 4 U1 2 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD SEP PY 2014 VL 48 IS 9 BP 1177 EP 1186 DI 10.1177/1060028014539142 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AN1MR UT WOS:000340348500010 PM 24915735 ER PT J AU Singh, H Meyer, AND Thomas, EJ AF Singh, Hardeep Meyer, Ashley N. D. Thomas, Eric J. TI The frequency of diagnostic errors in outpatient care: estimations from three large observational studies involving US adult populations SO BMJ QUALITY & SAFETY LA English DT Article ID CANCER DIAGNOSIS; ADVERSE EVENTS; MISSED OPPORTUNITIES; MALPRACTICE CLAIMS; UNITED-STATES; FOLLOW-UP; NEGLIGENT AB Background The frequency of outpatient diagnostic errors is challenging to determine due to varying error definitions and the need to review data across multiple providers and care settings over time. We estimated the frequency of diagnostic errors in the US adult population by synthesising data from three previous studies of clinic-based populations that used conceptually similar definitions of diagnostic error. Methods Data sources included two previous studies that used electronic triggers, or algorithms, to detect unusual patterns of return visits after an initial primary care visit or lack of follow-up of abnormal clinical findings related to colorectal cancer, both suggestive of diagnostic errors. A third study examined consecutive cases of lung cancer. In all three studies, diagnostic errors were confirmed through chart review and defined as missed opportunities to make a timely or correct diagnosis based on available evidence. We extrapolated the frequency of diagnostic error obtained from our studies to the US adult population, using the primary care study to estimate rates of diagnostic error for acute conditions (and exacerbations of existing conditions) and the two cancer studies to conservatively estimate rates of missed diagnosis of colorectal and lung cancer (as proxies for other serious chronic conditions). Results Combining estimates from the three studies yielded a rate of outpatient diagnostic errors of 5.08%, or approximately 12 million US adults every year. Based upon previous work, we estimate that about half of these errors could potentially be harmful. Conclusions Our population-based estimate suggests that diagnostic errors affect at least 1 in 20 US adults. This foundational evidence should encourage policymakers, healthcare organisations and researchers to start measuring and reducing diagnostic errors. C1 [Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Vet Affairs Ctr Innovat Qual Effectivenes, Houston, TX 77030 USA. [Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Med Sch Houston, Div Gen Med, Dept Med, Univ Texas Houston,Mem Hermann Ctr Healthcare Qua, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd,VAMC 152, Houston, TX 77030 USA. EM hardeeps@bcm.edu OI Meyer, Ashley/0000-0001-7993-8584 FU NIH K23 Career Development Award [K23CA125585]; VA National Center of Patient Safety; Agency for Healthcare Research and Quality [R18HS017820, R18HS17244-02]; Houston VA Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX Studies mentioned in this paper were supported by an NIH K23 Career Development Award (K23CA125585), the VA National Center of Patient Safety, and Agency for Healthcare Research and Quality (R18HS017820 and R18HS17244-02). HS and ANDM were supported in part by the Houston VA Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). NR 28 TC 36 Z9 36 U1 1 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD SEP PY 2014 VL 23 IS 9 BP 727 EP 731 DI 10.1136/bmjqs-2013-002627 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AN0AR UT WOS:000340244000006 PM 24742777 ER PT J AU Fazeli, PK Klibanski, A AF Fazeli, Pouneh K. Klibanski, Anne TI Anorexia nervosa and bone metabolism SO BONE LA English DT Review DE Anorexia nervosa; Bone mineral density ID GROWTH-FACTOR-I; HYPOTHALAMIC-PITUITARY FUNCTION; LOW SERUM TRIIODOTHYRONINE; THYROID-HORMONE RECEPTORS; MARROW ADIPOSE-TISSUE; IGF-BINDING PROTEINS; ADOLESCENT GIRLS; MINERAL DENSITY; HEALTHY ADOLESCENTS; SECRETORY DYNAMICS AB Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importantly, this low bone mass is also associated with a seven-fold increased risk of fracture. Therefore, strategies to effectively prevent bone loss and increase bone mass are critical. We will review hormonal adaptations that contribute to bone loss in this population as well as promising new therapies that may increase bone mass and reduce fracture risk in AN. (C) 2014 Elsevier Inc. All rights reserved. C1 [Fazeli, Pouneh K.; Klibanski, Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unil, Boston, MA USA. RP Fazeli, PK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM pkfazeli@partners.org FU [K23 DK094820]; [R24 DK092759] FX Sources of support: K23 DK094820 (Fazeli) and R24 DK092759 (Klibanski). NR 117 TC 7 Z9 7 U1 3 U2 19 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 SEP PY 2014 VL 66 BP 39 EP 45 DI 10.1016/j.bone.2014.05.014 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM7DB UT WOS:000340023800006 PM 24882734 ER PT J AU Bredella, MA Fazeli, PK Daley, SM Miller, KK Rosen, CJ Klibanski, A Torriani, M AF Bredella, Miriam A. Fazeli, Pouneh K. Daley, Scott M. Miller, Karen K. Rosen, Clifford J. Klibanski, Anne Torriani, Martin TI Marrow fat composition in anorexia nervosa SO BONE LA English DT Article DE Anorexia nervosa; MR spectroscopy; Bone marrow fat; Marrow fat composition; Saturated lipids ID BONE-MINERAL DENSITY; PROTON MR SPECTROSCOPY; PREADIPOCYTE FACTOR-I; INTRAMYOCELLULAR LIPIDS; INSULIN-RESISTANCE; BODY-COMPOSITION; ADIPOSE-TISSUE; NORMAL-WEIGHT; WOMEN; OBESE AB Purpose: Women with anorexia nervosa (AN) have increased marrow fat despite severe depletion of body fat. Recent studies have suggested that marrow fat composition may serve as a biomarker for bone quality. The purpose of our study was to investigate marrow fat composition of the femur using proton MR spectroscopy (H-1 MRS), and the relationship between measures of marrow fat composition and BMD and body composition in women with AN and normal-weight controls. Materials and methods: 14 women with AN (29.5 +/- 1.9 years) and 12 age-matched normal-weight controls underwent 1H MRS to determine total marrow fat content and marrow fat composition of the femoral diaphysis and soleus intramyocellular lipids und unsaturated muscle lipids. MRI was performed to quantify abdominal fat, thigh fat and muscle areas. Lumbar spine BMD, fat and lean mass were assessed by DXA. Results: Subjects with AN had higher marrow fat content (p < 0.05), but similar marrow fat composition (p > 0.05) compared to normal-weight controls. There was an inverse association between marrow methylene protons, an estimate of fatty acid (FA) saturated bonds, and lumbar spine BMD (r = -0.52, p = 0.008) independent of %ideal body weight (%IBW). Olefinic protons at 53 ppm, an estimate of FA unsaturated bonds, were inversely associated with body fat depots, independent of %IBW, and positively associated with soleus unsaturation (p <= 0.05). Conclusion: Women with AN have higher total femoral marrow fat but similar composition compared to normal-weight controls. The degree of marrow FA saturation correlates inversely with BMD, suggesting that saturated lipids may have negative effects on BMD. The degree of marrow FA unsaturation correlates positively with soleus unsaturation, suggesting that marrow fat composition may be influenced by the same factors as ectopic lipid composition in muscle. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bredella, Miriam A.; Daley, Scott M.; Torriani, Martin] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fazeli, Pouneh K.; Miller, Karen K.; Klibanski, Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA USA. [Rosen, Clifford J.] Maine Med Ctr Res Inst, Scarborough, ME USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org FU NIH [R24 DK084970, R01 HL-077674, R01 DK052625, M01 RR01066, UL1 RR025758, K23 RR-23090] FX This study was supported through the following NIH grants: R24 DK084970, R01 HL-077674, R01 DK052625, M01 RR01066, UL1 RR025758, and K23 RR-23090. NR 42 TC 20 Z9 20 U1 0 U2 14 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 SEP PY 2014 VL 66 BP 199 EP 204 DI 10.1016/j.bone.2014.06.014 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM7DB UT WOS:000340023800026 PM 24953711 ER PT J AU Pivonello, R Petersenn, S Newell-Price, J Findling, JW Gu, F Maldonado, M Trovato, A Hughes, G Salgado, LR Lacroix, A Schopohl, J Biller, BMK AF Pivonello, Rosario Petersenn, Stephan Newell-Price, John Findling, James W. Gu, Feng Maldonado, Mario Trovato, Andrew Hughes, Gareth Salgado, Luiz R. Lacroix, Andre Schopohl, Jochen Biller, Beverly M. K. CA Pasireotide B2305 Study Grp TI Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study SO CLINICAL ENDOCRINOLOGY LA English DT Article ID QUALITY-OF-LIFE; CARDIOVASCULAR RISK; SOM230; HYPERTENSION; PREVALENCE; REMISSION; SECRETION; ADENOMAS; BURDEN; CURE AB Objective Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. Design Phase III study with double-blind randomization of two pasireotide doses. Methods Patients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels >= 1.5 x upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 mu g bid). At month 3, patients with UFC <= 2 x ULN and not exceeding the baseline value continued their randomized dose; all others received 300 mu g bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200 mu g bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control. Results Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72.8% of patients. Conclusions In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased. C1 [Pivonello, Rosario] Univ Naples Federico II, Sez Endocrinol, Dipartimento Med Clin & Chirurg, IT-80131 Naples, Italy. [Petersenn, Stephan] ENDOC Ctr Endocrine Tumors, Hamburg, Germany. [Newell-Price, John] Univ Sheffield, Sch Med, Sheffield, S Yorkshire, England. [Findling, James W.] Med Coll Wisconsin, Div Endocrinol Metab & Clin Nutr, Milwaukee, WI 53226 USA. [Gu, Feng] Chinese Acad Med Sci, Dept Endocrinol, Key Lab Endocrinol, Minist Hlth,Peking Union Med Coll Hosp, Beijing 100730, Peoples R China. [Maldonado, Mario; Trovato, Andrew] Novartis Pharma AG, Oncol Business Unit, Clin Dev, Basel, Switzerland. [Hughes, Gareth] Novartis Pharmaceut, E Hanover, NJ USA. [Salgado, Luiz R.] Univ Sao Paulo, Sch Med, Div Gen Internal Med, Hosp Clin, Sao Paulo, Brazil. [Lacroix, Andre] Ctr Hosp Univ Montreal, Dept Med, Div Endocrinol, Montreal, PQ, Canada. [Schopohl, Jochen] Univ Munich, Med Klin 4, Munich, Germany. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. RP Pivonello, R (reprint author), Univ Naples Federico II, Sez Endocrinol, Dipartimento Med Clin & Chirurg, IT-80131 Naples, Italy. EM rosario.pivonello@unina.it RI IBIS, ENDOCRINAS/P-3831-2015; OI Brue, Thierry/0000-0001-8482-6691; Carvalho, Davide/0000-0002-3156-3741 FU Novartis Pharma AG; Novartis Pharmaceuticals Corporation FX This study was funded by Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank Daniel Webber PhD, Mudskipper Business Ltd, for medical editorial assistance with this manuscript. We thank all investigators who contributed to the CSOM230B2305 study, as well as the numerous nurses, study co-ordinators and patients. NR 33 TC 28 Z9 30 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 2014 VL 81 IS 3 BP 408 EP 417 DI 10.1111/cen.12431 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM9GG UT WOS:000340188300014 PM 24533697 ER PT J AU Santhakumar, A Balasubramanian, R Miller, M Quinton, R AF Santhakumar, Anjali Balasubramanian, Ravikumar Miller, Margaret Quinton, Richard TI Reversal of isolated hypogonadotropic hypogonadism: long-term integrity of hypothalamo-pituitary-testicular axis in two men is dependent on intermittent androgen exposure SO CLINICAL ENDOCRINOLOGY LA English DT Letter C1 [Santhakumar, Anjali; Miller, Margaret; Quinton, Richard] Newcastle Upon Tyne Hosp Fdn NHS Trust, Royal Victoria Infirm, Endocrine Unit, Newcastle Upon Tyne, Tyne & Wear, England. [Balasubramanian, Ravikumar] Harvard Univ, Reprod Endocrine Sci Ctr, Boston, MA 02115 USA. [Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Quinton, Richard] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Santhakumar, A (reprint author), Newcastle Upon Tyne Hosp Fdn NHS Trust, Royal Victoria Infirm, Endocrine Unit, Newcastle Upon Tyne, Tyne & Wear, England. EM richard.quinton@ncl.ac.uk NR 7 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 2014 VL 81 IS 3 BP 473 EP 476 DI 10.1111/cen.12347 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM9GG UT WOS:000340188300024 PM 24118132 ER PT J AU Tiberi, JV Hansen, V El-Abbadi, N Bedair, H AF Tiberi, John V., III Hansen, Viktor El-Abbadi, Naglaa Bedair, Hany TI Increased Complication Rates After Hip and Knee Arthroplasty in Patients With Cirrhosis of the Liver SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PERIPROSTHETIC JOINT INFECTION; MEDICARE PATIENTS; RISK-FACTORS; POSTOPERATIVE MORTALITY; EARLY REVISION; DISEASE; MODEL; SURVIVAL; TKA AB Risk stratification is critical in patients with cirrhosis undergoing THAs and TKAs, as they may be more likely to have serious medical and surgical complications. As opposed to the Child-Pugh scoring system, which has limited use for orthopaedic surgeons inexperienced in assessing ascites and hepatic encephalopathy, the Model for End-stage Liver Disease (MELD) is an easily calculated, validated scoring system for severity of liver disease based on common laboratory values; however, its usefulness for predicting complications after elective arthroplasty has not been studied. The purposes of this study were to determine the differences between patients with cirrhosis and control subjects in (1) hospital length of stay, discharge disposition, and readmission within 90 days; (2) early postoperative (90 days) medical complications potentially related to liver disease; (3) surgical complications within 90 days and any time after the procedure; (4) mortality rates after THA and TKA; and in addition, (5) to use the MELD score as a predictor for risk of complications and mortality. Institutional database query software used coding data identified 115 patients with liver cirrhosis before having THAs or TKAs from 2000 to 2012 and 115 control subjects without cirrhosis matched by age, sex, procedure, and year of surgery. Early postoperative and longer-term medical and surgical complications were compared. Regression analysis was used to determine a MELD score that predicted greater risk of complications. Compared with matched control subjects, patients with cirrhosis had prolonged length of stay and higher rates of discharge to nursing facilities, readmission in 90 days, and urinary tract infections (p < 0.01), renal failure (p = 0.03), blood transfusions (p < 0.01), gastrointestinal hemorrhage (p = 0.04), dislocations (p = 0.01), infections (p = 0.02), and revisions (p = 0.04) within 90 days. One-year (p = 0.01) and longer-term (p = 0.0002) mortality rates were greater in patients with cirrhosis. A MELD score of 10 or greater predicted a three times increased likelihood (odds ratio [OR]) of any complication (95% CI, 1.28-7.00; p = 0.01) and 4.1 times increased likelihood (OR) of death (95% CI, 1.42-11.86; p < 0.01). Patients with cirrhosis undergoing THAs and TKAs should be counseled regarding their increased risk of medical complications, surgical complications, and death. A MELD score of 10 or greater is associated with a high rate of complications, although this finding needs further validation because we were unable to control for all medical confounders. Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence. C1 [Tiberi, John V., III; Bedair, Hany] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Tiberi, John V., III; Bedair, Hany] Harvard Univ, Sch Med, Boston, MA USA. [Hansen, Viktor] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [El-Abbadi, Naglaa] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Bedair, Hany] Kaplan Ctr Joint Reconstruct Surg, Newton, MA USA. RP Tiberi, JV (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM jvtiberi@gmail.com NR 16 TC 5 Z9 5 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2014 VL 472 IS 9 BP 2774 EP 2778 DI 10.1007/s11999-014-3681-z PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AM7LR UT WOS:000340049200031 PM 24993141 ER PT J AU Menendez, ME Neuhaus, V van Dijk, CN Ring, D AF Menendez, Mariano E. Neuhaus, Valentin van Dijk, C. Niek Ring, David TI The Elixhauser Comorbidity Method Outperforms the Charlson Index in Predicting Inpatient Death After Orthopaedic Surgery SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; IN-HOSPITAL MORTALITY; TOTAL JOINT ARTHROPLASTY; ADMINISTRATIVE DATA; RISK-ADJUSTMENT; PERIOPERATIVE-OUTCOMES; UNITED-STATES; SHOULDER ARTHROPLASTY; METABOLIC SYNDROME AB Scores derived from comorbidities can help with risk adjustment of quality and safety data. The Charlson and Elixhauser comorbidity measures are well-known risk adjustment models, yet the optimal score for orthopaedic patients remains unclear. We determined whether there was a difference in the accuracy of the Charlson and Elixhauser comorbidity-based measures in predicting (1) in-hospital mortality after major orthopaedic surgery, (2) in-hospital adverse events, and (3) nonroutine discharge. Among an estimated 14,007,813 patients undergoing orthopaedic surgery identified in the National Hospital Discharge Survey (1990-2007), 0.80% died in the hospital. The association of each Charlson comorbidity measure and Elixhauser comorbidity measure with mortality was assessed in bivariate analysis. Two main multivariable logistic regression models were constructed, with in-hospital mortality as the dependent variable and one of the two comorbidity-based measures (and age, sex, and year of surgery) as independent variables. A base model that included only age, sex, and year of surgery also was evaluated. The discriminative ability of the models was quantified using the area under the receiver operating characteristic curve (AUC). The AUC quantifies the ability of our models to assign a high probability of mortality to patients who die. Values range from 0.50 to 1.0, with 0.50 indicating no ability to discriminate and 1.0 indicating perfect discrimination. Elixhauser comorbidity adjustment provided a better prediction of in-hospital case mortality (AUC, 0.86; 95% CI, 0.86-0.86) compared with the Charlson model (AUC, 0.83; 95% CI, 0.83-0.84) and to the base model with no comorbidities (AUC, 0.81; 95% CI, 0.81-0.81). In terms of relative improvement in predictive performance, the Elixhauser measure performed 60% better than the Charlson score in predicting mortality. The Elixhauser model discriminated inpatient morbidity better than the Charlson measure, but the discriminative ability of the model was poor and the difference in the absolute improvement in predictive power between the two models (AUC, 0.01) is of dubious clinical importance. Both comorbidity models exhibited the same degree of discrimination for estimating nonroutine discharge (AUC, 0.81; 95% CI, 0.81-0.82 for both models). Provider-specific outcomes, particularly inpatient mortality, may be evaluated differently depending on the comorbidity risk adjustment model selected. Future research assessing and comparing the performance of the Charlson and Elixhauser measures in predicting long-term outcomes would be of value. Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence. C1 [Menendez, Mariano E.; Neuhaus, Valentin; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [van Dijk, C. Niek] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM marianofurrer@gmail.com OI Neuhaus, Valentin/0000-0003-4012-5628 NR 61 TC 23 Z9 24 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2014 VL 472 IS 9 BP 2878 EP 2886 DI 10.1007/s11999-014-3686-7 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AM7LR UT WOS:000340049200048 PM 24867450 ER PT J AU Burris, HH Camargo, CA AF Burris, Heather H. Camargo, Carlos A., Jr. TI Time for large randomised trials of vitamin D for women with gestational diabetes mellitus to improve perinatal health outcomes SO DIABETOLOGIA LA English DT Editorial Material DE GDM; Gestational diabetes; Pregnancy; Vitamin D ID GLUCOSE-TOLERANCE; PREGNANCY; METAANALYSIS; DEFICIENCY; COMMON AB Gestational diabetes mellitus (GDM) affects 7-14% of pregnancies in the USA and its incidence is rising. Several small trials have demonstrated improved insulin sensitivity and glucose tolerance with vitamin D supplementation among women with GDM. In this issue of Diabetologia (DOI: 10.1007/s00125-014-3293-x), Asemi and colleagues report that co-supplementation of vitamin D and calcium among women with diet-controlled GDM improves several biomarkers of metabolic status, including insulin, glucose and cholesterol. Whether such improvements in biomarkers would translate into clinically meaningful reductions in the harmful sequelae of GDM remains unknown. The promising results from Asemi and colleagues justify investment in large randomised, double-blind, placebo-controlled trials of vitamin D ( with or without calcium) for women with GDM. Such trials should be powered for perinatal outcomes such as Caesarean section for macrosomia, postnatal hypoglycaemia and respiratory distress; ideally, the trials would include long-term follow-up of mothers and infants for later metabolic consequences of GDM. C1 [Burris, Heather H.] Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02215 USA. [Burris, Heather H.] Harvard Univ, Sch Med, Dept Pediat, Boston Childrens Hosp,Div Newborn Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. RP Burris, HH (reprint author), Beth Israel Deaconess Med Ctr, Dept Neonatol, 330 Brookline Ave,RO 318, Boston, MA 02215 USA. EM heburris@bidmc.harvard.edu OI Burris, Heather/0000-0003-4510-9547 FU NIEHS NIH HHS [K23 ES022242] NR 22 TC 4 Z9 4 U1 3 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2014 VL 57 IS 9 BP 1746 EP 1748 DI 10.1007/s00125-014-3314-9 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM7MG UT WOS:000340050800002 PM 24989998 ER PT J AU Meigs, JB Grant, RW Piccolo, R Lopez, L Florez, JC Porneala, B Marceau, L McKinlay, JB AF Meigs, James B. Grant, Richard W. Piccolo, Rebecca Lopez, Lenny Florez, Jose C. Porneala, Bianca Marceau, Lisa McKinlay, John B. TI Association of African genetic ancestry with fasting glucose and HbA(1c) levels in non-diabetic individuals: the Boston Area Community Health (BACH) Prediabetes Study SO DIABETOLOGIA LA English DT Article DE Fasting glucose; Genetic ancestry; Genetic association study; Genetic epidemiology; Genetics; HbA(1c); Health disparities; Prediabetes; Type 2 diabetes ID TYPE-2 DIABETES RISK; SINGLE NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; HEMOGLOBIN A(1C) LEVELS; ADMIXTURE MAP; LOCI; AMERICANS; INSULIN; POPULATIONS; VARIANTS AB Aims/hypothesis To test among diabetes-free urban community-dwelling adults the hypothesis that the proportion of African genetic ancestry is positively associated with glycaemia, after accounting for other continental ancestry proportions, BMI and socioeconomic status (SES). Methods The Boston Area Community Health cohort is a multi-stage 1:1:1 stratified random sample of self-identified African-American, Hispanic and white adults from three Boston inner city areas. We measured 62 ancestry informative markers, fasting glucose (FG), HbA(1c), BMI and SES (income, education, occupation and insurance status) and analysed 1,387 eligible individuals (379 African-American, 411 Hispanic, 597 white) without clinical or biochemical evidence of diabetes. We used three-heritage multinomial linear regression models to test the association of FG or HbA(1c) with genetic ancestry proportion adjusted for: (1) age and sex; (2) age, sex and BMI; and (3) age, sex, BMI and SES. Results Mean age- and sex-adjusted FG levels were 5.73 and 5.54 mmol/l among those with 100% African or European ancestry, respectively. Using per cent European ancestry as the referent, each 1% increase in African ancestry proportion was associated with an age- and sex-adjusted FG increase of 0.0019 mmol/l (p = 0.01). In the BMI- and SES-adjusted model the slope was 0.0019 (p = 0.02). Analysis of HbA(1c) gave similar results. Conclusions/interpretation A greater proportion of African genetic ancestry is independently associated with higher FG levels in a non-diabetic community-based cohort, even accounting for other ancestry proportions, obesity and SES. The results suggest that differences between African-Americans and whites in type 2 diabetes risk may include genetically mediated differences in glucose homeostasis. C1 [Meigs, James B.; Porneala, Bianca] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Grant, Richard W.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Piccolo, Rebecca; Marceau, Lisa; McKinlay, John B.] New England Res Inst, Watertown, MA 02172 USA. [Lopez, Lenny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dispar Solut Ctr,Mongan Inst Hlth Policy, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res & Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Boston, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK [R01 DK080786, K24 DK080140, R01 DK078616] FX This study was supported by NIDDK R01 DK080786 'Upstream contributors to downstream disparities in type 2 diabetes', as well as by NIDDK K24 DK080140 and R01 DK078616 (JBM). NR 43 TC 4 Z9 4 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2014 VL 57 IS 9 BP 1850 EP 1858 DI 10.1007/s00125-014-3301-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM7MG UT WOS:000340050800015 PM 24942103 ER PT J AU McKay, RR Lin, X Perkins, JJ Heng, DYC Simantov, R Choueiri, TK AF McKay, Rana R. Lin, Xun Perkins, Julia J. Heng, Daniel Y. C. Simantov, Ronit Choueiri, Toni K. TI Prognostic Significance of Bone Metastases and Bisphosphonate Therapy in Patients with Renal Cell Carcinoma SO EUROPEAN UROLOGY LA English DT Article DE Bisphosphonates; Bone metastases; mTOR inhibitors; Renal cell carcinoma; VEGF-targeted therapy ID POPULATION-BASED ANALYSIS; SKELETAL-RELATED EVENTS; US MEDICARE BENEFICIARIES; ZOLEDRONIC ACID; TARGETED THERAPY; PROGRESSION-FREE; BREAST-CANCER; DOUBLE-BLIND; PHASE-III; OSTEONECROSIS AB Background: Bone metastases (BMs) are frequently present in patients with metastatic renal cell carcinoma (mRCC) and cause significant morbidity. Objective: The purpose of this analysis was to assess the impact of BMs and bisphosphonate therapy (BT) on outcomes in mRCC. Design, setting, and participants: We conducted a pooled analysis of patients with mRCC treated from 2003 to 2011 in phase 2 and 3 trials. Outcome measurements and statistical analysis: Statistical analyses were performed using Cox regression and the Kaplan-Meier method. Results and limitations: We identified 2749 patients treated with sunitinib (n = 1059), sorafenib (n = 355), axitinib (n = 359), temsirolimus (n = 208), temsirolimus plus interferon-alpha (IFN-alpha) (n = 208), or IFN-alpha (n = 560), with 28% (n = 781) having BMs. A total of 285 patients (10.4%) received BT. The presence of BMs in patients was associated with shorter overall survival (OS) when compared with patients without BMs (13.2 vs 20.2 mo, respectively; p < 0.0001) and shorter progression-free survival (PFS) (5.1 vs 6.7 mo, respectively; p < 0.0008). When stratified by risk groups, the presence of BMs was associated with shorter OS in all risk groups. The use of BT in patients with BMs was not associated with improved OS compared with patientswho did not receive BT (13.3 vs 13.1 mo, respectively; p = 0.3801) or improved PFS (5.1 vs 4.9 mo, respectively; p = 0.1785). Bisphosphonate users with BMs did not have a decreased rate of skeletal-related events (SREs) compared with nonusers (8.6% vs 5.8%, respectively; p = 0.191). In addition, BT was associated with increased rates of hypocalcemia, renal insufficiency, and osteonecrosis of the jaw (p < 0.0001). Data were analyzed retrospectively. Conclusions: We confirm that the presence of BMs is associated with shorter survival in mRCC. BT did not affect survival or SRE prevention and was associated with increased toxicity. Patient summary: In this analysis, we demonstrate that bone metastases are associated with shorter survival in patients with metastatic renal cell carcinoma. In addition, we call into question the utility of bisphosphonate therapy in this population. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [McKay, Rana R.; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lin, Xun; Perkins, Julia J.; Simantov, Ronit] Pfizer Oncol, New York, NY USA. [Heng, Daniel Y. C.] Tom Baker Canc Clin, Calgary, AB, Canada. RP Choueiri, TK (reprint author), Harvard Univ, Dana Farber Canc Inst, Brigham & Womens Hosp, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM toni_choueiri@DFCI.harvard.edu FU Pfizer FX Toni K. Choueiri certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Toni K. Choueiri has received research funding from Pfizer and has an advisory role at Aveo, Pfizer, Novartis, GlaxoSmithKline, Genentech, and Bayer and Onyx. Daniel Y.C. Heng has an advisory role at Aveo, Pfizer, Novartis, and Bayer. Xun Lin, Julia J. Perkins, and Ronit Simantov are employees at Pfizer. NR 27 TC 13 Z9 13 U1 0 U2 12 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 SEP PY 2014 VL 66 IS 3 BP 502 EP 509 DI 10.1016/j.eururo.2014.02.040 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AN0FZ UT WOS:000340260900027 PM 24613250 ER PT J AU Leow, JJ Martin-Doyle, W Fay, AP Choueiri, TK Chang, SL Bellmunt, J AF Leow, Jeffrey J. Martin-Doyle, William Fay, Andre P. Choueiri, Toni K. Chang, Steven L. Bellmunt, Joaquim TI A Systematic Review and Meta-analysis of Adjuvant and Neoadjuvant Chemotherapy for Upper Tract Urothelial Carcinoma SO EUROPEAN UROLOGY LA English DT Review DE Upper tract urothelial carcinoma; Ureteral neoplasms; Renal pelvic tumors; Kidney neoplasms; Urothelial carcinoma; Adjuvant; Neoadjuvant; Chemotherapy; Nephroureterectomy ID UPPER URINARY-TRACT; TRANSITIONAL-CELL CARCINOMA; INVASIVE BLADDER-CANCER; MICROSATELLITE INSTABILITY; PERIOPERATIVE CHEMOTHERAPY; PROMOTER HYPERMETHYLATION; CLINICAL-TRIALS; UPDATE; CISPLATIN; TUMORS AB Context: The role of adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NC) remains poorly defined for the management of upper tract urothelial carcinoma (UTUC), although some studies suggest a benefit. Objective: To update the current evidence on the role of NC and AC for UTUC patients. Evidence acquisition: We searched for all studies investigating NC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings prior to February 2014. A systematic review and meta-analysis were performed. Evidence synthesis: No randomized trials investigated the role of AC for UTUC. There was one prospective study (n = 36) investigating adjuvant carboplatin-paclitaxel and nine retrospective studies, with a total of 482 patients receiving cisplatin-based or non-cisplatin-based AC after nephroureterectomy (NU) and 1300 patients receiving NU alone. Across three cisplatin-based studies, the pooled hazard ratio (HR) for overall survival (OS) was 0.43 (95% confidence interval [CI], 0.21-0.89; p = 0.023) compared with those who received surgery alone. For disease-free survival (DFS), the pooled HR across two studies was 0.49 (95% CI, 0.24-0.99; p = 0.048). Benefit was not seen for non-cisplatin-based regimens. For NC, two phase 2 trials demonstrated favorable pathologic downstaging rates, with 3-yr OS and disease-specific survival (DSS) <= 93%. Across two retrospective studies investigating NC, there was a DSS benefit, with a pooled HR of 0.41 (95% CI, 0.22-0.76; p = 0.005). Conclusions: There appears to be an OS and DFS benefit for cisplatin-based AC in UTUC. This evidence is limited by the retrospective nature of studies and their relatively small sample size. NC appears to be promising, but more trials are needed to confirm its utility. Patient summary: After a comprehensive search of studies examining the role of chemotherapy for upper tract urothelial cancer, the pooled evidence shows that cisplat-in-based adjuvant chemotherapy was beneficial for prolonging survival. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Leow, Jeffrey J.; Fay, Andre P.; Choueiri, Toni K.; Chang, Steven L.; Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Bladder Canc Ctr, Boston, MA USA. [Leow, Jeffrey J.; Chang, Steven L.] Harvard Univ, Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Leow, Jeffrey J.; Chang, Steven L.] Harvard Univ, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Martin-Doyle, William] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Bellmunt, J (reprint author), Dana Farber Brigham & Womens Canc Ctr, Bladder Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM joaquim_bellmunt@dfci.harvard.edu NR 54 TC 41 Z9 43 U1 0 U2 13 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 SEP PY 2014 VL 66 IS 3 BP 529 EP 541 DI 10.1016/j.eururo.2014.03.003 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA AN0FZ UT WOS:000340260900034 PM 24680361 ER PT J AU Gandaglia, G Popa, I Abdollah, F Schiffmann, J Shariat, SF Briganti, A Montorsi, F Trinh, QD Karakiewicz, PI Sun, M AF Gandaglia, Giorgio Popa, Ioana Abdollah, Firas Schiffmann, Jonas Shariat, Shahrokh F. Briganti, Alberto Montorsi, Francesco Quoc-Dien Trinh Karakiewicz, Pierre I. Sun, Maxine TI The Effect of Neoadjuvant Chemotherapy on Perioperative Outcomes in Patients Who Have Bladder Cancer Treated with Radical Cystectomy: A Population-based Study SO EUROPEAN UROLOGY LA English DT Article DE Neoadjuvant chemotherapy; Muscle-invasive bladder cancer; Radical cystectomy; Complications ID EAU GUIDELINES; CLAIMS DATA; COMPLICATIONS; TRENDS; IMPACT; IDENTIFICATION; COMORBIDITY; CISPLATIN; DATABASE; UPDATE AB Background: Although therapeutic guidelines recommend the use of neoadjuvant chemotherapy before radical cystectomy (RC) in patients who have muscle-invasive bladder cancer (MIBC), this approach remains largely underused. One of the main reasons for this phenomenon might reside in concerns regarding the risk of morbidity and mortality associated with neoadjuvant chemotherapy. Objective: To compare perioperative outcomes between patients receiving neoadjuvant chemotherapy and those treated with RC alone. Design, setting, and participants: Relying on the Surveillance Epidemiology and End Results-Medicare-linked database, 3760 patients diagnosed with MIBC between 2000 and 2009 were evaluated. Intervention: RC alone or RC plus neoadjuvant chemotherapy. Outcome measurements and statistical analysis: Complications occurred within 30 and 90 d after surgery. Heterologous blood transfusions (HBTs), length of stay (LoS), readmission, and perioperative mortality were compared. To decrease the effect of unmeasured confounders associated with treatment selection, propensity scorematched analyses were performed. Results and limitations: Overall, 416 (11.1%) of patients received neoadjuvant chemotherapy. Following propensity score matching, 416 (20%) and 1664 (80%) patients treated with RC plus neoadjuvant chemotherapy and RC alone remained, respectively. The 30-d complication, readmission, and mortality rates were 66.0%, 32.2%, and 5.3%, respectively. The 90-d complication, readmission, and mortality rates were 72.5%, 46.6%, and 8.2%, respectively. When patients were stratified according to neoadjuvant chemotherapy status, no significant differences were observed in the rates of complications, HBT, prolonged LoS, readmission, and mortality between the two groups (all p < 0.1). These results were confirmed in multivariate analyses, where the use of neoadjuvant chemotherapy was not associated with higher risk of 30-and 90-d complications, HBT, prolonged LoS, readmission, and mortality (all p < 0.1). Our study is limited by its retrospective nature. Conclusions: The use of neoadjuvant chemotherapy is not associated with higher perioperative morbidity or mortality. These results should encourage wider use of neoadjuvant chemotherapy when clinically indicated. Patient summary: Chemotherapy before radical cystectomy in patients with muscleinvasive bladder cancer does not increase the risk of complications or death. The use of chemotherapy should be strongly encouraged, as recommended by clinical guidelines, given its benefits. (C) 2014 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Gandaglia, Giorgio; Popa, Ioana; Schiffmann, Jonas; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 3J4, Canada. [Gandaglia, Giorgio; Abdollah, Firas; Briganti, Alberto; Montorsi, Francesco] Univ Vita Salute San Raffaele, Dept Urol, Milan, Italy. [Popa, Ioana; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ H2X 3J4, Canada. [Schiffmann, Jonas] Prostate Canc Ctr Hamburg Eppendorf, Martini Clin, Hamburg, Germany. [Shariat, Shahrokh F.] Med Univ Vienna, Dept Urol, Vienna, Austria. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Urol Surg,Dept Surg Oncol, Boston, MA 02115 USA. RP Gandaglia, G (reprint author), Univ Montreal, Ctr Hlth, 1058 Rue St Denis, Montreal, PQ H2X 3J4, Canada. EM giorgio.gandaglia@gmail.com OI , Jonas/0000-0002-0654-5920 NR 37 TC 18 Z9 18 U1 0 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 SEP PY 2014 VL 66 IS 3 BP 561 EP 568 DI 10.1016/j.eururo.2014.01.014 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AN0FZ UT WOS:000340260900037 PM 24486024 ER PT J AU Benzer, JK Miller, CJ Mohr, DC Burgess, JF Charns, MP AF Benzer, Justin K. Miller, Christopher J. Mohr, David C. Burgess, James F., Jr. Charns, Martin P. TI Industrial-Organizational Psychology Programs Need to Differentiate From Business Schools: One Opportunity in Behavioral Health SO INDUSTRIAL AND ORGANIZATIONAL PSYCHOLOGY-PERSPECTIVES ON SCIENCE AND PRACTICE LA English DT Article ID SERVICES RESEARCH; CARE; IMPLEMENTATION; FRAMEWORK; SCIENCE C1 [Benzer, Justin K.; Mohr, David C.; Burgess, James F., Jr.; Charns, Martin P.] Boston Univ, Sch Publ Hlth, Ctr Healthcare Org & Implementat Res, Boston, MA 02215 USA. RP Benzer, JK (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. EM justin.benzer@va.gov OI Benzer, Justin/0000-0001-5151-2127 NR 14 TC 0 Z9 0 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1754-9426 EI 1754-9434 J9 IND ORGAN PSYCHOL-US JI Ind. Organ. Psychol. PD SEP PY 2014 VL 7 IS 3 BP 351 EP 355 DI 10.1111/iops.12162 PG 5 WC Psychology, Applied SC Psychology GA AN0BA UT WOS:000340245100013 ER PT J AU Isokuortti, H Luoto, TM Kataja, A Brander, A Siironen, J Liimatainen, S Iverson, GL Ylinen, A Ohman, J AF Isokuortti, Harri Luoto, Teemu M. Kataja, Anneli Brander, Antti Siironen, Jari Liimatainen, Suvi Iverson, Grant L. Ylinen, Aarne Ohman, Juha TI Necessity of monitoring after negative head CT in acute head injury SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Head injury; Traumatic brain injury; Computed tomography; Hospital discharge; Mortality ID TRAUMATIC BRAIN-INJURY; COMPUTED-TOMOGRAPHY; INTRACRANIAL HEMORRHAGE; MILD; IMMEDIATE; ADMISSION; RULE AB Objective: The main objective of this study was to evaluate the incidence of delayed complications in acute head injury (HI) patients with an initial normal head computed tomography (CT). Materials and methods: This retrospective study included 3023 consecutive patients who underwent head CT due to an acute HI at the Emergency Department (ED) of Tampere University Hospital (August 2010-July 2012). Regardless of clinical injury severity, the patients with a normal head CT were selected (n = 2444, 80.9%). The medical records of these patients were reviewed to identify the individuals with a serious clinically significant complication related to the primary HI. The time window considered was the following 72 h after the primary head CT. A repeated head CT in the hospital ward, death, or return to the ED were indicative of a possible complication. Results: The majority (n = 1811, 74.1%) of the patients with a negative head CT were discharged home and 1.1% (n = 27) of these patients returned to ED within 72 h post-CT. A repeated head CT was performed on 12 (44.4%) of the returned patients and none of the scans revealed an acute lesion. Of the 632 (25.9%) CT-negative patients admitted to the hospital ward from the ED, a head CT was repeated in 46 (7.3%) patients within 72 h as part of routine practice. In the repeated CT sample, only one (0.2%) patient had a traumatic intracranial lesion. This lesion did not need neurosurgical intervention. The overall complication rate was 0.04%. Conclusion: In the present study, which includes head injuries of all severity, the probability of delayed life-threatening complications was negligible when the primary CT scan revealed no acute traumatic lesions. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Isokuortti, Harri; Ylinen, Aarne] Univ Helsinki, Dept Neurol Sci, Helsinki, Finland. [Luoto, Teemu M.; Liimatainen, Suvi; Ohman, Juha] Tampere Univ Hosp, Dept Neurosci & Rehabil, Tampere, Finland. [Kataja, Anneli; Brander, Antti] Tampere Univ Hosp, Dept Radiol, Med Imaging Ctr, Tampere, Finland. [Siironen, Jari] Univ Helsinki, Cent Hosp, Dept Neurosurg, Helsinki, Finland. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn & Massachusetts Gen Hosp, Home Base Program, Boston, MA USA. [Ylinen, Aarne] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. RP Isokuortti, H (reprint author), Hosp Dist Helsinki & Uusimaa, Brain Injury Outpatient Clin, POB 302,Paciuksenkatu 21, Helsinki 00029, Finland. EM harri.isokuortti@helsinki.fi OI Luoto, Teemu/0000-0002-7329-3284; Ohman, Juha/0000-0002-6592-1367 NR 24 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD SEP PY 2014 VL 45 IS 9 BP 1340 EP 1344 DI 10.1016/j.injury.2014.04.012 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA AN0NI UT WOS:000340280900010 PM 24810669 ER PT J AU Vaccarino, V Goldberg, J Magruder, KM Forsberg, CW Friedman, MJ Litz, BT Heagerty, PJ Huang, GD Gleason, TC Smith, NL AF Vaccarino, Viola Goldberg, Jack Magruder, Kathryn M. Forsberg, Christopher W. Friedman, Matthew J. Litz, Brett T. Heagerty, Patrick J. Huang, Grant D. Gleason, Theresa C. Smith, Nicholas L. TI Posttraumatic stress disorder and incidence of type-2 diabetes: A prospective twin study SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Posttraumatic stress disorder; Diabetes; Twin studies; Epidemiology; Stress ID METABOLIC SYNDROME; MAJOR DEPRESSION; MENTAL-HEALTH; ERA VETERANS; VIETNAM; ASSOCIATION; PREVALENCE; RISK; CARE; PARTICIPANTS AB Growing evidence has linked posttraumatic stress disorder (PTSD) to insulin resistance and type-2 diabetes, but most previous studies were cross-sectional. We examined the association between PTSD and incidence of diabetes in a prospective study of middle-aged male twins from the Vietnam Era Twin Registry. Lifetime PTSD was diagnosed at baseline with the Diagnostic Interview Schedule (DIS) according to DSM-III-R criteria. Subthreshold PTSD was defined by meeting some, but not all, criteria for PTSD. A total of 4340 respondents without self-reported diabetes at baseline were included. Of these, 658 reported a new diagnosis of treated diabetes over a median of 19.4 years of follow-up. At baseline, twins with PTSD showed more behavioral and metabolic risk factors such as overweight and hypertension. The age-adjusted cumulative incidence of diabetes was significantly higher in twins with PTSD (18.9%) than those without PTSD (14.4%), [odds ratio (OR) = 1.4, 95% confidence interval (CI) 1.03-1.8], and intermediate in those with subthreshold PTSD (16.4%) (OR = 1.2, 95% CI 0.9-1.5, p for trend = 0.03). Adjustment for military, lifestyle and metabolic factors diminished the association. No significant association was found comparing twin pairs discordant for PTSD. In conclusion, PTSD was prospectively associated with a 40% increased risk of new-onset type-2 diabetes which was partially explained by a cluster of metabolic and behavioral risk factors known to influence insulin resistance. Shared biological or behavioral precursors which occur within families may lead to both PTSD and insulin resistance/diabetes. Thus, PTSD could be a marker of neuroendocrine and metabolic dysregulation which may lead to type-2 diabetes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Vaccarino, Viola] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Goldberg, Jack; Forsberg, Christopher W.; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Goldberg, Jack; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Magruder, Kathryn M.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Friedman, Matthew J.] White River Junction VA Med Ctr, VA Natl Ctr PTSD, White River Jct, VT USA. [Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Litz, Brett T.] Boston Univ, Boston, MA 02215 USA. [Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Huang, Grant D.; Gleason, Theresa C.] VA Off Res & Dev, Cooperat Studies Program, Washington, DC USA. RP Vaccarino, V (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM viola.vaccarino@emory.edu FU Cooperative Studies Program (CSP) of the Office of Research and Development, Clinical Science Research and Development, of the United States Department of Veterans Affairs (VA) [569]; National Institutes of Health [K24 HL077506] FX The Cooperative Studies Program (CSP) of the Office of Research and Development, Clinical Science Research and Development, of the United States Department of Veterans Affairs (VA), has provided financial support for Cooperative Study #569 and the development and maintenance of the Vietnam Era Twin (VET) Registry. Dr. Viola Vaccarino was supported in part by a National Institutes of Health award K24 HL077506. NR 38 TC 12 Z9 12 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2014 VL 56 BP 158 EP 164 DI 10.1016/j.jpsychires.2014.05.019 PG 7 WC Psychiatry SC Psychiatry GA AN1BV UT WOS:000340318600021 PM 24950602 ER PT J AU Poghosyan, H Bell, JF Joseph, JG Cooley, ME AF Poghosyan, Hermine Bell, Janice F. Joseph, Jill G. Cooley, Mary E. TI The association between having a first-degree family history of cancer and smoking status SO PREVENTIVE MEDICINE LA English DT Article DE Smoking status; Family cancer history; Smoking cessation ID HEALTH BEHAVIORS; BREAST-CANCER; LUNG-CANCER; RISK; DIAGNOSIS; FRIENDS AB Objective. A diagnosis of cancer within the family provides an opportunity for smokers to adopt a health-promoting behavior. This study examines the associations between having a first-degree family history of cancer and smoking status using population-based data with a large and diverse sample. Method. Cross-sectional data from the 2009 California Health Interview Survey on 47,331 adults were analyzed. Sample weights were applied to account for the survey design with results generalizable to non-institutionalized adults in California (27.4 million). Results. In 2009, 3.7 million (13.6%) adults were current-smokers, 63 million (23.0%) were former smokers and 17.4 million (63.4%) were never-smokers. Nine-million-six-hundred-thousand (35%) had a first-degree family history of cancer. Controlling for all covariates, first-degree family history of cancer was significantly associated with being a current smoker (OR = 1.16; 95% CI = 1.01-1.35) and to being a former smoker (OR = 1.17; 95% CI = 1.05-130). Conclusion. In California, although many adults with a first-degree family history of cancer quit smoking, a significant subset still smoke which places them at higher risk for poor health outcomes. This subset represents an important target population for smoking cessation interventions. (C) 2014 Elsevier Inc. All rights reserved. C1 [Poghosyan, Hermine] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Bell, Janice F.; Joseph, Jill G.] Univ Calif Davis, Betty Irene Moore Sch Nursing, Sacramento, CA 95817 USA. [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02215 USA. RP Poghosyan, H (reprint author), Univ Massachusetts, Coll Nursing & Hlth Sci, 100 Morrissey Blvd, Boston, MA 02125 USA. EM hermine.poghosyan@umb.edu; janice.bell@ucdmc.ucdavis.edu; Jill.Joseph@ucdmc.ucdavis.edu; mary_cooley@dfci.harvard.edu NR 26 TC 2 Z9 2 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD SEP PY 2014 VL 66 BP 12 EP 16 DI 10.1016/j.ypmed.2014.05.013 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AM9RB UT WOS:000340217600003 PM 24875232 ER PT J AU Morton, SMB Grant, CC Wall, CR Carr, PEA Bandara, DK Schmidt, JM Ivory, V Inskip, HM Camargo, CA AF Morton, Susan M. B. Grant, Cameron C. Wall, Clare R. Carr, Polly E. Atatoan Bandara, Dinusha K. Schmidt, Johanna M. Ivory, Vivienne Inskip, Hazel M. Camargo, Carlos A., Jr. TI Adherence to nutritional guidelines in pregnancy: evidence from the Growing Up in New Zealand birth cohort study SO PUBLIC HEALTH NUTRITION LA English DT Article DE Diet; Ethnic groups; New Zealand; Nutrition policy; Pregnancy ID VITAMIN-D DEFICIENCY; DIETARY PATTERNS; ADULT DISEASE; WOMEN; BEHAVIORS; INFANTS; ORIGINS AB Objective: To determine adherence to nutritional guidelines by pregnant women in New Zealand and maternal characteristics associated with adherence. Design: A cohort of the pregnant women enrolled into New Zealand's new birth cohort study, Growing Up in New Zealand. Setting: Women residing within a North Island region of New Zealand, where one-third of the national population lives. Subjects: Pregnant women (n 5664) were interviewed during 2009-2010. An FFQ was administered during the face-to-face interview. Results: The recommended daily number of servings of vegetables and fruit (>= 6) were met by 25 % of the women; of breads and cereals (>= 6) by 26 %; of milk and milk products (= 3) by 58 %; and of lean meat, meat alternatives and eggs (= 2) by 21 %. One in four women did not meet the recommendations for any food group. Only 3 % met all four food group recommendations. Although adherence to recommendation for the vegetables/fruit group did not vary by ethnicity (P = 0.38), it did vary for the breads/cereals, milk/milk products and meat/eggs groups (all P < 0.001). Adherence to recommendations for the vegetables/fruit group was higher among older women (P = 0.001); for the breads/cereals group was higher for women with previous children (P < 0.001) and from lower-income households (P < 0.001); and for the meat/eggs group was higher for women with previous children (P = 0.003) and from lower-income households (P = 0.004). Conclusions: Most pregnant women in New Zealand do not adhere to nutritional guidelines in pregnancy, with only 3 % meeting the recommendations for all four food groups. Adherence varies more so with ethnicity than with other sociodemographic characteristics. C1 [Morton, Susan M. B.; Grant, Cameron C.; Wall, Clare R.; Carr, Polly E. Atatoan; Bandara, Dinusha K.; Schmidt, Johanna M.; Ivory, Vivienne] Univ Auckland, Sch Populat Hlth, Auckland 1, New Zealand. [Morton, Susan M. B.; Grant, Cameron C.; Wall, Clare R.; Carr, Polly E. Atatoan; Bandara, Dinusha K.; Schmidt, Johanna M.; Ivory, Vivienne] Univ Auckland, Ctr Longitudinal Res He Ara Ki Mua, Auckland 1, New Zealand. [Grant, Cameron C.] Univ Auckland, Auckland 1, New Zealand. [Grant, Cameron C.] Auckland Dist Hlth Board, Starship Childrens Hosp, Auckland, New Zealand. [Grant, Cameron C.] Univ Auckland, Sch Med Sci, Discipline Nutr, Auckland 1, New Zealand. [Carr, Polly E. Atatoan] Univ Auckland, Waikato Clin Sch, Auckland 1, New Zealand. [Schmidt, Johanna M.] Univ Waikato, Sch Social Sci, Hamilton, New Zealand. [Ivory, Vivienne] Univ Otago, Sch Med & Hlth Sci, Dept Publ Hlth, Wellington, New Zealand. [Inskip, Hazel M.] Univ Southampton, MRC, Lifecourse Epidemiol Unit, Southampton, Hants, England. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Grant, CC (reprint author), Univ Auckland, Sch Populat Hlth, Private Bag 92019, Auckland 1, New Zealand. EM cc.grant@auckland.ac.nz OI Inskip, Hazel/0000-0001-8897-1749; Grant, Cameron/0000-0002-4032-7230 FU University of Auckland; Ministry of Health; New Zealand Police; Ministry of Justice; Families Commission; Children's Commission; Department of Labour; Ministry of Education; Housing New Zealand; Sport and Recreation New Zealand FX Financial support: The authors acknowledge the key role of the Ministry of Social Development in identifying the need for a longitudinal study that reflects the diversity of today's New Zealand and for its ongoing support. Other agencies, as well as The University of Auckland, have contributed to the cost of the study to date. These are: the Ministry of Health, the New Zealand Police, the Ministry of Justice, the Families Commission, the Children's Commission, the Department of Labour, the Ministry of Education, Housing New Zealand and Sport and Recreation New Zealand. The funders have had no role in the design, analysis or writing of this article. NR 48 TC 6 Z9 6 U1 0 U2 8 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 EI 1475-2727 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD SEP PY 2014 VL 17 IS 9 BP 1919 EP 1929 DI 10.1017/S1368980014000482 PG 11 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA AM8YY UT WOS:000340166800003 PM 24717981 ER PT J AU Kabrhel, C Okechukwu, I Hariharan, P Takayesu, JK MacMahon, P Haddad, F Chang, YC AF Kabrhel, Christopher Okechukwu, Ikenna Hariharan, Praveen Takayesu, James Kimo MacMahon, Peter Haddad, Faris Chang, Yuchiao TI Factors associated with clinical deterioration shortly after PE SO THORAX LA English DT Article ID ACUTE PULMONARY-EMBOLISM; LOW-RISK PATIENTS; BRAIN NATRIURETIC PEPTIDE; CARDIAC TROPONIN-T; SEVERITY INDEX; OUTPATIENT TREATMENT; PROGNOSTIC MODEL; EMERGENCY-DEPARTMENT; INPATIENT TREATMENT; FOLLOW-UP AB Background Several factors have been associated with mortality in the months after PE. Factors associated with short-term clinical deterioration or need for hospital-based intervention are less well known. Methods We prospectively enrolled consecutive emergency department patients with PE and recorded clinical, biomarker and radiographic data. We assessed hospitalised patients daily to identify clinical deterioration or need for hospital-based intervention for 5 days after PE. We captured postdischarge events via 5-day and 30-day interviews. We used univariate and multivariable models to assess associations with clinical deterioration, severe clinical deterioration and 30-day all-cause mortality. We also assessed the test characteristics of three published clinical decision rules. Results We enrolled 298 patients with PE: mean age 59 (SD +/- 17) years; 152 (51%) male and 268 (90%) white race. 101 (34%) patients clinically deteriorated or required a hospital-based intervention within 5 days, and 197 (66%) did not. 27 (9%) patients suffered severe clinical deterioration and 12 died within 30 days. Factors independently associated with clinical deterioration were hypotension (p=0.001), hypoxia (p<0.001), coronary disease (p=0.004), residual deep vein thrombosis (p=0.006) and right heart strain on echocardiogram (p<0.001). In contrast, factors associated with 30-day all-cause mortality were active malignancy (p<0.001) and congestive heart failure (p=0.009). The sensitivity of clinical decision rules was moderate (39-80%) for 5-day clinical deterioration but higher (67-100%) for 30-day mortality. Conclusions Most patients do not clinically deteriorate after PE diagnosis. Several factors are associated with short-term clinical deterioration, but these factors differ from those associated with 30-day mortality. C1 [Kabrhel, Christopher; Okechukwu, Ikenna; Hariharan, Praveen; Takayesu, James Kimo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,Ctr Vasc Emergencies, Boston, MA USA. [MacMahon, Peter] Mater Misericordiae Univ Hosp, Dept Radiol, Dublin, Ireland. [Haddad, Faris] Inova Fairfax Hosp, Dept Radiol, Falls Church, VA USA. [Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Kabrhel, C (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Ctr Vasc Emergencies, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM ckabrhel@partners.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU Harvard Milton Fund FX This work was funded by a grant from the Harvard Milton Fund. The funding agency had no role in the design of the study, analysis or writing the manuscript. NR 36 TC 13 Z9 14 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 EI 1468-3296 J9 THORAX JI Thorax PD SEP PY 2014 VL 69 IS 9 BP 835 EP 842 DI 10.1136/thoraxjnl-2013-204762 PG 8 WC Respiratory System SC Respiratory System GA AM9ZH UT WOS:000340239900012 PM 24846902 ER PT J AU Chodosh, J AF Chodosh, J. TI Challenges to globalizing keratoprothesis surgery SO ACTA OPHTHALMOLOGICA LA English DT Meeting Abstract C1 [Chodosh, J.] Harvard Univ, Massachusetts Eye & Ear Infirm, 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 1755-375X EI 1755-3768 J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD SEP PY 2014 VL 92 SU 253 SI SI AR 4436 DI 10.1111/j.1755-3768.2014.4436.x PG 2 WC Ophthalmology SC Ophthalmology GA V43SZ UT WOS:000209702400172 ER PT J AU Greiner, J AF Greiner, J. TI Automatic application of warmth and expression - a breakthrough in physical therapy of dry eye SO ACTA OPHTHALMOLOGICA LA English DT Meeting Abstract C1 [Greiner, J.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-375X EI 1755-3768 J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD SEP PY 2014 VL 92 SU 253 SI SI MA 2673 DI 10.1111/j.1755-3768.2014.2673.x PG 2 WC Ophthalmology SC Ophthalmology GA V43SZ UT WOS:000209702400204 ER PT J AU Rajaiya, J Yousuf, MA Mukherjee, S Lee, JS Zhou, X Ramke, M Lee, JY Chodosh, J AF Rajaiya, J. Yousuf, M. A. Mukherjee, S. Lee, J. S. Zhou, X. Ramke, M. Lee, J. Y. Chodosh, J. TI Specifics of viral entry in epidemic keratoconjunctivitis SO ACTA OPHTHALMOLOGICA LA English DT Meeting Abstract C1 [Rajaiya, J.; Yousuf, M. A.; Mukherjee, S.; Lee, J. S.; Zhou, X.; Ramke, M.; Lee, J. Y.; Chodosh, J.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 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 1755-375X EI 1755-3768 J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD SEP PY 2014 VL 92 SU 253 SI SI MA 2644 DI 10.1111/j.1755-3768.2014.2644.x PG 3 WC Ophthalmology SC Ophthalmology GA V43SZ UT WOS:000209702400325 ER PT J AU Joukov, V Walter, JC De Nicolo, A AF Joukov, V. Walter, J. C. De Nicolo, A. TI The Cep192-organized Aurora A-Plk1 cascade is essential for centrosome cycle and bipolar spindle assembly SO FEBS JOURNAL LA English DT Meeting Abstract CT FEBS EMBO 2014 Conference CY AUG 30-SEP 04, 2014 CL Paris, FRANCE SP FEBS, EMBO DE Cell Division; Centrosome cycle; Kinases C1 [Joukov, V.; Walter, J. C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Howard Hughes Med Inst, Boston, MA 02115 USA. [De Nicolo, A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [De Nicolo, A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 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 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD SEP PY 2014 VL 281 SU 1 SI SI MA SUN-048 BP 80 EP 81 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CP1WE UT WOS:000359666801046 ER PT J AU Botezatu, A Bleotu, C Nastase, A Anton, G Bacalbasa, N Duda, DG Dima, SO Popescu, I AF Botezatu, A. Bleotu, C. Nastase, A. Anton, G. Bacalbasa, N. Duda, D. G. Dima, S. O. Popescu, I. TI CpG islands promoter methylation the main cause for GNMT gene decreased expression in pancreatic adenocarcinoma SO FEBS JOURNAL LA English DT Meeting Abstract CT FEBS EMBO 2014 Conference CY AUG 30-SEP 04, 2014 CL Paris, FRANCE SP FEBS, EMBO DE epigenetic alteration; promoter methylation; pancreatic cancer C1 [Botezatu, A.; Anton, G.] Acad Romana, Stefan S Nicolau Inst Virol, Viral Genet Engn Lab, Bucharest, Romania. [Bleotu, C.] Acad Romana, Stefan S Nicolau Inst Virol, Antiviral Therapy, Bucharest, Romania. [Nastase, A.; Dima, S. O.; Popescu, I.] Fundeni Clin Inst, Ctr Gen Surg & Liver Transplantat Dan Setlacec, Bucharest, Romania. [Bacalbasa, N.] Carol Davila Univ Med & Pharm, Bucharest, Romania. [Duda, D. G.] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. RI Coralia, Bleotu/B-5976-2011; Bacalbasa, Nicolae/A-4222-2017 OI Coralia, Bleotu/0000-0002-9031-338X; NR 0 TC 0 Z9 0 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD SEP PY 2014 VL 281 SU 1 SI SI MA MON-145 BP 299 EP 299 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CP1WE UT WOS:000359666802129 ER PT J AU Lascombe, MB van Agthoven, J Kragelund, BB Goffin, V Phan, G Broutin, I AF Lascombe, M-B van Agthoven, J. Kragelund, B. B. Goffin, V. Phan, G. Broutin, I. TI Insight into the comprehension of prolactin receptor mechanistic activation by a structural approach SO FEBS JOURNAL LA English DT Meeting Abstract CT FEBS EMBO 2014 Conference CY AUG 30-SEP 04, 2014 CL Paris, FRANCE SP FEBS, EMBO DE allostery; Cancer signaling; Cytokines C1 [Lascombe, M-B; Broutin, I.] Univ Paris 05, Lab Cristallog & RMN Biol, Fac Pharm, CNRS UMR 8015, Paris, France. [van Agthoven, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. [Kragelund, B. B.] Univ Copenhagen, Dept Biol, Struct Biol & NMR Lab, Copenhagen, Denmark. [Goffin, V.] Univ Paris 05, Fac Med, Ctr Rech Croissance & Signalisat, NSERM U845, Paris, France. [Phan, G.] Univ Paris 05, CNRS UMR 8015, Dept Biol, Struct Biol & NMR Lab, Paris, France. NR 2 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD SEP PY 2014 VL 281 SU 1 SI SI MA TUE-140 BP 479 EP 479 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CP1WE UT WOS:000359666803135 ER PT J AU Hagemann, A Kurz, J Kauffeld, S Chen, Q Reeves, P Davidson, G Kirchhausen, T Scholpp, S AF Hagemann, A. Kurz, J. Kauffeld, S. Chen, Q. Reeves, P. Davidson, G. Kirchhausen, T. Scholpp, S. TI In-vivo analysis of formation and endocytosis of the Wnt/beta-catenin signaling complex in zebrafish embryos SO FEBS JOURNAL LA English DT Meeting Abstract CT FEBS EMBO 2014 Conference CY AUG 30-SEP 04, 2014 CL Paris, FRANCE SP FEBS, EMBO DE AP2; WNT signalling; zebrafish C1 [Hagemann, A.; Kurz, J.; Kauffeld, S.; Chen, Q.; Davidson, G.; Scholpp, S.] Karlsruhe Inst Technol, ITG, Leopoldshafen, Germany. [Reeves, P.; Kirchhausen, T.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Reeves, P.; Kirchhausen, T.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Reeves, P.; Kirchhausen, T.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. RI Scholpp, Steffen/H-2060-2013 OI Scholpp, Steffen/0000-0002-4903-9657 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 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD SEP PY 2014 VL 281 SU 1 SI SI MA TUE-149 BP 482 EP 482 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CP1WE UT WOS:000359666803143 ER PT J AU Sohani, AR Zukerberg, LR AF Sohani, Aliyah R. Zukerberg, Lawrence R. TI Small B-cell lymphomas of the spleen: how to tell them apart SO JOURNAL OF HEMATOPATHOLOGY LA English DT Review DE Spleen; Lymphoma; Splenic marginal zone lymphoma; Hairy cell leukemia; Flow cytometry; Molecular diagnostics ID MARGINAL-ZONE LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; VILLOUS LYMPHOCYTES; FOLLICULAR LYMPHOMA; CLINICOPATHOLOGICAL FEATURES; SPLENIC LYMPHOMA; RED PULP; SOX11 EXPRESSION; HCV INFECTION; VARIANT FORM AB Various subtypes of small B-cell lymphoma can involve the spleen, and their classification in splenectomy specimens may be challenging. Accurate diagnosis of these entities may be critical to ensuring appropriate treatment and prognostication. We describe the types of small B-cell lymphoma that may involve the spleen and their differential diagnosis, using splenic compartment of involvement (white pulp vs. red pulp) as a diagnostic framework. Published literature on various lymphomas of the spleen, with an emphasis on recently recognized entities and emerging molecular genetic data, is reviewed. A multifaceted approach to diagnosis, using clinical and laboratory data, morphology, immunophenotype, and molecular genetic testing, is discussed. Although relatively few small B-cell lymphoma entities involve the spleen primarily, many systemic lymphomas may involve the spleen secondarily, and some recently described entities are encountered with relative infrequency. Fortunately, an understanding of the unique anatomy of the spleen as reflected by its unusual diversity of functions, in concert with a multiparameter approach to diagnosis, can help in narrowing this broad differential diagnosis considerably, in order to reach a specific diagnosis with certainty. C1 [Sohani, Aliyah R.; Zukerberg, Lawrence R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. [Sohani, Aliyah R.; Zukerberg, Lawrence R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org NR 61 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1868-9256 EI 1865-5785 J9 J HEMATOP JI J. Hematop. PD SEP PY 2014 VL 7 IS 3 BP 109 EP 121 DI 10.1007/s12308-014-0208-1 PG 13 WC Hematology; Pathology SC Hematology; Pathology GA CU7ZN UT WOS:000363760500004 ER PT J AU Ferry, JA AF Ferry, Judith A. TI Thomas Hodgkin and Hodgkin lymphoma SO JOURNAL OF HEMATOPATHOLOGY LA English DT Review DE Hodgkin lymphoma; Reed-Sternberg cell; Nodular lymphocyte predominant Hodgkin lymphoma; Classical Hodgkin lymphoma; Immunophenotype; Differential diagnosis ID B-CELL LYMPHOMA; IMMUNOGLOBULIN GENE REARRANGEMENTS; GRAY ZONE LYMPHOMA; STERNBERG CELLS; DIFFERENTIAL-DIAGNOSIS; MOLECULAR PATHOGENESIS; PROGNOSTIC-FACTORS; EBV GENOMES; DISEASE; EXPRESSION AB In 1832 Thomas Hodgkin, a physician at Guy's Hospital in London, published a description of seven cases of lymph nodes with unusual changes. Little did he suspect that this publication would lead to recognition of the now-familiar entity that has come to be known as Hodgkin lymphoma. In the years that have passed since that publication, diagnostic criteria and a straightforward system for subclassification of Hodgkin lymphoma have been established. The cell of origin for the characteristic neoplastic cell, the Reed-Sternberg cell, was identified after much scientific struggle. With improvements in therapy, the prognosis for Hodgkin lymphoma patients has improved remarkably; indeed, the development of effective treatment for Hodgkin lymphoma serves as a medical success story. Current investigation focuses on better understanding of the intricacies of the complex biology of Hodgkin lymphoma, including the genetic changes underlying its pathogenesis, and improving therapy for the minority of patients who do not respond well to currently available treatment. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 79 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1868-9256 EI 1865-5785 J9 J HEMATOP JI J. Hematop. PD SEP PY 2014 VL 7 IS 3 BP 123 EP 138 DI 10.1007/s12308-014-0214-3 PG 16 WC Hematology; Pathology SC Hematology; Pathology GA CU7ZN UT WOS:000363760500005 ER PT J AU Aylward, E Long, JD MacDonald, ME Lee, JM Paulsen, J Gusella, J AF Aylward, E. Long, J. D. MacDonald, M. E. Lee, J-M Paulsen, J. Gusella, J. CA PREDICT-HD Investigators Coordinators Huntington Study Grp TI CAG REPEAT LENGTH PREDICTS RATE OF STRIATAL ATROPHY, BUT RELATIONSHIP IS NONLINEAR SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT 8th European-Huntington's-Disease-Network Plenary Meeting CY SEP 19-21, 2014 CL Barcelona, SPAIN SP European Huntingtons Disease Network C1 [Aylward, E.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA USA. [Long, J. D.; Paulsen, J.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [MacDonald, M. E.; Lee, J-M; Gusella, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD SEP PY 2014 VL 85 SU 1 MA E01 BP A35 EP A35 DI 10.1136/jnnp-2014-309032.104 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA CS3KF UT WOS:000361971900105 ER PT J AU Jones, L Gusella, JF MacDonald, ME Wheeler, V Lee, JM Myers, RH Latourelle, J Jones, L Harold, D Holmans, P Orth, M Kwak, S AF Jones, L. Gusella, J. F. MacDonald, M. E. Wheeler, V. Lee, J-M Myers, R. H. Latourelle, J. Jones, L. Harold, D. Holmans, P. Orth, M. Kwak, S. CA Cardiff Univ CHDI GeM Consortium HD Ctr Without Walls HD MAPS Collaboration COHORT Huntington Study Grp European Huntingtons Dis Network TI GENETIC MODIFIERS AFFECTING THE AGE AT MOTOR ONSET IN HUNTINGTON'S DISEASE SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT 8th European-Huntington's-Disease-Network Plenary Meeting CY SEP 19-21, 2014 CL Barcelona, SPAIN SP European Huntingtons Disease Network C1 [Gusella, J. F.; MacDonald, M. E.; Wheeler, V.; Lee, J-M] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Latourelle, J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Jones, L.; Harold, D.; Holmans, P.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genet, Cardiff CF10 3AX, S Glam, Wales. [Orth, M.] Univ Ulm, Dept Neurol, D-089081 Ulm, Germany. [Kwak, S.] CHDI Fdn, New York, NY 10001 USA. NR 0 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 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD SEP PY 2014 VL 85 SU 1 MA A03 BP A1 EP A2 DI 10.1136/jnnp-2014-309032.3 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA CS3KF UT WOS:000361971900004 ER PT J AU Weston, R Rodier, J Coffey, S Glickenhaus, A Boros, LG MacDonald, ME Carroll, JB AF Weston, R. Rodier, J. Coffey, S. Glickenhaus, A. Boros, L. G. MacDonald, M. E. Carroll, J. B. TI INVESTIGATING HEPATIC DYSFUNCTION IN THE HTTQ111/+ MOUSE WITH A PERTURBAGEN-BASED PRIMARY HEPATOCYTE SYSTEM SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT 8th European-Huntington's-Disease-Network Plenary Meeting CY SEP 19-21, 2014 CL Barcelona, SPAIN SP European Huntingtons Disease Network C1 [Weston, R.; Rodier, J.; Coffey, S.; Glickenhaus, A.; Carroll, J. B.] Western Washington Univ, Bellingham, WA 98225 USA. [Rodier, J.] Univ Lyon 1, F-69100 Villeurbanne, France. [Boros, L. G.] SiDMAP, Los Angeles, CA 90064 USA. [MacDonald, M. E.; Carroll, J. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD SEP PY 2014 VL 85 SU 1 MA B30 BP A19 EP A20 DI 10.1136/jnnp-2014-309032.58 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA CS3KF UT WOS:000361971900059 ER PT J AU Reisner, SL White, JM Bradford, JB Mimiaga, MJ AF Reisner, Sari L. White, Jaclyn M. Bradford, Judith B. Mimiaga, Matthew J. TI Transgender Health Disparities: Comparing Full Cohort and Nested Matched-Pair Study Designs in a Community Health Center SO LGBT HEALTH LA English DT Article DE gender identity; health disparity; methods; study design; transgender ID RISK BEHAVIORS; HIV PREVALENCE; SEXUAL RISK; FEMALE; CARE; DISCRIMINATION; WOMEN; EXPERIENCES; PREGNANCY; VIOLENCE AB Purpose: U.S. health surveillance systems infrequently include measures to identify transgender respondents or monitor the health of this underserved and marginalized population. Methods: From 2001 to 2002, transgender and nontransgender adults were sampled at a Massachusetts clinic. Health differences were formatively examined by transgender identity using a cross-sectional, clinic-based sample (n = 2,653) and a nested matched-pair subsample (n = 155). Results: Both designs produced virtually identical findings: (1) the prevalence of HIV, substance abuse, and smoking did not differ significantly for transgender and nontransgender patients; (2) transgender patients were more likely to endorse a lifetime suicide attempt and ideation compared with nontransgender patients (p < 0.05); (3) transgender patients disproportionately reported social stressors (violence, discrimination, childhood abuse) relative to nontransgender patients (p < 0.05). Conclusion: Findings suggest that a nested design may provide an effective methodology for using clinical data to study transgender health and underscore the need for routine collection of gender identity in clinical settings. C1 [Reisner, Sari L.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Reisner, Sari L.; White, Jaclyn M.; Bradford, Judith B.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Reisner, SL (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02115 USA. EM sreisner@hsph.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [R21HD051178] FX The project described was partially supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) under Award Number R21HD051178. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the National Institutes of Health. NR 52 TC 18 Z9 18 U1 5 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD SEP PY 2014 VL 1 IS 3 BP 177 EP U127 DI 10.1089/lgbt.2014.0009 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QF UT WOS:000361690900008 PM 25379511 ER PT J AU Sherman, MD Kauth, MR Shipherd, JC Street, RL AF Sherman, Michelle D. Kauth, Michael R. Shipherd, Jillian C. Street, Richard L., Jr. TI Provider Beliefs and Practices About Assessing Sexual Orientation in Two Veterans Health Affairs Hospitals SO LGBT HEALTH LA English DT Article DE lesbian/gay; patient-provider communication; sexual orientation; veterans; Veterans Affairs hospital ID PRIMARY-CARE PHYSICIANS; GENERAL-PRACTITIONERS; MINORITY VETERANS; MEDICAL SOCIETY; NATIONAL-SURVEY; GAY; ATTITUDES; LESBIANS; WOMEN; COMMUNICATION AB Purpose: Despite known health disparities for lesbian, gay, and bisexual (LGB) individuals, research in the civilian sector has documented low rates of patient disclosure and provider assessment of this domain. Very little is known about Veterans Health Affairs (VHA) providers' care of LGB veterans, a population that has been relatively invisible until recently because of the vestiges of the Department of Defense policy of "Don't Ask, Don't Tell." This study examined the attitudes, beliefs, and clinical practices of VHA healthcare providers regarding sexual minority veterans. Methods: Physical and mental health VHA healthcare providers (n = 202) from two southern VHA hospitals completed an anonymous self-report questionnaire. Measures included comfort in providing care to LGB veterans, factors affecting decisions about assessing sexual orientation with veterans, and attitudes toward sexual minority individuals. Results: Although approximately half of VHA providers thought that sexual orientation should be routinely discussed, the providers rarely assessed this issue with their patients. Over half of providers believed that veterans would disclose their sexual orientation if it was important to them, and almost half of providers believed sexual orientation is not relevant to healthcare. Conclusion: Many VHA providers may be unaware of the unique health disparities experienced by LGB individuals. Culturally appropriate care cannot be provided to LGB veterans unless providers explicitly assess sexual orientation in healthcare visits. Central to this assessment is providing patients with a clear rationale for the purpose of the assessment and related documentation. Staff training is needed to address providers' beliefs and reservations about discussing sexual orientation that emerged in this investigation. C1 [Sherman, Michelle D.] Oklahoma City VA Med Ctr, Oklahoma City, OK USA. [Sherman, Michelle D.; Kauth, Michael R.] South Cent Mental Illness Res Educ & Clin Ctr, North Little Rock, AR USA. [Sherman, Michelle D.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Kauth, Michael R.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kauth, Michael R.; Shipherd, Jillian C.] Houston Ctr Excellence, VA Hlth Serv Res & Dev, Patient Care Serv Lesbian Gay Bisexual & Transgen, VA Cent Off, Houston, TX USA. [Kauth, Michael R.; Street, Richard L., Jr.] Baylor Coll Med, Houston, TX 77030 USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Street, Richard L., Jr.] Texas A&M Univ, College Stn, TX USA. [Kauth, Michael R.; Street, Richard L., Jr.] Houston Ctr Excellence, VA Hlth Serv Res & Dev, Houston, TX USA. [Shipherd, Jillian C.] Natl Ctr PTSD, Womens Hlth Sci Div, White River Jct, VT USA. RP Sherman, MD (reprint author), 921 NE 13th St,116A, Oklahoma City, OK 73104 USA. EM michelle-sherman@ouhsc.edu FU Department of Veterans Affairs, Veterans Health Administration, South Central Mental Illness Research, Education and Clinical Center (MIRECC); VA Health Services Research & Development Houston Center of Excellence FX This article is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, South Central Mental Illness Research, Education and Clinical Center (MIRECC), and the VA Health Services Research & Development Houston Center of Excellence. Thank you to Drs. Lauren Ridener, Gregory Beaulieu, and Kristi Bratkovich for their contribution to the project. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 43 TC 7 Z9 7 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD SEP PY 2014 VL 1 IS 3 BP 185 EP U135 DI 10.1089/lgbt.2014.0008 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QF UT WOS:000361690900009 PM 26789711 ER PT J AU Wolfe, J AF Wolfe, Joanne TI Response HOPE IS IN THE EYE OF THE BEHOLDER SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Joanne_Wolfe@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0031-5982 EI 1529-8795 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD FAL PY 2014 VL 57 IS 4 BP 558 EP 559 PG 2 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA CU2LB UT WOS:000363353900011 PM 26497243 ER PT J AU Paschalis, EI Eliott, D Vavvas, DG AF Paschalis, Eleftherios I. Eliott, Dean Vavvas, Demetrios G. TI Removal of Silicone Oil From Intraocular Lens Using Novel Surgical Materials SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY LA English DT Article DE silicone oil; vitrectomy; retinal detachment; IOL; tamponade; ALD; PDMS; lithography; super hydrophobicity; oleophilicity AB Purpose: To design, fabricate, and evaluate novel materials to remove silicone oil (SiO) droplets from intraocular lenses (IOL) during vitreoretinal surgery. Methods: Three different designs were fabricated using soft lithography of polydimethylsiloxane (PDMS), three-dimensional (3D) inverse PDMS fabrication using water dissolvable particles, and atomic layer deposition (ALD) of alumina (Al2O3) on surgical cellulose fibers. Laboratory tests included static and dynamic contact angle (CA) measurements with water and SiO, nondestructive x-ray microcomputer tomography (micro-CT), and microscopy. SiO removal was performed in vitro and ex vivo using implantable IOLs and explanted porcine eyes. Results: All designs exhibited enhanced hydrophobicity and oleophilicity. Static CA measurements with water ranged from 131 degrees to 160 degrees and with SiO CA approximately 0 degrees in 120 seconds following exposure. Nondestructive x-ray analysis of the 3D PDMS showed presence of interconnected polydispersed porosity of 100 to 300 mu m in diameter. SiO removal from IOLs was achieved in vitro and ex vivo using standard 20-G vitrectomy instrumentation. Conclusion: Removal of SiO from IOLs can be achieved using materials with lower surface energy than that of the IOLs. This can be achieved using appropriate surface chemistry and surface topography. Three designs, with enhanced hydrophobic properties, were fabricated and tested in vitro and ex vivo. All materials remove SiO within an aqueous environment. Preliminary ex vivo results were very promising, opening new possibilities for SiO removal in vitreoretinal surgeries. Translational Relevance: This is the first report of an instrument that can lead to successful removal of SiO from the surface of IOL. In addition to the use of this instrument/material in medicine it can also be used in the industry, for example, retrieval of oil spills from bodies of water. C1 [Paschalis, Eleftherios I.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston Keratoprosthesis Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. [Paschalis, Eleftherios I.; Vavvas, Demetrios G.] Harvard Med Sch, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Paschalis, EI (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston Keratoprosthesis Lab, Boston, MA 02114 USA.; Paschalis, EI; Vavvas, DG (reprint author), Harvard Med Sch, Schepens Eye Res Inst, Boston, MA 02114 USA.; Vavvas, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Boston, MA 02114 USA. EM eleftherios_paschalis@meei.harvard.edu NR 18 TC 2 Z9 2 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 2164-2591 J9 TRANSL VIS SCI TECHN JI Transl. Vis. Sci. Technol. PD SEP PY 2014 VL 3 IS 5 AR 4 DI 10.1167/tvst.3.5.4 PG 7 WC Ophthalmology SC Ophthalmology GA V45JV UT WOS:000209813800004 ER PT J AU Long, TJ Sprenger, CC Plymate, SR Ratner, BD AF Long, Thomas J. Sprenger, Cynthia C. Plymate, Stephen R. Ratner, Buddy D. TI Prostate cancer xenografts engineered from 3D precision-porous poly(2-hydroxyethyl methacrylate) hydrogels as models for tumorigenesis and dormancy escape SO BIOMATERIALS LA English DT Article DE PolyHEMA; Scaffold; Xenograft; Prostate cancer; Dormancy; Tumor microenvironment ID PROTEIN-RELATED PROTEIN-1; MAMMARY EPITHELIAL-CELLS; IN-VITRO EVALUATION; TUMOR DORMANCY; GROWTH; PROGRESSION; CULTURE; EXPRESSION; METASTASIS; BIOLOGY AB Synthetic biomaterial scaffolds show promise for in vitro and in vivo 3D cancer models. Tumors engineered in biomaterial scaffolds have shown evidence of being more physiologically relevant than some traditional preclinical model systems, and synthetic biomaterials provide the added benefit of defined and consistent microenvironmental control. Here, we examine sphere-templated poly(2-hydroxyethyl methacrylate) (pHEMA) scaffolds as the basis for engineering xenografts from multiple human prostate cancer cell lines. pHEMA scaffolds seeded and pre-cultured with tumorigenic M12 cells prior to implantation generated tumors in athymic nude mice, demonstrating the ability of the scaffolds to be used as a synthetic vehicle for xenograft generation. pHEMA scaffolds seeded with LNCaP C4-2 cells, which require Matrigel or stromal cell support for tumor formation, were poorly tumorigenic up to 12 weeks after implantation even when Matrigel was infused into the scaffold, demonstrating a lack of necessary pro-tumorigenic signaling within the scaffolds. Finally, M12mac25 cells, which are ordinarily rendered non-tumorigenic through the expression of the tumor suppressor insulin-like growth factor binding protein 7 (IGFBP7), displayed a tumorigenic response when implanted within porous pHEMA scaffolds. These M12mac25 tumors showed significant macrophage infiltration within the scaffolds driven by the foreign body response to the materials. These findings show the potential for this biomaterials-based model system to be used in the study of prostate cancer tumorigenesis and dormancy escape. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Long, Thomas J.; Ratner, Buddy D.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Sprenger, Cynthia C.; Plymate, Stephen R.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Ratner, BD (reprint author), Univ Washington, Dept Bioengn, Box 355061,3720 15th Ave NE, Seattle, WA 98195 USA. EM ratner@uweb.engr.washington.edu FU Nanotechnology and Physical Science in Cancer Research Training Program NIH [T32CA138312]; TMEN [U54-CAl26540, P01 CA085859]; Veterans Affairs Research Service FX The authors would like to thank Shihua Sun, Colleen Irvin, Kathryn Soriano, and Gerry Hammer for technical assistance. This work was supported by the Nanotechnology and Physical Science in Cancer Research Training Program NIH T32CA138312 (TJL and BDR), TMEN U54-CAl26540 (SRP), P01 CA085859 (SRP), and the Veterans Affairs Research Service (SRP). NR 56 TC 8 Z9 8 U1 2 U2 50 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 SEP PY 2014 VL 35 IS 28 BP 8164 EP 8174 DI 10.1016/j.biomaterials.2014.04.090 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AM3TC UT WOS:000339774700011 PM 24942815 ER PT J AU Huang, YY Sharma, SK Yin, R Agrawal, T Chiang, LY Hamblin, MR AF Huang, Ying-Ying Sharma, Sulbha K. Yin, Rui Agrawal, Tanupriya Chiang, Long Y. Hamblin, Michael R. TI Functionalized Fullerenes in Photodynamic Therapy SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY LA English DT Review DE Fullerene; Photodynamic Therapy; Reactive Oxygen Species; Cancer; Infections; Electron Transfer; Singlet Oxygen; Cationic Charge ID GRAM-NEGATIVE BACTERIA; SMALL-ANGLE NEUTRON; ELECTRON-TRANSFER; ESCHERICHIA-COLI; C-60 DERIVATIVES; PHOTOPHYSICAL PROPERTIES; 2-PHOTON EXCITATION; AQUEOUS-SOLUTIONS; STATE PROPERTIES; SINGLET OXYGEN AB Since the discovery of C-60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C-60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine C-60, mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C-60, C-70 and C-84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT. C1 [Huang, Ying-Ying; Yin, Rui; Agrawal, Tanupriya; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Yin, Rui; Agrawal, Tanupriya; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Sharma, Sulbha K.] Raja Ramanna Ctr Adv Technol, Indore 452013, Madhya Pradesh, India. [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. [Chiang, Long Y.] Univ Massachusetts, Inst Nanosci & Engn Technol, Dept Chem, Lowell, MA 01854 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01CA137108, R01AI050875] FX Long Y. Chiang was supported by US NIH grant R01CA137108. Michael R. Hamblin was supported by US NIH grant R01AI050875. NR 115 TC 17 Z9 17 U1 10 U2 85 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1550-7033 EI 1550-7041 J9 J BIOMED NANOTECHNOL JI J. Biomed. Nanotechnol. PD SEP PY 2014 VL 10 IS 9 SI SI BP 1918 EP 1936 DI 10.1166/jbn.2014.1963 PG 19 WC Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Science & Technology - Other Topics; Materials Science GA AL9AC UT WOS:000339430600012 PM 25544837 ER PT J AU Avci, P Erdem, SS Hamblin, MR AF Avci, Pinar Erdem, S. Sibel Hamblin, Michael R. TI Photodynamic Therapy: One Step Ahead with Self-Assembled Nanoparticles SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY LA English DT Review DE Cancer; Photodynamic Therapy; Self Assembly; Dendrimers; Block Copolymers; Nanoparticles; Micelles ID DIBLOCK COPOLYMER MICELLES; PLURONIC BLOCK-COPOLYMERS; 5-AMINOLEVULINIC ACID; DRUG-DELIVERY; IN-VIVO; PHOTOCHEMICAL INTERNALIZATION; PROTOPORPHYRIN-IX; CANCER-CELLS; MULTIDRUG-RESISTANCE; SINGLET-OXYGEN AB Photodynamic therapy (PDT) is a promising treatment modality for cancer with possible advantages over current treatment alternatives. It involves combination of light and a photosensitizer (PS), which is activated by absorption of specific wavelength light and creates local tissue damage through generation of reactive oxygen species (ROS) that induce a cascade of cellular and molecular events. However, as of today, PDT is still in need of improvement and nanotechnology may play a role. PDT frequently employs PS with molecular structures that are highly hydrophobic, water insoluble and prone to aggregation. Aggregation of PS leads to reduced ROS generation and thus lowers the PDT activity. Some PS such as 5-aminolevulinic acid (ALA) cannot penetrate through the stratum corneum of the skin and systemic administration is not an option due to frequently encountered side effects. Therefore PS are often encapsulated or conjugated in/on nano-drug delivery vehicles to allow them to be better taken up by cells and to more selectively deliver them to tumors or other target tissues. Several nano-drug delivery vehicles including liposomes, fullerosomes and nanocells have been tested and reviewed. Here we cover non-liposomal self-assembled nanoparticles consisting of polymeric micelles including block co-polymers, polymeric micelles, dendrimers and porphysomes. C1 [Avci, Pinar; Erdem, S. Sibel; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Avci, Pinar; Erdem, S. Sibel; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Avci, Pinar] Semmelweis Univ, Sch Med, Dept Dermatol Dermatooncol & Venerol, H-1085 Budapest, Hungary. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875] FX We are grateful to Timur Zhiyen-tayev for his valuable input and discussions. Research in the Hamblin laboratory is supported by US NIH grant R01AI050875. NR 128 TC 16 Z9 17 U1 8 U2 142 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1550-7033 EI 1550-7041 J9 J BIOMED NANOTECHNOL JI J. Biomed. Nanotechnol. PD SEP PY 2014 VL 10 IS 9 SI SI BP 1937 EP 1952 DI 10.1166/jbn.2014.1953 PG 16 WC Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Science & Technology - Other Topics; Materials Science GA AL9AC UT WOS:000339430600013 PM 25580097 ER PT J AU Schuman-Olivier, Z Weiss, RD Hoeppner, BB Borodovsky, J Albanese, MJ AF Schuman-Olivier, Zev Weiss, Roger D. Hoeppner, Bettina B. Borodovsky, Jacob Albanese, Mark J. TI Emerging adult age status predicts poor buprenorphine treatment retention SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Buprenorphine; Opioid dependence; Emerging adult; Young adult; Retention; Toxicology; Outcome; Development; Treatment ID OPIOID-DEPENDENT OUTPATIENTS; SUBSTANCE USE DISORDERS; CONTINGENCY MANAGEMENT; MAINTENANCE TREATMENT; BRAIN-DEVELOPMENT; PRIMARY-CARE; DRUG-USE; OUTCOMES; ALCOHOL; ABUSE AB Emerging adults (18-25 years old) are often poorly retained in substance use disorder treatment. Office-based buprenorphine often enhances treatment retention among people with opioid dependence. In this study, we examined the records of a collaborative care buprenorphine treatment program to compare the treatment retention rates of emerging adults versus older adults. Subjects were 294 adults, 71(24%) aged 18-25, followed in treatment with buprenorphine, nurse care management, and an intensive outpatient program followed by weekly psychosocial treatment. Compared to older adults, emerging adults remained in treatment at a significantly lower rate at 3 months (56% versus 78%) and 12 months (17% versus 45%), and were significantly more likely to test positive for illicit opioids, relapse, or drop out of treatment. Further research into factors associated with buprenorphine treatment retention among emerging adults is needed to improve treatment and long-term outcomes in this group. (C) 2014 Elsevier Inc. All rights reserved. C1 [Schuman-Olivier, Zev; Borodovsky, Jacob; Albanese, Mark J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge Hlth Alliance, Somerville, MA 02143 USA. [Schuman-Olivier, Zev] Geisel Sch Med Dartmouth, Psychiat Res Ctr, Hanover, NH USA. [Weiss, Roger D.] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Somerville, MA 02143 USA. [Hoeppner, Bettina B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Somerville, MA 02143 USA. RP Schuman-Olivier, Z (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Cambridge Hlth Alliance,Outpatient Addict Serv, 26 Cent St, Somerville, MA 02143 USA. EM zschuman@cha.harvard.edu OI Schuman-Olivier, Zev/0000-0001-9216-2039; Borodovsky, Jacob T./0000-0001-7112-5677 FU NCRR NIH HHS [UL1 RR025758, UL1RR025758]; NIDA NIH HHS [K01 DA027097, K01DA027097, K24 DA022288, K24DA022288, L30 DA027330, U10 DA015831, U10 DA15831] NR 73 TC 17 Z9 17 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP PY 2014 VL 47 IS 3 BP 202 EP 212 DI 10.1016/j.jsat.2014.04.006 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AM3VH UT WOS:000339780400004 PM 24953168 ER PT J AU Manning, J Hedden, T Wickens, N Whitfield-Gabrieli, S Prelec, D Gabrieli, JDE AF Manning, Joshua Hedden, Trey Wickens, Nina Whitfield-Gabrieli, Susan Prelec, Drazen Gabrieli, John D. E. TI Personality influences temporal discounting preferences: Behavioral and brain evidence SO NEUROIMAGE LA English DT Article DE Personality; Decision making; Delayed discounting; Reward; fMRI ID INTERTEMPORAL DECISION-MAKING; INDIVIDUAL-DIFFERENCES; PREFRONTAL CORTEX; SELF-CONTROL; DELAY; TIME; CONSCIENTIOUSNESS; IMPULSIVITY; PERFORMANCE; CHOICE AB Personality traits are stable predictors of many life outcomes that are associated with important decisions that involve tradeoffs over time. Therefore, a fundamental question is how tradeoffs over time vary from person to person in relation to stable personality traits. We investigated the influence of personality, as measured by the Five-Factor Model, on time preferences and on neural activity engaged by intertemporal choice. During functional magnetic resonance imaging (fMRI), participants made choices between smaller-sooner and larger-later monetary rewards. For each participant, we estimated a constant-sensitivity discount function that dissociates impatience (devaluation of future consequences) from time sensitivity (consistency with rational, exponential discounting). Overall, higher neuroticism was associated with a relatively greater preference for immediate rewards and higher conscientiousness with a relatively greater preference for delayed rewards. Specifically, higher conscientiousness correlated positively with lower short-term impatience and more exponential time preferences, whereas higher neuroticism (lower emotional stability) correlated positively with higher short-term impatience and less exponential time preferences. Cognitive-control and reward brain regions were more activated when higher conscientiousness participants selected a smaller-sooner reward and, conversely, when higher neuroticism participants selected a larger-later reward. The greater activations that occurred when choosing rewards that contradicted personality predispositions may reflect the greater recruitment of mental resources needed to override those predispositions. These findings reveal that stable personality traits fundamentally influence how rewards are chosen over time. (C) 2014 Elsevier Inc. All rights reserved C1 [Manning, Joshua; Wickens, Nina; Whitfield-Gabrieli, Susan; Prelec, Drazen; Gabrieli, John D. E.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Manning, Joshua; Wickens, Nina; Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Hedden, Trey] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Hedden, Trey] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Prelec, Drazen] MIT, Sloan Sch Management, Cambridge, MA 02139 USA. [Prelec, Drazen] MIT, Dept Econ, Cambridge, MA 02139 USA. RP Manning, J (reprint author), 43 Vassar St,46-4033A, Cambridge, MA 02139 USA. EM joshuam@mit.edu FU NIH/NIA [R21 AG030770, K01 AG040197] FX This work was conducted at the Athinoula A. Martinos Imaging Center at The McGovern Institute for Brain Research, MIT and supported by the NIH/NIA R21 AG030770. T.H. is supported by NIH/NIA K01 AG040197. We thank Jack Murtagh and Aaron Mattfeld for assistance with the manuscript. NR 38 TC 7 Z9 7 U1 8 U2 40 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2014 VL 98 BP 42 EP 49 DI 10.1016/j.neuroimage.2014.04.066 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM2UQ UT WOS:000339706700005 PM 24799134 ER PT J AU Hicks, JW Parkes, J Tong, JC Houle, S Vasdev, N Wilson, AA AF Hicks, Justin W. Parkes, Jun Tong, Junchao Houle, Sylvain Vasdev, Neil Wilson, Alan A. TI Radiosynthesis and ex vivo evaluation of [C-11-carbonyl]carbamate- and urea-based monoacylglycerol lipase inhibitors SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Radiotracer development; Monoacylglycerol lipase; Carbon-11; CO2 fixation; Positron emission tomography ID ACID AMIDE HYDROLASE; POSITRON-EMISSION-TOMOGRAPHY; PERIPHERAL BENZODIAZEPINE-RECEPTORS; IN-VIVO; ACETYLCHOLINESTERASE ACTIVITY; 2-ARACHIDONOYLGLYCEROL HYDROLYSIS; ENDOCANNABINOID HYDROLASES; PET; BRAIN; RADIOTRACERS AB Introduction: Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are the two primary enzymes that regulate the tone of endocannabinoid signaling. Although new PET radiotracers have been discovered for imaging FAAH in vivo, no such radiotracer exists for imaging MAGL. Here we report the radiosynthesis of five candidate MAGL radiotracers and their ex vivo evaluations in mice and rats. Methods: Candidate carbamate and urea MAGL inhibitors were radiolabeled at the carbonyl position by [C-11]CO2 fixation. Radiotracers were administered (tail-vein injection) to rodents and brain uptake of radioactivity measured at early and late time points ex vivo. Specificity of uptake was explored by pretreatment with unlabeled inhibitors (2 mg/kg, ip) 30 min prior to radiotracer administration. Results: All five candidate MAGL radiotracers were prepared in high specific activity (>65 GBg/mu mol) and radiochemical purity (>98%). Moderate brain uptake (0.2-0.8 SUV) was observed for each candidate while pretreatment did not reduce uptake for four of the five tested. For two candidates ([C-11]12 and [C-11]14), high retention of radioactivity was observed in the blood (ca. 10 and 4 SUV at 40 min) which was blocked by pretreatment with unlabeled inhibitors. The most promising candidate, [C-11]18, demonstrated moderate brain uptake (ca. 0.8 SUV) which showed circa 50% blockade by pretreatment with unlabeled 18. Conclusion: One putative and four reported potent and selective MAGL inhibitors have been radiolabeled via [C-11]CO2 fixation as radiotracers for this enzyme. Despite the promising in vitro pharmacological profile, none of the five candidate radiotracers exhibited in vivo behavior suitable for PET neuroimaging. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hicks, Justin W.; Parkes, Jun; Tong, Junchao; Houle, Sylvain; Wilson, Alan A.] CAMH, Res Imaging Ctr, Toronto, ON M5T 1R8, Canada. [Hicks, Justin W.; Wilson, Alan A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada. [Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. RP Wilson, AA (reprint author), CAMH, Res Imaging Ctr, 250 Coll St, Toronto, ON M5T 1R8, Canada. EM alan.wilson@camhpet.ca FU NIMH NIH HHS [1R21MH094424-01, R21 MH094424] NR 40 TC 7 Z9 7 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 EI 1872-9614 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD SEP PY 2014 VL 41 IS 8 BP 688 EP 694 DI 10.1016/j.nucmedbio.2014.05.001 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AM2UW UT WOS:000339707300006 PM 24969632 ER PT J AU Nagler, RH Puleo, E Sprunck-Harrild, K Viswanath, K Emmons, KM AF Nagler, Rebekah H. Puleo, Elaine Sprunck-Harrild, Kim Viswanath, K. Emmons, Karen M. TI Health media use among childhood and young adult cancer survivors who smoke SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Childhood cancer survivors; Young adult cancer survivors; Information seeking; Media exposure; Smoking cessation ID SERVICE NEEDS; INFORMATION-SEEKING; CESSATION; BEHAVIORS; PARTNERSHIP; POPULATION; INTERVENTIONS; ADOLESCENT; ONCOLOGY; OUTCOMES AB Promoting healthy behaviors may reduce the risk of co-morbidities among childhood and young adult (CYA) cancer survivors. Although behavioral interventions are one way to encourage such activities, there is increasing evidence that health media use-particularly health information seeking-also may influence health knowledge, beliefs, and behaviors. The current study explores patterns of health media use among survivors of CYA cancer. Our focus is on survivors who smoke and thus are at even greater risk of co-morbidities. We analyzed data from the Partnership for Health-2 study, a web-based smoking cessation intervention, to examine the prevalence of and factors associated with health media use (N = 329). Nearly two thirds (65.3 %) of CYA survivors who smoke reported infrequent or no online health information seeking. Many reported never reading health sections of newspapers or general magazines (46.2 %) or watching health segments on local television news (32.3 %). Factors associated with health media use include education and employment, cancer-related distress, and smoking quit attempts. Health information engagement is low among CYA survivors who smoke, particularly active seeking of health information online. Population subgroups differ in their media use patterns; some of these differences reflect communication inequalities, which have the potential to exacerbate health disparities. Clinicians have an opportunity to guide CYA survivors towards useful and reliable information sources. This guidance could help survivors fulfill their unmet information and support needs and may be particularly important for less educated survivors and other underserved populations. C1 [Nagler, Rebekah H.] Univ Minnesota, Sch Journalism & Mass Commun, Minneapolis, MN 55455 USA. [Puleo, Elaine] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Sprunck-Harrild, Kim; Viswanath, K.; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Viswanath, K.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Emmons, Karen M.] Kaiser Fdn Res Inst, Oakland, CA USA. RP Nagler, RH (reprint author), Univ Minnesota, Sch Journalism & Mass Commun, 111 Murphy Hall,206 Church St SE, Minneapolis, MN 55455 USA. EM nagle026@umn.edu FU National Cancer Institute [5 R01-CA106914-05, K05-CA124415]; National Cancer Institute by the Harvard Education Programin Cancer Prevention [5 R25-CA057711] FX This research was supported by grants 5 R01-CA106914-05 and K05-CA124415 from the National Cancer Institute. Funding support for R.H.N. was provided through the National Cancer Institute by the Harvard Education Programin Cancer Prevention (5 R25-CA057711). The authors would like to thank Nancy Klockson for her assistance in manuscript preparation, as well as the participating survivorship programs: St. Jude Children's Research Hospital, Memorial Sloan Kettering Cancer Center, Princess Margaret Hospital, The Hospital for Sick Children, and Dana-Farber Cancer Institute/Partners HealthCare. NR 44 TC 2 Z9 2 U1 2 U2 15 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 SEP PY 2014 VL 22 IS 9 BP 2497 EP 2507 DI 10.1007/s00520-014-2236-x PG 11 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA AM6LQ UT WOS:000339976900024 PM 24728617 ER PT J AU Sloan, DM AF Sloan, Denise M. TI Using Experimental Psychopathology Studies to Advance Treatment Research SO BEHAVIOR THERAPY LA English DT Article DE experimental psychopathology; trauma; PTSD; clinical trials ID POSTTRAUMATIC-STRESS-DISORDER; PROLONGED EXPOSURE TREATMENT; RESEARCH DOMAIN CRITERIA; VIETNAM VETERANS; FEAR ACTIVATION; THERAPY; PTSD; IMAGERY; HABITUATION; INFORMATION AB Cognitive behavioral therapy evolved from systematic studies testing learning theories. This research led to the development of effective treatment approaches for a variety of disorders. In more recent years we have moved away from relying on experimental psychopathology studies to directly inform our treatment approaches. This paper describes why the alienation from experimental psychopathology studies is detrimental to the advancement of treatment approaches. Examples of how systematic research can be conducted to address questions regarding treatment mechanisms and moderators are provided. Drawing on experimental psychopathology research can also lead to a better understanding of core processes of psychopathology, which in turn can lead to transdiagnostic treatment approaches. C1 [Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, VA Natl Ctr PTSD, Behav Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@va.gov NR 29 TC 1 Z9 1 U1 3 U2 9 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD SEP PY 2014 VL 45 IS 5 BP 589 EP 593 PG 5 WC Psychology, Clinical SC Psychology GA AL9KY UT WOS:000339461200001 PM 25022770 ER PT J AU Otto, MW Moshier, SJ Kinner, DG Simon, NM Pollack, MH Orr, SP AF Otto, Michael W. Moshier, Samantha J. Kinner, Dina G. Simon, Naomi M. Pollack, Mark H. Orr, Scott P. TI De Novo Fear Conditioning Across Diagnostic Groups in the Affective Disorders: Evidence for Learning Impairments SO BEHAVIOR THERAPY LA English DT Article DE fear conditioning; classical conditioning; extinction learning; anxiety disorders; depression ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; PANIC DISORDER; ANXIETY DISORDERS; SOCIAL PHOBIA; MEMORY DYSFUNCTION; EXECUTIVE FUNCTION; SEX-DIFFERENCES; WAR VETERANS; FEMALE RATS AB De novo fear conditioning paradigms have served as a model for how clinical anxiety may be acquired and maintained. To further examine variable findings in the acquisition and extinction of fear responses between clinical and nonclinical samples, we assessed de novo fear conditioning outcomes in outpatients with either anxiety disorders or depression and healthy subjects recruited from the community. Overall, we found evidence for attenuated fear conditioning, as measured by skin conductance, among the patient sample, with significantly lower fear acquisition among patients with depression and posttraumatic stress disorder. These acquisition deficits were evident in both the simple (considering the CS+ only) and differential (evaluating the CS+ in relation to the CS-) paradigms. Examination of extinction outcomes were hampered by the low numbers of patients who achieved adequate conditioning, but the available data indicated slower extinction among the patient, primarily panic disorder, sample. Results are interpreted in the context of the cognitive deficits that are common to the anxiety and mood disorders, with attention to a range of potential factors, including mood comorbidity, higher-and lower-order cognitive processes and deficits, and medication use, that may modulate outcomes in fear conditioning studies, and, potentially, in exposure-based cognitive behavioral therapy. C1 [Otto, Michael W.; Moshier, Samantha J.; Kinner, Dina G.] Boston Univ, Boston, MA 02215 USA. [Simon, Naomi M.; Pollack, Mark H.; Orr, Scott P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Simon, Naomi M.; Pollack, Mark H.; Orr, Scott P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Boston Univ, 648 Beacon St, Boston, MA 02215 USA. EM mwotto@bu.edu FU NIMH NIH HHS [R21 MH072165, MH072165] NR 41 TC 10 Z9 10 U1 5 U2 11 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD SEP PY 2014 VL 45 IS 5 BP 619 EP 629 PG 11 WC Psychology, Clinical SC Psychology GA AL9KY UT WOS:000339461200004 PM 25022773 ER PT J AU Liverant, GI Sloan, DM Pizzagalli, DA Harte, CB Kamholz, BW Rosebrock, LE Cohen, AL Fava, M Kaplan, GB AF Liverant, Gabrielle I. Sloan, Denise M. Pizzagalli, Diego A. Harte, Christopher B. Kamholz, Barbara W. Rosebrock, Laina E. Cohen, Andrew L. Fava, Maurizio Kaplan, Gary B. TI Associations Among Smoking, Anhedonia, and Reward Learning in Depression SO BEHAVIOR THERAPY LA English DT Article DE depression; smoking; anhedonia; reward learning; veteran ID NICOTINE DEPENDENCE; CIGARETTE-SMOKING; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; TRIPARTITE MODEL; UNITED-STATES; PSYCHOMETRIC EVALUATION; POSITIVE AFFECT; MOOD DISORDERS; ANXIETY AB Depression and cigarette smoking co-occur at high rates. However, the etiological mechanisms that contribute to this relationship remain unclear. Anhedonia and associated impairments in reward learning are key features of depression, which also have been linked to the onset and maintenance of cigarette smoking., However, few studies have investigated differences in anhedonia and reward learning among depressed smokers and depressed nonsmokers. The goal of this study was to examine putative differences in anhedonia and reward learning in depressed smokers (n = 36) and depressed nonsmokers (n = 44). To this end, participants completed self-report measures of anhedonia and behavioral activation (BAS reward responsiveness scores) and as well as a probabilistic reward task rooted in signal detection theory, which measures reward learning (Pizzagalli, Jahn, & O'Shea, 2005). When considering self-report measures, depressed smokers reported higher trait anhedonia and reduced BAS reward responsiveness scores compared to depressed nonsmokers. In contrast to self-report measures, nicotine-satiated depressed smokers demonstrated greater acquisition of reward-based learning compared to depressed nonsmokers as indexed by the probabilistic reward task. Findings may point to a potential mechanism underlying the frequent co-occurrence of smoking and depression. These results highlight the importance of continued investigation of the role of anhedonia and reward system functioning in the co-occurrence of depression and nicotine abuse. Results also may support the use of treatments targeting reward learning (e.g., behavioral activation) to enhance smoking cessation among individuals with depression. C1 [Liverant, Gabrielle I.; Harte, Christopher B.; Kamholz, Barbara W.; Kaplan, Gary B.] VA Boston Healthcare Syst 116A, Brockton, MA 02301 USA. [Liverant, Gabrielle I.; Harte, Christopher B.; Kamholz, Barbara W.; Kaplan, Gary B.] Boston Univ, Sch Med, Boston, MA USA. [Sloan, Denise M.] Boston Univ, Sch Med, Natl Ctr PTSD, Behav Sci Div,VA Boston Healthcare Syst, Boston, MA USA. [Pizzagalli, Diego A.] McLean Hosp, Harvard Med Sch, Mclean, VA USA. [Kamholz, Barbara W.] Boston Univ, Boston, MA USA. [Rosebrock, Laina E.] Northwestern Univ, Evanston, IL 60208 USA. [Cohen, Andrew L.] McLean Hosp, Mclean, VA USA. [Fava, Maurizio] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RP Liverant, GI (reprint author), VA Boston Healthcare Syst 116A, 940 Belmont St, Brockton, MA 02301 USA. EM gabrielle.liverant@va.gov FU NIMH NIH HHS [R01 MH068376] NR 62 TC 6 Z9 6 U1 11 U2 21 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD SEP PY 2014 VL 45 IS 5 BP 651 EP 663 PG 13 WC Psychology, Clinical SC Psychology GA AL9KY UT WOS:000339461200007 PM 25022776 ER PT J AU Yokoyama, JS Evans, DS Coppola, G Kramer, JH Tranah, GJ Yaffe, K AF Yokoyama, Jennifer S. Evans, Daniel S. Coppola, Giovanni Kramer, Joel H. Tranah, Gregory J. Yaffe, Kristine TI Genetic Modifiers of Cognitive Maintenance Among Older Adults SO HUMAN BRAIN MAPPING LA English DT Article DE genetics; genomics; aging; cognition; genome wide association study; neuroimaging ID GENOME-WIDE ASSOCIATION; MINI-MENTAL STATE; ALZHEIMERS-DISEASE; METABOLIC SYNDROME; OSTEOPOROTIC FRACTURES; SUSCEPTIBILITY LOCI; DECLINE; BRAIN; RISK; METAANALYSIS AB Objective: Identify genetic factors associated with cognitive maintenance in late life and assess their association with gray matter (GM) volume in brain networks affected in aging. Methods: We conducted a genome-wide association study of similar to 2.4 M markers to identify modifiers of cognitive trajectories in Caucasian participants (N=7,328) from two population-based cohorts of non-demented elderly. Standardized measures of global cognitive function (z-scores) over 10 and 6 years were calculated among participants and mixed model regression was used to determine subject-specific cognitive slopes. "Cognitive maintenance" was defined as a change in slope of >= 0 and was compared with all cognitive decliners (slope <0). In an independent cohort of cognitively normal older Caucasians adults (N=122), top association findings were then used to create genetic scores to assess whether carrying more cognitive maintenance alleles was associated with greater GM volume in specific brain networks using voxel-based morphometry. Results: The most significant association was on chromosome 11 (rs7109806, P=7.8 x 10(-8)) near RIC3. RIC3 modulates activity of alpha 7 nicotinic acetylcholine receptors, which have been implicated in synaptic plasticity and beta-amyloid binding. In the neuroimaging cohort, carrying more cognitive maintenance alleles was associated with greater volume in the right executive control network (RECN; P-FWE=0.01). Conclusions: These findings suggest that there may be genetic loci that promote healthy cognitive aging and that they may do so by conferring robustness to GM in the RECN. Future work is required to validate top candidate genes such as RIC3 for involvement in cognitive maintenance. Hum Brain Mapp 35:4556-4565, 2014. (C) 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. C1 [Yokoyama, Jennifer S.; Kramer, Joel H.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Evans, Daniel S.; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Yokoyama, JS (reprint author), UCSF Memory & Aging Ctr, 675 Nelson Rising Ln,Suite 190, San Francisco, CA 94158 USA. EM jyokoyama@memory.ucsf.edu FU Larry L. Hillblom Foundation [2012-A-015-FEL]; National Institute on Aging (NIA) [P50-AG023501-08S1, R01 AG032289, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, RC1 AG035610]; National Institutes of Health (NIH) [K24 AG031155]; NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (GWAS in MrOS and SOF) [RC2AR058973]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Research Resources (NCRR) [2007/2I] FX Contract grant sponsor: Larry L. Hillblom Foundation; Contract grant number: 2012-A-015-FEL; Contract grant sponsor: National Institute on Aging (NIA); Contract grant number: P50-AG023501-08S1; Contract grant sponsor: National Institutes of Health (NIH); Contract grant number: K24 AG031155; Contract grant sponsor: National Institute on Aging (NIA); Contract grant numbers: R01 AG032289, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, and RC1 AG035610; Contract grant sponsor: NIH Roadmap for Medical Research; Contract grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140; Contract grant sponsor: The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (GWAS in MrOS and SOF); Contract grant number: RC2AR058973; Contract grant sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Center for Research Resources (NCRR); Contract grant number: 2007/2I NR 61 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4556 EP 4565 DI 10.1002/hbm.22494 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000022 PM 24616004 ER PT J AU Yu, RJ Gollub, RL Vangel, M Kaptchuk, T Smoller, JW Kong, J AF Yu, Rongjun Gollub, Randy L. Vangel, Mark Kaptchuk, Ted Smoller, Jordan W. Kong, Jian TI Placebo Analgesia and Reward Processing: Integrating Genetics, Personality, and Intrinsic Brain Activity SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; conditioning; resting state; regional homogeneity; placebo analgesia ID RESTING-STATE FMRI; MAJOR DEPRESSIVE DISORDER; WHITE-MATTER INTEGRITY; REGIONAL HOMOGENEITY; INDIVIDUAL-DIFFERENCES; FUNCTIONAL CONNECTIVITY; INTERINDIVIDUAL DIFFERENCES; SUBJECTIVE EXPERIENCE; ACUPUNCTURE TREATMENT; COGNITIVE MODULATION AB Our expectations about an event can strongly shape our subjective evaluation and actual experience of events. This ability, applied to the modulation of pain, has the potential to affect therapeutic analgesia substantially and constitutes a foundation for non-pharmacological pain relief. A typical example of such modulation is the placebo effect. Studies indicate that placebo may be regarded as a reward, and brain activity in the reward system is involved in this modulation process. In the present study, we combined resting-state functional magnetic resonance imaging (rs-fMRI) measures, genotype at a functional COMT polymorphism (Val158Met), and personality measures in a model to predict the magnitude of placebo conditioning effect indicated by subjective pain rating reduction to calibrated noxious stimuli. We found that the regional homogeneity (ReHo), an index of local neural coherence, in the ventral striatum, was significantly associated with conditioning effects on pain rating changes. We also found that the number of Met alleles at the COMT polymorphism was linearly correlated to the suppression of pain. In a fitted regression model, we found the ReHo in the ventral striatum, COMT genotype, and Openness scores accounted for 59% of the variance in the change in pain ratings. The model was further tested using a separate data set from the same study. Our findings demonstrate the potential of combining resting-state connectivity, genetic information, and personality to predict placebo effect. Hum Brain Mapp 35:4583-4593, 2014. (C) 2014 Wiley Periodicals, Inc. C1 [Yu, Rongjun; Gollub, Randy L.; Smoller, Jordan W.; Kong, Jian] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Gollub, Randy L.; Vangel, Mark; Kong, Jian] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Kaptchuk, Ted] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Program Placebo Studies, Boston, MA 02215 USA. RP Kong, J (reprint author), 120 2nd Ave,Room 101C, Charlestown, MA 02129 USA. EM kongj@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU NCCAM [KO1AT003883, R21AT004497, R01AT006364, R01AT005280, K24 AT004095]; NIDA [R03AT218317]; NIMH [K24MH094614] FX Contract grant sponsor: NCCAM; Contract grant numbers: KO1AT003883; R21AT004497; R01AT006364; Contract grant sponsor: NIDA; Contract grant number: R03AT218317 to Jian Kong; Contract grant sponsor: NCCAM; Contract grant number: R01AT005280 to Randy Gollub.; Contract grant sponsor: NIMH; Contract grant number: K24MH094614 to Jordan W. Smoller.; Contract grant sponsor: NCCAM; Contract grant number: K24 AT004095 to Ted Kaptchuk. NR 88 TC 15 Z9 16 U1 4 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4583 EP 4593 DI 10.1002/hbm.22496 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000024 PM 24578196 ER PT J AU Lee, J Cohen, MS Engel, SA Glahn, D Nuechterlein, KH Wynn, JK Green, MF AF Lee, Junghee Cohen, Mark S. Engel, Stephen A. Glahn, David Nuechterlein, Keith H. Wynn, Jonathan K. Green, Michael F. TI Neural Substrates of Visual Masking by Object Substitution in Schizophrenia SO HUMAN BRAIN MAPPING LA English DT Article DE object substitution masking; schizophrenia; visual backward masking; fMRI ID FUNCTIONAL MRI; SEPARATING PROCESSES; OCCIPITAL CORTEX; BACKWARD-MASKING; AWARENESS; ATTENTION; FMRI; REPRESENTATION; CONSCIOUSNESS; OPTIMIZATION AB Despite a well-known behavioral finding of visual backward masking impairment in schizophrenia, its underlying neural mechanism remains obscure. This study examined neural correlates of a distinct type of visual backward masking, object substitution masking (OSM), in schizophrenia. Twenty schizophrenia patients and 26 healthy controls completed a 4-Dot OSM task and three functional localizer tasks for the lateral occipital (LO), human motion-sensitive (hMT+), and retinotopic areas in the scanner. In 4-dot masking, subjects detected a target that was followed by a mask consisting of 4 dots that surrounded a target. Stimulus-onset asynchrony (SOA) between target and mask was varied to examine the modulation of masking: (1) within three visual processing areas regions of interest (ROI) (i.e., ROI analysis) and (2) in brain regions outside the three visual processing areas (i.e., whole brain analysis). In the ROI analyses, LO and retinotopic areas showed increased peak amplitude when SOA become longer in both patients and controls. There was also an effect of ROI in that both groups showed higher activation in LO and hMT+ compared with the retinotopic areas. The whole brain analyses revealed a significantly activated area for longer SOAs vs. a short SOA in the occipital cortex in controls only, but the group contrast was not significant. Overall, this study did not find strong evidence for neural abnormalities of OSM in schizophrenia, suggesting that neural substrates of OSM in schizophrenia are not as compromised as those involved in the more common masking methods that rely on disruption of object formation. (C) 2014 Wiley Periodicals, Inc. C1 [Lee, Junghee; Cohen, Mark S.; Nuechterlein, Keith H.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Lee, Junghee; Wynn, Jonathan K.; Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Engel, Stephen A.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Glahn, David] Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT USA. [Glahn, David; Nuechterlein, Keith H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Lee, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza 77-361, Los Angeles, CA 90024 USA. EM jungheelee@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [MH43292, MH065707]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund FX Contract grant sponsor: National Institute of Mental Health; Contract grant number: MH43292, MH065707; Contract grant sponsors: Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family, the Northstar Fund. NR 38 TC 2 Z9 2 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4654 EP 4662 DI 10.1002/hbm.22501 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000029 PM 24677632 ER PT J AU Huang, C Altbach, MI El Fakhri, G AF Huang, Chuan Altbach, Maria I. El Fakhri, Georges TI Pattern recognition for rapid T2 mapping with stimulated echo compensation SO MAGNETIC RESONANCE IMAGING LA English DT Article DE Quantitative MRI; T2 mapping; MR parameter; Stimulated echoes; Indirect echoes; Slice imperfection ID RELAXOMETRY; DIFFERENTIATION; HEMANGIOMAS AB Indirect echoes (such as stimulated echoes) are a source of signal contamination in multi-echo spin-echo T-2 quantification and can lead to T-2 overestimation if a conventional exponential T-2 decay model is assumed. Recently, nonlinear least square fitting of a slice-resolved extended phase graph (SEPG) signal model has been shown to provide accurate T-2 estimates with indirect echo compensation. However, the iterative nonlinear least square fitting is computationally expensive and the T-2 map generation time is long. In this work, we present a pattern recognition T-2 mapping technique based on the SEPG model that can be performed with a single pre-computed dictionary for any arbitrary echo spacing. Almost identical T-2 and B-1 maps were obtained from in vivo data using the proposed technique compared to conventional iterative nonlinear least square fitting, while the computation time was reduced by more than 14-fold. (C) 2014 Elsevier Inc. All rights reserved. C1 [Huang, Chuan; El Fakhri, Georges] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Dept Imaging, Boston, MA 02114 USA. [Huang, Chuan; El Fakhri, Georges] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Altbach, Maria I.] Univ Arizona, Dept Med Imaging, Tucson, AZ USA. RP Huang, C (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, 55 Fruit St,White Bldg 427, Boston, MA 02114 USA. EM huang.chuan@mgh.harvard.edu OI Huang, Chuan/0000-0001-6052-0663 FU NIH [R01-CA165221, R21-EB012326, R01-HL085385] FX This research was supported in part by NIH grants R01-CA165221, R21-EB012326 (El Fakhri) and R01-HL085385 (Altbach). NR 15 TC 3 Z9 3 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X EI 1873-5894 J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD SEP PY 2014 VL 32 IS 7 BP 969 EP 974 DI 10.1016/j.mri.2014.04.014 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AM0JN UT WOS:000339531900023 PM 24853466 ER PT J AU Cash, TV Konig, A Eonta, AM Vrana, SR AF Cash, Therese V. Konig, Andrea Eonta, Alison M. Vrana, Scott R. TI RESPIRATORY SINUS ARRYTHMIA PREDICTS MENTAL HEALTH OUTCOMES IN AN EXPRESSIVE WRITING TASK SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE respiratory sinus arrhythmia; expressive writing C1 [Cash, Therese V.; Konig, Andrea; Vrana, Scott R.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Eonta, Alison M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-49 BP S55 EP S55 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500303 ER PT J AU Howard, A Verona, E Sadeh, N AF Howard, Aisha Verona, Edelyn Sadeh, Naomi TI PSYCHOPATHY AND ERP RESPONSES IN THE CONTEXT OF EMOTIONAL PROCESSING AND VISUAL COMPLEXITY SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE psychopathy; event-related potentials C1 [Howard, Aisha; Verona, Edelyn] Univ Illinois, Urbana, IL 61801 USA. [Sadeh, Naomi] VA Boston Healthcare Syst, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 4-32 BP S68 EP S69 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500377 ER PT J AU Jahshan, C Wynn, JK Mathis, KI Green, MF AF Jahshan, Carol Wynn, Jonathan K. Mathis, Kristopher I. Green, Michael F. TI THE NEUROPHYSIOLOGY OF BIOLOGICAL MOTION PERCEPTION IN SCHIZOPHRENIA SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE biological motion; electroencephalography; schizophrenia C1 VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-17 BP S49 EP S49 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500271 ER PT J AU MacNamara, A Fitzgerald, DA Shankman, SA Milad, MR Phan, KL AF MacNamara, Annmarie Fitzgerald, Daniel A. Shankman, Stewart A. Milad, Mohammed R. Phan, K. Luan TI NEURAL AND PSYCHOPHYSIOLOGICAL SUBSTRATES OF FEAR LEARNING SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE fear learning; fMRI; skin conductance C1 [MacNamara, Annmarie; Fitzgerald, Daniel A.; Shankman, Stewart A.; Phan, K. Luan] Univ Illinois, Chicago, IL USA. [Fitzgerald, Daniel A.; Phan, K. Luan] Jesse Brown Vet Adm, Med Ctr, Mental Hlth Serv Line, Chicago, IL USA. [Milad, Mohammed R.] Harvard Univ, Cambridge, MA 02138 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 4-7 BP S64 EP S64 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500352 ER PT J AU Wangelin, BC Tuerk, PW AF Wangelin, Bethany C. Tuerk, Peter W. TI TAKING THE PULSE OF PROLONGED EXPOSURE THERAPY: CHANGES IN TRAUMA-RELATED PHYSIOLOGICAL AROUSAL ACROSS THE COURSE OF PTSD TREATMENT SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE PTSD; anxiety; emotion C1 [Wangelin, Bethany C.; Tuerk, Peter W.] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 4-81 BP S77 EP S77 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500426 ER PT J AU Wynn, JK Roach, BJ Lee, J Horan, WP Ford, JM Jimenez, AM Weiner, K Ghermezi, L Green, MF AF Wynn, Jonathan K. Roach, Brian J. Lee, Junghee Horan, William P. Ford, Judith M. Jimenez, Amy M. Weiner, Katherine Ghermezi, Livon Green, Michael F. TI EEG FINDINGS OF REDUCED NEURAL SYNCHRONIZATION DURING VISUAL INTEGRATION IN SCHIZOPHRENIA SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE schizophrenia; event-related potentials; visual integration C1 [Wynn, Jonathan K.; Horan, William P.; Jimenez, Amy M.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Wynn, Jonathan K.; Lee, Junghee; Horan, William P.; Weiner, Katherine; Ghermezi, Livon; Green, Michael F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Roach, Brian J.] Vet Affairs San Francisco Med Ctr, San Francisco, CA USA. [Ford, Judith M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-16 BP S49 EP S49 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500270 ER PT J AU Kapoor, N Shinagare, AB Jagannathan, JP Shah, SH Krajewski, KM Hornick, JL Ramaiya, NH AF Kapoor, Neena Shinagare, Atul B. Jagannathan, Jyothi P. Shah, Shaan H. Krajewski, Katherine M. Hornick, Jason L. Ramaiya, Nikhil H. TI Clinical and radiologic features of extraskeletal myxoid chondrosarcoma including initial presentation, local recurrence, and metastases SO RADIOLOGY AND ONCOLOGY LA English DT Article DE extraskeletal myxoid chondrosarcoma; CT; MRI; FDG-PET/CT ID SMALL PULMONARY ADENOCARCINOMAS; ABNORMALITY; T(9-22)(Q22-Q12) AB Background. The aim of the study was to evaluate the clinical and imaging features of extraskeletal myxoid chondrosarcoma (EMC) including initial presentation, recurrence, and metastases. Patients and methods. In this institutional review board-approved retrospective study, imaging features of 13 patients with pathologically proven EMC seen from August 1995 to December 2011 were analyzed. The group included 3 women and 10 men and the mean age was 54 years (range 29-73 years). Imaging studies were evaluated by two radiologists in consensus. Location, size, and imaging features of primary tumors were recorded as well as the presence of recurrent disease and location of metastases. Results. Among 13 patients, 3 died during the timeframe of this study. Nine patients had primary tumor in the lower extremity, and average tumor size was 9.3 cm (range 3.3-18 cm). On MRI, primary tumors were hyperintense on T2, isointense to muscle on T1, and demonstrated peripheral/septal enhancement. Three patients had local recurrence and 12 had metastatic disease, with lung involvement being the most common. Tumor density on contrast enhanced CT ranged from 8.2 to 82.9 Hounsfield unit (HU). FDG-PET/CT imaging was performed in 3 patients. One patient had no FDG avid disease and 2 patients had metastatic disease with standard uptake values (SUV) of 2.8 and 7.4. The patient with intense FDG uptake demonstrated more solid appearing tumor burden and had the shortest survival. Conclusions. EMC is a rare tumor that often occurs in the lower extremities and frequently metastasizes to the lungs. Increased tumor density and increased FDG uptake may be related to more aggressive disease. C1 [Kapoor, Neena; Shinagare, Atul B.; Jagannathan, Jyothi P.; Shah, Shaan H.; Krajewski, Katherine M.; Hornick, Jason L.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Imaging,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kapoor, N (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Imaging,Dept Radiol, 450 Brookline Ave, Boston, MA 02115 USA. EM nkapoor@partners.org NR 16 TC 4 Z9 4 U1 1 U2 1 PU ASSOC RADIOLOGY & ONCOLOGY PI LJUBLJANA PA INST ONCOLOGY, ZALOSKA CESTA 2, LJUBLJANA, 1000, SLOVENIA SN 1318-2099 EI 1581-3207 J9 RADIOL ONCOL JI Radiol. Oncol. PD SEP PY 2014 VL 48 IS 3 BP 235 EP 242 DI 10.2478/raon-2014-0005 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AL8ND UT WOS:000339395100003 PM 25177237 ER PT J AU Sher, L Grunebaum, MF Sullivan, GM Burke, AK Cooper, TB Mann, JJ Oquendo, MA AF Sher, Leo Grunebaum, Michael F. Sullivan, Gregory M. Burke, Ainsley K. Cooper, Thomas B. Mann, J. John Oquendo, Maria A. TI Association of testosterone levels and future suicide attempts in females with bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar; Female; Testosterone; Suicide ID HUMAN-AGGRESSION; GONADAL AXIS; WOMEN; DEPRESSION; BEHAVIOR; ANDROGENS; SCALE; RISK; METAANALYSIS; METABOLITES AB Background: Considerable evidence suggests that testosterone may play a role in the pathophysiology of mood disorders in females. This is the first prospective study to examine whether blood testosterone levels predict suicide attempts in females with bipolar disorder. Methods: Females with a DSM-PI diagnosis of a bipolar disorder in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. Patients were followed up prospectively for up to 2.5 years. Results: At baseline, testosterone levels positively correlated with the number of previous major depressive episodes and suicide attempts. Cox proportional hazards regression analysis found that higher baseline testosterone levels predicted suicide attempts during the follow-up period. Limitations: A limitation of the study is that the sample size is modest. Another limitation is that we did not have a bipolar nonattempter or healthy volunteer control group for comparison. Conclusion: Testosterone levels may predict suicidal behavior in women with bipolar disorder. Published by Elsevier B.V. C1 [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY 10468 USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 West Kingsbridge Rd, New York, NY 10468 USA. EM Leo.Sher@mssm.edu FU NIH [R01 MH59710, P50 MH62185, R01 MH48514] FX This study was supported by grants R01 MH59710, P50 MH62185, and R01 MH48514 from the NIH. The funding source had no role in study design; data collection, analysis, or interpretation; or in writing of the manuscript and submission process. NR 54 TC 5 Z9 5 U1 2 U2 9 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 SEP PY 2014 VL 166 BP 98 EP 102 DI 10.1016/j.jad.2014.04.068 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK8UV UT WOS:000338705000014 PM 25012416 ER PT J AU Hebenstreit, C Madden, E Maguen, S AF Hebenstreit, Claire Madden, Erin Maguen, Shira TI Latent classes of PTSD symptoms in Iraq and Afghanistan female veterans SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Posttraumatic stress disorder; Women's health services; Veterans/psychology; Female ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSES; MENTAL-HEALTH DIAGNOSES; DISSOCIATIVE SUBTYPE; CARE; BARRIERS; VA; ETHNICITY; CONFLICTS; SERVICES AB Background: Recent studies have used latent class analysis (LCA) to identify subgroups of individuals who slut e similar patterns of PTSD symptom endorsement; however, further study is needed among Female veterans, whose PTSD symptom expression may vary from that of their male counterparts. The current study examined latent PTSD symptom classes in female veterans who returned from recent military service in Iraq and Afghanistan, and explored military and demographic variables associated with distinct PTSD symptom presentations. Methods: A retrospective analysis was conducted using existing medical records from female Iraq and Afghanistan veterans who were new users of VA mental health outpatient (MHO) care, had received a PTSD diagnosis anytime during the post-deployment period, and completed the PTSD checklist within 30 days of their first MHO visit (N=2425). Results: The LCA results identified four latent classes of PTSD symptom profiles in the sample: High Symptom, Intermediate Symptom, Intermediate Symptom with High Emotional Numbing (EN), and Low Symptom. Race/ethnicity, age, Lime since last deployment, and distance from a VA facility emerged as predictors of PTSD symptom presentation. Limitations: The current study was cross-sectional and utilized administrative data. The results may not be generalizable to female veterans from other service eras. Conclusions: Longer times between end of last deployment and initiation of MHO services were associated with more symptomatic classes. Exploration of PTSD symptom presentation may enhance our understanding of the service needs of female veterans with PTSD, and suggests potential benefits to engaging veterans in MHO soon after last deployment. Published by Elsevier B.V. C1 [Hebenstreit, Claire; Madden, Erin; Maguen, Shira] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Hebenstreit, Claire; Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Hebenstreit, C (reprint author), San Francisco VA Med Ctr, PTSD Program 116P, 4150 Clement St, San Francisco, CA 94121 USA. EM Claire.Hebenstreit@va.gov OI Hebenstreit, Claire/0000-0001-5970-2195 FU Department of Defense Award Grant [W81XWH-11-2-0189] FX This research was supported by Department of Defense Award Grant (W81XWH-11-2-0189). NR 52 TC 7 Z9 7 U1 0 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 SEP PY 2014 VL 166 BP 132 EP 138 DI 10.1016/j.jad.2014.04.061 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK8UV UT WOS:000338705000019 PM 25012421 ER PT J AU Jeon, HJ Park, JI Ava, M DavidMischoulon, C Sohn, JH Seong, S Park, JE Yoo, I Cho, MJ AF Jeon, Hong Jin Park, Jong-Ik Fava, Maurizio Mischoulon, David Sohn, Jee Hoon Seong, Sujeong Park, Jee Eun Yoo, Ikki Cho, Maeng Je TI Feelings of worthlessness, traumatic experience, and their comorbidity in relation to lifetime suicide attempt in community adults with major depressive disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Worthlessness; Trauma; Suicide attempt; Major depressive disorder; Korea ID NATIONAL EPIDEMIOLOGIC SURVEY; CHILDHOOD TRAUMA; MELANCHOLIC FEATURES; RISK-FACTORS; PREVALENCE; HISTORY; COMPLETION; PREDICTORS; ATTRITION; ALCOHOL AB Background: Major depressive disorder (MDD) and traumatic experience are independent risk factors for lifetime suicide attempt (LSA). However, the relationships between trauma history and depressive symptornatology as they relate to LSA are not fully understood. Methods: A total of 12,532 adults, randomly selected through one method, completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) and a questionnaire for LSA (response rate 80.2%). Results: Among 825 subjects with MDD, 141 subjects reported an LSA (17.14 LSAs were significantly greater in those who had experienced any trauma than in those who had not (chi(2)=34.66, p < 0.0001). Multivariate logistic regression showed that only feelings of worthlessness were significantly associated with LSA among 20 depression symptoms in individuals with MDD (AOR=3.08, 95% CI 1.70-5.60). Feelings of worthlessness was associated with LSA in those who had experienced serious trauma (AOR=5.02, 95% CI 3.35-7.52), but not in those who had not. Serious traumas associated with LSA included military combat, witnessing a violent crime, rape or sexual assault, a bad beating, being threatened by others, and learning about traumas to others. Serious trauma showed no significant association with LSA in those who did not have feelings of worthlessness. PTSD was a comorbidity that showed the highest odds ratio with LSA in individuals with MDD. Conclusions: Feelings of worthlessness are more strongly associated with LSA than other depression symptoms in individuals with MOD, and it is significantly associated with LSA in those who experienced serious trauma but not in those who did not. (C) 2014 Elsevier B.V. All rights reserved. C1 [Jeon, Hong Jin; Yoo, Ikki] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Depression Ctr,Dept Psychiat, Seoul, South Korea. [Jeon, Hong Jin] SAIHST, Seoul, South Korea. [Jeon, Hong Jin; Fava, Maurizio; Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Park, Jong-Ik] Kangwon Natl Univ, Coll Med, Dept Psychiat, Chunchon, South Korea. [Sohn, Jee Hoon; Seong, Sujeong; Park, Jee Eun; Cho, Maeng Je] Seoul Natl Univ, Coll Med, Dept Psychiat & Behav Sci, Seoul 110744, South Korea. RP Cho, MJ (reprint author), Seoul Natl Univ, Coll Med, Dept Psychiat & Behav Sci, 28 Yeongeon Dong, Seoul 110744, South Korea. EM mjcho@snu.ac.kr FU Korean Ministry of Health Welfare; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [20110013064]; Samsung Medical Center Clinical Research Development Program (CRDP) [SM01131461] FX The authors wish to express their gratitude to 12 local investigators and 160 interviewers. This study was supported by the Korean Ministry of Health & Welfare for their cooperation and assistance. This research was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (no. 20110013064), and the Samsung Medical Center Clinical Research Development Program (CRDP) Grant SM01131461. NR 45 TC 8 Z9 8 U1 3 U2 20 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 SEP PY 2014 VL 166 BP 206 EP 212 DI 10.1016/j.jad.2014.05.010 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK8UV UT WOS:000338705000031 PM 25012433 ER PT J AU Mandeville, JB Liu, CH Vanduffel, W Marota, JJA Jenkins, BG AF Mandeville, Joseph B. Liu, Christina H. Vanduffel, Wim Marota, John J. A. Jenkins, Bruce G. TI Data collection and analysis strategies for phMRI SO NEUROPHARMACOLOGY LA English DT Article DE phMRI; fMRI; General linear model; Remifentanil; Dopamine; PET/MRI ID CEREBRAL BLOOD-VOLUME; INDEPENDENT COMPONENT ANALYSIS; EXOGENOUS CONTRAST AGENT; HUMAN BRAIN ACTIVITY; EVENT-RELATED FMRI; PHARMACOLOGICAL MRI; SPIN-ECHO; DOPAMINE CONCENTRATION; SPATIAL NORMALIZATION; TEMPORAL RESPONSES AB Although functional MRI traditionally has been applied mainly to study changes in task-induced brain function, evolving acquisition methodologies and improved knowledge of signal mechanisms have increased the utility of this method for studying responses to pharmacological stimuli, a technique often dubbed "phMRI". The proliferation of higher magnetic field strengths and the use of exogenous contrast agent have boosted detection power, a critical factor for successful phMRI due to the restricted ability to average multiple stimuli within subjects. Receptor-based models of neurovascular coupling, including explicit pharmacological models incorporating receptor densities and affinities and data-driven models that incorporate weak biophysical constraints, have demonstrated compelling descriptions of phMRI signal induced by dopaminergic stimuli. This report describes phMRI acquisition and analysis methodologies, with an emphasis on data-driven analyses. As an example application, statistically efficient data-driven regressors were used to describe the biphasic response to the mu-opioid agonist remifentanil, and antagonism using dopaminergic and GABAergic ligands revealed modulation of the mesolimbic pathway. Results illustrate the power of phMRI as well as our incomplete understanding of mechanisms underlying the signal. Future directions are discussed for phMRI acquisitions in human studies, for evolving analysis methodologies, and for interpretative studies using the new generation of simultaneous PET/MRI scanners. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Mandeville, Joseph B.; Vanduffel, Wim; Marota, John J. A.; Jenkins, Bruce G.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Liu, Christina H.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20817 USA. RP Mandeville, JB (reprint author), Martinos Ctr Biomed Imaging, Suite 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM jbm@nmr.mgh.harvard.edu OI Vanduffel, Wim/0000-0002-9399-343X; Liu, Christina/0000-0002-5723-177X FU NIH [P41RR14075, P20DA026002, R01-EB001782] FX This research was supported by NIH grants P41RR14075, P20DA026002, and R01-EB001782. NR 95 TC 2 Z9 2 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2014 VL 84 SI SI BP 65 EP 78 DI 10.1016/j.neuropharm.2014.02.018 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AK7OC UT WOS:000338616600008 PM 24613447 ER PT J AU Bjork, JM Gilman, JM AF Bjork, James M. Gilman, Jodi M. TI The effects of acute alcohol administration on the human brain: Insights from neuroimaging SO NEUROPHARMACOLOGY LA English DT Review DE Alcohol; Neuroimaging; fMRI; Positron Emission Tomography; Addiction ID CEREBRAL-BLOOD-FLOW; MAGNETIC-RESONANCE-SPECTROSCOPY; TERM ABSTINENT ALCOHOLICS; CENTRAL-NERVOUS-SYSTEM; CORTICAL GRAY-MATTER; GLUCOSE-METABOLISM; DOPAMINE RELEASE; DECISION-MAKING; FUNCTIONAL CONNECTIVITY; DETOXIFIED ALCOHOLICS AB Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled Neuroimaging in Neuropharmacology'. Published by Elsevier Ltd. C1 [Bjork, James M.] NIDA, Div Clin Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. [Gilman, Jodi M.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, MGH Div Psychiat Neurosci, Lab Neuroimaging & Genet, Boston, MA 02114 USA. RP Bjork, JM (reprint author), NIDA, Div Clin Neurosci & Behav Res, NIH, 6001 Executive Blvd,Room 3163, Bethesda, MD 20892 USA. EM jbjork@mail.nih.gov OI Bjork, James/0000-0003-0593-3291 FU National Institute on Alcohol Abuse and Alcoholism FX We are indebted to the training, fellowship, and inspiration of our former mentor, Dr. Daniel W. Hommer. Cited original research performed by the authors was funded by intramural funding of the National Institute on Alcohol Abuse and Alcoholism. NR 121 TC 14 Z9 16 U1 6 U2 46 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2014 VL 84 SI SI BP 101 EP 110 DI 10.1016/j.neuropharm.2013.07.039 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AK7OC UT WOS:000338616600011 PM 23978384 ER PT J AU Jasinska, AJ Zorick, T Brody, AL Stein, EA AF Jasinska, Agnes J. Zorick, Todd Brody, Arthur L. Stein, Elliot A. TI Dual role of nicotine in addiction and cognition: A review of neuroimaging studies in humans SO NEUROPHARMACOLOGY LA English DT Review DE Nicotine; Tobacco; Smoking; Dopamine; PET; SPECT; fMRI; Addiction; Cognition ID CEREBRAL-BLOOD-FLOW; STRIATAL DOPAMINE RELEASE; ACETYLCHOLINE-RECEPTOR OCCUPANCY; STATE FUNCTIONAL CONNECTIVITY; POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY TASK; HUMAN-BRAIN; SMOKING-CESSATION; CIGARETTE-SMOKING; TOBACCO SMOKERS AB Substantial evidence demonstrates both nicotine's addiction liability and its cognition-enhancing effects. However, the neurobiological mechanisms underlying nicotine's impact on brain function and behavior remain incompletely understood. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation as well as for a number of cognitive disorders such as schizophrenia. Neuroimaging techniques such as positron emission tomography (PET), single photon emission computed tomography (SPEC), and functional magnetic resonance imaging (fMRI), which make it possible to study the actions of nicotine in the human brain in vivo, play an increasingly important role in identifying these dual mechanisms of action. In this review, we summarize the current state of knowledge and discuss outstanding questions and future directions in human neuroimaging research on nicotine and tobacco. This research spans from receptor-level PET and SPECT studies demonstrating nicotine occupancy at nicotinic acetylcholine receptors (nAChRs) and upregulation of nAChRs induced by chronic smoking; through nicotine's interactions with the mesocorticolimbic dopamine system believed to mediate nicotine's reinforcing effects leading to dependence; to functional activity and connectivity fMRI studies documenting nicotine's complex behavioral and cognitive effects manifest by its actions on large-scale brain networks engaged both during task performance and at rest. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Published by Elsevier Ltd. C1 [Jasinska, Agnes J.; Stein, Elliot A.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. [Zorick, Todd; Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Zorick, Todd; Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Jasinska, AJ (reprint author), NIDA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jasinskaaj@mail.nih.gov; abrody@ucla.edu; EStein@intra.nida.nih.gov FU Intramural Research Program of NIDA; National Institute on Drug Abuse [R01 DA20872]; Tobacco-Related Disease Research Program [19XT-0135]; Merit Review Award from the Department of Veterans Affairs, Office of Research and Development FX Supported by the Intramural Research Program of NIDA (E.A.S., NJ.) and grants R01 DA20872 from the National Institute on Drug Abuse (A.L.B.), 19XT-0135 from the Tobacco-Related Disease Research Program (A.L.B.), and a Merit Review Award from the Department of Veterans Affairs, Office of Research and Development (A.L.B.). NR 156 TC 24 Z9 27 U1 5 U2 55 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2014 VL 84 SI SI BP 111 EP 122 DI 10.1016/j.neuropharm.2013.02.015 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AK7OC UT WOS:000338616600012 PM 23474015 ER PT J AU Kellner, V Menkes-Caspi, N Beker, S Stern, EA AF Kellner, Vered Menkes-Caspi, Noa Beker, Shlomit Stern, Edward A. TI Amyloid-beta alters ongoing neuronal activity and excitability in the frontal cortex SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; In vivo; Hyperexcitability; APPswe/PS1dE9; Mouse model; Background activity; Membrane potential; Up state; Down state ID APPSWE/PS1DE9 MOUSE MODEL; ALZHEIMERS-DISEASE; IN-VIVO; CORTICAL-NEURONS; SYNAPTIC INTEGRATION; NEOCORTICAL NEURONS; NETWORK ACTIVITY; FIRING PATTERNS; TRANSGENIC MICE; NEURAL-NETWORKS AB The effects of amyloid-beta on the activity and excitability of individual neurons in the early and advanced stages of the pathological progression of Alzheimer's disease remain unknown. We used in vivo intracellular recordings to measure the ongoing and evoked activity of pyramidal neurons in the frontal cortex of APPswe/PS1dE9 transgenic mice and age-matched nontransgenic littermate controls. Evoked excitability was altered in both transgenic groups: neurons in young transgenic mice displayed hypoexcitability, whereas those in older transgenic mice displayed hyperexcitability, suggesting changes in intrinsic electrical properties of the neurons. However, the ongoing activity of neurons in both young and old transgenic groups showed signs of hyperexcitability in the depolarized state of the membrane potential. The membrane potential of neurons in old transgenic mice had an increased tendency to fail to transition to the depolarized state, and the depolarized states had shorter durations on average than did controls. This suggests a combination of both intrinsic electrical and synaptic dysfunctions as mechanisms for activity changes at later stages of the neuropathological progression. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kellner, Vered; Menkes-Caspi, Noa; Beker, Shlomit; Stern, Edward A.] Bar Ilan Univ, Gonda Interdisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel. [Stern, Edward A.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. RP Stern, EA (reprint author), Bar Ilan Univ, Brain Res Ctr, IL-52900 Ramat Gan, Israel. EM sterned@mail.biu.ac.il FU National Institute on Aging [AG024238]; Legacy Heritage Bio-Medical Program of the Israel Science Foundation [688/10] FX The authors thank Professor Moshe Abeles, Professor Israel Nelken, and Professor Bradley T. Hyman for their valuable suggestions. Funding for this study was provided by the National Institute on Aging (AG024238) and the Legacy Heritage Bio-Medical Program of the Israel Science Foundation (688/10). NR 47 TC 8 Z9 8 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2014 VL 35 IS 9 BP 1982 EP 1991 DI 10.1016/j.neurobiolaging.2014.04.001 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AK1SB UT WOS:000338195100007 PM 24792906 ER PT J AU Koppel, J Acker, C Davies, P Lopez, OL Jimenez, H Azose, M Greenwald, BS Murray, PS Kirkwood, CM Kofler, J Sweet, RA AF Koppel, Jeremy Acker, Chris Davies, Peter Lopez, Oscar L. Jimenez, Heidy Azose, Miriam Greenwald, Blaine S. Murray, Patrick S. Kirkwood, Caitlin M. Kofler, Julia Sweet, Robert A. TI Psychotic Alzheimer's disease is associated with gender-specific tau phosphorylation abnormalities SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Psychosis; Tau; Dementia with Lewy bodies; Alpha-synuclein; Neurofibrillary tangles ID INCREASED FAMILIAL RISK; NEUROFIBRILLARY TANGLES; ATYPICAL ANTIPSYCHOTICS; LEWY BODY; DEMENTIA; DELUSIONS; HALLUCINATIONS; CONSORTIUM; EPIDEMIOLOGY; TRAJECTORIES AB Converging evidence suggests that psychotic Alzheimer's disease (AD + P) is associated with an acceleration of frontal degeneration, with tau pathology playing a primary role. Previous histopathologic and biomarker studies have specifically implicated tau pathology in this condition. To precisely quantify tau abnormalities in the frontal cortex in AD + P, we used a sensitive biochemical assay of total tau and 4 epitopes of phospho-tau relevant in AD pathology in a postmortem sample of AD + P and AD - P. Samples of superior frontal gyrus from 26 AD subjects without psychosis and 45 AD + P subjects with psychosis were analyzed. Results of enzyme-linked immunosorbent assay demonstrate that AD + P females, but not males, had significantly higher levels of phosphorylated tau in the frontal cortex. In males, but not females, AD + P was associated with the presence of alpha-synuclein pathology. These results support a gender dissociation of pathology in AD + P. The design of future studies aimed at the elucidation of cognitive and/or functional outcomes; regional brain metabolic deficits; or genetic correlates of AD + P should take gender into consideration. (C) 2014 Elsevier Inc. All rights reserved. C1 [Koppel, Jeremy; Acker, Chris; Davies, Peter; Jimenez, Heidy; Sweet, Robert A.] Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis, Manhasset, NY USA. [Koppel, Jeremy; Greenwald, Blaine S.] North Shore LIJ Hlth Syst, Zucker Hillside Hosp, Glen Oaks, NY USA. [Lopez, Oscar L.; Murray, Patrick S.; Kirkwood, Caitlin M.; Kofler, Julia; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Lopez, Oscar L.; Murray, Patrick S.; Kirkwood, Caitlin M.; Kofler, Julia; Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Azose, Miriam] Touro Coll, Brooklyn, NY USA. VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC Q2, Pittsburgh, PA USA. RP Koppel, J (reprint author), Zucker Hillside Hosp, Litwin Zucker Res Ctr Study Alzheimers Dis, 350 Community Dr, Manhasset, NY 11030 USA. EM jkoppel@nshs.edu OI Murray, Patrick/0000-0002-6525-2888 FU Veterans Health Administration [BX000452]; National Institute on Aging [AG005133, AG027224] FX This work was supported by the Veterans Health Administration (BX000452 to Robert A. Sweet) and the National Institute on Aging (AG005133 to Oscar L. Lopez, AG027224 to Robert A. Sweet). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the National Institutes of Health, or the United States Government. NR 52 TC 9 Z9 9 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2014 VL 35 IS 9 BP 2021 EP 2028 DI 10.1016/j.neurobiolaging.2014.03.003 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AK1SB UT WOS:000338195100011 PM 24731519 ER PT J AU Milad, MR Radulovic, J AF Milad, Mohammed R. Radulovic, Jelena TI Introduction to the special issue of Neurobiology of Learning and Memory on Fear Extinction SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Editorial Material C1 [Milad, Mohammed R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Radulovic, Jelena] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. RP Milad, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. EM milad@nmr.mgh.harvard.edu; j-radulovic@northwestern.edu NR 0 TC 0 Z9 0 U1 1 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 EI 1095-9564 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD SEP PY 2014 VL 113 BP 1 EP 2 DI 10.1016/j.nlm.2014.04.004 PG 2 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AJ6DR UT WOS:000337780400001 PM 24727221 ER PT J AU VanElzakker, MB Dahlgren, MK Davis, FC Dubois, S Shin, LM AF VanElzakker, Michael B. Dahlgren, M. Kathryn Davis, F. Caroline Dubois, Stacey Shin, Lisa M. TI From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and anxiety disorders SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Review DE Fear extinction; Fear conditioning; Posttraumatic stress disorder; Anxiety; Treatment; Amygdala; Prefrontal cortex ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; CHILDHOOD SEXUAL-ABUSE; COGNITIVE-BEHAVIORAL THERAPY; REALITY EXPOSURE THERAPY; TRANSCRANIAL MAGNETIC STIMULATION; OBSESSIVE-COMPULSIVE DISORDER; POTENTIATED STARTLE PARADIGM; RANDOMIZED CONTROLLED-TRIAL; ANTERIOR CINGULATE CORTEX AB Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders. (C) 2013 Elsevier Inc. All rights reserved. C1 [VanElzakker, Michael B.; Dahlgren, M. Kathryn; Dubois, Stacey; Shin, Lisa M.] Tufts Univ Psychol, Medford, MA 02155 USA. [VanElzakker, Michael B.; Dahlgren, M. Kathryn; Davis, F. Caroline; Shin, Lisa M.] Massachusetts Gen Hosp Psychiat, Charlestown, MA 02129 USA. RP VanElzakker, MB (reprint author), Tufts Univ Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM michael.vanelzakker@gmail.com FU NIMH [5R01MH054636]; National Defense Science and Engineering Graduate Fellowship (NDSEG) FX The authors are supported in part by NIMH 5R01MH054636. MBV is supported by a National Defense Science and Engineering Graduate Fellowship (NDSEG). NR 236 TC 61 Z9 61 U1 24 U2 117 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 EI 1095-9564 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD SEP PY 2014 VL 113 BP 3 EP 18 DI 10.1016/j.nlm.2013.11.014 PG 16 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AJ6DR UT WOS:000337780400002 PM 24321650 ER PT J AU Shvil, E Sullivan, GM Schafer, S Markowitz, JC Campeas, M Wager, TD Milad, MR Neria, Y AF Shvil, Erel Sullivan, Gregory M. Schafer, Scott Markowitz, John C. Campeas, Miriam Wager, Tor D. Milad, Mohammed R. Neria, Yuval TI Sex differences in extinction recall in posttraumatic stress disorder: A pilot fMRI study SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE PTSD; Trauma; Gender; Sex; Fear; Extinction; Recall; dACC ID ANTERIOR CINGULATE CORTEX; FEAR EXTINCTION; GENDER-DIFFERENCES; NEGATIVE AFFECT; FEMALE RATS; AMYGDALA; WOMEN; HUMANS; VULNERABILITY; SENSITIVITY AB Recent research has found that individuals with posttraumatic stress disorder (PTSD) exhibit an impaired memory of fear extinction compounded by deficient functional activation of key nodes of the fear network including the amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC). Research has shown these regions are sexually dimorphic and activate differentially in healthy men and women during fear learning tasks. To explore biological markers of sex differences following exposure to psychological trauma, we used a fear learning and extinction paradigm together with functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) to assess 31 individuals with PTSD (18 women; 13 men) and 25 matched trauma-exposed healthy control subjects (13 women; 12 men). Whereas no sex differences appeared within the trauma-exposed healthy control group, both psychophysiological and neural activation patterns within the PTSD group indicated deficient recall of extinction memory among men and not among women. Men with PTSD exhibited increased activation in the left rostral dACC during extinction recall compared with women with PTSD. These findings highlight the importance of tracking sex differences in fear extinction when characterizing the underlying neurobiological mechanisms of PTSD psychopathology. (C) 2014 Elsevier Inc. All rights reserved. C1 [Shvil, Erel; Sullivan, Gregory M.; Markowitz, John C.; Neria, Yuval] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Shvil, Erel; Sullivan, Gregory M.; Markowitz, John C.; Campeas, Miriam; Neria, Yuval] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Neria, Yuval] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA. [Neria, Yuval] Coll Phys & Surg, New York, NY 10032 USA. [Schafer, Scott; Wager, Tor D.] Univ Colorado, Boulder Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Shvil, E (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM es2297@columbia.edu FU NIMH [MH015144-34, MH072833] FX This study is supported by NIMH grants MH015144-34 and MH072833 (Y. Neria). NR 44 TC 21 Z9 21 U1 12 U2 46 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 EI 1095-9564 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD SEP PY 2014 VL 113 BP 101 EP 108 DI 10.1016/j.nlm.2014.02.003 PG 8 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AJ6DR UT WOS:000337780400012 PM 24560771 ER PT J AU Rabinak, CA Angstadt, M Lyons, M Mori, S Milad, MR Liberzon, I Phan, KL AF Rabinak, Christine A. Angstadt, Mike Lyons, Maryssa Mori, Shoko Milad, Mohammed R. Liberzon, Israel Phan, K. Luan TI Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE Extinction; fMRI; Ventromedial prefrontal cortex; Hippocampus; Amygdala; Delta 9-Tetrahydrocannabinol ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; D-CYCLOSERINE; EXPOSURE THERAPY; CONDITIONED FEAR; PROLONGED EXPOSURE; CB1 RECEPTORS; MEMORY RECONSOLIDATION; POTENTIATED STARTLE; ANXIETY DISORDERS AB Pre-extinction administration of Delta(9)-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely occurs via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N = 14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 h after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS + E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders. (C) 2013 Elsevier Inc. All rights reserved. C1 [Rabinak, Christine A.; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Liberzon, Israel; Phan, K. Luan] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Phan, K. Luan] Univ Illinois, Dept Psychiat, Chicago, IL 60608 USA. RP Rabinak, CA (reprint author), Univ Michigan, Dept Psychiat, Rachel Upjohn Bldg,4250 Plymouth Rd Rm 2239, Ann Arbor, MI 48109 USA. EM rabinak@med.umich.edu RI Angstadt, Mike/K-2942-2016; OI Angstadt, Mike/0000-0003-4870-7649; Liberzon, Israel/0000-0002-4990-556X FU National Center for Research Resources [UL1RR024986]; National Institute of Mental Health [1R21MH093917-01A1] FX This work was supported by a grant from the National Center for Research Resources (UL1RR024986) and from the National Institute of Mental Health (1R21MH093917-01A1) to KLP. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. The authors declare no competing financial interests. NR 80 TC 15 Z9 16 U1 4 U2 39 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 EI 1095-9564 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD SEP PY 2014 VL 113 BP 125 EP 134 DI 10.1016/j.nlm.2013.09.009 PG 10 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AJ6DR UT WOS:000337780400015 PM 24055595 ER PT J AU Liang, S Salas, T Gencaslan, E Li, BJ Habib, SL AF Liang, Sitai Salas, Tiffanie Gencaslan, Emre Li, Baojie Habib, Samy L. TI Tuberin-deficiency downregulates N-cadherin and upregulates vimentin in kidney tumor of TSC patients SO ONCOTARGET LA English DT Article DE N-cadherin; vimentin; Akt; tuberin; mTOR and angiomyolipomas ID REPAIR ENZYME OGG1; SCLEROSIS COMPLEX; MESENCHYMAL-TRANSITION; 3-KINASE/AKT PATHWAY; GAP ACTIVITY; EXPRESSION; GENE; ANGIOMYOLIPOMAS; DISEASE; TISSUES AB Angiomyolipomas (AMLs) are associated with cell fibrosis in kidney of Tuberous Sclerosis Complex patients. The mechanism by which the fibrotic proteins accumulated in AMLs has not been explored. In the present study, we investigated the role of Akt/tuberin/mTOR pathway in the regulation cell fibrosis proteins. AML cells that expressed low levels of tuberin showed less expression of N-cadherin and higher of vimentin proteins compared to HEK293 cells. AML cells infected with Ad-tuberin showed a significant decrease in vimentin and an increase in N-cadherin protein expression. In addition, cells treated with rapamycin showed a significant increase in p-Akt and a decrease in p-p70S6K that was associated with a decrease expression of vimentin and a slight increase expression in N-cadherin. On the other hand, cells treated with Akt inhibitor revealed a significant decrease in p-Akt and p-p70S6K that was associated with a significant decrease in vimentin and an increase in N-cadherin expression. In addition, cells transfected with DN-Akt or DN-S6K show significant increase expression in N-cadherin and a decrease in vimentin. Moreover, cells transfected with siRNA against rictor or siRNA against raptor resulted in a decrease in vimentin and an increase N-cadherin expression. Kidney tumors from TSC patients showed significant decrease in N-cadherin and significant increased in vimentin protein expression compared to control kidney tissues. These data comprise the first report to provide the role of Akt/tuberin/mTORC1/2 in the regulation of N-cadherin and vimentin that are involved in the progression of fibrosis in kidney tumor of TSC patients. C1 [Liang, Sitai; Salas, Tiffanie; Habib, Samy L.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Gencaslan, Emre] Akdeniz Univ, Sch Med, TR-07058 Antalya, Turkey. [Li, Baojie] Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiatr Disorders, BioX Inst, Shanghai 200030, Peoples R China. [Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM habib@uthscsa.edu FU American Heart Association; Merit Review Award from South Texas Veterans Healthcare System FX This work was supported in part by grants from the American Heart Association, and Merit Review Award from South Texas Veterans Healthcare System (to S.L.H.). NR 39 TC 3 Z9 4 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 30 PY 2014 VL 5 IS 16 BP 6936 EP 6946 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ0EX UT WOS:000347920100034 PM 25149531 ER PT J AU Delmonico, FL Capron, AM Danovitch, GM Levin, A O'Connell, PJ AF Delmonico, Francis L. Capron, Alexander M. Danovitch, Gabriel M. Levin, Adeera O'Connell, Philip J. TI Organ transplantation in China-not yet a new era SO LANCET LA English DT Letter C1 [Delmonico, Francis L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Capron, Alexander M.] Univ So Calif, Los Angeles, CA USA. [Danovitch, Gabriel M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Levin, Adeera] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [O'Connell, Philip J.] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. RP Delmonico, FL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM francis_delmonico@neob.org NR 4 TC 1 Z9 1 U1 0 U2 5 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 AUG 30 PY 2014 VL 384 IS 9945 BP 741 EP 741 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AO5DD UT WOS:000341361500021 PM 25176538 ER PT J AU Sun, QQ Gao, XP Ko, DSC Li, XC AF Sun, Qiquan Gao, Xinpu Ko, Dicken Shiu-Chung Li, Xian Chang TI Organ transplantation in China-not yet a new era Reply SO LANCET LA English DT Letter ID DONATION C1 [Sun, Qiquan] Sun Yat Sen Univ, Div Renal Transplantat, Affiliated Hosp 3, Guangzhou 510530, Guangdong, Peoples R China. [Gao, Xinpu] China Organ Donat Adm Ctr, Beijing, Peoples R China. [Ko, Dicken Shiu-Chung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Li, Xian Chang] Houston Methodist Hosp, Texas Med Ctr, Houston, TX USA. RP Sun, QQ (reprint author), Sun Yat Sen Univ, Div Renal Transplantat, Affiliated Hosp 3, Guangzhou 510530, Guangdong, Peoples R China. EM sunqiquan@hotmail.com NR 3 TC 1 Z9 1 U1 1 U2 6 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 AUG 30 PY 2014 VL 384 IS 9945 BP 741 EP 742 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AO5DD UT WOS:000341361500022 PM 25176539 ER PT J AU Corbo, V Salat, DH Amick, MM Leritz, EC Milberg, WP McGlinchey, RE AF Corbo, Vincent Salat, David H. Amick, Melissa M. Leritz, Elizabeth C. Milberg, William P. McGlinchey, Regina E. TI Reduced cortical thickness in veterans exposed to early life trauma SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Posttraumatic stress disorder (PTSD); Trauma; Posterior cingulate; Amygdala; Cortical thickness ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; CORTICOTROPIN-RELEASING-FACTOR; SMALLER HIPPOCAMPAL VOLUME; ANTERIOR CINGULATE CORTEX; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; PREFRONTAL CORTEX; LONG-TERM; BRAIN AB Studies have shown that early life trauma may influence neural development and increase the risk of developing psychological disorders in adulthood. We used magnetic resonance imaging to examine the impact of early life trauma on the relationship between current posttraumatic stress disorder (PTSD) symptoms and cortical thickness/subcortical volumes in a sample of deployed personnel from Operation Enduring Freedom/Operation Iraqi Freedom. A group of 108 service members enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) were divided into those with interpersonal early life trauma (EL-Trauma+) and Control (without interpersonal early life trauma) groups based on the Traumatic Life Events Questionnaire. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale. Cortical thickness and subcortical volumes were analyzed using the FreeSurfer image analysis package. Thickness of the paracentral and posterior cingulate regions was positively associated with PTSD severity in the EL-Trauma+ group and negatively in the Control group. In the EL-Trauma+ group, both the right amygdala and the left hippocampus were positively associated with PTSD severity. This study illustrates a possible influence of early life trauma on the vulnerability of specific brain regions to stress. Changes in neural morphometry may provide information about the emergence and maintenance of symptoms in individuals with PTSD. Published by Elsevier Ireland Ltd. C1 [Corbo, Vincent; Salat, David H.; Amick, Melissa M.; Leritz, Elizabeth C.; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Geriatr Res Educ & Clin Ctr, Jamaica Plain, MA USA. [Corbo, Vincent; Amick, Melissa M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Corbo, Vincent; Salat, David H.] VA Boston Healthcare, Neuroimaging Res Vet NeRVe Ctr, Jamaica Plain, MA USA. [Salat, David H.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Leritz, Elizabeth C.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Corbo, V (reprint author), Boston Univ, VA Boston Healthcare, Boston, MA 02215 USA. EM vincent.corbo@mail.mcgill.ca RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C] FX This research was support by the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C). NR 68 TC 11 Z9 11 U1 2 U2 9 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 AUG 30 PY 2014 VL 223 IS 2 BP 53 EP 60 DI 10.1016/j.pscychresns.2014.04.013 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AM6ZK UT WOS:000340014300001 PM 24862391 ER PT J AU Holsen, LM Lawson, EA Christensen, K Klibanski, A Goldstein, JM AF Holsen, Laura M. Lawson, Elizabeth A. Christensen, Kara Klibanski, Anne Goldstein, Jill M. TI Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Appetite; Reward; fMRI; Hormones; Eating disorders ID EATING-DISORDERS; BULIMIA-NERVOSA; PLASMA GHRELIN; GROWTH-HORMONE; NUCLEUS-ACCUMBENS; HIGH-CARBOHYDRATE; ADOLESCENT GIRLS; BRAIN ACTIVITY; MESSENGER-RNA; REWARD AB Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Holsen, Laura M.; Christensen, Kara; Goldstein, Jill M.] Dept Med, Div Womens Hlth, Boston, MA USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Holsen, Laura M.; Lawson, Elizabeth A.; Klibanski, Anne; Goldstein, Jill M.] Harvard Univ, Sch Med, Boston, MA USA. [Lawson, Elizabeth A.; Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Goldstein, Jill M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Goldstein, Jill M.] MIT, Charlestown, MA USA. RP Holsen, LM (reprint author), Div Womens Hlth, BC-3 1620 Tremont St, Boston, MA 02120 USA. EM lholsen@partners.org FU NCRR NIH HHS [UL1 RR025758]; NICHD NIH HHS [K12 HD051959]; NIMH NIH HHS [K01 MH091222, K23 MH092560] NR 67 TC 7 Z9 7 U1 2 U2 14 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 AUG 30 PY 2014 VL 223 IS 2 BP 94 EP 103 DI 10.1016/j.pscychresns.2014.04.015 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AM6ZK UT WOS:000340014300006 PM 24862390 ER PT J AU Simhadri, S Peterson, S Patel, DS Huo, YY Cai, H Bowman-Colin, C Miller, S Ludwig, T Ganesan, S Bhaumik, M Bunting, SF Jasin, M Xia, B AF Simhadri, Srilatha Peterson, Shaun Patel, Dharm S. Huo, Yanying Cai, Hong Bowman-Colin, Christian Miller, Shoreh Ludwig, Thomas Ganesan, Shridar Bhaumik, Mantu Bunting, Samuel F. Jasin, Maria Xia, Bing TI Male Fertility Defect Associated with Disrupted BRCA1-PALB2 Interaction in Mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE BRCA1; DNA Damage Response; Homologous Recombination; Meiosis; Spermatogenesis; BRCA2; FANCN; Fanconi Anemia; PALB2; Male Infertility ID RAD51 FILAMENT FORMATION; DOUBLE-STRAND BREAKS; HOMOLOGOUS RECOMBINATION; FANCONI-ANEMIA; DNA-REPAIR; MOUSE MEIOSIS; PALB2; BRCA2; CANCER; SPERMATOGENESIS AB Background: BRCA1 and PALB2 interact with each other to promote homologous recombination and DNA double strand break repair. Results: Mice with abrogated PALB2-BRCA1 interaction show male fertility defect. Conclusion: PALB2 and BRCA1 function together to ensure normal male meiosis. Significance: This work demonstrates the importance of the PALB2-BRCA1 interaction in vivo and reveals a novel role of PALB2 in sex chromosome synapsis. PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). Like Brca1 and Brca2, systemic knock-out of Palb2 in mice results in embryonic lethality. In this study, we generated a hypomorphic Palb2 allele expressing a mutant PALB2 protein unable to bind BRCA1. Consistent with an FA-like phenotype, cells from the mutant mice showed hypersensitivity and chromosomal breakage when treated with mitomycin C, a DNA interstrand crosslinker. Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect. Our results underscore the in vivo importance of the PALB2-BRCA1 complex formation in DSB repair and male meiosis. C1 [Simhadri, Srilatha; Huo, Yanying; Cai, Hong; Ganesan, Shridar; Bhaumik, Mantu; Xia, Bing] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Simhadri, Srilatha; Huo, Yanying; Cai, Hong; Xia, Bing] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Radiat Oncol, New Brunswick, NJ 08901 USA. [Miller, Shoreh; Bhaumik, Mantu] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Pediat, New Brunswick, NJ 08901 USA. [Ganesan, Shridar] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08901 USA. [Peterson, Shaun; Jasin, Maria] Mem Sloan Kettering Canc Ctr, Dev Biol Program, Sloan Kettering Inst, New York, NY 10065 USA. [Patel, Dharm S.; Bunting, Samuel F.] Rutgers State Univ, Sch Arts & Sci, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. [Bowman-Colin, Christian] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ludwig, Thomas] Ohio State Univ, Dept Mol & Cellular Biochem, Wexner Med Ctr, Columbus, OH 43210 USA. RP Xia, B (reprint author), Rutgers Canc Inst New Jersey, Dept Radiat Oncol, 195 Little Albany St, New Brunswick, NJ 08903 USA. EM xiabi@cinj.rutgers.edu RI Ludwig, Thomas/Q-6484-2016; OI Ludwig, Thomas/0000-0003-3461-2585; Peterson, Shaun/0000-0002-0906-8939 FU NCI CCSG Grant [P30CA072720]; Robert Wood Johnson Foundation [67038] FX We thank Florent le Masson for valuable technical assistance, Scott Keeney for critical comments on the manuscript, and Reena Shakya for helpful discussions. We thank the Transgenic and Knockout Mouse Shared Resource of the Rutgers Cancer Institute of New Jersey, which is supported by an NCI CCSG Grant (P30CA072720) and by a Robert Wood Johnson Foundation grant to the Child Health Institute of New Jersey (Grant 67038). NR 51 TC 11 Z9 11 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 2014 VL 289 IS 35 BP 24617 EP 24629 DI 10.1074/jbc.M114.566141 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7AY UT WOS:000341505600052 PM 25016020 ER PT J AU Shanmugasundaram, K Nayak, B Shim, EH Livi, CB Block, K Sudarshan, S AF Shanmugasundaram, Karthigayan Nayak, Bijaya Shim, Eun-Hee Livi, Carolina B. Block, Karen Sudarshan, Sunil TI The Oncometabolite Fumarate Promotes Pseudohypoxia Through Noncanonical Activation of NF-kappa B Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cancer Biology; Cell Metabolism; Hypoxia-inducible Factor (HIF); NF-B (NF-KB); Small Molecule; Small ID RENAL-CELL CANCER; PROLINE HYDROXYLATION; PROLYL HYDROXYLATION; KIDNEY CANCER; HIF-ALPHA; HYPOXIA; HYDRATASE; HEREDITARY; KINASES; TBK1 AB Background: We examined alternative mechanisms by which fumarate levels contribute to hypoxia inducible factor (HIF)-1 accumulation and fumarate hydratase (FH)-deficient renal carcinogenesis. Results: Fumarate promotes HIF-1 transcription through Tank binding kinase 1 (TBK1)-dependent noncannonical activation of NF-B signaling. Conclusion: Fumarate-mediated, TBK-dependent accumulation of HIF-1 mediates cell invasion in FH-deficient RCC. Significance: TBK is a novel putative therapeutic target for the treatment of aggressive fumarate-driven tumors. Inactivating mutations of the gene encoding the tricarboxylic acid cycle enzyme fumarate hydratase (FH) have been linked to an aggressive variant of hereditary kidney cancer (hereditary leiomyomatosis and renal cell cancer). These tumors accumulate markedly elevated levels of fumarate. Fumarate is among a growing list of oncometabolites identified in cancers with mutations of genes involved in intermediary metabolism. FH-deficient tumors are notable for their pronounced accumulation of the transcription factor hypoxia inducible factor-1 (HIF-1) and aggressive behavior. To date, HIF-1 accumulation in hereditary leiomyomatosis and renal cell cancer tumors is thought to result from fumarate-dependent inhibition of prolyl hydroxylases and subsequent evasion from von Hippel-Lindau-dependent degradation. Here, we demonstrate a novel mechanism by which fumarate promotes HIF-1 mRNA and protein accumulation independent of the von Hippel-Lindau pathway. Here we demonstrate that fumarate promotes p65 phosphorylation and p65 accumulation at the HIF-1 promoter through non-canonical signaling via the upstream Tank binding kinase 1 (TBK1). Consistent with these data, inhibition of the TBK1/p65 axis blocks HIF-1 accumulation in cellular models of FH loss and markedly reduces cell invasion of FH-deficient RCC cancer cells. Collectively, our data demonstrate a novel mechanism by which pseudohypoxia is promoted in FH-deficient tumors and identifies TBK1 as a novel putative therapeutic target for the treatment of aggressive fumarate-driven tumors. C1 [Shanmugasundaram, Karthigayan; Nayak, Bijaya; Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Livi, Carolina B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Shim, Eun-Hee; Sudarshan, Sunil] Univ Alabama Birmingham, Dept Urol, Birmingham, AL 35294 USA. [Block, Karen] South Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX 78229 USA. RP Block, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM block@uthscsa.edu; sudarshan@uab.edu FU National Institutes of Health [K08 CA138774]; Urology Care Foundation; Astellas Pharma Rising Star Award; America Cancer Society [RSG-12-127-01 CNE]; Veterans Affairs Merit Grants [CPRIT RP120190, P30CA054174] FX This work was supported, in whole or in part, by National Institutes of Health Grant K08 CA138774 (to S. S.), Urology Care Foundation and Astellas Pharma Rising Star Award, and America Cancer Society RSG-12-127-01 CNE (to S. S.) and Veterans Affairs Merit Grants CPRIT RP120190 and P30CA054174 (to K. B). NR 35 TC 7 Z9 8 U1 0 U2 6 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 AUG 29 PY 2014 VL 289 IS 35 BP 24691 EP 24699 DI 10.1074/jbc.M114.568162 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7AY UT WOS:000341505600058 PM 25028521 ER PT J AU Duarte, NDC Grecco, LAC Galli, M Fregni, F Oliveira, CS AF Carvalho Duarte, Natalia de Almeida Collange Grecco, Luanda Andre Galli, Manuela Fregni, Felipe Oliveira, Claudia Santos TI Effect of Transcranial Direct-Current Stimulation Combined with Treadmill Training on Balance and Functional Performance in Children with Cerebral Palsy: A Double-Blind Randomized Controlled Trial SO PLOS ONE LA English DT Article ID MAGNETIC STIMULATION; MOTOR CORTEX; GAIT; EXCITABILITY; DISABILITY; CONCURRENT AB Background: Cerebral palsy refers to permanent, mutable motor development disorders stemming from a primary brain lesion, causing secondary musculoskeletal problems and limitations in activities of daily living. The aim of the present study was to determine the effects of gait training combined with transcranial direct-current stimulation over the primary motor cortex on balance and functional performance in children with cerebral palsy. Methods: A double-blind randomized controlled study was carried out with 24 children aged five to 12 years with cerebral palsy randomly allocated to two intervention groups (blocks of six and stratified based on GMFCS level (levels I-II or level III). The experimental group (12 children) was submitted to treadmill training and anodal stimulation of the primary motor cortex. The control group (12 children) was submitted to treadmill training and placebo transcranial direct-current stimulation. Training was performed in five weekly sessions for 2 weeks. Evaluations consisted of stabilometric analysis as well as the administration of the Pediatric Balance Scale and Pediatric Evaluation of Disability Inventory one week before the intervention, one week after the completion of the intervention and one month after the completion of the intervention. All patients and two examiners were blinded to the allocation of the children to the different groups. Results: The experimental group exhibited better results in comparison to the control group with regard to anteroposterior sway (eyes open and closed; p<0.05), mediolateral sway (eyes closed; p<0.05) and the Pediatric Balance Scale both one week and one month after the completion of the protocol. Conclusion: Gait training on a treadmill combined with anodal stimulation of the primary motor cortex led to improvements in static balance and functional performance in children with cerebral palsy. C1 [Carvalho Duarte, Natalia de Almeida; Collange Grecco, Luanda Andre; Oliveira, Claudia Santos] Univ Nove de Julho, Movement Anal Lab, Sao Paulo, Brazil. [Galli, Manuela] Politecn Milan, Dept Elect Informat & Bioengn, Rome, Italy. [Galli, Manuela] IRCCS San Raffaele Pisana, Rome, Italy. [Fregni, Felipe] Harvard Univ, Lab Neuromodulat, Sch Med, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Ctr Clin Res Learning,Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Duarte, NDC (reprint author), Univ Nove de Julho, Movement Anal Lab, Sao Paulo, Brazil. EM natycarvalho_fisio@hotmail.com RI Oliveira, Claudia/H-2328-2013; Grecco , Luanda/N-5075-2015; Duarte, Natalia/K-5260-2016 OI Duarte, Natalia/0000-0003-1486-1330 FU Brazilian fostering agencies Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Fundacao de Amparo a Pesquisa (FAPESP) [2012/24019-0] FX The authors gratefully acknowledge financial support from the Brazilian fostering agencies Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), and Fundacao de Amparo a Pesquisa (FAPESP - 2012/24019-0). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 6 Z9 6 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 29 PY 2014 VL 9 IS 8 AR e105777 DI 10.1371/journal.pone.0105777 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO2EE UT WOS:000341127500067 ER PT J AU Valenza, G Citi, L Barbieri, R AF Valenza, Gaetano Citi, Luca Barbieri, Riccardo TI Estimation of Instantaneous Complex Dynamics through Lyapunov Exponents: A Study on Heartbeat Dynamics SO PLOS ONE LA English DT Article ID MULTISCALE ENTROPY ANALYSIS; TIME-SERIES ANALYSIS; RATE-VARIABILITY; APPROXIMATE ENTROPY; NONLINEAR DYNAMICS; SYSTEMS; FAILURE; CHAOS; IDENTIFICATION; ALGORITHM AB Measures of nonlinearity and complexity, and in particular the study of Lyapunov exponents, have been increasingly used to characterize dynamical properties of a wide range of biological nonlinear systems, including cardiovascular control. In this work, we present a novel methodology able to effectively estimate the Lyapunov spectrum of a series of stochastic events in an instantaneous fashion. The paradigm relies on a novel point-process high-order nonlinear model of the event series dynamics. The long-term information is taken into account by expanding the linear, quadratic, and cubic Wiener-Volterra kernels with the orthonormal Laguerre basis functions. Applications to synthetic data such as the Henon map and Rossler attractor, as well as two experimental heartbeat interval datasets (i.e., healthy subjects undergoing postural changes and patients with severe cardiac heart failure), focus on estimation and tracking of the Instantaneous Dominant Lyapunov Exponent (IDLE). The novel cardiovascular assessment demonstrates that our method is able to effectively and instantaneously track the nonlinear autonomic control dynamics, allowing for complexity variability estimations. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab,Dept Anesthesia Crit Care &, Boston, MA 02163 USA. [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Valenza, Gaetano] Univ Pisa, Res Ctr E Piaggio, Pisa, Italy. [Valenza, Gaetano] Univ Pisa, Dept Informat Engn, Pisa, Italy. [Citi, Luca] Univ Essex, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab,Dept Anesthesia Crit Care &, Boston, MA 02163 USA. EM g.valenza@ieee.org RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Valenza, Gaetano/0000-0001-6574-1879 FU Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital; Harvard Medical School, Boston, MA, USA; European Union Seventh Framework Programme FP7 [601165] FX The research leading to these results has received partial funding from the Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA, and European Union Seventh Framework Programme FP7/2007-2013 under Grant No. 601165 of the project "WEARHAP''. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 12 Z9 12 U1 3 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 AUG 29 PY 2014 VL 9 IS 8 AR e105622 DI 10.1371/journal.pone.0105622 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO2EE UT WOS:000341127500062 PM 25170911 ER PT J AU Zhang, H Singh, KK AF Zhang, Hengshan Singh, Keshav K. TI Global Genetic Determinants of Mitochondrial DNA Copy Number SO PLOS ONE LA English DT Article ID CONGENITAL MUSCULAR-DYSTROPHY; RENAL-CELL CARCINOMA; SACCHAROMYCES-CEREVISIAE; THYMIDINE KINASE; GASTRIC-CANCER; LARGE SUBUNIT; HUMAN-DISEASE; MUTATIONS; DEPLETION; EXPRESSION AB Many human diseases including development of cancer is associated with depletion of mitochondrial DNA (mtDNA) content. These diseases are collectively described as mitochondrial DNA depletion syndrome (MDS). High similarity between yeast and human mitochondria allows genomic study of the budding yeast to be used to identify human disease genes. In this study, we systematically screened the pre-existing respiratory-deficient Saccharomyces cerevisiae yeast strains using fluorescent microscopy and identified 102 nuclear genes whose deletions result in a complete mtDNA loss, of which 52 are not reported previously. Strikingly, these genes mainly encode protein products involved in mitochondrial protein biosynthesis process (54.9%). The rest of these genes either encode protein products associated with nucleic acid metabolism (14.7%), oxidative phosphorylation (3.9%), or other protein products (13.7%) responsible for bud-site selection, mitochondrial intermembrane space protein import, assembly of cytochrome-c oxidase, vacuolar protein sorting, protein-nucleus import, calcium-mediated signaling, heme biosynthesis and iron homeostasis. Thirteen (12.7%) of the genes encode proteins of unknown function. We identified human orthologs of these genes, conducted the interaction between the gene products and linked them to human mitochondrial disorders and other pathologies. In addition, we screened for genes whose defects affect the nuclear genome integrity. Our data provide a systematic view of the nuclear genes involved in maintenance of mitochondrial DNA. Together, our studies i) provide a global view of the genes regulating mtDNA content; ii) provide compelling new evidence toward understanding novel mechanism involved in mitochondrial genome maintenance and iii) provide useful clues in understanding human diseases in which mitochondrial defect and in particular depletion of mitochondrial genome plays a critical role. C1 [Zhang, Hengshan] Fujian Med Univ, Affiliated Hosp 1, Dept Cent Lab, Fuzhou, Peoples R China. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Genet, Ctr Free Radical Biol, Ctr Aging, Birmingham, AL 35294 USA. [Singh, Keshav K.] Univ Alabama Birmingham, UAB Comprehens Canc Ctr, Birmingham, AL USA. [Singh, Keshav K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Singh, KK (reprint author), Univ Alabama Birmingham, Dept Genet, Ctr Free Radical Biol, Ctr Aging, Birmingham, AL 35294 USA. EM kksingh@uab.edu FU Veterans Administration [1I01BX001716]; National Institutes of Health (NIH) [R01CA121904] FX Studies reported in this manuscript were supported in part by Veterans Administration grant 1I01BX001716 and National Institutes of Health (NIH) R01CA121904 (to KKS). Funding agencies has no role in design or data collection. NR 51 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 AUG 29 PY 2014 VL 9 IS 8 AR e105242 DI 10.1371/journal.pone.0105242 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO2EE UT WOS:000341127500037 PM 25170845 ER PT J AU Pevnick, JM Li, N Asch, SM Jackevicius, CA Bell, DS AF Pevnick, Joshua M. Li, Ning Asch, Steven M. Jackevicius, Cynthia A. Bell, Douglas S. TI Effect of electronic prescribing with formulary decision support on medication tier, copayments, and adherence SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Clinical decision support; Electronic prescribing; Medication adherence ID DRUG-THERAPY; HEALTH; IMPACT; CARE; INTERVENTIONS; PERSISTENCE; ADOPTION; RECORDS; ASTHMA; COST AB Background: Medication non-adherence is prevalent. We assessed the effect of electronic prescribing (e-prescribing) with formulary decision support on preferred formulary tier usage, copayment, and concomitant adherence. Methods: We retrospectively analyzed 14,682 initial pharmaceutical claims for angiotensin receptor blocker and inhaled steroid medications among 14,410 patients of 2189 primary care physicians (PCPs) who were offered e-prescribing with formulary decision support, including 297 PCPs who adopted it. Formulary decision support was initially non-interruptive, such that formulary tier symbols were displayed adjacent to medication names. Subsequently, interruptive formulary decision support alerts also interrupted e-prescribing when preferred-tier alternatives were available. A difference in differences design was used to compare the pre-post differences in medication tier for each new prescription attributed to non-adopters, low user (<30% usage rate), and high user PCPs (>30% usage rate). Second, we modeled the effect of formulary tier on prescription copayment. Last, we modeled the effect of copayment on adherence (proportion of days covered) to each new medication. Results: Compared with non-adopters, high users of e-prescribing were more likely to prescribe preferred-tier medications (vs. non-preferred tier) when both non-interruptive and interruptive formulary decision support were in place (OR 1.9 [95% CI 1.0-3.4], p = 0.04), but no more likely to prescribe preferred-tier when only non-interruptive formulary decision support was in place (p = 0.90). Preferred-tier claims had only slightly lower mean monthly copayments than non-preferred tier claims (angiotensin receptor blocker: $ 10.60 versus $ 11.81, inhaled steroid: $ 14.86 versus $ 16.42, p < 0.0001). Medication possession ratio was 8% lower for each $ 1.00 increase in monthly copayment to the one quarter power (p < 0.0001). However, we detected no significant direct association between formulary decision support usage and adherence. Conclusion: Interruptive formulary decision support shifted prescribing toward preferred tiers, but these medications were only minimally less expensive in the studied patient population. In this context, formulary decision support did not significantly increase adherence. To impact cost-related non-adherence, formulary decision support will likely need to be paired with complementary drug benefit design. Formulary decision support should be studied further, with particular attention to its effect on adherence in the setting of different benefit designs. C1 [Pevnick, Joshua M.] Cedars Sinai Hlth Syst, Dept Med, Div Gen Internal Med, Los Angeles, CA 90048 USA. [Pevnick, Joshua M.; Bell, Douglas S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Li, Ning] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Asch, Steven M.] Stanford Sch Med, Palo Alto, CA USA. [Asch, Steven M.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA USA. [Bell, Douglas S.] RAND Hlth, Santa Monica, CA USA. RP Pevnick, JM (reprint author), Cedars Sinai Hlth Syst, Dept Med, Div Gen Internal Med, 8700 Beverly Blvd,PACT 400-8G, Los Angeles, CA 90048 USA. EM jpevnick@gmail.com FU Agency for Healthcare Research and Quality [1U18HS016391-01]; Burns and Allen Research Institute at Cedars-Sinai Medical Center; National Center for Advancing Translational Science [UL1TR000124] FX This data was initially gathered during work on grant 1U18HS016391-01 funded by the Agency for Healthcare Research and Quality as part of a larger set of e-prescribing pilot studies (Dr. Bell). This work was also supported by a Clinical Scholars Research Grant from the Burns and Allen Research Institute at Cedars-Sinai Medical Center (Dr. Pevnick), and by the National Center for Advancing Translational Science, Grant UL1TR000124 (Drs. Bell and Pevnick). The authors have no conflicts of interest to disclose. NR 30 TC 2 Z9 2 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD AUG 28 PY 2014 VL 14 AR 79 DI 10.1186/1472-6947-14-79 PG 12 WC Medical Informatics SC Medical Informatics GA AS2KJ UT WOS:000344108600001 PM 25167807 ER PT J AU Dimopoulos, MA Kastritis, E Owen, RG Kyle, RA Landgren, O Morra, E Leleu, X Garcia-Sanz, R Munshi, N Anderson, KC Terpos, E Ghobrial, IM Morel, P Maloney, D Rummel, M Leblond, V Advani, RH Gertz, MA Kyriakou, C Thomas, SK Barlogie, B Gregory, SA Kimby, E Merlini, G Treon, SP AF Dimopoulos, Meletios A. Kastritis, Efstathios Owen, Roger G. Kyle, Robert A. Landgren, Ola Morra, Enrica Leleu, Xavier Garcia-Sanz, Ramon Munshi, Nikhil Anderson, Kenneth C. Terpos, Evangelos Ghobrial, Irene M. Morel, Pierre Maloney, David Rummel, Mathias Leblond, Veronique Advani, Ranjana H. Gertz, Morie A. Kyriakou, Charalampia Thomas, Sheeba K. Barlogie, Bart Gregory, Stephanie A. Kimby, Eva Merlini, Giampaolo Treon, Steven P. TI Treatment recommendations for patients with Waldenstrom macroglobulinemia (WM) and related disorders: IWWM-7 consensus SO BLOOD LA English DT Review ID 2ND INTERNATIONAL WORKSHOP; PHASE-II TRIAL; BORTEZOMIB-MELPHALAN-PREDNISONE; RANDOMIZED CONTROLLED-TRIAL; PROGNOSTIC SCORING SYSTEM; PLACEBO-CONTROLLED TRIAL; PANEL RECOMMENDATIONS; AL AMYLOIDOSIS; WAIDENSTROMS MACROGLOBULINEMIA; MULTIPLE-MYELOMA AB Waldenstrom macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM(IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mammalian target of rapamycin inhibitors, and Bruton's tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged. C1 [Dimopoulos, Meletios A.; Kastritis, Efstathios; Terpos, Evangelos] Univ Athens, Dept Clin Therapeut, Sch Med, Athens 11528, Greece. [Owen, Roger G.] St Jamess Inst Oncol, Leeds, W Yorkshire, England. [Kyle, Robert A.; Gertz, Morie A.] Mayo Clin, Rochester, MN USA. [Landgren, Ola] NCI, Bethesda, MD 20892 USA. [Morra, Enrica] Osped Niguarda Ca Granda, Dept Hematol, Milan, Italy. [Leleu, Xavier] CHRU Lille, Serv Malad Sang, Hop Huriez, F-59037 Lille, France. [Garcia-Sanz, Ramon] Hosp Univ Salamanca, Serv Hematol, Inst Invest Biomed Salamanca, Salamanca, Spain. [Munshi, Nikhil; Anderson, Kenneth C.; Ghobrial, Irene M.; Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Morel, Pierre] Ctr Hosp Schaffner, Serv Hematol Clin, Lens, France. [Maloney, David] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Rummel, Mathias] Hosp Justus Liebig Univ Giessen, Med Klin 4, Giessen, Germany. [Leblond, Veronique] Univ Paris 06, AP HP, Hop La Pitie Salpetriere, GRC 11,Grp Rech Clin Hemopathie Lymphoide, Paris, France. [Advani, Ranjana H.] Stanford Canc Inst, Stanford, CA USA. [Kyriakou, Charalampia] Royal Free Hosp, London NW3 2QG, England. [Thomas, Sheeba K.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Barlogie, Bart] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Gregory, Stephanie A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Kimby, Eva] Karolinska Univ Hosp, Dept Hematol, Solna, Sweden. [Merlini, Giampaolo] Univ Pavia, Amyloidosis Res & Treatment Ctr, Fdn Ist Ricovero & Cura Carattere Sci Policlin Sa, Dept Mol Med, I-27100 Pavia, Italy. RP Dimopoulos, MA (reprint author), Univ Athens, Dept Clin Therapeut, Sch Med, 80 Vas Sofias Ave, Athens 11528, Greece. EM mdimop@med.uoa.gr RI Merlini, Giampaolo/A-3817-2008; Garcia-Sanz, Ramon/B-7986-2017 OI Merlini, Giampaolo/0000-0001-7680-3254; Garcia-Sanz, Ramon/0000-0003-4120-2787 FU Celgene; Onyx; Janssen; Onyx/Amgen; Millenium/Takeda; Novartis; LeoPahrma; GSK; MundiPharma; Pharmacyclics; Amgen; Astellas; Roche; Gilead; BMS; Seattle Genetics; Onyx and Pharmacyclics FX M.D. has received honoraria from Celgene and Orthobiotech; R.G.O. has received research funding from Celgene and Onyx, is on the advisory board for Pharmacyclics and Celgene, and receives honoraria and lecture fees from Janssen and Celgene; R.A.K. sits on the disease monitoring committees for Celgene, Novartis, Merck, Bristol-Myers Squibb, AeternaZentaris, and Onyx and has received honoraria from Binding Site; X. L. has received honoraria and lecture fees from Celgene, Janssen, Onyx/Amgen, Millenium/Takeda, Novartis, and LeoPahrma; R.G.-S. has received honoraria and lecture fees from Janssen, Millenium/Takeda, GSK, MundiPharma, and Pharmacyclics; K. C. A. is on the advisory bard for Celgene, Millennium, Onyx, Gilead, and Sanofi Aventis and is a scientific founder of AcetylonOncopep; I. M. G. is on the advisory board for BMS, Celgene, Millennium, and Onyx; D. M. is a consultant for Roche/Genentech; M. R. has received honoraria and lecture fees from Amgen, Astellas, Celgene, GSK, Janssen, Mundipharma, and Roche; V. L. has received honoraria and lecture fees from Roche, GSK, Mundipharma, Janssen, Gilead, and BMS; R. H. A. has received research funding from Pharmacyclics, Celgene, Genentech, Millennium, and Seattle Genetics; M. A. G. has received honoraria from Onyx, Celgene, and Neotope; S. K. T. has received research funding from Novartis, Celgene, Millenium, and Idera Pharmaceuticals and is a consultant/advisor for Celgene and Pharmacyclics; S. A. G. is the chair of the safety data monitoring board for Genentech; is part of the speakers bureau for Celgene and Pharmacyclics, and is a consultant for Gilead; G. M. has received honoraria from Millennium; and S. P. T. has received research funding from Onyx and Pharmacyclics. The remaining authors declare no competing financial interests. NR 59 TC 41 Z9 42 U1 1 U2 11 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 AUG 28 PY 2014 VL 124 IS 9 BP 1404 EP 1411 DI 10.1182/blood-2014-03-565135 PG 8 WC Hematology SC Hematology GA AQ4JM UT WOS:000342762100012 PM 25027391 ER PT J AU Springer, TA AF Springer, Timothy A. TI von Willebrand factor, Jedi knight of the bloodstream SO BLOOD LA English DT Review ID PLATELET GLYCOPROTEIN IB; FACTOR A1 DOMAIN; WEIBEL-PALADE BODIES; FACTOR A2 DOMAIN; THROMBOTIC THROMBOCYTOPENIC PURPURA; HUMAN VONWILLEBRAND-FACTOR; IX-V COMPLEX; LEUCINE-RICH REPEATS; DEEP-VEIN THROMBOSIS; FACTOR A3 DOMAIN AB When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended threadlike in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multi-meric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. C1 [Springer, Timothy A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Springer, Timothy A.] Boston Childrens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA. [Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM timothy.springer@childrens.harvard.edu FU National Institutes of Health, National Heart, Lung, and Blood Institute [HL-103526, HL-108248] FX This work was supported by National Institutes of Health, National Heart, Lung, and Blood Institute grants HL-103526 and HL-108248. NR 112 TC 32 Z9 33 U1 0 U2 31 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 AUG 28 PY 2014 VL 124 IS 9 BP 1412 EP 1425 DI 10.1182/blood-2014-05-378638 PG 14 WC Hematology SC Hematology GA AQ4JM UT WOS:000342762100013 PM 24928861 ER PT J AU Shaul, YD Freinkman, E Comb, WC Cantor, JR Tam, WL Thiru, P Kim, D Kanarek, N Pacold, ME Chen, WW Bierie, B Possemato, R Reinhardt, F Weinberg, RA Yaffe, MB Sabatini, DM AF Shaul, Yoav D. Freinkman, Elizaveta Comb, William C. Cantor, Jason R. Tam, Wai Leong Thiru, Prathapan Kim, Dohoon Kanarek, Naama Pacold, Michael E. Chen, Walter W. Bierie, Brian Possemato, Richard Reinhardt, Ferenc Weinberg, Robert A. Yaffe, Michael B. Sabatini, David M. TI Dihydropyrimidine Accumulation Is Required for the Epithelial-Mesenchymal Transition SO CELL LA English DT Article ID CANCER-CELL METABOLISM; BREAST-CANCER; STEM-CELLS; THYMIDINE GLYCOL; DIABETIC-NEPHROPATHY; GENE; PLASTICITY; 5-FLUOROURACIL; DEHYDROGENASE; METASTASIS AB It is increasingly appreciated that oncogenic transformation alters cellular metabolism to facilitate cell proliferation, but less is known about the metabolic changes that promote cancer cell aggressiveness. Here, we analyzed metabolic gene expression in cancer cell lines and found that a set of high-grade carcinoma lines expressing mesenchymal markers share a unique 44 gene signature, designated the "mesenchymal metabolic signature'' (MMS). A FACS-based shRNA screen identified several MMS genes as essential for the epithelial-mesenchymal transition (EMT), but not for cell proliferation. Dihydropyrimidine dehydrogenase (DPYD), a pyrimidine-degrading enzyme, was highly expressed upon EMT induction and was necessary for cells to acquire mesenchymal characteristics in vitro and for tumorigenic cells to extravasate into the mouse lung. This role of DPYD was mediated through its catalytic activity and enzymatic products, the dihydropyrimidines. Thus, we identify metabolic processes essential for the EMT, a program associated with the acquisition of metastatic and aggressive cancer cell traits. C1 [Shaul, Yoav D.; Freinkman, Elizaveta; Comb, William C.; Cantor, Jason R.; Tam, Wai Leong; Thiru, Prathapan; Kim, Dohoon; Kanarek, Naama; Pacold, Michael E.; Chen, Walter W.; Bierie, Brian; Possemato, Richard; Reinhardt, Ferenc; Weinberg, Robert A.; Sabatini, David M.] Whitehead Inst Biomed Res, Nine Cambridge Ctr, Cambridge, MA 02142 USA. [Shaul, Yoav D.; Yaffe, Michael B.; Sabatini, David M.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Sabatini, David M.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Weinberg, Robert A.; Yaffe, Michael B.; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Yaffe, Michael B.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Weinberg, Robert A.] MIT, Ludwig Ctr Mol Oncol, Cambridge, MA 02139 USA. [Pacold, Michael E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Sabatini, David M.] Broad Inst, Cambridge, MA 02142 USA. [Tam, Wai Leong] Genome Inst Singapore, Singapore 138672, Singapore. RP Sabatini, DM (reprint author), Whitehead Inst Biomed Res, Nine Cambridge Ctr, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM sabatini@wi.mit.edu OI Tam, Wai Leong/0000-0003-2365-5264 FU NIH [RO1 CA103866, AI047389, K99 CA168940]; Life Science Research Foundation and Ludwig Postdoctoral Fellowship; American Cancer Society fellowship [PF-12-099-01-TGB]; Sally Gordon Fellowship of the Damon Runyon Cancer Research Foundation [DRG112-12]; American Cancer Society-Ellison Foundation Postdoctoral Fellowship [PF-13-356-01-TBE]; Ruth L. Kirchstein NRSA F30 fellowship; Hope Funds for Cancer Research Fellowship [HFCR-13-03-03]; Department of Defense Breast Cancer Research Program [BC123066]; NIH grants [CA112967, ES015339] FX We thank all members of the Sabatini Lab for helpful suggestions and Tom DiCesare for graphical assistance. This work was supported by grants from the NIH (RO1 CA103866 and AI047389 to D. M. S.; K99 CA168940 to R. P.), the Life Science Research Foundation and Ludwig Postdoctoral Fellowship (to Y.D.S.), the American Cancer Society fellowship (PF-12-099-01-TGB) (to J.R.C.), the Sally Gordon Fellowship of the Damon Runyon Cancer Research Foundation (DRG112-12) (to M. E. P.), American Cancer Society-Ellison Foundation Postdoctoral Fellowship (PF-13-356-01-TBE) (to W. C. C.), the Ruth L. Kirchstein NRSA F30 fellowship (to W. W. C.), and the Hope Funds for Cancer Research Fellowship (HFCR-13-03-03) and Department of Defense Breast Cancer Research Program (BC123066) (to E. F.). M.B.Y. is supported by NIH grants (CA112967 and ES015339). D. M. S. is an investigator of the Howard Hughes Medical Institute. NR 47 TC 30 Z9 30 U1 6 U2 27 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 AUG 28 PY 2014 VL 158 IS 5 BP 1094 EP 1109 DI 10.1016/j.cell.2014.07.032 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AN9RI UT WOS:000340945000015 PM 25171410 ER PT J AU Aceto, N Bardia, A Miyamoto, DT Donaldson, MC Wittner, BS Spencer, JA Yu, M Pely, A Engstrom, A Zhu, HL Brannigan, BW Kapur, R Stott, SL Shioda, T Ramaswamy, S Ting, DT Lin, CP Toner, M Haber, DA Maheswaran, S AF Aceto, Nicola Bardia, Aditya Miyamoto, David T. Donaldson, Maria C. Wittner, Ben S. Spencer, Joel A. Yu, Min Pely, Adam Engstrom, Amanda Zhu, Huili Brannigan, Brian W. Kapur, Ravi Stott, Shannon L. Shioda, Toshi Ramaswamy, Sridhar Ting, David T. Lin, Charles P. Toner, Mehmet Haber, Daniel A. Maheswaran, Shyamala TI Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis SO CELL LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; BONE METASTASIS; PROSTATE-CANCER; GAMMA-CATENIN; ADHESION; MORPHOGENESIS; MOLECULES; SIGNALS; GENES; BLOOD AB Circulating tumor cell clusters (CTC clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Using mouse models with tagged mammary tumors, we demonstrate that CTC clusters arise from oligoclonal tumor cell groupings and not from intravascular aggregation events. Although rare in the circulation compared with single CTCs, CTC clusters have 23- to 50-fold increased metastatic potential. In patients with breast cancer, single-cell resolution RNA sequencing of CTC clusters and single CTCs, matched within individual blood samples, identifies the cell junction component plakoglobin as highly differentially expressed. In mouse models, knockdown of plakoglobin abrogates CTC cluster formation and suppresses lung metastases. In breast cancer patients, both abundance of CTC clusters and high tumor plakoglobin levels denote adverse outcomes. Thus, CTC clusters are derived from multicellular groupings of primary tumor cells held together through plakoglobin-dependent intercellular adhesion, and though rare, they greatly contribute to the metastatic spread of cancer. C1 [Aceto, Nicola; Bardia, Aditya; Miyamoto, David T.; Donaldson, Maria C.; Wittner, Ben S.; Yu, Min; Engstrom, Amanda; Zhu, Huili; Brannigan, Brian W.; Stott, Shannon L.; Shioda, Toshi; Ramaswamy, Sridhar; Ting, David T.; Haber, Daniel A.; Maheswaran, Shyamala] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. [Aceto, Nicola; Bardia, Aditya; Donaldson, Maria C.; Wittner, Ben S.; Yu, Min; Engstrom, Amanda; Zhu, Huili; Brannigan, Brian W.; Stott, Shannon L.; Shioda, Toshi; Ramaswamy, Sridhar; Ting, David T.; Haber, Daniel A.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02129 USA. [Spencer, Joel A.; Pely, Adam; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Program, Boston, MA 02114 USA. [Spencer, Joel A.; Pely, Adam; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Spencer, Joel A.; Pely, Adam; Lin, Charles P.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Miyamoto, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02129 USA. [Kapur, Ravi; Stott, Shannon L.; Toner, Mehmet] Harvard Univ, Ctr Bioengn Med, Sch Med, Boston, MA 02129 USA. [Toner, Mehmet; Maheswaran, Shyamala] Harvard Univ, Dept Surg, Sch Med, Boston, MA 02129 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. EM dhaber@mgh.harvard.edu; maheswaran@helix.mgh.harvard.edu RI Aceto, Nicola/O-2484-2014; OI Aceto, Nicola/0000-0001-9579-6918; Ting, David/0000-0002-3261-2322 FU Breast Cancer Research Foundation; Stand Up to Cancer; National Foundation for Cancer Research; Howard Hughes Medical Institute; NIH [CA129933, P41 E8015903-02S1, P50 CA086355-12]; National Institute of Biomedical Imaging and Bioengineering (NIBIB) [EB008047]; Susan G. Komen for the Cure [KG09042]; ESSCO Breast Cancer Fund; NCI Federal Share Program and Income; MGH-Johnson & Johnson Center for Excellence in CTCs FX We express our gratitude to all the patients who participated in this study. We thank C. Hart, A. McGovern, K. Harrington, L. C. Davis, and the Massachusetts General Hospital (MGH) clinical research coordinators for help with the clinical studies; Drs. P. S. Spuhler and T. A. Barber for support with the CTC-iChip technology; L. Libby and J. Brockmann for excellent technical support. This work was supported by grants from the Breast Cancer Research Foundation (D. A. H.), Stand Up to Cancer (D. A. H., M. T., S. M.), National Foundation for Cancer Research (D. A. H.), Howard Hughes Medical Institute (D. A. H.), NIH CA129933 (D. A. H.), National Institute of Biomedical Imaging and Bioengineering (NIBIB) EB008047 (M. T., D. A. H.), Susan G. Komen for the Cure KG09042 (S. M.), ESSCO Breast Cancer Fund (S. M.), NCI Federal Share Program and Income (S. M.), NIH P41 E8015903-02S1 (C. P. L.), NIH P50 CA086355-12 (C. P. L.), and the MGH-Johnson & Johnson Center for Excellence in CTCs (M. T., S. M.). N.A. is a fellow of the Human Frontiers Science Program, the Swiss National Science Foundation, and the Swiss Foundation for Grants in Biology and Medicine. NR 38 TC 249 Z9 256 U1 29 U2 176 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 AUG 28 PY 2014 VL 158 IS 5 BP 1110 EP 1122 DI 10.1016/j.cell.2014.07.013 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AN9RI UT WOS:000340945000016 PM 25171411 ER PT J AU Ho, JWK June, YL Liu, T Alver, BH Lee, S Ikegami, K Sohn, KA Minoda, A Tolstorukov, MY Appert, A Parker, SCJ Gu, TT Kundaje, A Riddle, NC Bishop, E Egelhofer, TA Hu, SS Alekseyenko, AA Rechtsteiner, A Asker, D Belsky, JA Bowmanm, SK Chens, QB Chen, RAJ Day, DS Dong, Y Dose, AC Duan, XK Epstein, CB Ercan, S Feingold, EA Ferrari, F Garrigues, JM Gehlenborg, N Good, PJ Haseley, P He, D Herrmann, M Hoffman, MM Jeffers, TE Kharchenko, PV Kolasinska-Zwierz, P Kotwaliwale, CV Kumar, N Langley, SA Larschan, EN Latorre, I Libbrecht, MW Lin, XQ Park, R Pazin, MJ Pham, HN Plachetka, A Qin, B Schwartz, YB Shoresh, N Stempor, P Vielle, A Wang, CY Whittle, CM Xue, HL Kingstonm, RE Kim, JH Bernstein, BE Dernburg, AF Pirrotta, V Kuroda, MI Noble, WS Tullius, TD Kellis, M MacAlpine, DM Strome, S Elgin, SCR Liu, XS Lieb, JD Ahringer, J Karpen, GH Park, PJ AF Ho, Joshua W. K. June, Youngsook L. Liu, Tao Alver, Burak H. Lee, Soohyun Ikegami, Kohta Sohn, Kyung-Ah Minoda, Aki Tolstorukov, Michael Y. Appert, Alex Parker, Stephen C. J. Gu, Tingting Kundaje, Anshul Riddle, Nicole C. Bishop, Eric Egelhofer, Thea A. Hu, Sheng'en Shawn Alekseyenko, Artyom A. Rechtsteiner, Andreas Asker, Dalal Belsky, Jason A. Bowmanm, Sarah K. Chens, Q. Brent Chen, Ron A. -J. Day, Daniel S. Dong, Yan Dose, Andrea C. Duan, Xikun Epstein, Charles B. Ercan, Sevinc Feingold, Elise A. Ferrari, Francesco Garrigues, Jacob M. Gehlenborg, Nils Good, Peter J. Haseley, Psalm He, Daniel Herrmann, Moritz Hoffman, Michael M. Jeffers, Tess E. Kharchenko, Peter V. Kolasinska-Zwierz, Paulina Kotwaliwale, Chitra V. Kumar, Nischay Langley, Sasha A. Larschan, Erica N. Latorre, Isabel Libbrecht, Maxwell W. Lin, Xueqiu Park, Richard Pazin, Michael J. Pham, Hoang N. Plachetka, Annette Qin, Bo Schwartz, Yuri B. Shoresh, Noam Stempor, Przemyslaw Vielle, Anne Wang, Chengyang Whittle, Christina M. Xue, Huiling Kingstonm, Robert E. Kim, Ju Han Bernstein, Bradley E. Dernburg, Abby F. Pirrotta, Vincenzo Kuroda, Mitzi I. Noble, William S. Tullius, Thomas D. Kellis, Manolis MacAlpine, David M. Strome, Susan Elgin, Sarah C. R. Liu, Xiaole Shirley Lieb, Jason D. Ahringer, Julie Karpen, Gary H. Park, Peter J. TI Comparative analysis of metazoan chromatin organization SO NATURE LA English DT Article ID CENTROMERIC CHROMATIN; DROSOPHILA GENOME; MODENCODE; ELEMENTS; ELEGANS; STATE; TRANSCRIPTION; METHYLATION; DOMAINS; ENCODE AB Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function. C1 [Ho, Joshua W. K.; June, Youngsook L.; Alver, Burak H.; Lee, Soohyun; Tolstorukov, Michael Y.; Bishop, Eric; Day, Daniel S.; Ferrari, Francesco; Gehlenborg, Nils; Haseley, Psalm; Kharchenko, Peter V.; Park, Richard; Xue, Huiling; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Ho, Joshua W. K.; June, Youngsook L.; Tolstorukov, Michael Y.; Alekseyenko, Artyom A.; Haseley, Psalm; Plachetka, Annette; Xue, Huiling; Kuroda, Mitzi I.; Park, Peter J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. [Liu, Tao; Liu, Xiaole Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Liu, Tao; Liu, Xiaole Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Liu, Tao; Liu, Xiaole Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Ikegami, Kohta; Chens, Q. Brent; Ercan, Sevinc; Jeffers, Tess E.; Lieb, Jason D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Ikegami, Kohta; Chens, Q. Brent; Ercan, Sevinc; Jeffers, Tess E.; Lieb, Jason D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Sohn, Kyung-Ah] Ajou Univ, Dept Informat & Comp Engn, Suwon 443749, South Korea. [Sohn, Kyung-Ah; Kim, Ju Han] Seoul Natl Univ, Coll Med, Syst Biomed Informat Res Ctr, Seoul 110799, South Korea. [Minoda, Aki; Langley, Sasha A.; Pham, Hoang N.; Vielle, Anne; Dernburg, Abby F.; Karpen, Gary H.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Dept Genome Dynam, Berkeley, CA 94720 USA. [Minoda, Aki; He, Daniel; Kotwaliwale, Chitra V.; Langley, Sasha A.; Pham, Hoang N.; Whittle, Christina M.; Dernburg, Abby F.; Karpen, Gary H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Tolstorukov, Michael Y.; Bowmanm, Sarah K.; Kingstonm, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Tolstorukov, Michael Y.; Bowmanm, Sarah K.; Kingstonm, Robert E.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Appert, Alex; Chen, Ron A. -J.; Dong, Yan; Herrmann, Moritz; Kolasinska-Zwierz, Paulina; Latorre, Isabel; Stempor, Przemyslaw; Vielle, Anne; Ahringer, Julie] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England. [Appert, Alex; Chen, Ron A. -J.; Dong, Yan; Herrmann, Moritz; Kolasinska-Zwierz, Paulina; Latorre, Isabel; Stempor, Przemyslaw; Vielle, Anne; Ahringer, Julie] Univ Cambridge, Dept Genet, Cambridge CB2 1QN, England. [Parker, Stephen C. J.] NIGMS, NIH, Bethesda, MD 20892 USA. [Parker, Stephen C. J.; Feingold, Elise A.; Good, Peter J.; Pazin, Michael J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Gu, Tingting; Riddle, Nicole C.; Elgin, Sarah C. R.] Washington Univ, Dept Biol, St Louis, MO 63130 USA. [Kundaje, Anshul; Kumar, Nischay; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Alver, Burak H.; Kundaje, Anshul; Epstein, Charles B.; Gehlenborg, Nils; Kumar, Nischay; Shoresh, Noam; Vielle, Anne; Bernstein, Bradley E.; Kellis, Manolis; Liu, Xiaole Shirley] Broad Inst, Cambridge, MA 02141 USA. [Bishop, Eric; Park, Richard; Tullius, Thomas D.] Boston Univ, Program Bioinformat, Boston, MA 02215 USA. [Egelhofer, Thea A.; Rechtsteiner, Andreas; Garrigues, Jacob M.; Strome, Susan] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA. [Hu, Sheng'en Shawn; Duan, Xikun; Lin, Xueqiu; Qin, Bo; Wang, Chengyang] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Alekseyenko, Artyom A.; Plachetka, Annette; Kuroda, Mitzi I.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Asker, Dalal; Schwartz, Yuri B.; Pirrotta, Vincenzo] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. [Asker, Dalal] Univ Alexandria, Fac Agr, Food Sci & Technol Dept, Alexandria 21545, Egypt. [Belsky, Jason A.; MacAlpine, David M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Day, Daniel S.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Dose, Andrea C.] Univ Calif Davis, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. [Ercan, Sevinc] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA. [Hoffman, Michael M.] Princess Margaret Canc Ctr, Toronto, ON M6G 1L7, Canada. [Kotwaliwale, Chitra V.; Pham, Hoang N.; Whittle, Christina M.; Bernstein, Bradley E.; Dernburg, Abby F.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Larschan, Erica N.] Brown Univ, Dept Mol Biol Cellular Biol & Biochem, Providence, RI 02912 USA. [Libbrecht, Maxwell W.; Noble, William S.] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. [Schwartz, Yuri B.] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden. [Kim, Ju Han] Seoul Natl Univ, Coll Med, Div Biomed Informat, Seoul Natl Univ Biomed Informat, Seoul 110799, South Korea. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Noble, William S.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Tullius, Thomas D.] Boston Univ, Dept Chem, Boston, MA 02215 USA. [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02215 USA. RP MacAlpine, DM (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. EM david.macalpine@duke.edu; sstrome@ucsc.edu; selgin@biology2.wustl.edu; xsliu@jimmy.harvard.edu; jdlieb@uchicago.edu; ja219@cam.ac.uk; ghkarpen@lbl.gov; peter_park@hms.harvard.edu RI Ferrari, Francesco/H-5007-2012; Asker, Dalal/B-5722-2009; Minoda, Aki/D-5335-2017; Tullius, Thomas/A-9685-2008; Liu, Tao/G-3585-2010; Hoffman, Michael/I-1924-2012 OI Stempor, Przemyslaw/0000-0002-9464-7475; Jeffers, Tess/0000-0003-4908-0796; Latorre, Isabel/0000-0003-0638-1783; Alver, Burak/0000-0002-5019-7652; Gehlenborg, Nils/0000-0003-0327-8297; Pazin, Michael/0000-0002-7561-3640; Ferrari, Francesco/0000-0002-9811-3753; Minoda, Aki/0000-0002-2927-5791; Belsky, Jason/0000-0003-2945-6282; Chen, Ron/0000-0001-9186-6747; Liu, Tao/0000-0003-0446-9001; Sohn, Kyung-Ah/0000-0001-8941-1188; Tullius, Thomas/0000-0003-4425-796X; Liu, Tao/0000-0002-8818-8313; Hoffman, Michael/0000-0002-4517-1562 FU NHGRI [U01HG004258, U01 HG004270, U01HG004279, U54HG004570, U01HG004695, K99HG006259]; NHBIB [5RL9EB008539]; NIGMS; NIH [U54CA121852]; NSF [1122374]; National Natural Science Foundation of China [31028011]; MEST Korea [MHW-2013-HI13C2164]; Wellcome Trust [54523]; [NRF-2012-0000994] FX This project was mainly funded by NHGRI U01HG004258 (G.H.K., S.C.R.E., M.I.K., P.J.P., V.P.), U01 HG004270 (J.D.L., J.A., A.F.D., X.S.L., S.S.), U01HG004279 (D.M.M.), U54HG004570 (B.E.B.) and U01HG004695 (W.S.N.). It is also supported by NHBIB 5RL9EB008539 (J.W.K.H.), NHGRI K99HG006259 (M.M.H.), NIGMS fellowships (S.C.J.P., E.N.L.), NIH U54CA121852 (T.D.T.), NSF 1122374 (D.S.D.), National Natural Science Foundation of China 31028011 (X.S.L.), MEST Korea MHW-2013-HI13C2164 (J.H.K.), NRF-2012-0000994 (K-AS.), and Wellcome Trust 54523 (J.A.). We thank D. Acevedo and C. Kennedy for technical assistance. NR 24 TC 79 Z9 81 U1 1 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 AUG 28 PY 2014 VL 512 IS 7515 BP 449 EP U507 DI 10.1038/nature13415 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN8GC UT WOS:000340840600038 PM 25164756 ER PT J AU Berger, AH Imielinski, M Duke, F Wala, J Kaplan, N Shi, GX Andres, DA Meyerson, M AF Berger, A. H. Imielinski, M. Duke, F. Wala, J. Kaplan, N. Shi, G-X Andres, D. A. Meyerson, M. TI Oncogenic RIT1 mutations in lung adenocarcinoma SO ONCOGENE LA English DT Article DE lung adenocarcinoma; cancer genetics; RAS pathway; signal transduction; oncogene; GTPase ID EML4-ALK FUSION GENE; NEURONAL DIFFERENTIATION; KINASE INHIBITOR; KRAS MUTATIONS; CANCER; GEFITINIB; PROTEIN; SENSITIVITY; ACTIVATION; GENOME AB Lung adenocarcinoma is comprised of distinct mutational subtypes characterized by mutually exclusive oncogenic mutations in RTK/RAS pathway members KRAS, EGFR, BRAF and ERBB2, and translocations involving ALK, RET and ROS1. Identification of these oncogenic events has transformed the treatment of lung adenocarcinoma via application of therapies targeted toward specific genetic lesions in stratified patient populations. However, such mutations have been reported in only similar to 55% of lung adenocarcinoma cases in the United States, suggesting other mechanisms of malignancy are involved in the remaining cases. Here we report somatic mutations in the small GTPase gene RIT1 in similar to 2% of lung adenocarcinoma cases that cluster in a hotspot near the switch II domain of the protein. RIT1 switch II domain mutations are mutually exclusive with all other known lung adenocarcinoma driver mutations. Ectopic expression of mutated RIT1 induces cellular transformation in vitro and in vivo, which can be reversed by combined PI3K and MEK inhibition. These data identify RIT1 as a driver oncogene in a specific subset of lung adenocarcinomas and suggest PI3K and MEK inhibition as a potential therapeutic strategy in RIT1-mutated tumors. C1 [Berger, A. H.; Imielinski, M.; Duke, F.; Wala, J.; Meyerson, M.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Berger, A. H.; Imielinski, M.; Wala, J.; Kaplan, N.; Meyerson, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Imielinski, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Imielinski, M.; Meyerson, M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wala, J.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Shi, G-X; Andres, D. A.] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Ctr Canc Genome Discovery, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu FU American Cancer Society; NCI Training Grant [T32CA9216]; NIH Training Grant [T32HG002295]; NIH [NS045103]; KSCHIRT [12-1A]; University of Kentucky Research Professorship; Department of Defense [W81XWH-12-1-0269]; National Cancer Institute [P01CA154303, R01CA109038]; Uniting Against Lung Cancer; Lung Cancer Research Foundation; American Lung Association FX We thank A. Brooks, P. Choi, H. Gannon, H. Greulich, L. De Waal, B. Kaplan, R. Liao, T. Sharifnia, J. Boehm and A. Koehler for critical advice and discussion. AHB is supported by a postdoctoral fellowship from the American Cancer Society. MI is supported by NCI Training Grant T32CA9216. JW is supported by NIH Training Grant T32HG002295. DAA is supported by NIH NS045103, KSCHIRT 12-1A, and a University of Kentucky Research Professorship. This work was supported by grants from the Department of Defense (#W81XWH-12-1-0269) National Cancer Institute (P01CA154303 and R01CA109038), Uniting Against Lung Cancer, the Lung Cancer Research Foundation and the American Lung Association to MM. NR 43 TC 25 Z9 25 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 AUG 28 PY 2014 VL 33 IS 35 BP 4418 EP 4423 DI 10.1038/onc.2013.581 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AO2MR UT WOS:000341157800006 PM 24469055 ER PT J AU Levanon, K Sapoznik, S Bahar-Shany, K Brand, H Shapira-Frommer, R Korach, J Hirsch, MS Roh, MH Miron, A Liu, JF Vena, N Ligon, AH Fotheringham, S Bailey, D Flavin, RJ Birrer, MJ Drapkin, RI AF Levanon, K. Sapoznik, S. Bahar-Shany, K. Brand, H. Shapira-Frommer, R. Korach, J. Hirsch, M. S. Roh, M. H. Miron, A. Liu, J. F. Vena, N. Ligon, A. H. Fotheringham, S. Bailey, D. Flavin, R. J. Birrer, M. J. Drapkin, R. I. TI FOXO3a loss is a frequent early event in high-grade pelvic serous carcinogenesis SO ONCOGENE LA English DT Article DE serous ovarian carcinoma; fallopian tube epithelium; FOXO3a; AKT; ERK; miRNA-182 ID LUNG-CANCER CELLS; TRANSCRIPTION FACTOR; OVARIAN-CANCER; FALLOPIAN-TUBE; PROMOTES TUMORIGENESIS; CANDIDATE PRECURSOR; EXPRESSION; INHIBITORS; CARCINOMA; CHEMOTHERAPY AB Serous ovarian carcinoma is the most lethal gynecological malignancy in Western countries. The molecular events that underlie the development of the disease have been elusive for many years. The recent identification of the fallopian tube secretory epithelial cells (FTSECs) as the cell-of-origin for most cases of this disease has led to studies aimed at elucidating new candidate therapeutic pathways through profiling of normal FTSECs and serous carcinomas. Here we describe the results of transcriptional profiles that identify the loss of the tumor suppressive transcription factor FOXO3a in a vast majority of high-grade serous ovarian carcinomas. We show that FOXO3a loss is a hallmark of the earliest stages of serous carcinogenesis and occurs both at the DNA, RNA and protein levels. We describe several mechanisms responsible for FOXO3a inactivity, including chromosomal deletion (chromosome 6q21), upregulation of miRNA-182 and destabilization by activated PI3K and MEK. The identification of pathways involved in the pathogenesis of ovarian cancer can advance the management of this disease from being dependant on surgery and cytotoxic chemotherapy alone to the era of targeted therapy. Our data strongly suggest FOXO3a as a possible target for clinical intervention. C1 [Levanon, K.] Chaim Sheba Med Ctr, Sheba Canc Res Ctr, Dr Pinchas Borenstein Talpiot Med Leadership Prog, IL-52621 Ramat Gan, Israel. [Levanon, K.; Drapkin, R. I.] Dept Med Oncol, Boston, MA USA. [Levanon, K.; Drapkin, R. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sapoznik, S.; Bahar-Shany, K.; Brand, H.] Sheba Canc Res Ctr, Ramat Gan, Israel. [Sapoznik, S.; Bahar-Shany, K.; Brand, H.] Chaim Sheba Med Ctr, IL-52621 Ramat Gan, Israel. [Brand, H.] Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel. [Shapira-Frommer, R.] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Ramat Gan, Israel. [Korach, J.; Ligon, A. H.] Chaim Sheba Med Ctr, Dept Gynecol Oncol, IL-52621 Ramat Gan, Israel. [Hirsch, M. S.; Roh, M. H.; Drapkin, R. I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Miron, A.; Liu, J. F.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, J. F.; Ligon, A. H.; Drapkin, R. I.] Harvard Univ, Sch Med, Boston, MA USA. [Vena, N.; Ligon, A. H.; Fotheringham, S.; Bailey, D.; Flavin, R. J.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Birrer, M. J.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Levanon, K (reprint author), Chaim Sheba Med Ctr, Sheba Canc Res Ctr, Dr Pinchas Borenstein Talpiot Med Leadership Prog, IL-52621 Ramat Gan, Israel. EM Keren.Levanon@sheba.health.gov.il RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU National Institutes of Health/National Cancer Institute [P50 CA105009, U01 CA152990, R21 CA156021]; Ovarian Cancer Research Fund; Mary Kay Foundation; Tina Brozman Foundation; Robert and Debra First Fund; Gamel Family Fund for Ovarian Cancer; Marsha Rivkin Foundation Scientific Scholar Award; AACR- George and Patricia Sehl Fellowship; American Physicians Fellowship for Medicine in Israel-Claire and Emmanuel G. Rosenblatt Foundation Grant; Israel Science Foundation Legacy Heritage Clinical Research Initiative; Israel Cancer Research Fund Clinical Research Career Development Award; Chaim Sheba Medical Center Dr Pinchas Bornstein Talpiot Medical Leadership Program FX This work was supported by research grants from the National Institutes of Health/National Cancer Institute (P50 CA105009, U01 CA152990, and R21 CA156021), the Ovarian Cancer Research Fund, The Mary Kay Foundation, The Tina Brozman Foundation, The Robert and Debra First Fund, the Gamel Family Fund for Ovarian Cancer, the Marsha Rivkin Foundation Scientific Scholar Award, the AACR- George and Patricia Sehl Fellowship for Cancer Genetics Research, the American Physicians Fellowship for Medicine in Israel-Claire and Emmanuel G. Rosenblatt Foundation Grant, The Israel Science Foundation Legacy Heritage Clinical Research Initiative, The Israel Cancer Research Fund Clinical Research Career Development Award and the Chaim Sheba Medical Center Dr Pinchas Bornstein Talpiot Medical Leadership Program. We thank Drs. John Quackenbush, Massimo Loda, Keith Ligon and Sekhar Duraisamy, Dana-Farber Cancer Institute, for their suggestions and generous assistance with reagents and bioinformatics; Dr Ravid Straussman, the Broad Institute, for his guidance with methylation detection; Dr Sol Efroni and Rotem Ben-Hamo, Bar Ilan University, Israel, for bioinformatic support; and The Chaim Sheba Tissue Bank. NR 47 TC 7 Z9 7 U1 0 U2 2 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 AUG 28 PY 2014 VL 33 IS 35 BP 4424 EP 4432 DI 10.1038/onc.2013.394 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AO2MR UT WOS:000341157800007 PM 24077281 ER PT J AU Zhang, XL Shi, HJ Wang, JP Tang, HS Wu, YB Fang, ZY Cui, SZ Wang, LT AF Zhang, Xiang-Liang Shi, Hui-Juan Wang, Ji-Ping Tang, Hong-Sheng Wu, Yin-Bing Fang, Zhi-Yuan Cui, Shu-Zhong Wang, Lian-Tang TI MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Advanced gastric cancer; Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy miR-218; Multi-drug resistance; MicroRNA ID PERITONEAL CARCINOMATOSIS; DOWN-REGULATION; CHEMOHYPERTHERMIA; MORTALITY; PERFUSION; ADENOCARCINOMA; DISSEMINATION; EXPRESSION; MORBIDITY; GENES AB AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A miRNA microarray containing human mature and precursor miRNA sequences was used to compare expression profiles in serum samples of 5 patients with AGC before and after CRS + HIPEC. The upregulation of miR-218 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in SGC7901 gastric cancer cells. RESULTS: miRNA microarray chip analysis found that the level of miR-218 expression was upregulated more than 8 fold after CRS + HIPEC. Furthermore, miR-218 increased gastric cancer cell chemosensitivity to cisplatin in vitro and inhibited gastric cell tumor growth in nude mice in vivo (0.5 vs 0.78, P < 0.05). CONCLUSION: Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and reverse the multi-drug resistance of gastric cell lines. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. C1 [Zhang, Xiang-Liang; Tang, Hong-Sheng; Wu, Yin-Bing; Fang, Zhi-Yuan; Cui, Shu-Zhong] Guangzhou Med Univ, Affiliated Tumor Hosp, Dept Abdominal Surg, Guangzhou 510095, Guangdong, Peoples R China. [Shi, Hui-Juan; Wang, Lian-Tang] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China. [Wang, Ji-Ping] Brigham & Womens Hosp, Dept Surg, Boston, MA 02114 USA. [Wang, Ji-Ping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Wang, Ji-Ping] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wang, LT (reprint author), Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China. EM wanglt@mail.sysu.edu.cn FU Start-up Funds of Guangzhou Medical College, Guangdong Province, China [2012C66, 2012C69]; Guangdong Province Natural Science Fund [S2013010016662]; National Natural Science Foundation of China [81201932, 81372493] FX Supported by The PhD Start-up Funds of Guangzhou Medical College, Guangdong Province, China, No. 2012C66 and No. 2012C69; Guangdong Province Natural Science Fund, No. S2013010016662; and the National Natural Science Foundation of China, No. 81201932 and No. 81372493 NR 39 TC 14 Z9 14 U1 0 U2 8 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD AUG 28 PY 2014 VL 20 IS 32 BP 11347 EP 11355 DI 10.3748/wjg.v20.i32.11347 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO0RM UT WOS:000341019200030 PM 25170221 ER PT J AU Asch, DA Weinstein, DF AF Asch, David A. Weinstein, Debra F. TI Innovation in Medical Education SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Asch, David A.] Univ Penn, Perelman Sch Med, Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Weinstein, Debra F.] Massachusetts Gen Hosp, Dept Med, Partners Hlth Care Syst, Boston, MA 02114 USA. [Weinstein, Debra F.] Harvard Univ, Sch Med, Boston, MA USA. RP Asch, DA (reprint author), Univ Penn, Perelman Sch Med, Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. NR 5 TC 28 Z9 28 U1 0 U2 7 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 AUG 28 PY 2014 VL 371 IS 9 BP 794 EP 795 DI 10.1056/NEJMp1407463 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AN7ZN UT WOS:000340819800004 PM 25075620 ER PT J AU Sahai, I Mochida, GH Grabowski, EF Caruso, PA AF Sahai, Inderneel Mochida, Ganeshwaran H. Grabowski, Eric F. Caruso, Paul A. TI Case 27-2014: A 10-Month-Old Boy with Microcephaly and Episodic Cyanosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DEFICIENCY; THROMBOSIS; CHILDREN; BRAIN; MR C1 [Sahai, Inderneel; Grabowski, Eric F.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mochida, Ganeshwaran H.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Sahai, Inderneel; Mochida, Ganeshwaran H.; Grabowski, Eric F.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Caruso, Paul A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Sahai, I (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. FU UCB Japan; Otsuka; Roche FX Dr. Mochida reports receiving lecture fees from UCB Japan and Otsuka and grant support from Roche. No other potential conflict of interest relevant to this article was reported. NR 15 TC 3 Z9 3 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 AUG 28 PY 2014 VL 371 IS 9 BP 847 EP 858 DI 10.1056/NEJMcpc1400833 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AN7ZN UT WOS:000340819800012 PM 25162892 ER PT J AU Witus, LS Hartlieb, KJ Wang, YP Prokofjevs, A Frasconi, M Barnes, JC Dale, EJ Fahrenbach, AC Stoddart, JF AF Witus, Leah S. Hartlieb, Karel J. Wang, Yuping Prokofjevs, Aleksandrs Frasconi, Marco Barnes, Jonathan C. Dale, Edward J. Fahrenbach, Albert C. Stoddart, J. Fraser TI Relative contractile motion of the rings in a switchable palindromic [3]rotaxane in aqueous solution driven by radical-pairing interactions SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID ARTIFICIAL MOLECULAR MUSCLES; LINEAR ROTAXANE DIMER; DONOR-ACCEPTOR; MACHINES; POLYMERS; MOTORS; CHAIN; LIGHT; ION; ELASTOMERS AB Artificial muscles are an essential component for the development of next-generation prosthetic devices, minimally invasive surgical tools, and robotics. This communication describes the design, synthesis, and characterisation of a mechanically interlocked molecule (MIM), capable of switchable and reversible linear molecular motion in aqueous solution that mimics muscular contraction and extension. Compatibility with aqueous solution was achieved in the doubly bistable palindromic (3)rotaxane design by using radical-based molecular recognition as the driving force to induce switching. C1 [Witus, Leah S.; Hartlieb, Karel J.; Wang, Yuping; Prokofjevs, Aleksandrs; Frasconi, Marco; Barnes, Jonathan C.; Dale, Edward J.; Fahrenbach, Albert C.; Stoddart, J. Fraser] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. [Barnes, Jonathan C.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Fahrenbach, Albert C.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Fahrenbach, Albert C.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Fahrenbach, Albert C.] Tokyo Inst Technol, Earth Life Sci Inst, Meguro Ku, Tokyo 1528551, Japan. RP Stoddart, JF (reprint author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM stoddart@northwestern.edu RI Frasconi, Marco/C-4767-2014 OI Frasconi, Marco/0000-0003-2010-175X FU National Institute of General Medical Sciences of the National Institutes of Health (NIH) [F32GM105403]; Joint Center of Excellence in Integrated Nano-Systems (JCIN) at King Abdul-Aziz City for Science and Technology (KACST) [34-949]; NU; KACST; National Science Foundation (NSF); International Institute for Nanotechnology (IIN) at NU; Department of Defense FX The research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Award Number F32GM105403. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This research is part (Project #34-949) of the Joint Center of Excellence in Integrated Nano-Systems (JCIN) at King Abdul-Aziz City for Science and Technology (KACST) and Northwestern University (NU). The authors would like to thank both KACST and NU for their continued support of this research. A.C.F. was and E.J.D. is supported by the National Science Foundation (NSF) Graduate Research Fellowship Program. L.S.W. acknowledges support from the International Institute for Nanotechnology (IIN) at NU. J.C.B. was supported by a National Defense Science and Engineering Graduate Fellowship from the Department of Defense and gratefully acknowledges receipt of a Ryan Fellowship from the IIN while at NU. NR 63 TC 11 Z9 11 U1 36 U2 76 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PD AUG 28 PY 2014 VL 12 IS 32 BP 6089 EP 6093 DI 10.1039/c4ob01228c PG 5 WC Chemistry, Organic SC Chemistry GA AN1OH UT WOS:000340352700009 PM 25010832 ER PT J AU Rotstein, BH Zaretsky, S Rai, V Yudin, AK AF Rotstein, Benjamin H. Zaretsky, Serge Rai, Vishal Yudin, Andrei K. TI Small Heterocycles in Multicomponent Reactions SO CHEMICAL REVIEWS LA English DT Review ID CARBONYL CATALYZED REACTION; 3-COMPONENT COUPLING REACTION; TRICHLOROALKYL PHENYL ETHERS; UNPROTECTED AMINO ALDEHYDES; RING-OPENING CARBONYLATION; CIS-AZIRIDINE CARBOXYLATES; BETA-LACTAM ANTIBIOTICS; ANION RELAY CHEMISTRY; ONE-POT SYNTHESIS; CYCLIC ETHERS C1 [Rotstein, Benjamin H.; Zaretsky, Serge; Rai, Vishal; Yudin, Andrei K.] Univ Toronto, Dept Chem, Davenport Res Labs, Toronto, ON M5S 3H6, Canada. [Rotstein, Benjamin H.] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Rotstein, Benjamin H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Rai, Vishal] Indian Inst Sci Educ & Res IISER Bhopal, Dept Chem, Bhopal 462066, MP, India. RP Yudin, AK (reprint author), Univ Toronto, Dept Chem, Davenport Res Labs, 80 St George St, Toronto, ON M5S 3H6, Canada. EM ayudin@chem.utoronto.ca OI Rotstein, Benjamin/0000-0001-9707-9357 FU Ontario Graduate Scholarships (OGS); Science and Engineering Research Board (SERB), India FX B.H.R. is a Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Fellow. S.Z. would like to acknowledge Ontario Graduate Scholarships (OGS) for financial support. V.R. is thankful to Science and Engineering Research Board (SERB), India, for a Ramanujan Fellowship. NR 205 TC 172 Z9 172 U1 8 U2 117 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 EI 1520-6890 J9 CHEM REV JI Chem. Rev. PD AUG 27 PY 2014 VL 114 IS 16 BP 8323 EP 8359 DI 10.1021/cr400615v PG 37 WC Chemistry, Multidisciplinary SC Chemistry GA AO0IL UT WOS:000340992200013 PM 25032909 ER PT J AU Yamada, K Tasaki, M Sekijima, M Wilkinson, RA Villani, V Moran, SG Cormack, TA Hanekamp, IM Arn, JS Fishman, JA Shimizu, A Sachs, DH AF Yamada, Kazuhiko Tasaki, Masayuki Sekijima, Mitsuhiro Wilkinson, Robert A. Villani, Vincenzo Moran, Shannon G. Cormack, Taylor A. Hanekamp, Isabel M. Arn, J. Scott Fishman, Jay A. Shimizu, Akira Sachs, David H. TI Porcine Cytomegalovirus Infection Is Associated With Early Rejection of Kidney Grafts in a Pig to Baboon Xenotransplantation Model SO TRANSPLANTATION LA English DT Article DE Porcine CMV; Kidney xenotransplantation; GalT-KO pigs; Thymokidney ID TRANSPLANT RECIPIENTS; EPITHELIAL-CELLS; NUCLEAR TRANSFER; THYMIC TISSUE; THYMOKIDNEY; EXPRESSION; GANCICLOVIR; EVEROLIMUS; SIROLIMUS; SURVIVAL AB Background. Recent survivals of our pig-to-baboon kidney xenotransplants have been markedly shorter than the graft survivals we previously reported. The discovery of high levels of porcine cytomegalovirus (pCMV) in one of the rejected xenografts led us to evaluate whether this reduction in graft survival might be because of the inadvertent introduction of pCMV into our alpha 1,3-galactosyltransferase gene knockout swine herd. Methods. Archived frozen sections of xeno-kidney grafts over the past 10 years were analyzed for the presence of pCMV, using real-time polymerase chain reaction. Three prospective pig-to-baboon renal transplants using kidneys from swine delivered by cesarean section (C-section) and raised in isolation were likewise analyzed. Results. Kidney grafts, from which 8 of the 18 archived samples were derived were found to be pCMV-negative, showed a mean graft survival of 48.3 days and were from transplants performed before 2008. None showed signs of disseminated intravascular coagulopathy and were lost because of proteinuria or infectious complications. In contrast, 10 of the archived samples were pCMV positive, were from kidney transplants with a mean graft survival of 14.1 days, had been performed after 2008, and demonstrated early vascular changes and decreased platelet counts. Three prospective xenografts from swine delivered by C-section were pCMV negative and survived an average of 53.0 days. Conclusions. Decreased survivals of alpha 1,3-galactosyltransferase gene knockout renal xenografts in this laboratory correlate temporally with latent pCMV in the donor animals and pCMV in the rejected xeno-kidneys. Transmission of pCMV to swine offspring may be avoided by C-section delivery and scrupulous isolation of donor animals. C1 [Yamada, Kazuhiko; Tasaki, Masayuki; Sekijima, Mitsuhiro; Wilkinson, Robert A.; Villani, Vincenzo; Moran, Shannon G.; Cormack, Taylor A.; Hanekamp, Isabel M.; Arn, J. Scott; Fishman, Jay A.; Shimizu, Akira; Sachs, David H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Cambridge, MA 02138 USA. RP Yamada, K (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Organ Transplantat Tolerance & Xenotransplantat L, MGH East, Bldg 149-9019,13th St, Boston, MA 02114 USA. EM kaz.yamada@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766 FU Project 1 of the NIH/NIAID [2P01AI45897]; core facility of NIH/NIAID [2P01AI45897]; MGH Swine Facility Grant [C06 RR020135-01] FX This research was supported by the Project 1 of the NIH/NIAID 2P01AI45897 (K.Y.), the core facility of NIH/NIAID 2P01AI45897 (J.A.F. and R. A. W.), and the MGH Swine Facility Grant C06 RR020135-01 (D.H.S.). NR 24 TC 20 Z9 20 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2014 VL 98 IS 4 BP 411 EP 418 DI 10.1097/TP.0000000000000232 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AN8UJ UT WOS:000340880000017 PM 25243511 ER PT J AU Sekijima, M Waki, S Sahara, H Tasaki, M Wilkinson, RA Villani, V Shimatsu, Y Nakano, K Matsunari, H Nagashima, H Fishman, JA Shimizu, A Yamada, K AF Sekijima, Mitsuhiro Waki, Shiori Sahara, Hisashi Tasaki, Masayuki Wilkinson, Robert A. Villani, Vincenzo Shimatsu, Yoshiki Nakano, Kazuaki Matsunari, Hitomi Nagashima, Hiroshi Fishman, Jay A. Shimizu, Akira Yamada, Kazuhiko TI Results of Life-Supporting Galactosyltransferase Knockout Kidneys in Cynomolgus Monkeys Using Two Different Sources of Galactosyltransferase Knockout Swine SO TRANSPLANTATION LA English DT Article DE GalT-KO swine; Xenotransplantation; Life-supporting kidney xenografts; Porcine CMV ID ALPHA-1,3-GALACTOSYLTRANSFERASE GENE; CYTOMEGALOVIRUS-INFECTION; ALLOGRAFT-REJECTION; NUCLEAR TRANSFER; XENOTRANSPLANTATION; PORCINE; PIG; EXPRESSION; RECIPIENTS; XENOGRAFTS AB Background. Various durations of survival have been observed in the xenotransplantation of life-supporting alpha-1,3-galactosyltransferase knockout (GalT-KO) porcine kidneys into nonhuman primates. Although others have demonstrated loss of GalT-KOV-transplanted kidneys within 2 weeks, we have reported an average survival of 51 days with the cotransplantation of the kidney and vascularized thymus and an average of 29 days with the kidney alone. To determine the factors responsible for this difference in survival time, we performed xenogeneic kidney transplantations into cynomolgus monkeys with an anti-CD40L/based regimen using two different strains of GalT-KO swine, one derived from MGH miniature swine and the other obtained from Meji University. Materials and Methods. Eight cynomolgus moneys received GalT-KO kidneys. Three kidney grafts were from Massachusetts General Hospital (MGH)-Nippon Institute for Biological Science (NIBS) GalT-KO pigs and five GalT-KO grafts were from MEIJI GalT-KO swine. All cynomolgus recipients were treated identically. Results. Recipients of kidneys from the MGH GalT-KO kidneys swine, produced by nuclear transfer in Japan, survived an average of 28.7 days, whereas recipients of MEIJI GalT-KO kidneys swine survived an average of 9.2 days. Among the differences between these two groups, one potentially revealing disparity was that the MEIJI swine were positive for porcine cytomegalovirus, whereas the MGH-derived swine were negative. Conclusion. This is the first study comparing renal xenotransplantation from two different sources of GalT-KO swine into nonhuman primates at a single center. The results demonstrate that porcine cytomegalovirus may be responsible for early loss of GalT-KO swine kidney xenografts. C1 [Sekijima, Mitsuhiro; Waki, Shiori; Sahara, Hisashi; Tasaki, Masayuki; Yamada, Kazuhiko] Kagoshima Univ, Ctr Adv Biomed Sci & Swine Res, Div Organ Replacement & Xenotransplantat Surg, Kagoshima 8908520, Japan. [Waki, Shiori] Gifu Univ, Fac Appl Biol Sci, Gifu, Japan. [Wilkinson, Robert A.; Villani, Vincenzo; Fishman, Jay A.; Shimizu, Akira; Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Shimatsu, Yoshiki] Nippon Inst Biol Sci, Dept Res & Dev, Tokyo, Japan. [Nakano, Kazuaki; Matsunari, Hitomi] Meiji Univ, Sch Agr, Lab Dev Engn, Tokyo 101, Japan. RP Yamada, K (reprint author), Kagoshima Univ, Ctr Adv Biomed Sci & Swine Res, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. EM kaz.yamada@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766 FU Kagoshima University; Project 1 of NIH/NIAID [2P01AI45897]; core facility of NIH/NIAID [2P01AI45897] FX This research was supported by a Grant-in-Aid for Scientific Research (A) (K.Y.), the Kagoshima University Research Awards (K.Y.), Project 1 of NIH/NIAID 2P01AI45897 (K.Y.) and the core facility of NIH/NIAID 2P01AI45897 (J.A.F. and R.A.W.). NR 24 TC 14 Z9 14 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2014 VL 98 IS 4 BP 419 EP 426 DI 10.1097/TP.0000000000000314 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AN8UJ UT WOS:000340880000018 PM 25243512 ER PT J AU Bucholz, EM Butala, NM Rathore, SS Dreyer, RP Lansky, AJ Krumholz, HM AF Bucholz, Emily M. Butala, Neel M. Rathore, Saif S. Dreyer, Rachel P. Lansky, Alexandra J. Krumholz, Harlan M. TI Sex Differences in Long-Term Mortality After Myocardial Infarction A Systematic Review SO CIRCULATION LA English DT Review DE epidemiology; follow-up studies; mortality; myocardial infarction; sex; women ID NORTHERN SWEDEN MONICA; CORONARY-HEART-DISEASE; COMMUNITY-WIDE PERSPECTIVE; DIABETES-MELLITUS; FOLLOW-UP; GENDER-DIFFERENCES; 10-YEAR MORTALITY; CASE-FATALITY; RISK-FACTORS; SURVIVAL AB Background-Studies of sex differences in long-term mortality after acute myocardial infarction have reported mixed results. A systematic review is needed to characterize what is known about sex differences in long-term outcomes and to define gaps in knowledge. Methods and Results-We searched the Medline database from 1966 to December 2012 to identify all studies that provided sex-based comparisons of mortality after acute myocardial infarction. Only studies with at least 5 years of follow-up were reviewed. Of the 1877 identified abstracts, 52 studies met the inclusion criteria, of which 39 were included in this review. Most studies included fewer than one-third women. There was significant heterogeneity across studies in patient populations, methodology, and risk adjustment, which produced substantial variability in risk estimates. In general, most studies reported higher unadjusted mortality for women compared with men at both 5 and 10 years after acute myocardial infarction; however, many of the differences in mortality became attenuated after adjustment for age. Multivariable models varied between studies; however, most reported a further reduction in sex differences after adjustment for covariates other than age. Few studies examined sex-by-age interactions; however, several studies reported interactions between sex and treatment whereby women have similar mortality risk as men after revascularization. Conclusions-Sex differences in long-term mortality after acute myocardial infarction are largely explained by differences in age, comorbidities, and treatment use between women and men. Future research should aim to clarify how these differences in risk factors and presentation contribute to the sex gap in mortality. C1 [Bucholz, Emily M.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Bucholz, Emily M.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Robert Wood Johnson Fdn Clin Scholars Program, Dept Internal Med, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT 06510 USA. [Butala, Neel M.; Rathore, Saif S.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Dreyer, Rachel P.; Krumholz, Harlan M.] Yale Univ, Ctr Outcomes Res & Evaluat, New Haven, CT 06510 USA. [Lansky, Alexandra J.; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Dept Internal Med, 1 Church St,Ste 200, New Haven, CT 06510 USA. EM harlan.krumholz@yale.edu FU National Heart, Lung, and Blood Institute [1U01HL105270-04]; NIGMS [T32GM07205] FX Dr Krumholz is supported by grant 1U01HL105270-04 (Center for Cardiovascular Outcomes Research at Yale University) from the National Heart, Lung, and Blood Institute. Mr. Bucholz is supported by NIGMS Medical Scientist Training Program grant T32GM07205. NR 61 TC 30 Z9 34 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD AUG 26 PY 2014 VL 130 IS 9 BP 757 EP + DI 10.1161/CIRCULATIONAHA.114.009480 PG 18 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AO7GT UT WOS:000341521200012 PM 25052403 ER PT J AU Sadat, U Jaffer, FA van Zandvoort, MAMJ Nicholls, SJ Ribatti, D Gillard, JH AF Sadat, Umar Jaffer, Farouc A. van Zandvoort, Marc A. M. J. Nicholls, Stephen J. Ribatti, Domenico Gillard, Jonathan H. TI Inflammation and Neovascularization Intertwined in Atherosclerosis Imaging of Structural and Molecular Imaging Targets SO CIRCULATION LA English DT Review DE atherosclerosis; imaging, three-dimensional; inflammation; magnetic resonance imaging; neovascularization, physiologic; nuclear medicine; ultrasonography ID CONTRAST-ENHANCED ULTRASOUND; CELL-ADHESION MOLECULE-1; CAROTID PLAQUE NEOVASCULARIZATION; IRON-OXIDE; IN-VIVO; VASA VASORUM; MRI; ATHEROMA; RABBITS; AGENT C1 [Sadat, Umar] Cambridge Univ Hosp Natl Hlth Serv Fdn Trust, Cambridge Vasc Unit, Cambridge CB2 0QQ, England. [Sadat, Umar; Gillard, Jonathan H.] Cambridge Univ Hosp Natl Hlth Serv Fdn Trust, Univ Dept Radiol, Cambridge CB2 0QQ, England. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr,Med Sch, Cambridge, MA 02138 USA. [van Zandvoort, Marc A. M. J.] Maastricht Univ, Adv Microscopy Unit, Dept Genet & Cell Biol Mol Cell Biol, Maastricht, Netherlands. [van Zandvoort, Marc A. M. J.] Univ Aachen, Inst Mol Cardiovasc Res, Aachen, Germany. [Nicholls, Stephen J.] Univ Adelaide, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia. [Nicholls, Stephen J.] Univ Adelaide, Heart Fdn Heart Hlth, Adelaide, SA, Australia. [Nicholls, Stephen J.] Royal Adelaide Hosp, Adelaide, SA 5000, Australia. [Ribatti, Domenico] Univ Bari, Sch Med, Dept Basic Med Sci Neurosci & Sensory Organs, Bari, Italy. [Ribatti, Domenico] Natl Canc Inst Giovanni Paolo II, Bari, Italy. RP Sadat, U (reprint author), Cambridge Univ Hosp Natl Hlth Serv Fdn Trust, Addenbrookes Hosp, Cambridge Vasc Unit, Box 201,Hills Rd, Cambridge CB2 0QQ, England. EM sadat.umar@gmail.com OI RIBATTI, Domenico/0000-0003-4768-8431 FU National Institutes of Health [HL-R01-108229]; European Union [278570] FX Dr Jaffer's research is supported by National Institutes of Health grant HL-R01-108229. Dr Ribatti's research is supported by the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement 278570. NR 50 TC 18 Z9 21 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD AUG 26 PY 2014 VL 130 IS 9 BP 786 EP 794 DI 10.1161/CIRCULATIONAHA.114.010369 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AO7GT UT WOS:000341521200015 PM 25156914 ER PT J AU Muenchhoff, M Madurai, S Hempenstall, AJ Adland, E Carlqvist, A Moonsamy, A Jaggernath, M Mlotshwa, B Siboto, E Ndung'u, T Goulder, PJR AF Muenchhoff, Maximilian Madurai, Savathee Hempenstall, Allison Jo Adland, Emily Carlqvist, Anna Moonsamy, Angeline Jaggernath, Manjeetha Mlotshwa, Busisiwe Siboto, Emma Ndung'u, Thumbi Goulder, Philip Jeremy Renshaw TI Evaluation of the NucliSens EasyQ v2.0 Assay in Comparison with the Roche Amplicor v1.5 and the Roche CAP/CTM HIV-1 Test v2.0 in Quantification of C-Clade HIV-1 in Plasma SO PLOS ONE LA English DT Article ID AMPLIPREP/COBAS TAQMAN HIV-1; VIRAL LOAD ASSAYS; TEST VERSION 2.0; RNA QUANTITATION; SUBTYPE-C; GENETIC DIVERSITY; PERFORMANCE; VIRUS; VARIANTS; IMPACT AB Human immunodeficiency virus type 1 (HIV-1) genetic diversity poses a challenge to reliable viral load monitoring. Discrepancies between different testing platforms have been observed, especially for non-clade-B virus. Therefore we compare, in antiretroviral therapy (ART)-naive South African subjects predominantly infected with HIV-1 clade-C, three commercially available assays: the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test version 2.0 by Roche (CAP/CTM v2.0), the BioMerieux NucliSens Version 2.0 Easy Q/Easy Mag (NucliSens v2.0) and the Roche COBAS Amplicor HIV-1 Monitor Test Version 1.5 (Amplicor v1.5). Strong linear correlation was observed and Bland-Altman analyses showed overall good agreement between the assays with mean viral load differences of 0.078 log cp/ml (NucliSens v2.0 - Amplicor v1.5), 0.260 log cp/ml (CAP/CTM v2.0 - Amplicor v1.5) and 0.164 log cp/ml (CAP/CTM v2.0 - NucliSens v2.0), indicating lower mean viral load results for the Amplicor v1.5 and higher mean readings for the CAP/CTM v2.0. Consistent with observations following previous comparisons of CAP/CTM v2.0 versus Amplicor v1.5, the CAP/CTM v2.0 assay detected low-level viremia (median 65 cp/ml) in more than one-third of those in whom viremia had been undetectable (<20 cp/ml) in assays using the NucliSens platform. These levels of viremia are of uncertain clinical significance but may be of importance in early detection of ART resistance in those on treatment. Overall the three assays showed good comparability of results but with consistent, albeit relatively small, discrepancies for HIV-1 clade-C samples, especially in the low-viremic range that should be taken into account when interpreting viral load data. C1 [Muenchhoff, Maximilian; Hempenstall, Allison Jo; Adland, Emily; Carlqvist, Anna; Goulder, Philip Jeremy Renshaw] Univ Oxford, Dept Paediat, Oxford, England. [Muenchhoff, Maximilian; Moonsamy, Angeline; Jaggernath, Manjeetha; Mlotshwa, Busisiwe; Siboto, Emma; Ndung'u, Thumbi; Goulder, Philip Jeremy Renshaw] Univ KwaZulu Natal, HIV Pathogenesis Programme, Durban, KwaZulu Natal, South Africa. [Madurai, Savathee] Global Clin & Viral Labs, Amanzimtoti, KwaZulu Natal, South Africa. [Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV K RITH, Durban, South Africa. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. [Ndung'u, Thumbi; Goulder, Philip Jeremy Renshaw] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. [Ndung'u, Thumbi; Goulder, Philip Jeremy Renshaw] Harvard Univ, Boston, MA 02115 USA. RP Goulder, PJR (reprint author), Univ Oxford, Dept Paediat, Oxford, England. EM philip.goulder@paediatrics.ox.ac.uk OI Ndung'u, Thumbi/0000-0003-2962-3992 FU National Institutes of Health [R01 W251] FX NIH R01 grant W251 was awarded to PG by the National Institutes of Health (www.nih.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 5 Z9 5 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 AUG 26 PY 2014 VL 9 IS 8 AR e103983 DI 10.1371/journal.pone.0103983 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO4JK UT WOS:000341303200007 PM 25157919 ER PT J AU Jang, TH Zheng, C Li, JX Richards, C Hsiao, YS Walz, T Wu, H Park, HH AF Jang, Tae-ho Zheng, Chao Li, Jixi Richards, Claire Hsiao, Yu-Shan Walz, Thomas Wu, Hao Park, Hyun Ho TI Structural Study of the RIPoptosome Core Reveals a Helical Assembly for Kinase Recruitment SO BIOCHEMISTRY LA English DT Article ID CELL-DEATH; PROGRAMMED NECROSIS; CRYSTAL-STRUCTURE; TNF-ALPHA; APOPTOSIS; COMPLEX; NECROPTOSIS; INFLAMMATION; MECHANISM; IMAGES AB Receptor interaction protein kinase 1 (RIP1) is a molecular cell-fate switch. RIP1, together with Fas-associated protein with death domain (FADD) and caspase-8, forms the RIPoptosome that activates apoptosis. RIP1 also associates with RIP3 to form the necrosome that triggers necroptosis. The RIPoptosome assembles through interactions between the death domains (DDs) of RIP1 and FADD and between death effector domains (DEDs) of FADD and caspase-8. In this study, we analyzed the overall structure of the RIP1 DD/FADD DD complex, the core of the RIPoptosome, by negative-stain electron microscopy and modeling. The results show that RIP1 DD and FADD DD form a stable complex in vitro similar to the previously described Fas DD/FADD DD complex, suggesting that the RIPoptosome and the Fas death-inducing signaling complex share a common assembly mechanism. Both complexes adopt a helical conformation that requires type I, II, and III interactions between the death domains. C1 [Jang, Tae-ho; Park, Hyun Ho] Yeungnam Univ, Sch Biotechnol, Kyongsan 712749, South Korea. [Jang, Tae-ho; Park, Hyun Ho] Yeungnam Univ, Grad Sch Biochem, Kyongsan 712749, South Korea. [Zheng, Chao; Li, Jixi; Richards, Claire; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zheng, Chao; Li, Jixi; Richards, Claire; Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Hsiao, Yu-Shan; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Park, HH (reprint author), Yeungnam Univ, Sch Biotechnol, Kyongsan 712749, South Korea. EM hyunho@ynu.ac.kr FU National Research Foundation of Korea (NRF) of Ministry of Education, Science and Technology [NRF-2012R1A2A2A01010870]; Ministry of Health & Welfare, Republic of Korea [HI13C1449] FX This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (Grant NRF-2012R1A2A2A01010870) and a grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant HI13C1449). T.W. is an investigator with the Howard Hughes Medical Institute. NR 32 TC 8 Z9 8 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 26 PY 2014 VL 53 IS 33 BP 5424 EP 5431 DI 10.1021/bi500585u PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO0IW UT WOS:000340993300006 PM 25119434 ER PT J AU Seed, KD Yen, MM Shapiro, BJ Hilaire, IJ Charles, RC Teng, JE Ivers, LC Boncy, J Harris, JB Camilli, A AF Seed, Kimberley D. Yen, Minmin Shapiro, B. Jesse Hilaire, Isabelle J. Charles, Richelle C. Teng, Jessica E. Ivers, Louise C. Boncy, Jacques Harris, Jason B. Camilli, Andrew TI Evolutionary consequences of intra-patient phage predation on microbial populations SO ELIFE LA English DT Article ID VIBRIO-CHOLERAE; TOXR REGULON; OMPU; HOST; VIRULENCE; TRANSCRIPTION; EPIDEMICS; ACTIVATOR; PROTEINS; ORIGIN AB The impact of phage predation on bacterial pathogens in the context of human disease is not currently appreciated. Here, we show that predatory interactions of a phage with an important environmentally transmitted pathogen, Vibrio cholerae, can modulate the evolutionary trajectory of this pathogen during the natural course of infection within individual patients. We analyzed geographically and temporally disparate cholera patient stool samples from Haiti and Bangladesh and found that phage predation can drive the genomic diversity of intra-patient V. cholerae populations. Intra-patient phage-sensitive and phage-resistant isolates were isogenic except for mutations conferring phage resistance, and moreover, phage-resistant V. cholerae populations were composed of a heterogeneous mix of many unique mutants. We also observed that phage predation can significantly alter the virulence potential of V. cholerae shed from cholera patients. We provide the first molecular evidence for predatory phage shaping microbial community structure during the natural course of infection in humans. C1 [Seed, Kimberley D.; Yen, Minmin; Camilli, Andrew] Tufts Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Shapiro, B. Jesse] Univ Montreal, Dept Sci Biol, Montreal, PQ H3C 3J7, Canada. [Hilaire, Isabelle J.; Teng, Jessica E.; Ivers, Louise C.] Partners Hlth, Boston, MA USA. [Charles, Richelle C.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Harris, Jason B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Teng, Jessica E.; Ivers, Louise C.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Boncy, Jacques] Natl Publ Hlth Lab, Port Au Prince, Haiti. [Ivers, Louise C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Camilli, A (reprint author), Tufts Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu OI Shapiro, B. Jesse/0000-0001-6819-8699 FU Howard Hughes Medical Institute; National Institutes of Health [AI055058, AI099243, AI089721]; Massachusetts General Hospital; Natural Sciences and Engineering Research Council of Canada [950-228996]; Canada Research Chairs [950-228996]; Charles A. King Trust FX Howard Hughes Medical Institute Andrew Camilli; National Institutes of Health AI055058 Andrew Camilli; Massachusetts General Hospital Richelle C Charles; Natural Sciences and Engineering Research Council of Canada 950-228996 B Jesse Shapiro; Canada Research Chairs 950-228996 B Jesse Shapiro; Charles A. King Trust Kimberley D Seed; National Institutes of Health AI099243 Louise C Ivers, Jason B Harris; National Institutes of Health AI089721 Richelle C Charles NR 30 TC 18 Z9 18 U1 4 U2 33 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD AUG 26 PY 2014 VL 3 AR e03497 DI 10.7554/eLife.03497 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AO3SI UT WOS:000341255400002 PM 25161196 ER PT J AU Timp, W Bravo, HC McDonald, OG Goggins, M Umbricht, C Zeiger, M Feinberg, AP Irizarry, RA AF Timp, Winston Bravo, Hector Corrada McDonald, Oliver G. Goggins, Michael Umbricht, Chris Zeiger, Martha Feinberg, Andrew P. Irizarry, Rafael A. TI Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors SO GENOME MEDICINE LA English DT Article ID REPRESSIVE CHROMATIN; CANCER GENOME; METHYLATION; DOMAINS; VARIABILITY; GENES; CELLS AB Background: One of the most provocative recent observations in cancer epigenetics is the discovery of large hypomethylated blocks, including single copy genes, in colorectal cancer, that correspond in location to heterochromatic LOCKs (large organized chromatin lysine-modifications) and LADs (lamin-associated domains). Methods: Here we performed a comprehensive genome-scale analysis of 10 breast, 28 colon, nine lung, 38 thyroid, 18 pancreas cancers, and five pancreas neuroendocrine tumors as well as matched normal tissue from most of these cases, as well as 51 premalignant lesions. We used a new statistical approach that allows the identification of large hypomethylated blocks on the Illumina HumanMethylation450 BeadChip platform. Results: We find that hypomethylated blocks are a universal feature of common solid human cancer, and that they occur at the earliest stage of premalignant tumors and progress through clinical stages of thyroid and colon cancer development. We also find that the disrupted CpG islands widely reported previously, including hypermethylated island bodies and hypomethylated shores, are enriched in hypomethylated blocks, with flattening of the methylation signal within and flanking the islands. Finally, we found that genes showing higher between individual gene expression variability are enriched within these hypomethylated blocks. Conclusion: Thus hypomethylated blocks appear to be a universal defining epigenetic alteration in human cancer, at least for common solid tumors. C1 [Timp, Winston; McDonald, Oliver G.; Feinberg, Andrew P.; Irizarry, Rafael A.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21218 USA. [Timp, Winston] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Timp, Winston; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [McDonald, Oliver G.; Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Bravo, Hector Corrada] Univ Maryland, Dept Comp Sci, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Umbricht, Chris; Zeiger, Martha] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Umbricht, Chris; Zeiger, Martha] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. [Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Irizarry, Rafael A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Irizarry, Rafael A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Feinberg, AP (reprint author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21218 USA. EM afeinberg@jhu.edu; rafa@jimmy.harvard.edu RI Timp, Winston/B-5215-2008; OI Timp, Winston/0000-0003-2083-6027; Corrada Bravo, Hector/0000-0002-1255-4444 FU NIH [HG003223, CA054358, GM083084, RR021967/GM103552] FX This work was supported by NIH grants HG003223 and CA054358 to APF, and GM083084 and RR021967/GM103552 to RAI. NR 27 TC 25 Z9 25 U1 0 U2 15 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 AUG 26 PY 2014 VL 6 AR 61 DI 10.1186/s13073-014-0061-y PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AO4OT UT WOS:000341320600001 PM 25191524 ER PT J AU Yeh, RW Wimmer, NJ AF Yeh, Robert W. Wimmer, Neil J. TI Blood Transfusion in Myocardial Infarction Opening Old Wounds for Comparative-Effectiveness Research SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE comparative-effectiveness research; myocardial infarction; transfusion ID PERCUTANEOUS CORONARY INTERVENTION; CELL TRANSFUSION; CLINICAL-OUTCOMES; REGISTRY; IMPACT; TRIAL; THRESHOLDS; STENTS C1 [Yeh, Robert W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. [Wimmer, Neil J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800, Boston, MA 02114 USA. EM ryeh@partners.org FU NHLBI NIH HHS [1K23HL118138] NR 21 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 26 PY 2014 VL 64 IS 8 BP 820 EP 822 DI 10.1016/j.jacc.2014.05.041 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AN8WX UT WOS:000340887500011 PM 25145527 ER PT J AU Taqueti, VR AF Taqueti, Viviany R. TI Inspiring Possibility SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material C1 [Taqueti, Viviany R.] Heart & Vasc Ctr, Boston, MA USA. [Taqueti, Viviany R.] Dept Radiol, Boston, MA USA. [Taqueti, Viviany R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Taqueti, Viviany R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Taqueti, Viviany R.] VA Boston Healthcare Syst, Cardiol Sect, Boston, MA USA. RP Taqueti, VR (reprint author), Brigham & Womens Hosp, 75 Francis St,ASBI L1-037G, Boston, MA 02115 USA. EM vtaqueti@partners.org NR 2 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 AUG 26 PY 2014 VL 64 IS 8 BP 843 EP 844 DI 10.1016/j.jacc.2014.07.006 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AN8WX UT WOS:000340887500015 PM 25145531 ER PT J AU Berkowitz, AL Westover, MB Bianchi, MT Chou, SHY AF Berkowitz, Aaron L. Westover, M. Brandon Bianchi, Matt T. Chou, Sherry H. -Y. TI Aspirin for acute stroke of unknown etiology in resource-limited settings A decision analysis SO NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; INTRACEREBRAL HEMORRHAGE; DEVELOPING-COUNTRIES; DISEASE; TRIAL; BURDEN; SCAN; RISK AB Objective: To analyze the potential impact of aspirin on outcome at hospital discharge after acute stroke in resource-limited settings without access to neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH). Methods: A decision analysis was conducted to evaluate aspirin use in all patients with acute stroke of unknown type for the duration of initial hospitalization. Data were obtained from the International Stroke Trial and Chinese Acute Stroke Trial. Predicted in-hospital mortality and stroke recurrence risk were determined across the worldwide reported range of the proportion of strokes caused by ICH. Sensitivity analyses were performed on aspirin-associated relative risks in patients with ICH. Results: At the highest reported proportion of strokes due to ICH from a large epidemiologic study (34% in sub-Saharan Africa), aspirin initiation after acute stroke of undetermined etiology is predicted to reduce in-hospital mortality (from 85/1,000 without treatment to 81/1,000 with treatment), in-hospital stroke recurrence (58/1,000 to 50/1,000), and combined risk of in-hospital mortality or stroke recurrence (127/1,000 to 114/1,000). Benefits of aspirin therapy remained in sensitivity analyses across a range of plausible parameter estimates for relative risks associated with aspirin initiation after ICH. Conclusion: Aspirin treatment for the period of initial hospitalization after acute stroke of undetermined etiology is predicted to decrease acute stroke-related mortality and in-hospital stroke recurrence even at the highest reported proportion of acute strokes due to ICH. In the absence of clinical trials to test this approach empirically, clinical decisions require patient-specific evaluation of risks and benefits of aspirin in this context. C1 [Berkowitz, Aaron L.; Chou, Sherry H. -Y.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Westover, M. Brandon; Bianchi, Matt T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Berkowitz, AL (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM aberkowitz3@partners.org RI Chou, Sherry/G-5779-2015 FU American Heart Association; NIH; National Institute of Neurological Disorders and Stroke; Novartis FX A. Berkowitz receives royalties from Clinical Pathophysiology Made Ridiculously Simple (Medmaster, Inc.) and The Improvising Mind (Oxford University Press). M. Brandon Westover and M. Bianchi report no disclosures relevant to the manuscript. S. Chou has been funded by the American Heart Association and the NIH, is currently funded by National Institute of Neurological Disorders and Stroke, and serves on the endpoint committee of a clinical trial funded by Novartis. Go to Neurology.org for full disclosures. NR 27 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 26 PY 2014 VL 83 IS 9 BP 787 EP 793 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AO1SY UT WOS:000341096100007 PM 25056582 ER PT J AU Thanprasertsuk, S Martinez-Ramirez, S Pontes-Neto, OM Ni, J Ayres, A Reed, A Swords, K Gurol, ME Greenberg, SM Viswanathan, A AF Thanprasertsuk, Sekh Martinez-Ramirez, Sergi Marques Pontes-Neto, Octavio Ni, Jun Ayres, Alison Reed, Anne Swords, Kyleen Gurol, M. Edip Greenberg, Steven M. Viswanathan, Anand TI Posterior white matter disease distribution as a predictor of amyloid angiopathy SO NEUROLOGY LA English DT Article ID VIRCHOW-ROBIN SPACES; SMALL VESSEL DISEASE; ALZHEIMER-DISEASE; INTRACEREBRAL HEMORRHAGE; CEREBRAL MICROBLEEDS; PERIVASCULAR SPACES; ELDERLY-PEOPLE; ROTTERDAM SCAN; MRI MARKERS; PREVALENCE AB Objectives: We sought to examine whether a posterior distribution of white matter hyperintensities (WMH) is an independent predictor of pathologically confirmed cerebral amyloid angiopathy (CAA) and whether it is associated with MRI markers of CAA, in patients without lobar intracerebral hemorrhage. Methods: We developed a quantitative method to measure anteroposterior (AP) distribution of WMH. A retrospective cohort of patients without intracerebral hemorrhage and with pathologic evaluation of CAA was examined to determine whether posterior WMH distribution was an independent predictor of CAA (n = 59). The relationship of AP distributions of WMH to strictly lobar microbleeds (MBs) (n = 259) and location of dilated perivascular spaces (DPVS) (n = 85) was examined in a separate cohort of patients evaluated in a memory clinic. Results: A more posterior WMH distribution was found to be an independent predictor of pathologic evidence of CAA (p = 0.001, odds ratio [95% confidence interval] = 1.19 [1.07-1.32]), even in the subgroup without lobar MBs (p = 0.016, odds ratio [95% confidence interval] = 1.18 [1.03-1.36]). In the memory clinic cohort, strictly lobar MBs were independently associated with more posterior WMH distribution (p = 0.009). AP distribution of WMH was also associated with location of DPVS (p = 0.001), in that patients with predominant DPVS in the white matter over the basal ganglia harbored a more posterior WMH distribution. Conclusions: Our results suggest that AP distribution ofWMH may represent an additional marker of CAA, irrespective of the presence of lobar hemorrhages. Classification of evidence: This study provides Class III evidence that there is a significant association between the AP distribution of WMH on MRI with the presence of pathologically confirmed CAA pathology. C1 [Thanprasertsuk, Sekh; Martinez-Ramirez, Sergi; Marques Pontes-Neto, Octavio; Ni, Jun; Ayres, Alison; Reed, Anne; Gurol, M. Edip; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Thanprasertsuk, Sekh] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand. [Martinez-Ramirez, Sergi] Univ Autonoma Barcelona, Escola Postgrau, Bellaterra, Cerdanyola Del, Spain. RP Viswanathan, A (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. EM aviswanathan1@partners.org RI Pontes-Neto, Octavio/G-4294-2012 OI Pontes-Neto, Octavio/0000-0003-0317-843X FU NIH [5P50AG005134-30, 5K23AG028726-04, 5R01AG026484-09, R01 NS070834-05] FX Supported by NIH grants 5P50AG005134-30, 5K23AG028726-04, 5R01AG026484-09, and R01 NS070834-05. NR 29 TC 19 Z9 21 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 26 PY 2014 VL 83 IS 9 BP 794 EP 800 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AO1SY UT WOS:000341096100008 PM 25063759 ER PT J AU Papay, K Xie, SX Stern, M Hurtig, H Siderowf, A Duda, JE Minger, J Weintraub, D AF Papay, Kimberly Xie, Sharon X. Stern, Matthew Hurtig, Howard Siderowf, Andrew Duda, John E. Minger, James Weintraub, Daniel TI Naltrexone for impulse control disorders in Parkinson disease A placebo-controlled study SO NEUROLOGY LA English DT Article ID ALZHEIMER-DISEASE; LONGITUDINAL DATA; DEPRESSION; BEHAVIORS; TRIAL; ANTAGONIST; AMANTADINE; DEPENDENCE; SYMPTOMS; MODELS AB Objective: Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD. Methods: Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1: 1), double-blind, placebo-controlled study of naltrexone 50-100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score. Results: Forty-five patients (90%) completed the study. The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8%(95% confidence interval [CI] -8.7% to 44.2%). While this difference was not significant (odds ratio = 1.6, 95% CI 0.5-5.2, Wald x(2) [df] = 0.5 [1], p = 0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model = 27.37, F[df] = 4.3 [1, 49], p = 0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo. Conclusions: Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD. Classification of evidence: This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates. C1 [Papay, Kimberly; Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Xie, Sharon X.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Stern, Matthew; Hurtig, Howard; Duda, John E.; Minger, James] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Siderowf, Andrew] Avid Radiopharmaceut, Philadelphia, PA USA. [Duda, John E.; Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Clinical Intervention Award from the Michael J. Fox Foundation for Parkinson's Research [NCT1052831] FX This study was funded by a Clinical Intervention Award from the Michael J. Fox Foundation for Parkinson's Research (D.W., NCT1052831). NR 39 TC 13 Z9 14 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 26 PY 2014 VL 83 IS 9 BP 826 EP 833 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AO1SY UT WOS:000341096100012 PM 25037206 ER PT J AU Cole, AJ So, NK Tandon, N Slater, JD Smith, MC AF Cole, Andrew J. So, Norman K. Tandon, Nitin Slater, Jeremy D. Smith, Michael C. TI JUDGMENT IS NOT IGNORANCE SO NEUROLOGY LA English DT Editorial Material C1 [Cole, Andrew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA 02138 USA. [So, Norman K.] Cleveland Clin, Epilepsy Ctr, Cleveland, OH USA. [Tandon, Nitin; Slater, Jeremy D.] Univ Texas Med Sch, Texas Comprehens Epilepsy Program, Mem Herman Texas Med Ctr, Houston, TX USA. [Smith, Michael C.] Rush Univ, Epilepsy Ctr, Chicago, IL 60612 USA. RP Cole, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA 02138 USA. EM Cole.andrew@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 26 PY 2014 VL 83 IS 9 BP 847 EP 847 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AO1SY UT WOS:000341096100016 PM 25156349 ER PT J AU So, NK Cole, AJ Tandon, N Slater, JD Smith, MC AF So, Norman K. Cole, Andrew J. Tandon, Nitin Slater, Jeremy D. Smith, Michael C. TI NEUROSTIMULATION FOR THE TREATMENT OF EPILEPSY: THE SKEPTICAL VIEW SO NEUROLOGY LA English DT Editorial Material ID VAGUS NERVE-STIMULATION; CONTROLLED TRIAL; EFFICACY; SURGERY; ADULTS C1 [So, Norman K.] Cleveland Clin, Epilepsy Ctr, Cleveland, OH 44106 USA. [Cole, Andrew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA USA. [Tandon, Nitin; Slater, Jeremy D.] Univ Texas Med Sch, Texas Comprehens Epilepsy Program, Mem Herman Texas Med Ctr, Houston, TX USA. [Smith, Michael C.] Rush Univ, Epilepsy Ctr, Chicago, IL 60612 USA. RP So, NK (reprint author), Cleveland Clin, Epilepsy Ctr, Cleveland, OH 44106 USA. EM son2@ccf.org NR 11 TC 2 Z9 2 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 26 PY 2014 VL 83 IS 9 BP 847 EP 849 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA AO1SY UT WOS:000341096100017 PM 25156350 ER PT J AU Montine, TJ Koroshetz, WJ Babcock, D Dickson, DW Galpern, WR Glymour, MM Greenberg, SM Hutton, ML Knopman, DS Kuzmichev, AN Manly, JJ Marder, KS Miller, BL Phelps, CH Seeley, WW Sieber, BA Silverberg, NB Sutherland, M Torborg, CL Waddy, SP Zlokovic, BV Corriveau, RA AF Montine, Thomas J. Koroshetz, Walter J. Babcock, Debra Dickson, Dennis W. Galpern, Wendy R. Glymour, M. Maria Greenberg, Steven M. Hutton, Michael L. Knopman, David S. Kuzmichev, Andrey N. Manly, Jennifer J. Marder, Karen S. Miller, Bruce L. Phelps, Creighton H. Seeley, William W. Sieber, Beth-Anne Silverberg, Nina B. Sutherland, Margaret Torborg, Christine L. Waddy, Salina P. Zlokovic, Berislav V. Corriveau, Roderick A. CA ADRD 2013 Conference Organizing TI Recommendations of the Alzheimer's Disease-Related Dementias Conference SO NEUROLOGY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; NATIONAL INSTITUTE; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES AB The National Alzheimer's Project Act, signed into law in 2011, mandates a National Plan to Address Alzheimer's Disease that is updated annually. In the Plan, the term Alzheimer disease includes not only Alzheimer disease ( AD) proper, but also several specified related dementias, namely, frontotemporal, Lewy body, vascular, and mixed dementia. In response to a specific action item in the 2012 National Plan, the National Institute of Neurological Disorders and Stroke, in collaboration with the National Institute on Aging, convened panels of experts and conducted a 2-day public conference to develop research priorities and timelines for addressing Alzheimer disease-related dementias (ADRD) in 5 topic areas: multiple etiology dementias, health disparities, Lewy body dementias including dementia with Lewy bodies and Parkinson disease dementia, frontotemporal dementia and related tauopathies, and vascular contributions to ADRD. By design, the product was up to 8 prioritized research recommendations in each topic area including estimated timelines from when work on a recommendation is started to completion or to full implementation of an ongoing activity, and recognition of shared research themes across recommendations. These included increased education and training of both researchers and health care professionals, addressing health disparities, fundamental neurobiology research, advanced diagnostics, collaborative biosample repositories, and a focus on developing effective interventions to prevent or treat ADRD by the year 2025 as targeted by the National Plan. C1 [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Koroshetz, Walter J.; Babcock, Debra; Galpern, Wendy R.; Kuzmichev, Andrey N.; Sieber, Beth-Anne; Sutherland, Margaret; Torborg, Christine L.; Waddy, Salina P.; Corriveau, Roderick A.] NINDS, Bethesda, MD 20892 USA. [Dickson, Dennis W.] Mayo Clin, Neuropathol Lab, Jacksonville, FL 32224 USA. [Glymour, M. Maria] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Program,Dept Neurol, Boston, MA USA. [Hutton, Michael L.] Eli Lilly & Co, Lilly Res Ctr, Neurodegenerat Dis DHT, Windlesham, Surrey, England. [Knopman, David S.] Mayo Clin Rochester, Dept Neurol, Rochester, MN USA. [Manly, Jennifer J.; Marder, Karen S.] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Manly, Jennifer J.; Marder, Karen S.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Miller, Bruce L.; Seeley, William W.] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Phelps, Creighton H.; Silverberg, Nina B.] NIA, Bethesda, MD 20892 USA. [Zlokovic, Berislav V.] Univ So Calif, Keck Sch Med, Zilhka Neurogenet Inst, Ctr Neurodegenerat & Regenerat, Los Angeles, CA 90033 USA. [Zlokovic, Berislav V.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. RP Corriveau, RA (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM roderick.corriveau@nih.gov FU NINDS; Alliance for Aging Research; Alzheimer's Association; Association for Frontotemporal Degeneration; USAgainstAlzheimer's FX This conference was supported by the NINDS, organized in collaboration with the NIA, with assistance from the FNIH, and with additional support from the Alliance for Aging Research, the Alzheimer's Association, the Association for Frontotemporal Degeneration and USAgainstAlzheimer's. NR 14 TC 23 Z9 23 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 26 PY 2014 VL 83 IS 9 BP 851 EP 860 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AO1SY UT WOS:000341096100019 PM 25080517 ER PT J AU Shen, HW Barabasi, AL AF Shen, Hua-Wei Barabasi, Albert-Laszlo TI Collective credit allocation in science SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE network science; scientific impact; team science ID RADIATION PRESSURE; SCIENTIFIC IMPACT; CITATION ANALYSIS; NETWORKS; INDEX; ATOMS; PUBLICATION; PARTICLES; AUTHOR; LAWS AB Collaboration among researchers is an essential component of the modern scientific enterprise, playing a particularly important role in multidisciplinary research. However, we continue to wrestle with allocating credit to the coauthors of publications with multiple authors, because the relative contribution of each author is difficult to determine. At the same time, the scientific community runs an informal field-dependent credit allocation process that assigns credit in a collective fashion to each work. Here we develop a credit allocation algorithm that captures the coauthors' contribution to a publication as perceived by the scientific community, reproducing the informal collective credit allocation of science. We validate the method by identifying the authors of Nobel-winning papers that are credited for the discovery, independent of their positions in the author list. The method can also compare the relative impact of researchers working in the same field, even if they did not publish together. The ability to accurately measure the relative credit of researchers could affect many aspects of credit allocation in science, potentially impacting hiring, funding, and promotion decisions. C1 [Shen, Hua-Wei] Chinese Acad Sci, Inst Comp Technol, Beijing 100190, Peoples R China. [Shen, Hua-Wei; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Shen, Hua-Wei; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Shen, Hua-Wei; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Shen, Hua-Wei; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, H-1051 Budapest, Hungary. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM barabasi@gmail.com RI Shen, Hua-Wei/E-8028-2010 OI Shen, Hua-Wei/0000-0002-1081-8119 FU National Basic Research Program of China (973 Program) [2014CB340401]; National High-Tech R&D Program of China (863 Program) [2014AA015103]; National Natural Science Foundation of China [61202215, 61232010]; Lockheed Martin Corporation [SRA 11.18.11]; Network Science Collaborative Technology Alliance; US Army Research Laboratory Agreement [W911NF-09-2-0053]; Defence Advanced Research Projects Agency Agreement [11645021]; Future and Emerging Technologies Project "Multiplex" - European Commission [317 532]; National Institutes of Health, Centers of Excellence of Genomic Science Agreement [1P50HG4233] FX We thank Dashun Wang, Chaoming Song, Roberta Sinatra, Santiago Gil, Pierre Deville, Qing Jin, Burcu Yucesoy, Elena Renda, and all other colleagues at Center for Complex Network Research for valuable discussions and comments. H.-W.S. is supported by National Basic Research Program of China (973 Program) Grant 2014CB340401, National High-Tech R&D Program of China (863 Program) Grant 2014AA015103, and National Natural Science Foundation of China Grants 61202215 and 61232010. A.-L.B. is supported by Lockheed Martin Corporation (SRA 11.18.11), and the Network Science Collaborative Technology Alliance is sponsored by US Army Research Laboratory Agreement W911NF-09-2-0053, Defence Advanced Research Projects Agency Agreement 11645021, the Future and Emerging Technologies Project 317 532 "Multiplex" financed by the European Commission, and National Institutes of Health, Centers of Excellence of Genomic Science Agreement 1P50HG4233. NR 52 TC 25 Z9 26 U1 8 U2 46 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 AUG 26 PY 2014 VL 111 IS 34 BP 12325 EP 12330 DI 10.1073/pnas.1401992111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN7LA UT WOS:000340780300025 PM 25114238 ER PT J AU Longoni, M High, FA Russell, MK Kashani, A Tracy, AA Coletti, CM Hila, R Shamia, A Wells, J Ackerman, KG Wilson, JM Bult, CJ Lee, C Lage, K Pober, BR Donahoea, PK AF Longoni, Mauro High, Frances A. Russell, Meaghan K. Kashani, Alireza Tracy, Adam A. Coletti, Caroline M. Hila, Regis Shamia, Ahmed Wells, Julie Ackerman, Kate G. Wilson, Jay M. Bult, Carol J. Lee, Charles Lage, Kasper Pober, Barbara R. Donahoea, Patricia K. TI Molecular pathogenesis of congenital diaphragmatic hernia revealed by exome sequencing, developmental data, and bioinformatics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE network analysis; diaphragm development; CDH genetics ID MUTATIONS; PROTEIN; DEFECTS; KIF7; DIFFERENTIATION; MYOGENESIS; FRAMEWORK; GENETICS; RECEPTOR; VARIANTS AB Congenital diaphragmatic hernia (CDH) is a common and severe birth defect. Despite its clinical significance, the genetic and developmental pathways underlying this disorder are incompletely understood. In this study, we report a catalog of variants detected by a whole exome sequencing study on 275 individuals with CDH. Predicted pathogenic variants in genes previously identified in either humans or mice with diaphragm defects are enriched in our CDH cohort compared with 120 size-matched random gene sets. This enrichment was absent in control populations. Variants in these critical genes can be found in up to 30.9% of individuals with CDH. In addition, we filtered variants by using genes derived from regions of recurrent copy number variations in CDH, expression profiles of the developing diaphragm, protein interaction networks expanded from the known CDH-causing genes, and prioritized genes with ultrarare and highly disruptive variants, in 11.3% of CDH patients. These strategies have identified several high priority genes and developmental pathways that likely contribute to the CDH phenotype. These data are valuable for comparison of candidate genes generated from whole exome sequencing of other CDH cohorts or multiplex kindreds and provide ideal candidates for further functional studies. Furthermore, we propose that these genes and pathways will enhance our understanding of the heterogeneous molecular etiology of CDH. C1 [Longoni, Mauro; High, Frances A.; Russell, Meaghan K.; Kashani, Alireza; Tracy, Adam A.; Coletti, Caroline M.; Hila, Regis; Shamia, Ahmed; Lage, Kasper; Pober, Barbara R.; Donahoea, Patricia K.] Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. [Longoni, Mauro; Russell, Meaghan K.; Lage, Kasper; Donahoea, Patricia K.] Harvard Med Sch, Dept Surg, Boston, MA 02115 USA. [High, Frances A.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Wilson, Jay M.; Pober, Barbara R.] Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Kashani, Alireza; Lage, Kasper; Donahoea, Patricia K.] Broad Inst, Cambridge, MA 02141 USA. [Wells, Julie; Bult, Carol J.] Jackson Lab, Bar Harbor, ME 04609 USA. [Ackerman, Kate G.] Univ Rochester, Med Ctr, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. [Ackerman, Kate G.] Univ Rochester, Med Ctr, Sch Med & Dent, Dept Biomed Genet, Rochester, NY 14642 USA. [Lee, Charles] Jackson Lab Genom Med, Farmington, CT 06032 USA. [Pober, Barbara R.] Quinnipiac Univ, Frank H Netter Sch Med, North Haven, CT 06473 USA. RP Donahoea, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. EM pdonahoe@partners.org FU National Institute of Child Health and Human Development [P01 HD068250-03]; National Research Service Award [2T32GM007748-35]; Northwest Genomics Center at the University of Washington, Department of Genome Sciences, under US Federal Government from the NHLBI [HHSN268201100037C] FX We thank The Association of Congenital Diaphragmatic Hernia Research, Awareness and Support (CHERUBS) for additional support; L. Kellndorfer, J. Kim, L. Luque-Bustamante, H. Al-Turkmani for technical assistance; and, for careful recruitment of patients, the surgeons at MassGeneral Hospital for Children and Boston Children's Hospital: T. Buchmiller, C. C. Chen, D. Doody, S. J. Fishman, A. Goldstein, L. Holmes, T. Jaksic, R. Jennings, C. Kelleher, D. Lawlor, C. W. Lillehei, P. Masiakos, D. P. Mooney, K. Papadakis, R. Pieretti, M. Puder, D. P. Ryan, R. C. Shamberger, C. Smithers, J. Vacanti, and C. Weldon. We are grateful to the CDH support groups, CHERUBS and Breath of Hope, for providing families and caregivers information about our research study. Funding was provided by National Institute of Child Health and Human Development P01 HD068250-03 (to P. K. D.) and National Research Service Award 2T32GM007748-35 (to F. A. H.). Sequencing services were provided through Resequencing and Genotyping Service by the Northwest Genomics Center at the University of Washington, Department of Genome Sciences, under US Federal Government contract no. HHSN268201100037C from the NHLBI. NR 42 TC 5 Z9 5 U1 1 U2 5 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 AUG 26 PY 2014 VL 111 IS 34 BP 12450 EP 12455 DI 10.1073/pnas.1412509111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN7LA UT WOS:000340780300046 PM 25107291 ER PT J AU Sundberg, TB Choi, HG Song, JH Russell, CN Hussain, MM Graham, DB Khor, B Gagnon, J O'Connell, DJ Narayan, K Dancik, V Perez, JR Reinecker, HC Gray, NS Schreiber, SL Xavier, RJ Shamji, AF AF Sundberg, Thomas B. Choi, Hwan Geun Song, Joo-Hye Russell, Caitlin N. Hussain, Mahmud M. Graham, Daniel B. Khor, Bernard Gagnon, John O'Connell, Daniel J. Narayan, Kavitha Dancik, Vlado Perez, Jose R. Reinecker, Hans-Christian Gray, Nathanael S. Schreiber, Stuart L. Xavier, Ramnik J. Shamji, Alykhan F. TI Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CHRONIC MYELOID-LEUKEMIA; CROHNS-DISEASE; EXPRESSING INTERLEUKIN-10; EXPERIMENTAL COLITIS; IL-10 PRODUCTION; RECEPTOR; MICE; MACROPHAGES; HOMEOSTASIS AB Genetic alterations that reduce the function of the immunoregulatory cytokine IL-10 contribute to colitis in mouse and man. Myeloid cells such as macrophages (M Phi s) and dendritic cells (DCs) play an essential role in determining the relative abundance of IL-10 versus inflammatory cytokines in the gut. As such, using small molecules to boost IL-10 production by DCs-MFs represents a promising approach to increase levels of this cytokine specifically in gut tissues. Toward this end, we screened a library of well-annotated kinase inhibitors for compounds that enhance production of IL-10 by murine bone-marrow-derived DCs stimulated with the yeast cell wall preparation zymosan. This approach identified a number of kinase inhibitors that robustly up-regulate IL-10 production including the Food and Drug Administration (FDA)approved drugs dasatinib, bosutinib, and saracatinib that target ABL, SRC-family, and numerous other kinases. Correlating the kinase selectivity profiles of the active compounds with their effect on IL-10 production suggests that inhibition of salt-inducible kinases (SIKs) mediates the observed IL-10 increase. This was confirmed using the SIK-targeting inhibitor HG-9-91-01 and a series of structural analogs. The stimulatory effect of SIK inhibition on IL-10 is also associated with decreased production of the proinflammatory cytokines IL-1 beta, IL-6, IL-12, and TNF-alpha, and these coordinated effects are observed in human DCs-M Phi s and anti-inflammatory CD11c(+) CX(3)CR1(hi) cells isolated from murine gut tissue. Collectively, these studies demonstrate that SIK inhibition promotes an anti-inflammatory phenotype in activated myeloid cells marked by robust IL-10 production and establish these effects as a previously unidentified activity associated with several FDA-approved multikinase inhibitors. C1 [Sundberg, Thomas B.; Hussain, Mahmud M.; Dancik, Vlado; Perez, Jose R.; Schreiber, Stuart L.; Shamji, Alykhan F.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Choi, Hwan Geun; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Choi, Hwan Geun; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Song, Joo-Hye; Russell, Caitlin N.; Reinecker, Hans-Christian; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Song, Joo-Hye; Russell, Caitlin N.; Reinecker, Hans-Christian; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Hussain, Mahmud M.; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Hussain, Mahmud M.; Schreiber, Stuart L.] Howard Hughes Med Inst, Cambridge, MA 02142 USA. [Graham, Daniel B.; Gagnon, John; O'Connell, Daniel J.; Narayan, Kavitha; Xavier, Ramnik J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Khor, Bernard; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Schreiber, SL (reprint author), Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. EM stuart_schreiber@harvard.edu; xavier@molbio.mgh.harvard.edu; ashamji@broadinstitute.org OI Gagnon, John/0000-0001-6208-5781; Khor, Bernard/0000-0003-4689-5092 FU Leona M. and Harry B. Helmsley Charitable Trust; [DK068181]; [DK043351]; [DK0330506] FX We are grateful to Phil Cohen (University of Dundee) for providing the p-CRTC3 (S370) antibody, Casey Weaver (University of Alabama Birmingham) for the 10BiT reporter mice, Natalia Nedelsky (Massachusetts General Hospital Center for Computational and Integrative Biology) for help with figure preparation, Stephen Johnston (Broad Institute) for pharmacokinetic evaluation of HG-9-91-01, and Isabel Latorre (Broad Institute) for expert assistance with project management. The Leona M. and Harry B. Helmsley Charitable Trust (R.J.X.) and DK068181, DK043351, and DK0330506 (H.-C. R. and J.-H.S.) supported this work. S. L. S. is an investigator of the Howard Hughes Medical Institute. NR 36 TC 8 Z9 8 U1 0 U2 12 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 AUG 26 PY 2014 VL 111 IS 34 BP 12468 EP 12473 DI 10.1073/pnas.1412308111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN7LA UT WOS:000340780300049 PM 25114223 ER PT J AU Maria, JPS Sadaka, A Moussa, SH Brown, S Zhang, YJ Rubin, EJ Gilmore, MS Walker, S AF Maria, John P. Santa, Jr. Sadaka, Ama Moussa, Samir H. Brown, Stephanie Zhang, Yanjia J. Rubin, Eric J. Gilmore, Michael S. Walker, Suzanne TI Compound-gene interaction mapping reveals distinct roles for Staphylococcus aureus teichoic acids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE synthetic lethality; TraDIS; Tn-seq ID GRAM-POSITIVE BACTERIA; VRAFG ABC TRANSPORTER; CELL-DIVISION; ANTIMICROBIAL PEPTIDES; LIPOTEICHOIC ACID; BACILLUS-SUBTILIS; WALL; RESISTANCE; MUTANTS; SURFACE AB Staphylococcus aureus contains two distinct teichoic acid ( TA) polymers, lipoteichoic acid (LTA) and wall teichoic acid (WTA), which are proposed to play redundant roles in regulating cell division. To gain insight into the underlying biology of S. aureus TAs, we used a small molecule inhibitor to screen a highly saturated transposon library for cellular factors that become essential when WTA is depleted. We constructed an interaction network connecting WTAs with genes involved in LTA synthesis, peptidoglycan synthesis, surface protein display, and D-alanine cell envelope modifications. Although LTAs and WTAs are synthetically lethal, we report that they do not have the same synthetic interactions with other cell envelope genes. For example, D-alanylation, a tailoring modification of both WTAs and LTAs, becomes essential when the former, but not the latter, are removed. Therefore, D-alanine-tailored LTAs are required for survival when WTAs are absent. Examination of terminal phenotoypes led to the unexpected discovery that cells lacking both LTAs and WTAs lose their ability to form Z rings and can no longer divide. We have concluded that the presence of either LTAs or WTAs on the cell surface is required for initiation of S. aureus cell division, but these polymers act as part of distinct cellular networks. C1 [Maria, John P. Santa, Jr.; Moussa, Samir H.; Brown, Stephanie; Zhang, Yanjia J.; Rubin, Eric J.; Gilmore, Michael S.; Walker, Suzanne] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02139 USA. [Sadaka, Ama; Gilmore, Michael S.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Zhang, Yanjia J.; Rubin, Eric J.] Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Gilmore, MS (reprint author), Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02139 USA. EM michael_gilmore@meei.harvard.edu; suzanne_walker@hms.harvard.edu FU National Institutes of Health [1P01AI083214, 1R01AI099144] FX We thank O. Schneewind for the bursa aurealis transposon system; A. Grundling for strains Delta ltaS4S5 and SEJ1; T. Meredith for strain TCM011; Tufts University Core Facility for Genomic Sequencing for processing of TnSeq samples; and L. Trakimas, M. Ericcson, and E. Benecchi of the Harvard Medical School Electron Microscopy Facility for processing of EM samples. This work was funded by National Institutes of Health Grants 1P01AI083214 (to S.W. and M.S.G.) and 1R01AI099144 (to S.W.). NR 45 TC 10 Z9 10 U1 1 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 AUG 26 PY 2014 VL 111 IS 34 BP 12510 EP 12515 DI 10.1073/pnas.1404099111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN7LA UT WOS:000340780300056 ER PT J AU Stefan, M Wei, CG Lombardi, A Li, CW Concepcion, ES Inabnet, WB Owen, R Zhang, WJ Tomer, Y AF Stefan, Mihaela Wei, Chengguo Lombardi, Angela Li, Cheuk Wun Concepcion, Erlinda S. Inabnet, William B., III Owen, Randall Zhang, Weijia Tomer, Yaron TI Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE histone modifications; interferon; thyroiditis ID INTERFERON-INDUCED THYROIDITIS; GRAVES-DISEASE; CHROMATIN-STRUCTURE; ALPHA; TRANSCRIPTION; ASSOCIATION; BINDING; CELLS; SUSCEPTIBILITY; TOLERANCE AB Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFN alpha, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261 site. Repression by PLZF depended on the rs12101261 disease susceptibility allele and was increased by IFNa. Intrathymic TSHR expression was decreased in individuals homozygous for the rs12101261 disease-associated genotype compared with carriers of the disease-protective allele. Our studies discovered a genetic-epigenetic interaction involving a noncoding SNP in the TSHR gene that regulates thymic TSHR gene expression and facilitates C1 [Stefan, Mihaela; Lombardi, Angela; Li, Cheuk Wun; Concepcion, Erlinda S.; Tomer, Yaron] Icahn Sch Med Mt Sinai, Div Endocrinol, New York, NY 10029 USA. [Stefan, Mihaela; Tomer, Yaron] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Wei, Chengguo; Zhang, Weijia] Icahn Sch Med Mt Sinai, Dept Med Bioinformat Core, New York, NY 10029 USA. [Inabnet, William B., III; Owen, Randall] Icahn Sch Med Mt Sinai, Dept Surg, New York, NY 10029 USA. RP Tomer, Y (reprint author), Icahn Sch Med Mt Sinai, Div Endocrinol, New York, NY 10029 USA. EM yaron.tomer@mssm.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK061659, DK067555, DK073681]; Department of Veterans Affairs (VA), Office of Research and Development; VA Biomedical Laboratory Research and Development Merit Award [1I01BX002031] FX We thank Dr. Rauf Latif for helpful advice. This work was supported in part by Grants DK061659, DK067555, and DK073681 from the National Institute of Diabetes and Digestive and Kidney Diseases (to Y.T.). In addition, this material is based upon work supported in part by the Department of Veterans Affairs (VA), Office of Research and Development, and by VA Biomedical Laboratory Research and Development Merit Award 1I01BX002031 (to Y.T.). NR 36 TC 15 Z9 18 U1 1 U2 15 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 AUG 26 PY 2014 VL 111 IS 34 BP 12562 EP 12567 DI 10.1073/pnas.1408821111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN7LA UT WOS:000340780300065 PM 25122677 ER PT J AU Caraveo, G Auluck, PK Whitesell, L Chung, CY Baru, V Mosharov, EV Yan, XH Ben-Johny, M Soste, M Picotti, P Kim, H Caldwell, KA Caldwell, GA Sulzer, D Yue, DT Lindquist, S AF Caraveo, Gabriela Auluck, Pavan K. Whitesell, Luke Chung, Chee Yeun Baru, Valeriya Mosharov, Eugene V. Yan, Xiaohui Ben-Johny, Manu Soste, Martin Picotti, Paola Kim, Hanna Caldwell, Kim A. Caldwell, Guy A. Sulzer, David Yue, David T. Lindquist, Susan TI Calcineurin determines toxic versus beneficial responses to alpha-synuclein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NFAT; TORC2; neuroinflammation; Crz1; Slm2 ID PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; CYCLOSPORINE-A; CAENORHABDITIS-ELEGANS; NEUROTROPHIC ACTIONS; OXIDANT STRESS; YEAST; CALCIUM; CALMODULIN; CHANNELS AB Calcineurin (CN) is a highly conserved Ca2+-calmodulin (CaM)dependent phosphatase that senses Ca2+ concentrations and transduces that information into cellular responses. Ca2+ homeostasis is disrupted by alpha-synuclein (alpha-syn), a small lipid binding protein whose misfolding and accumulation is a pathological hallmark of several neurodegenerative diseases. We report that alpha-syn, from yeast to neurons, leads to sustained highly elevated levels of cytoplasmic Ca2+, thereby activating a CaM-CN cascade that engages substrates that result in toxicity. Surprisingly, complete inhibition of CN also results in toxicity. Limiting the availability of CaM shifts CN's spectrum of substrates toward protective pathways. Modulating CN or CN's substrates with highly selective genetic and pharmacological tools (FK506) does the same. FK506 crosses the blood brain barrier, is well tolerated in humans, and is active in neurons and glia. Thus, a tunable response to CN, which has been conserved for a billion years, can be targeted to rebalance the phosphatase's activities from toxic toward beneficial substrates. These findings have immediate therapeutic implications for synucleinopathies. C1 [Caraveo, Gabriela; Auluck, Pavan K.; Whitesell, Luke; Chung, Chee Yeun; Baru, Valeriya; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Caraveo, Gabriela; Baru, Valeriya; Lindquist, Susan] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Auluck, Pavan K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Auluck, Pavan K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mosharov, Eugene V.; Sulzer, David] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Sulzer, David] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA. [Yan, Xiaohui; Kim, Hanna; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. [Ben-Johny, Manu; Yue, David T.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Ben-Johny, Manu; Yue, David T.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Soste, Martin; Picotti, Paola] Eidgenoss Tech Hsch Zurich, Inst Biochem, Dept Biol, CH-8093 Zurich, Switzerland. RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lindquist@wi.mit.edu FU Picower Foundation; JPB Foundation; Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award; Eleanor Schwartz Charitable Foundation; National Institutes of Health (NIH) [K01 AG038546]; Beeson Career Development Award in Aging (NIH) [K08 AG042774]; JPB and Parkinson's Disease Foundation; Udall Center of Excellence; National Institute of Neurological Disorders and Stroke [R01 NS075222] FX Special thanks to Y. Schmitz, A. Mungenast, J. Heitman, M. Cyert, D. Petranovic, and members of the S. L. laboratory for discussions and/or critical reading of the manuscript. This work was supported by the Picower Foundation, the JPB Foundation, a Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award, and the Eleanor Schwartz Charitable Foundation. C.Y.C. is supported by National Institutes of Health (NIH) Grant K01 AG038546, P.K.A., by a Beeson Career Development Award in Aging (NIH Grant K08 AG042774). E.V.M. and D.S. are supported by the JPB and Parkinson's Disease Foundation and the Udall Center of Excellence. E.V.M. is also supported by National Institute of Neurological Disorders and Stroke Grant R01 NS075222. S.L. is an HHMI Investigator. NR 66 TC 14 Z9 14 U1 0 U2 7 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 AUG 26 PY 2014 VL 111 IS 34 BP E3544 EP E3552 DI 10.1073/pnas.1413201111 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN7LA UT WOS:000340780300009 PM 25122673 ER PT J AU Marshall, KM He, SQ Zhong, Z Atkinson, C Tomlinson, S AF Marshall, Keely M. He, Songqing Zhong, Zhi Atkinson, Carl Tomlinson, Stephen TI Dissecting the complement pathway in hepatic injury and regeneration with a novel protective strategy SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MEMBRANE ATTACK COMPLEX; ISCHEMIA-REPERFUSION INJURY; C5A RECEPTOR ANTAGONIST; LIVER-REGENERATION; ISCHEMIA/REPERFUSION INJURY; MONOCLONAL-ANTIBODY; PARTIAL-HEPATECTOMY; NLRP3 INFLAMMASOME; KUPFFER CELLS; MICE AB Liver resection is commonly performed under ischemic conditions, resulting in two types of insult to the remnant liver: ischemia reperfusion injury (IRI) and loss of liver mass. Complement inhibition is recognized as a potential therapeutic modality for IRI, but early complement activation products are also essential for liver regeneration. We describe a novel site-targeted murine complement inhibitor, CR2-CD59, which specifically inhibits the terminal membrane attack complex (MAC), and we use this protein to investigate the complement-dependent balance between liver injury and regeneration in a clinical setting of pharmacological inhibition. CR2-CD59 did not impact in vivo generation of C3 and C5 activation products but was as effective as the C3 activation inhibitor CR2-Crry at ameliorating hepatic IRI, indicating that the MAC is the principle mediator of hepatic IRI. Furthermore, unlike C3 or C5 inhibition, CR2-CD59 was not only protective but significantly enhanced hepatocyte proliferation after partial hepatectomy, including when combined with ischemia and reperfusion. Remarkably, CR2-CD59 also enhanced regeneration after 90% hepatectomy and improved long-term survival from 0 to 70%. CR2-CD59 functioned by increasing hepatic TNF and IL-6 levels with associated STAT3 and Akt activation, and by preventing mitochondrial depolarization and allowing recovery of ATP stores. C1 [Marshall, Keely M.; He, Songqing; Atkinson, Carl; Tomlinson, Stephen] Med Univ S Carolina, Darby Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Zhong, Zhi] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [He, Songqing] Guilin Med Univ, Affiliated Hosp, Dept Hepatobiliary Surg, Guilin 541001, Guangxi, Peoples R China. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Darby Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU National Institutes of Health [R56 AI095657, R01 HL86576, R01 HL082485]; National Natural Science Foundation of China [81160066, 31370917]; Guangxi Natural Science Foundation [2013GXNSFCA019012]; Science & Technology Planning Project of Guangxi Province [1140003-79]; Science & Technology Planning Project of Guilin City [20110119-1-8] FX This work was supported by grants from the National Institutes of Health (R56 AI095657, R01 HL86576, and R01 HL082485), the National Natural Science Foundation of China (81160066 and 31370917), Guangxi Natural Science Foundation (2013GXNSFCA019012), the Science & Technology Planning Project of Guangxi Province (1140003-79), and the Science & Technology Planning Project of Guilin City (20110119-1-8). NR 55 TC 10 Z9 12 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD AUG 25 PY 2014 VL 211 IS 9 BP 1793 EP 1805 DI 10.1084/jem.20131902 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AQ4EA UT WOS:000342744500010 PM 25113972 ER PT J AU Penaloza-MacMaster, P Kamphorst, AO Wieland, A Araki, K Iyer, SS West, EE O'Mara, L Yang, S Konieczny, BT Sharpe, AH Freeman, GJ Rudensky, AY Ahmed, R AF Penaloza-MacMaster, Pablo Kamphorst, Alice O. Wieland, Andreas Araki, Koichi Iyer, Smita S. West, Erin E. O'Mara, Leigh Yang, Shu Konieczny, Bogumila T. Sharpe, Arlene H. Freeman, Gordon J. Rudensky, Alexander Y. Ahmed, Rafi TI Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; FUNCTIONAL IMPAIRMENT; MEDIATED SUPPRESSION; ANTITUMOR IMMUNITY; MEMORY CELLS; GRANZYME-B; IN-VIVO; PERSISTENCE; EXPRESSION; EFFECTOR AB Regulatory T (T reg) cells are critical for preventing autoimmunity mediated by self-reactive T cells, but their role in modulating immune responses during chronic viral infection is not well defined. To address this question and to investigate a role for T reg cells in exhaustion of virus-specific CD8 T cells, we depleted T reg cells in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). T reg cell ablation resulted in 10-100-fold expansion of functional LCMV-specific CD8 T cells. Rescue of exhausted CD8 T cells was dependent on cognate antigen, B7 costimulation, and conventional CD4 T cells. Despite the striking recovery of LCMV-specific CD8 T cell responses, T reg cell depletion failed to diminish viral load. Interestingly, T reg cell ablation triggered up-regulation of the molecule programmed cell death ligand-1 (PD-L1), which upon binding PD-1 on T cells delivers inhibitory signals. Increased PD-L1 expression was observed especially on LCMV-infected cells, and combining T reg cell depletion with PD-L1 blockade resulted in a significant reduction in viral titers, which was more pronounced than that upon PD-L1 blockade alone. These results suggest that T reg cells effectively maintain CD8 T cell exhaustion, but blockade of the PD-1 inhibitory pathway is critical for elimination of infected cells. C1 [Penaloza-MacMaster, Pablo; Kamphorst, Alice O.; Wieland, Andreas; Araki, Koichi; Iyer, Smita S.; West, Erin E.; O'Mara, Leigh; Yang, Shu; Konieczny, Bogumila T.; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Penaloza-MacMaster, Pablo; Kamphorst, Alice O.; Wieland, Andreas; Araki, Koichi; Iyer, Smita S.; West, Erin E.; O'Mara, Leigh; Yang, Shu; Konieczny, Bogumila T.; Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Yang, Shu] Cent S Univ, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA. [Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Program Immunol, Sloan Kettering Inst Canc Res, New York, NY 10065 USA. [Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Ludwig Ctr, New York, NY 10065 USA. RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. EM rudenska@mskcc.org; rahmed@emory.edu FU National Institutes of Health [R01 AI3004, P01 AI080192, P01 AI056299, R37 AI034206]; Ludwig Cancer Research; Cancer Research Institute's Irvington Institute Fellowship Program FX This work was supported by National Institutes of Health grants R01 AI3004 (R. Ahmed), P01 AI080192 (R. Ahmed and G.J. Freeman), P01 AI056299 (R. Ahmed, G.J. Freeman, and A.H. Sharpe), and R37 AI034206 (A.Y. Rudensky), by the Ludwig Cancer Research (A.Y. Rudensky), and by the Cancer Research Institute's Irvington Institute Fellowship Program (A.O. Kamphorst). A.Y. Rudensky is an investigator with the Howard Hughes Medical Institute. NR 64 TC 52 Z9 53 U1 2 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD AUG 25 PY 2014 VL 211 IS 9 BP 1905 EP 1918 DI 10.1084/jem.20132577 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AQ4EA UT WOS:000342744500018 PM 25113973 ER PT J AU Safren, SA Biello, KB Smeaton, L Mimiaga, MJ Walawander, A Lama, JR Rana, A Nyirenda, M Kayoyo, VM Samaneka, W Joglekar, A Celentano, D Martinez, A Remmert, JE Nair, A Lalloo, UG Kumarasamy, N Hakim, J Campbell, TB AF Safren, Steven A. Biello, Katie B. Smeaton, Laura Mimiaga, Matthew J. Walawander, Ann Lama, Javier R. Rana, Aadia Nyirenda, Mulinda Kayoyo, Virginia M. Samaneka, Wadzanai Joglekar, Anjali Celentano, David Martinez, Ana Remmert, Jocelyn E. Nair, Aspara Lalloo, Umesh G. Kumarasamy, Nagalingeswaran Hakim, James Campbell, Thomas B. CA PEARLS ACTG A175 Study Team TI Psychosocial Predictors of Non-Adherence and Treatment Failure in a Large Scale Multi-National Trial of Antiretroviral Therapy for HIV: Data from the ACTG A5175/PEARLS Trial SO PLOS ONE LA English DT Article ID SELF-REPORTED ADHERENCE; QUALITY-OF-LIFE; CLINICAL-TRIALS; MEDICATIONS; BARRIERS; UGANDA AB Background: PEARLS, a large scale trial of antiretroviral therapy (ART) for HIV (n = 1,571, 9 countries, 4 continents), found that a once-daily protease inhibitor (PI) based regimen (ATV+DDI+FTC), but not a once-daily non-nucleoside reverse transcriptase inhibitor/nucleoside reverse transcriptase inhibitor (NNRTI/NRTI) regimen (EFV+FTC/TDF), had inferior efficacy compared to a standard of care twice-daily NNRTI/NRTI regimen (EFV+3TC/ZDV). The present study examined nonadherence in PEARLS. Methods: Outcomes: non-adherence assessed by pill count and by self-report, and time to treatment failure. Longitudinal predictors: regimen, quality of life (general health perceptions = QOL-health, mental health = QOL-mental health), social support, substance use, binge drinking, and sexual behaviors. "Life-Steps'' adherence counseling was provided. Results: In both pill-count and self-report multivariable models, both once-a-day regimens had lower levels of non-adherence than the twice-a-day standard of care regimen; although these associations attenuated with time in the self-report model. In both multivariable models, hard-drug use was associated with non-adherence, living in Africa and better QOL-health were associated with less nonadherence. According to pill-count, unprotected sex was associated with non-adherence. According to self-report, soft-drug use was associated with nonadherence and living in Asia was associated with less nonadherence. Both pill-count (HR = 1.55, 95% CI: 1.15, 2.09, p<.01) and self-report (HR = 1.13, 95% CI: 1.08, 1.13, p<.01) nonadherence were significant predictors of treatment failure over 72 weeks. In multivariable models (including pill-count or self-report nonadherence), worse QOL-health, age group (younger), and region were also significant predictors of treatment failure. Conclusion: In the context of a large, multi-national, multi-continent, clinical trial there were variations in adherence over time, with more simplified regimens generally being associated with better adherence. Additionally, variables such as QOL-health, regimen, drug-use, and region play a role. Self-report and pill-count adherence, as well as additional psychosocial variables, such QOL-health, age, and region, were, in turn, associated with treatment failure. C1 [Safren, Steven A.; Mimiaga, Matthew J.; Remmert, Jocelyn E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Safren, Steven A.; Mimiaga, Matthew J.] Harvard Univ, Sch Med, Boston, MA USA. [Safren, Steven A.; Biello, Katie B.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Biello, Katie B.; Smeaton, Laura; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Walawander, Ann; Nair, Aspara] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Lama, Javier R.] Asociac Civil Impacta Salud & Educ, Lima, Peru. [Rana, Aadia] Miriam Hosp, Alpert Med Sch, Providence, RI 02906 USA. [Nyirenda, Mulinda] Johns Hopkins Res Project, Coll Med, Blantyre, Malawi. [Kayoyo, Virginia M.] Univ North Carolina Project, Lilongwe, Malawi. [Samaneka, Wadzanai] Univ Zimbabwe, Univ Calif San Francisco, Collaborat Res Program, Harare, Zimbabwe. [Joglekar, Anjali] Natl AIDS Res Inst, Pune, Maharashtra, India. [Celentano, David] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Martinez, Ana] NIH NIAD DAIDS Pharmaceut Affairs, Bethesda, MD USA. [Lalloo, Umesh G.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa. [Kumarasamy, Nagalingeswaran] YRGCARE Med Ctr, Madras, Tamil Nadu, India. [Hakim, James] Univ Zimbabwe, Harare, Zimbabwe. [Campbell, Thomas B.] Univ Colorado Denver, Aurora, CO USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ssafren@mgh.harvard.edu FU National Institute of Allergy and Infectious Diseases [U01AI068636]; National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR); General Clinical Research Center Units - National Center for Research Resources; AIDS Clinical Trials Group (ACTG) - National Institute of Allergy and Infectious Diseases, National Institutes of Health: grants [AI68636, AI68634, AI69450]; Clinical Trials Units (CTU): YRG CARE Medical Ctr., VHS CRS (Site 11701) CTU Grant [U01A1069432]; Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz CRS (Site 12101) CTU Grant [U01AI069476]; College of Med. JHU CRS (Site 30301) CTU Grant [1U01AI069518-01]; Durban Adult HIV CRS (Site 11201) CTU Grant [1U01AI069426-01]; UNC Project, Lilongwe (Site 12001) CTU Grant [5 U01 AI069518-04]; UZ-Parienyatwa CRS (Site 30313) CTU Grant [1U01AI069436-01]; Clinical HIV Research Unit University of Witwatersrand (Site 11101) CTU Grant [AI069463]; Chiang Mai Univ. ACTG CRS (Site 11501) CTU Grant [5 U01 AI069399-04]; Hospital Conceicao, Porto Alegre (Site 12201) CTU Grant [5U01AI069401]; Les Centres GHESKIO (Site 30022) CTU Grant [U01 AI069421-05]; National AIDS Research Institute (Site 11601); NARI Clinic at Gadikhana Dr. Kotnis Municipal Disp (Site 11602); NARI Clinic at NIV CRS (Site 11603) CTU Grant [5U01AI069417-04]; Asociacion Civil Impacta Salud y Educacion -Miraflores, CRS (Site 11301); Investigaciones Medicas en Salud -INMENSA. Lince CRS (Site 11302)-CTU Grant [5U01AI069438]; UT Southwestern Medical Center at Dallas (Site 3751) CTU Grant [3U01AI046376-05S4]; University of Cincinnati (Site 2401) CTU Grant [1U01AI069513-01]; UC Davis School of Medicine (Site 3851,3852) CTU Grant [AI38858-09S1]; University of Colorado Hospital (Site 6101) CTU Grant [AI69450, RR025780]; The Ohio State University (Site 2301) CTU Grant [AI069474]; Northwestern University CRS (Site 2701); Rush University Medical Center (Site 2702) CTU Grant [AI069471]; University of Minnesota (Site 1501) CTU Grant [AI27661]; Washington University (Site 2101) CTU Grant [U01AI069495]; Duke University Medical Center (Site 1601) CTU Grant [5U01 AI069 484-02]; Beth Israel Medical Center (Site 2851) CTU Grant [AI46370]; The Miriam Hospital (Site 2951) CTU Grant [AI069472]; University of Southern California (Site 1201) CTU Grant [AI069428]; UCLA CARE Center (Site 601); Harbor-UCLA (Site 603)-CTU Grant [AI069424]; GCRC Grant [RR00424]; University of North Carolina (Site 3201,3206) CTU Grant [AI069423-03]; CFAR Grant [AI050410, P30-AI045008-11]; CTSA Grant [UL 1RR 025747, UL1RR024156]; Vanderbilt Therapeutics (Site 3652) CTU Grant [AI-069439]; Hosp. of the Univ. of Pennsylvania (Site 6201) CTU Grant [001-AI069467-04]; Columbia University -HIV Prevention and Treatment CRS (Site 30329) CTU Grant [AI069470]; New York University/NYC HHC at Bellevue Hospital Center (Site 401) CTU Grant [AI27665, AI069532]; University of Texas Medical Branch, Galveston (Site 6301) CTU Grant [AI032782]; University of Rochester (Site 1101); AIDS Care (Site 1108) CTU Grant [U01AI069511-02]; Cook County Hospital Core Center (Site 2705) CTU Grant [AI25915]; University of Hawaii at Manoa (Site 5201) CTU Grant [AI34853]; Cornell CRS (Site 7804) CTU Grant [AI-69419]; Boehringer Ingelheim; Bristol-Myers Squibb; Gilead Sciences; GlaxoSmithKline; [MOI-RR00865]; [RR024996]; [K24 MH094214] FX The project described was supported by Award Number U01AI068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). The project was also supported in part by the General Clinical Research Center Units funded by the National Center for Research Resources. This work was also supported in part by the AIDS Clinical Trials Group (ACTG), funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health: grants AI68636, AI68634, AI69450 and the following grants to individual Clinical Trials Units (CTU): YRG CARE Medical Ctr., VHS CRS (Site 11701) CTU Grant #U01A1069432; Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz CRS (Site 12101) CTU Grant # U01AI069476; College of Med. JHU CRS (Site 30301) CTU Grant # 1U01AI069518-01; Durban Adult HIV CRS (Site 11201) CTU Grant # 1U01AI069426-01; UNC Project, Lilongwe (Site 12001) CTU Grant # 5 U01 AI069518-04; UZ-Parienyatwa CRS (Site 30313) CTU Grant # 1U01AI069436-01; Clinical HIV Research Unit University of Witwatersrand (Site 11101) CTU Grant # AI069463; Chiang Mai Univ. ACTG CRS (Site 11501) CTU Grant # 5 U01 AI069399-04; Hospital Conceicao, Porto Alegre (Site 12201) CTU Grant # 5U01AI069401; Les Centres GHESKIO (Site 30022) CTU Grant # U01 AI069421-05; National AIDS Research Institute (Site 11601); NARI Clinic at Gadikhana Dr. Kotnis Municipal Disp (Site 11602); NARI Clinic at NIV CRS (Site 11603) CTU Grant # 5U01AI069417-04; Asociacion Civil Impacta Salud y Educacion -Miraflores, CRS (Site 11301); Investigaciones Medicas en Salud -INMENSA. Lince CRS (Site 11302)-CTU Grant # 5U01AI069438; UT Southwestern Medical Center at Dallas (Site 3751) CTU Grant # 3U01AI046376-05S4; University of Cincinnati (Site 2401) CTU Grant # 1U01AI069513-01; UC Davis School of Medicine (Site 3851,3852) CTU Grant # AI38858-09S1; University of Colorado Hospital (Site 6101) CTU Grant # AI69450; RR025780; The Ohio State University (Site 2301) CTU Grant # AI069474; Northwestern University CRS (Site 2701); Rush University Medical Center (Site 2702) CTU Grant # AI069471; University of Minnesota (Site 1501) CTU Grant # AI27661; Washington University (Site 2101) CTU Grant # U01AI069495; Duke University Medical Center (Site 1601) CTU Grant # 5U01 AI069 484-02; Beth Israel Medical Center (Site 2851) CTU Grant # AI46370; The Miriam Hospital (Site 2951) CTU Grant # AI069472; University of Southern California (Site 1201) CTU Grant # AI069428; UCLA CARE Center (Site 601); Harbor-UCLA (Site 603)-CTU Grant # AI069424; Grant # MOI-RR00865; GCRC Grant # RR00424; University of North Carolina (Site 3201,3206) CTU Grant # AI069423-03; CFAR Grant # AI050410; CTSA Grant # UL 1RR 025747; Vanderbilt Therapeutics (Site 3652) CTU Grant # AI-069439; Hosp. of the Univ. of Pennsylvania (Site 6201) CTU Grant # 001-AI069467-04; CFAR Grant # P30-AI045008-11; Columbia University -HIV Prevention and Treatment CRS (Site 30329) CTU Grant # AI069470; CTSA Grant # UL1RR024156; New York University/NYC HHC at Bellevue Hospital Center (Site 401) CTU Grant # AI27665 and AI069532; The University of Texas Medical Branch, Galveston (Site 6301) CTU Grant # AI032782; University of Rochester (Site 1101); AIDS Care (Site 1108) CTU Grant # U01AI069511-02; Cook County Hospital Core Center (Site 2705) CTU Grant # AI25915; University of Hawaii at Manoa (Site 5201) CTU Grant # AI34853; Cornell CRS (Site 7804) CTU Grant # AI-69419; Grant # RR024996.; Finally, some of the author time was supported by grant K24 MH094214 (Safren). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The NIAID provided recommendations on the study design and approved the final study design and provided editorial review as a substudy team member, but had no role in data collection or analysis, or decision to publish. The pharmaceutical sponsors (Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline) provided study drug and Gilead Sciences provided funding to purchase study drug that was not otherwise available. Bristol Myers Squibb provided atazanavir, didanosine-EC and efavirenz (with consent of Merck); Gilead Sciences, Inc. provided emtricitabine, tenofovir-DF, emtricitabine/tenofovirDF; GlaxoSmithKline provided lamivudine, zidovudine and lamivudine/zidovudine; and Boehringer Ingelheim Pharmaceuticals, Inc. provided nevirapine. Representatives of the pharmaceutical company sponsors participated as study team members and authors of this manuscript, but did not participate in data collection, data analyses, or interpretation. Bristol Myers Squibb, Gilead Sciences Inc., GlaxoSmithKline and Boehringer Ingelheim Pharmaceuticals, Inc. had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Finally, some of the author time was supported by grant K24 MH094214 (Safren). NR 22 TC 16 Z9 16 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 AUG 25 PY 2014 VL 9 IS 8 AR e104178 DI 10.1371/journal.pone.0104178 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN9TR UT WOS:000340952200015 PM 25153084 ER PT J AU Simmons, DA Knowles, JK Belichenko, NP Banerjee, G Finkle, C Massa, SM Longo, FM AF Simmons, Danielle A. Knowles, Juliet K. Belichenko, Nadia P. Banerjee, Gargi Finkle, Carly Massa, Stephen M. Longo, Frank M. TI A Small Molecule p75(NTR) Ligand, LM11A-31, Reverses Cholinergic Neurite Dystrophy in Alzheimer's Disease Mouse Models with Mid- to Late-Stage Disease Progression SO PLOS ONE LA English DT Article ID P75 NEUROTROPHIN RECEPTOR; NERVE GROWTH-FACTOR; AMYLOID PRECURSOR PROTEIN; BASAL FOREBRAIN NEURONS; TRANSGENIC MICE; COGNITIVE IMPAIRMENT; BETA PROTEIN; EXPRESSION; BRAIN; DEFICITS AB Degeneration of basal forebrain cholinergic neurons contributes significantly to the cognitive deficits associated with Alzheimer's disease (AD) and has been attributed to aberrant signaling through the neurotrophin receptor p75 (p75(NTR)). Thus, modulating p75(NTR) signaling is considered a promising therapeutic strategy for AD. Accordingly, our laboratory has developed small molecule p75(NTR) ligands that increase survival signaling and inhibit amyloid-beta-induced degenerative signaling in in vitro studies. Previous work found that a lead p75(NTR) ligand, LM11A-31, prevents degeneration of cholinergic neurites when given to an AD mouse model in the early stages of disease pathology. To extend its potential clinical applications, we sought to determine whether LM11A-31 could reverse cholinergic neurite atrophy when treatment begins in AD mouse models having mid-to late stages of pathology. Reversing pathology may have particular clinical relevance as most AD studies involve patients that are at an advanced pathological stage. In this study, LM11A-31 (50 or 75 mg/kg) was administered orally to two AD mouse models, Thy-1 hAPP(Lond/Swe) (APP(L/S)) and Tg2576, at age ranges during which marked AD-like pathology manifests. In mid-stage male APP(L/S) mice, LM11A-31 administered for 3 months starting at 6-8 months of age prevented and/or reversed atrophy of basal forebrain cholinergic neurites and cortical dystrophic neurites. Importantly, a 1 month LM11A-31 treatment given to male APP(L/S) mice (12-13 months old) with late-stage pathology reversed the degeneration of cholinergic neurites in basal forebrain, ameliorated cortical dystrophic neurites, and normalized increased basal forebrain levels of p75(NTR). Similar results were seen in female Tg2576 mice. These findings suggest that LM11A-31 can reduce and/or reverse fundamental AD pathologies in late-stage AD mice. Thus, targeting p75(NTR) is a promising approach to reducing AD-related degenerative processes that have progressed beyond early stages. C1 [Simmons, Danielle A.; Knowles, Juliet K.; Belichenko, Nadia P.; Banerjee, Gargi; Finkle, Carly; Longo, Frank M.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Knowles, Juliet K.; Longo, Frank M.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Massa, Stephen M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Massa, Stephen M.] Univ Calif San Francisco, Lab Computat Neurochem & Drug Discovery, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Longo, FM (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. EM longo@stanford.edu FU Veteran's Administration; [NIA UO1 AG032225]; [NINDS F30 NA051971] FX This work was supported by grants NIA UO1 AG032225 (FML), NINDS F30 NA051971 (JKK) and the Veteran's Administration (SMM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 8 Z9 8 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 25 PY 2014 VL 9 IS 8 AR e102136 DI 10.1371/journal.pone.0102136 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN9TR UT WOS:000340952200004 PM 25153701 ER PT J AU Wheat, JC Krause, DS Shin, TH Chen, X Wang, JF Ding, DC Yamin, R Sweetser, DA AF Wheat, Justin C. Krause, Daniela S. Shin, Thomas H. Chen, Xi Wang, Jianfeng Ding, Dacheng Yamin, Rae'e Sweetser, David A. TI The Corepressor Tle4 Is a Novel Regulator of Murine Hematopoiesis and Bone Development SO PLOS ONE LA English DT Article ID STEM-CELLS; TRANSCRIPTIONAL REPRESSION; B LYMPHOPOIESIS; PAX5 BSAP; GROUCHO; FAMILY; DIFFERENTIATION; PATHWAYS; PROTEIN; MICE AB Hematopoiesis is a complex process that relies on various cell types, signaling pathways, transcription factors and a specific niche. The integration of these various components is of critical importance to normal blood development, as deregulation of these may lead to bone marrow failure or malignancy. Tle4, a transcriptional corepressor, acts as a tumor suppressor gene in a subset of acute myeloid leukemia, yet little is known about its function in normal and malignant hematopoiesis or in mammalian development. We report here that Tle4 knockout mice are runted and die at around four weeks with defects in bone development and BM aplasia. By two weeks of age, Tle4 knockout mice exhibit leukocytopenia, B cell lymphopenia, and significant reductions in hematopoietic stem and progenitor cells. Tle4 deficient hematopoietic stem cells are intrinsically defective in B lymphopoiesis and exhaust upon stress, such as serial transplantation. In the absence of Tle4 there is a profound decrease in bone mineralization. In addition, Tle4 knockout stromal cells are defective at maintaining wild-type hematopoietic stem cell function in vitro. In summary, we illustrate a novel and essential role for Tle4 in the extrinsic and intrinsic regulation of hematopoiesis and in bone development. C1 [Wheat, Justin C.; Shin, Thomas H.; Chen, Xi; Wang, Jianfeng; Ding, Dacheng; Yamin, Rae'e; Sweetser, David A.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02114 USA. [Wheat, Justin C.; Shin, Thomas H.; Chen, Xi; Wang, Jianfeng; Ding, Dacheng; Yamin, Rae'e; Sweetser, David A.] Massachusetts Gen Hosp, Div Med Genet, Boston, MA 02114 USA. [Krause, Daniela S.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Krause, Daniela S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Krause, Daniela S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shin, Thomas H.] Boston Univ, Sch Med, Dept Mol & Translat Med, Boston, MA 02118 USA. RP Sweetser, DA (reprint author), Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02114 USA. EM dsweetser@partners.org FU National Institutes of Health [K08 CA138916-02, R01 CA115772, T32 CA071345]; Hyundai Hope on Wheels; Mattina Proctor Foundation (75 Federal St, Boston, Massachusetts 02110) FX This work was supported by National Institutes of Health grants K08 CA138916-02 (DSK), R01 CA115772 (DAS, JCW, XC, JW), and T32 CA071345 (JW) as well as funding by Hyundai Hope on Wheels (DAS; http://www.hyundaihopeonwheels.org) and the Mattina Proctor Foundation (DAS; 75 Federal St, Boston, Massachusetts 02110). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 7 Z9 7 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 25 PY 2014 VL 9 IS 8 AR e105557 DI 10.1371/journal.pone.0105557 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN9TR UT WOS:000340952200060 PM 25153823 ER PT J AU Fox, IJ Daley, GQ Goldman, SA Huard, J Kamp, TJ Trucco, M AF Fox, Ira J. Daley, George Q. Goldman, Steven A. Huard, Johnny Kamp, Timothy J. Trucco, Massimo TI Use of differentiated pluripotent stem cells in replacement therapy for treating disease SO SCIENCE LA English DT Review ID DUCHENNE MUSCULAR-DYSTROPHY; FULMINANT HEPATIC-FAILURE; HUMAN SKELETAL-MUSCLE; CLINICAL ISLET TRANSPLANTATION; MYOBLAST TRANSFER THERAPY; HUMAN PANCREATIC-ISLETS; RED-BLOOD-CELLS; HEPATOCYTE TRANSPLANTATION; PROGENITOR CELLS; HUMAN ES AB Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful cell transplantation will require optimizing the best cell type and site for engraftment, overcoming limitations to cell migration and tissue integration, and occasionally needing to control immunologic reactivity, as well as a number of other challenges. Collaboration among scientists, clinicians, and industry is critical for generating new stem cell-based therapies. C1 [Fox, Ira J.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Fox, Ira J.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Daley, George Q.] Boston Childrens Hosp, Boston, MA USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Broad Inst, Dept Biol Chem & Mol Pharmacol, Cambridge, MA 02138 USA. [Daley, George Q.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Goldman, Steven A.] Univ Rochester, Med Ctr, Ctr Translat Neuromed, Rochester, NY 14642 USA. [Goldman, Steven A.] Univ Copenhagen, Ctr Basic & Translat Neurosci, DK-1168 Copenhagen, Denmark. [Huard, Johnny] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Stem Cell Res Ctr, Pittsburgh, PA 15261 USA. [Kamp, Timothy J.] Univ Wisconsin, Dept Med, Stem Cell & Regenerat Med Ctr, Cellular & Mol Arrhythmia Res Program,Sch Med & P, Madison, WI USA. [Trucco, Massimo] Univ Pittsburgh, Childrens Hosp Pittsburgh, Div Immunogenet, Pittsburgh, PA 15213 USA. RP Fox, IJ (reprint author), Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. EM foxi@upmc.edu OI Kamp, Timothy/0000-0003-2103-7876 FU NIH [R01DK48794, P01DK096990, R01DK099320, 1P01AG043376, U01HL099773]; National Institute of Neurological Disorders and Stroke; National Institute of Mental Health; Mathers Charitable Foundation; National Multiple Sclerosis Society; Adelson Medical Research Foundation; Child Health and Development Institute; New York Stem Cell Research Program; DOD [W81XWH-10-1-1055] FX We thank E. Tafaleng, N. Giannoukakis, and J. H. Cummins for providing figures and for text editing. This work was supported in part by NIH R01DK48794, P01DK096990, and R01DK099320 (I.J.F.); National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, the Mathers Charitable Foundation, the National Multiple Sclerosis Society, the Adelson Medical Research Foundation, Child Health and Development Institute, and the New York Stem Cell Research Program (S.A.G.); NIH 1P01AG043376 (J. H.); U01HL099773 (T.J.K.); and DOD W81XWH-10-1-1055 (M.T.). I.J.F. is a member of the Scientific Advisory Board of Regenerative Medicine Solutions, Inc.; G.Q.D. is a member of the Senior Advisory Board of MPM Capital, Inc.; S.A.G. is a consultant for Biogen Idec; T.J.K. is a founding shareholder in Cellular Dynamics International; and J. H. is a consultant for Cook Myosite. S.A.G. is an inventor on patents owned by the University of Rochester and Cornell University concerning the use of tissue-and iPSC-derived glial progenitor cells. NR 150 TC 86 Z9 87 U1 15 U2 63 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 AUG 22 PY 2014 VL 345 IS 6199 BP 889 EP + AR UNSP 1247391 DI 10.1126/science.1247391 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB6ZO UT WOS:000349775800001 PM 25146295 ER PT J AU Gallun, FJ Diedesch, AC Kampel, SD Jakien, KM AF Gallun, Frederick J. Diedesch, Anna C. Kampel, Sean D. Jakien, Kasey M. TI Independent impacts of age and hearing loss on spatial release in a complex auditory environment (vol 8, pg 264, 2014) SO FRONTIERS IN NEUROSCIENCE LA English DT Correction DE spatial hearing; aging; hearing loss; virtual spatial array; sensation level C1 [Gallun, Frederick J.; Kampel, Sean D.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Portland, OR 97239 USA. [Gallun, Frederick J.; Jakien, Kasey M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Diedesch, Anna C.] Vanderbilt Univ, Nashville, TN 37235 USA. RP Gallun, FJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Portland, OR 97239 USA. EM frederick.gallun@va.gov NR 2 TC 0 Z9 0 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD AUG 22 PY 2014 VL 8 AR 264 DI 10.3389/fnins.2014.00264 PG 1 WC Neurosciences SC Neurosciences & Neurology GA AW8KY UT WOS:000346511900001 ER PT J AU Rajabi, HN Takahashi, C Ewen, ME AF Rajabi, Hasan N. Takahashi, Chiaki Ewen, Mark E. TI Retinoblastoma Protein and MyoD Function Together to Effect the Repression of Fra-1 and in Turn Cyclin D1 during Terminal Cell Cycle Arrest Associated with Myogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cell Differentiation; Gene Regulation; Myogenesis; Transcription Enhancer; Transcription Factor; Fra-1; MyoD; pRb; Terminal Cell Cycle Arrest ID SKELETAL-MUSCLE DIFFERENTIATION; GENE-EXPRESSION; KINASE-ACTIVITY; MYOBLAST DIFFERENTIATION; SUPPRESSES APOPTOSIS; C-FOS; RB; ACTIVATION; TRANSCRIPTION; RAS AB Background: Repression of cyclin D1 is required for terminal cell cycle arrest associated with myogenesis. Results: pRb and MyoD function together to block induction of Fra-1 and in turn cyclin D1. Conclusion: MyoD and pRb cooperate to effect transcriptional repression during myogenesis. Significance: The findings reveal a link between MyoD, pRb, Fra-1, and cyclin D1, the latter three of which are often deregulated in cancer. The acquisition of skeletal muscle-specific function and terminal cell cycle arrest represent two important features of the myogenic differentiation program. These cellular processes are distinct and can be separated genetically. The lineage-specific transcription factor MyoD and the retinoblastoma protein pRb participate in both of these cellular events. Whether and how MyoD and pRb work together to effect terminal cell cycle arrest is uncertain. To address this question, we focused on cyclin D1, whose stable repression is required for terminal cell cycle arrest and execution of myogenesis. MyoD and pRb are both required for the repression of cyclin D1; their actions, however, were found not to be direct. Rather, they operate to regulate the immediate early gene Fra-1, a critical player in mitogen-dependent induction of cyclin D1. Two conserved MyoD-binding sites were identified in an intronic enhancer of Fra-1 and shown to be required for the stable repression of Fra-1 and, in turn, cyclin D1. Localization of MyoD alone to the intronic enhancer of Fra-1 in the absence of pRb was not sufficient to elicit a block to Fra-1 induction; pRb was also recruited to the intronic enhancer in a MyoD-dependent manner. These observations suggest that MyoD and pRb work together cooperatively at the level of the intronic enhancer of Fra-1 during terminal cell cycle arrest. This work reveals a previously unappreciated link between a lineage-specific transcription factor, a tumor suppressor, and a proto-oncogene in the control of an important facet of myogenic differentiation. C1 [Rajabi, Hasan N.; Takahashi, Chiaki; Ewen, Mark E.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Takahashi, Chiaki] Kanazawa Univ, Canc Res Inst, Kanazawa, Ishikawa 9200934, Japan. [Ewen, Mark E.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RP Ewen, ME (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, 800 Washington St,5609, Boston, MA 02111 USA. EM mewen@tuftsmedicalcenter.org FU National Institutes of Health [R01 CA065842]; Department of Defense Breast Cancer Research Program Fellowship [DAMD17-01-1-0224] FX This work was supported, in whole or in part, by National Institutes of Health Grant R01 CA065842 (to M. E. E.). This work was also supported by Department of Defense Breast Cancer Research Program Fellowship DAMD17-01-1-0224 (to H. N. R.). NR 69 TC 8 Z9 8 U1 0 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 AUG 22 PY 2014 VL 289 IS 34 BP 23417 EP 23427 DI 10.1074/jbc.M113.532572 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7AT UT WOS:000341505000016 PM 25006242 ER PT J AU Zumbrennen-Bullough, KB Wu, QF Core, AB Canali, S Chen, WJ Theurl, I Meynard, D Babitt, JL AF Zumbrennen-Bullough, Kimberly B. Wu, Qifang Core, Amanda B. Canali, Susanna Chen, Wenjie Theurl, Igor Meynard, Delphine Babitt, Jodie L. TI MicroRNA-130a Is Up-regulated in Mouse Liver by Iron Deficiency and Targets the Bone Morphogenetic Protein (BMP) Receptor ALK2 to Attenuate BMP Signaling and Hepcidin Transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Activin A Receptor; Type I (ACVR1); Bone Morphogenetic Protein (BMP); Iron Metabolism; MicroRNA (miRNA); Signal Transduction; SMAD Transcription Factor; ALK2; SMAD4; Hepcidin; miR-130a ID IN-VIVO; EXPRESSION; MICE; HOMEOSTASIS; HEMOJUVELIN; METABOLISM; INFECTION; OVERLOAD; MIR-130A; PATHWAY AB Background: Hepcidin controls systemic iron balance and is regulated by bone morphogenetic protein (BMP) signaling. Results: MicroRNA miR-130a is up-regulated by iron deficiency and targets BMP type I receptor ALK2 to suppress BMP signaling and hepcidin. Conclusion: miR-130a is a novel regulator of BMP signaling and hepcidin. Significance: This pathway may increase iron availability in the setting of iron deficiency. Systemic iron balance is controlled by the liver peptide hormone hepcidin, which is transcriptionally regulated by the bone morphogenetic protein (BMP)-SMAD pathway. In iron deficiency, liver BMP-SMAD signaling and hepcidin are suppressed as a compensatory mechanism to increase iron availability. MicroRNAs are small regulatory RNAs that have an increasingly recognized role in many biologic processes but are only recently implicated in iron homeostasis regulation. Here, we demonstrate that liver expression of the microRNA miR-130a is up-regulated by iron deficiency in mice. We identify the BMP6-SMAD signaling pathway as a functional target of miR-130a in hepatoma-derived Hep3B cells. Although the TGF-/BMP common mediator SMAD4 was previously reported to be an miR-130a target to inhibit TGF- signaling, we do not confirm SMAD4 as an miR-130a target in our biologic system. Instead, we determine that the BMP type I receptor ALK2 is a novel target of miR-130a and that miR-130a binds to two specific sites in the 3-untranslated region to reduce ALK2 mRNA stability. Moreover, we show in mice that the increased liver miR-130a during iron deficiency is associated with reduced liver Alk2 mRNA levels. Finally, we demonstrate that down-regulation of ALK2 by miR-130a has a functional effect to inhibit BMP6-induced hepcidin transcription in Hep3B cells. Our data suggest that iron deficiency increases liver miR-130a, which, by targeting ALK2, may contribute to reduce BMP-SMAD signaling, suppress hepcidin synthesis, and thereby promote iron availability. C1 [Zumbrennen-Bullough, Kimberly B.; Wu, Qifang; Core, Amanda B.; Canali, Susanna; Chen, Wenjie; Theurl, Igor; Meynard, Delphine; Babitt, Jodie L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Syst Biol, Program Anemia Signaling Res,Div Nephrol,Program, Boston, MA 02114 USA. RP Babitt, JL (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,CPZN-8208, Boston, MA 02114 USA. EM babitt.jodie@mgh.harvard.edu RI meynard, delphine/B-4236-2014 FU National Institutes of Health [RO1-DK087727, T32 DK007540]; William F. Milton Fund from Harvard University; Massachusetts General Hospital FX This work was supported, in whole or in part, by National Institutes of Health Grant RO1-DK087727 (to J. L. B.) and Training Grant T32 DK007540 (to K. Z. B. and A. B. C.). This work was also supported by the William F. Milton Fund from Harvard University and a Howard Goodman fellowship award from the Massachusetts General Hospital (to J. L. B.). J. L. B. has ownership interest in the start-up company Ferrumax Pharmaceuticals, which has licensed technology from the Massachusetts General Hospital based on work cited here and in prior publications. NR 35 TC 13 Z9 13 U1 1 U2 20 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 AUG 22 PY 2014 VL 289 IS 34 BP 23796 EP 23808 DI 10.1074/jbc.M114.577387 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7AT UT WOS:000341505000047 PM 25002578 ER PT J AU Cosgrove, C Berger, CT Kroy, DC Cheney, PC Ghebremichael, M Aneja, J Tomlinson, M Kim, AY Lauer, GM Alter, G AF Cosgrove, Cormac Berger, Christoph T. Kroy, Daniela C. Cheney, Patrick C. Ghebremichael, Musie Aneja, Jasneet Tomlinson, Michelle Kim, Arthur Y. Lauer, Georg M. Alter, Galit TI Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver SO PLOS ONE LA English DT Article ID HEPATITIS-C VIRUS; NATURAL-KILLER-CELLS; INHIBITORY RECEPTOR GENES; IG-LIKE RECEPTORS; T-CELLS; ACTIVATION; EXPRESSION; REPLICATION; RESPONSES; IMMUNITY AB Although epidemiological and functional studies have implicated NK cells in protection and early clearance of HCV, the mechanism by which they may contribute to viral control is poorly understood, particularly at the site of infection, the liver. We hypothesized that a unique immunophenotypic/functional NK cell signature exists in the liver that may provide insights into the contribution of NK cells to viral control. Intrahepatic and blood NK cells were profiled from chronically infected HCV-positive and HCV-negative individuals. Baseline expression of activating and inhibitory receptors was assessed, as well as functional responses following stimulation through classic NK cell pathways. Independent of HCV infection, the liver was enriched for the immunoregulatory CD56(bright) NK cell population, which produced less IFN gamma and CD107a but comparable levels of MIP1 beta, and was immunophenotypically distinct from their blood counterparts. This profile was mostly unaltered in chronic HCV infection, though different expression levels of NKp46 and NKG2D were associated with different grades of fibrosis. In contrast to the liver, chronic HCV infection associated with an enrichment of CD161(low) perforin(high) NK cells in the blood correlated with increased AST and 2B4 expression. However, the association of relatively discrete changes in the NK cell phenotype in the liver with the fibrosis stage nevertheless suggests an important role for the NK response. Overall these data suggest that tissue localization has a more pervasive effect on NK cells than the presence of chronic viral infection, during which these cells might be mostly attuned to limiting immunopathology. It will be important to characterize NK cells during early HCV infection, when they should have a critical role in limiting infection. C1 [Cosgrove, Cormac; Berger, Christoph T.; Cheney, Patrick C.; Ghebremichael, Musie; Alter, Galit] MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA. [Kroy, Daniela C.; Aneja, Jasneet; Tomlinson, Michelle; Kim, Arthur Y.; Lauer, Georg M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kroy, Daniela C.] Rhein Westfal TH Aachen, Univ Hosp, D-52062 Aachen, Germany. [Kim, Arthur Y.; Lauer, Georg M.] Harvard Univ, Sch Med, Boston, MA USA. RP Alter, G (reprint author), MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA. EM galter@mgh.harvard.edu FU National Institutes of Health [AI08230, AI066345] FX This work was funded by grants from the National Institutes of Health U19 #AI08230 and U19 #AI066345. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 3 Z9 3 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 AUG 22 PY 2014 VL 9 IS 8 AR e105950 DI 10.1371/journal.pone.0105950 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO3LL UT WOS:000341230600099 PM 25148254 ER PT J AU Shen, KZ Yakhnitsa, V Munhall, AC Johnson, SW AF Shen, K. -Z. Yakhnitsa, V. Munhall, A. C. Johnson, S. W. TI AMP KINASE REGULATES K-ATP CURRENTS EVOKED BY NMDA RECEPTOR STIMULATION IN RAT SUBTHALAMIC NUCLEUS NEURONS SO NEUROSCIENCE LA English DT Article DE AMP kinase; NMDA; Subthalamic nucleus; Brain slice; K-ATP; Patch-clamp ID ACTIVATED PROTEIN-KINASE; SENSITIVE POTASSIUM CHANNELS; CENTRAL-NERVOUS-SYSTEM; INSULIN-SECRETION; IN-VITRO; GLOBUS-PALLIDUS; CELLULAR-ENERGY; ARCUATE NUCLEUS; NEUROPEPTIDE-Y; BASAL GANGLIA AB Our lab recently showed that N-methyl-D-aspartate (NMDA) evokes ATP-sensitive K+ (K-ATP) currents in subthalamic nucleus (STN) neurons in slices of the rat brain. Both K-ATP channels and 5'-adenosine monophosphate-activated protein kinase (AMPK) are considered cellular energy sensors because their activities are influenced by the phosphorylation state of adenosine nucleotides. Moreover, AMPK has been shown to regulate K-ATP function in a variety of tissues including pancreas, cardiac myocytes, and hypothalamus. We used whole-cell patch clamp recordings to study the effect of AMPK activation on K-ATP channel function in STN neurons in slices of the rat brain. We found that bath or intracellular application of the AMPK activators A769662 and PT1 augmented tolbutamide-sensitive K-ATP currents evoked by NMDA receptor stimulation. The effect of AMPK activators was blocked by the AMPK inhibitor dorsomorphin (compound C), and by STO609, an inhibitor of the upstream AMPK activator CaMKK beta. AMPK augmentation of NMDA-induced K-ATP current was also blocked by intracellular BAPTA and by inhibitors of nitric oxide synthase and guanylyl cyclase. However, A769662 did not augment currents evoked by the K-ATP channel opener diazoxide. In the presence of NMDA, A769662 inhibited depolarizing plateau potentials and burst firing, both of which could be antagonized by tolbutamide or dorsomorphin. These studies show that AMPK augments NMDA-induced K-ATP currents by a Ca2+-dependent process that involves nitric oxide and cGMP. By augmenting K-ATP currents, AMPK activation would be expected to dampen the excitatory effect of glutamate-mediated transmission in the STN. Published by Elsevier Ltd. on behalf of IBRO. C1 [Shen, K. -Z.; Yakhnitsa, V.; Munhall, A. C.; Johnson, S. W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, S. W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, Portland, OR 97207 USA. EM johnsost@ohsu.edu FU NIH [NS038715]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This work was supported by NIH grant NS038715 and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. NR 59 TC 5 Z9 5 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD AUG 22 PY 2014 VL 274 BP 138 EP 152 DI 10.1016/j.neuroscience.2014.05.031 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AK8XO UT WOS:000338712300014 PM 24875176 ER PT J AU Cipriani, S Bakshi, R Schwarzschild, MA AF Cipriani, S. Bakshi, R. Schwarzschild, M. A. TI PROTECTION BY INOSINE IN A CELLULAR MODEL OF PARKINSON'S DISEASE SO NEUROSCIENCE LA English DT Article DE MES 23.5 cells; astrocytes; urate; HPLC; cell viability; oxidative stress ID RETINAL GANGLION-CELLS; ADENOSINE RECEPTORS; GLUCOSE DEPRIVATION; MULTIPLE-SCLEROSIS; PURINE NUCLEOSIDES; URATE; NEURONS; SERUM; ASTROCYTES; MECHANISM AB Inosine (hypoxanthine 9-beta-D-ribofuranoside), a purine nucleoside with multiple intracellular roles, also serves as an extracellular modulatory signal. On neurons, it can produce anti-inflammatory and trophic effects that confer protection against toxic influences in vivo and in vitro. The protective effects of inosine treatment might also be mediated by its metabolite urate. Urate in fact possesses potent antioxidant properties and has been reported to be protective in preclinical Parkinson's disease (PD) studies and to be an inverse risk factor for both the development and progression of PD. In this study we assessed whether inosine might protect rodent MES 23.5 dopaminergic cell line from oxidative stress in a cellular model of PD, and whether its effects could be attributed to urate. MES 23.5 cells cultured alone or in presence of enriched murine astroglial cultures MES 23.5-astrocytes co-cultures were pretreated with inosine (0.1-100 mu M) for 24 h before addition of the oxidative stress inducer H2O2 (200 mu M). Twenty-four hours later, cell viability was quantified by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or immunocytochemistry in pure and MES 23.5-astrocytes co-cultures, respectively. H2O2-toxic effect on dopaminergic cells was reduced when they were cultured with astrocytes, but not when they were cultured alone. Moreover, in MES 23.5-astrocytes co-cultures, indicators of free radical generation and oxidative damage, evaluated by nitrite (NO2-) release and protein carbonyl content, respectively, were attenuated. Conditioned medium experiments indicated that the protective effect of inosine relies on the release of a protective factor from inosine-stimulated astrocytes. Purine levels were measured in the cellular extract and conditioned medium using high-performance liquid chromatography (HPLC) method. Urate concentration was not significantly increased by inosine treatment however there was a significant increase in levels of other purine metabolites, such as adenosine, hypoxanthine and xanthine. In particular, in MES 23.5-astrocytes co-cultures, inosine medium content was reduced by 99% and hypoxanthine increased by 127-fold. Taken together these data raise the possibility that inosine might have a protective effect in PD that is independent of any effects mediated through its metabolite urate. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Cipriani, S.; Bakshi, R.; Schwarzschild, M. A.] Massachusetts Gen Hosp, Mol Neurobiol Lab, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. RP Cipriani, S (reprint author), Massachusetts Gen Hosp, Mol Neurobiol Lab, MassGen Inst Neurodegenerat Dis, 114 16th St, Boston, MA 02129 USA. EM pattona80@hotmail.com OI Bakshi, Rachit/0000-0002-8531-7941 FU American Parkinson Disease Association; U.S. National Institutes of Health [R21NS058324, K24NS060991]; U.S. Department of Defense [W81XWH-11-1-0150] FX This work was supported by the American Parkinson Disease Association, U.S. National Institutes of Health grants R21NS058324, K24NS060991 and the U.S. Department of Defense grant W81XWH-11-1-0150. MES 23.5 cells and technical advice were kindly provided by Weidong Le, Ken Rock and Hajime Kono. S. C. designed and performed the experiments, analyzed the data and wrote the manuscript. R. B performed the experiments and analyzed the data. M. A. S. designed the experiments and wrote the manuscript. We thank Cody Desjardins, Thomas Burdett and Robert Logan for excellent technical assistance. Authors declare no conflict of interest. NR 45 TC 4 Z9 5 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD AUG 22 PY 2014 VL 274 BP 242 EP 249 DI 10.1016/j.neuroscience.2014.05.038 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AK8XO UT WOS:000338712300023 PM 24880154 ER PT J AU Klig, JE Sharma, A Skolnik, AB AF Klig, Jean E. Sharma, Amita Skolnik, Aaron B. TI Case 26-2014: A 21-Month-Old Boy with Lethargy, Respiratory Distress, and Abdominal Distention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SALICYLATE INTOXICATION C1 [Klig, Jean E.; Sharma, Amita] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Klig, Jean E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Klig, Jean E.; Sharma, Amita] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Skolnik, Aaron B.] Banner Good Samaritan Med Ctr, Dept Med Toxicol, Phoenix, AZ USA. [Skolnik, Aaron B.] Univ Arizona, Coll Med, Dept Emergency Med, Phoenix, AZ USA. RP Klig, JE (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 18 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 AUG 21 PY 2014 VL 371 IS 8 BP 767 EP 773 DI 10.1056/NEJMcpc1400834 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AN3SV UT WOS:000340509900013 PM 25140963 ER PT J AU Wu, XG Wang, Y Wu, Q Cheng, WH Liu, WJ Zhao, YS Mayeur, C Schmidt, PJ Yu, PB Wang, FD Xia, Y AF Wu, Xing-gang Wang, Yang Wu, Qian Cheng, Wai-Hang Liu, Wenjing Zhao, Yueshui Mayeur, Claire Schmidt, Paul J. Yu, Paul B. Wang, Fudi Xia, Yin TI HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression SO BLOOD LA English DT Article ID HEREDITARY HEMOCHROMATOSIS PROTEIN; CELL-SURFACE EXPRESSION; TRANSFERRIN RECEPTOR; IRON OVERLOAD; MICE; HEMOJUVELIN; TFR2; BETA(2)-MICROGLOBULIN; METABOLISM; INDUCTION AB Mutations in HFE are the most common cause of hereditary hemochromatosis (HH). HFE mutations result in reduced expression of hepcidin, a hepatic hormone, which negatively regulates iron absorption from the duodenum and iron release from macrophages. However, the mechanism by which HFE regulates hepcidin expression in hepatocytes is not well understood. It is known that the bone morphogenetic protein (BMP) pathway plays a central role in controlling hepcidin expression in the liver. Here we show that HFE overexpression increased Smad1/5/8 phosphorylation and hepcidin expression, whereas inhibition of BMP signaling abolished HFE-induced hepcidin expression in Hep3B cells. HFE was found to associate with ALK3, inhibiting ALK3 ubiquitination and proteasomal degradation and increasing ALK3 protein expression and accumulation on the cell surface. The 2 HFE mutants associated with HH, HFE C282Y and HFE H63D, regulated ALK3 protein ubiquitination and trafficking differently, but both failed to increase ALK3 cell-surface expression. Deletion of Hfe in mice resulted in a decrease in hepatic ALK3 protein expression. Our results provide evidence that HFE induces hepcidin expression via the BMP pathway: HFE interacts with ALK3 to stabilize ALK3 protein and increase ALK3 expression at the cell surface. C1 [Wu, Xing-gang; Wang, Yang; Cheng, Wai-Hang; Liu, Wenjing; Zhao, Yueshui; Xia, Yin] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Key Lab Regenerat Med,Minist Educ, Shatin, Hong Kong, Peoples R China. [Wu, Qian; Wang, Fudi] Zhejiang Univ, Sch Med,Sch Publ Hlth, Collaborat Innovat Ctr Diag & Treatment Infect Di, Dept Nutr,Ctr Nutr & Hlth,Inst Nutr & Food Safety, Hangzhou 310003, Zhejiang, Peoples R China. [Mayeur, Claire] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Schmidt, Paul J.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Yu, Paul B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Xia, Yin] Chinese Univ Hong Kong, Shenzhen Res Inst, Sch Biomed Sci, Core Lab, Shenzhen, Peoples R China. RP Xia, Y (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. EM xia.yin@cuhk.edu.hk OI Yu, Paul/0000-0003-2145-4944; Cheng, Wai Hang/0000-0002-3408-9184 FU Chinese University of Hong Kong (CUHK), an RGC/GRF [CUHK477311]; RGC-NSFC [N_CUHK432/12, 81261160507]; CUHK [2041603, 2041747]; Shenzhen Science and Technology Research and Development Funding [JC201105201069A]; National Natural Science Foundation of China [31030039, 31225013]; CUHK FX This study was supported by the startup fund offered by The Chinese University of Hong Kong (CUHK), an RGC/GRF grant (CUHK477311), an RGC-NSFC joint grant (N_CUHK432/12 and 81261160507), CUHK direct grants (2041603 and 2041747), and Shenzhen Science and Technology Research and Development Funding (JC201105201069A) (Y.X.); grants from The National Natural Science Foundation of China (31030039 and 31225013) (F. W.); and CUHK postgraduate scholarships (X.-G. W., W. L., Y.Z.). NR 35 TC 22 Z9 24 U1 4 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 21 PY 2014 VL 124 IS 8 BP 1335 EP 1343 DI 10.1182/blood-2014-01-552281 PG 9 WC Hematology SC Hematology GA AQ4JK UT WOS:000342761900027 PM 24904118 ER PT J AU Cutler, C Logan, B Nakamura, R Johnston, L Choi, S Porter, D Hogan, WJ Pasquini, M MacMillan, ML Hsu, JW Waller, EK Grupp, S McCarthy, P Wu, J Hu, ZH Carter, SL Horowitz, MM Antin, JH AF Cutler, Corey Logan, Brent Nakamura, Ryotaro Johnston, Laura Choi, Sung Porter, David Hogan, William J. Pasquini, Marcelo MacMillan, Margaret L. Hsu, Jack W. Waller, Edmund K. Grupp, Stephan McCarthy, Philip Wu, Juan Hu, Zhen-Huan Carter, Shelly L. Horowitz, Mary M. Antin, Joseph H. TI Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE GRAFT; UNRELATED DONOR; THROMBOTIC MICROANGIOPATHY; ORAL MUCOSITIS; DOUBLE-BLIND; PHASE-II; SIROLIMUS AB Grades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination of tacrolimus and sirolimus(Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3, multicenter trial. The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects. There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival (67% vs 62%, P=5.38). Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms (26% vs 34%, P=.48). Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm (14 vs 16 days, P<.001; 16 vs 19 days, P=.03). Oropharyngeal mucositis was less severe in the Tac/Sir arm (peak Oral Mucositis Assessment Scale score 0.70 vs 0.96, P<.001), but otherwise toxicity was similar. Chronic GVHD, relapse-free survival, and overall survival at 2 years were no different between study arms (53% vs 45%, P=.06; 53% vs 54%, P=.77; and 59% vs 63%, P=.36). Based on similar long-term outcomes, more rapid engraftment, and less oropharyngeal mucositis, the combination of Tac/Sir is an acceptable alternative to Tac/Mtx after MRD HCT. This study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; and the trial was registered at www.clinicaltrials.gov as #NCT00406393. C1 [Cutler, Corey; Antin, Joseph H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Logan, Brent; Pasquini, Marcelo; Hu, Zhen-Huan; Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Nakamura, Ryotaro] City Hope Med Ctr, Duarte, CA USA. [Johnston, Laura] Stanford Univ, Stanford, CA 94305 USA. [Choi, Sung] Univ Michigan, Ann Arbor, MI 48109 USA. [Porter, David] Univ Penn, Philadelphia, PA 19104 USA. [Hogan, William J.] Mayo Clin, Rochester, MN USA. [MacMillan, Margaret L.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Hsu, Jack W.] Univ Florida, Gainesville, FL USA. [Waller, Edmund K.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Grupp, Stephan] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [McCarthy, Philip] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Wu, Juan; Carter, Shelly L.] EMMES Corp, Rockville, MD USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM corey_cutler@dfci.harvard.edu FU Stem Cell Cyclists of the Pan-Mass Challenge; Jock and Bunny Adams Research and Education Endowment; National Heart, Lung, and Blood Institute; National Cancer Institute [U01HL069294] FX C.C. was supported by the Stem Cell Cyclists of the Pan-Mass Challenge. J.H.A. was supported by the Jock and Bunny Adams Research and Education Endowment. This study was supported in part by the National Heart, Lung, and Blood Institute and the National Cancer Institute (#U01HL069294). NR 34 TC 44 Z9 44 U1 0 U2 3 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 AUG 21 PY 2014 VL 124 IS 8 BP 1372 EP 1377 DI 10.1182/blood-2014-04-567164 PG 6 WC Hematology SC Hematology GA AQ4JK UT WOS:000342761900031 PM 24982504 ER PT J AU Venkatesh, M Mukherjee, S Wang, HW Li, H Sun, K Benechet, AP Qiu, ZJ Maher, L Redinbo, MR Phillips, RS Fleet, JC Kortagere, S Mukherjee, P Fasano, A Le Ven, J Nicholson, JK Dumas, ME Khanna, KM Mani, S AF Venkatesh, Madhukumar Mukherjee, Subhajit Wang, Hongwei Li, Hao Sun, Katherine Benechet, Alexandre P. Qiu, Zhijuan Maher, Leigh Redinbo, Matthew R. Phillips, Robert S. Fleet, James C. Kortagere, Sandhya Mukherjee, Paromita Fasano, Alessio Le Ven, Jessica Nicholson, Jeremy K. Dumas, Marc E. Khanna, Kamal M. Mani, Sridhar TI Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4 SO IMMUNITY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; PREGNANE X RECEPTOR; INTESTINAL EPITHELIUM; CROHNS-DISEASE; MOUSE MODEL; METABOLOMICS; HOMEOSTASIS; MICROBIOTA; EXPRESSION; PROTECTION AB Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-alpha while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2(-/-)) mice showed a distinctly "leaky" gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2(-/-)Tlr4(-/-) mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4. C1 [Venkatesh, Madhukumar; Mukherjee, Subhajit; Wang, Hongwei; Li, Hao; Mukherjee, Paromita; Mani, Sridhar] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. [Venkatesh, Madhukumar; Mukherjee, Subhajit; Wang, Hongwei; Li, Hao; Mukherjee, Paromita; Mani, Sridhar] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Sun, Katherine] Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. [Benechet, Alexandre P.; Qiu, Zhijuan; Maher, Leigh; Khanna, Kamal M.] Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT 06030 USA. [Redinbo, Matthew R.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Phillips, Robert S.] Univ Georgia, Dept Chem, Athens, GA 30602 USA. [Fleet, James C.] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Kortagere, Sandhya] Drexel Univ, Coll Med, Dept Immunol & Microbiol, Philadelphia, PA 19129 USA. [Fasano, Alessio] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02114 USA. [Le Ven, Jessica; Nicholson, Jeremy K.; Dumas, Marc E.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Surg & Canc, Div Computat & Syst Med,Sect Biomol Med, London SW7 2AZ, England. RP Khanna, KM (reprint author), Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT 06030 USA. EM kkhanna@uchc.edu; sridhar.mani@einstein.yu.edu RI Dumas, Marc/C-1736-2008; OI Dumas, Marc/0000-0001-9523-7024; Benechet, Alexandre/0000-0001-8746-2459; Fleet, James/0000-0002-0142-9517; Nicholson, Jeremy/0000-0002-8123-8349 FU NIH [CA127231, CA161879, AI097375]; Damon Runyon Foundation [CI 1502, P30CA013330]; University of Connecticut Health Center; European Commission FP7 grant METACARDIS [FP7-HEALTH-2012-INNOVATION-I-305312] FX We thank the Analytical Imaging and Histotechnology and comparative pathology facilities of the Albert Einstein College of Medicine. We thank J. Staudinger (University of Kansas, Lawrence, KS) and W. Xie (University of Pittsburgh, Pittsburgh, PA) for providing Nr1i2-/- and humanized PXR transgenic mice (hNr1i2), respectively. This work was supported by NIH grants CA127231 (S. Mani), CA161879 (S. Mani), and AI097375 (K.M.K.), by Damon Runyon Foundation Clinical Investigatora Award (CI 1502) P30CA013330 (S. Mani), by institutional support funds from the University of Connecticut Health Center (K.M.K.), and by European Commission FP7 grant METACARDIS (FP7-HEALTH-2012-INNOVATION-I-305312 to J.L.V., J.K.N., and M.E.D.). NR 48 TC 63 Z9 64 U1 11 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD AUG 21 PY 2014 VL 41 IS 2 BP 296 EP 310 DI 10.1016/j.immuni.2014.06.014 PG 15 WC Immunology SC Immunology GA AO6JA UT WOS:000341455300016 PM 25065623 ER PT J AU Sun, PZ Longo, DL Hu, W Xiao, G Wu, RH AF Sun, Phillip Zhe Longo, Dario Livio Hu, Wei Xiao, Gang Wu, Renhua TI Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE chemical exchange saturation transfer (CEST); iopamidol; MRI; pH ID ACUTE CEREBRAL-ISCHEMIA; PROTON FRACTION RATIO; RF IRRADIATION; CONTRAST AGENT; IN-VIVO; PARACEST AGENTS; QUANTITATIVE DESCRIPTION; INTRACELLULAR PH; HUMAN BRAIN; 7 T AB pH-sensitive chemical exchange saturation transfer (CEST) MRI holds great promise for in vivo applications. However, the CEST effect depends on not only exchange rate and hence pH, but also on the contrast agent concentration, which must be determined independently for pH quantification. Ratiometric CEST MRI normalizes the concentration effect by comparing CEST measurements of multiple labile protons to simplify pH determination. Iopamidol, a commonly used x-ray contrast agent, has been explored as a ratiometric CEST agent for imaging pH. However, iopamidol CEST properties have not been solved, determination of which is important for optimization and quantification of iopamidol pH imaging. Our study numerically solved iopamidol multi-site pH-dependent chemical exchange properties. We found that iopamidol CEST MRI is suitable for measuring pH between 6 and 7.5 despite that T-1 and T-2 measurements varied substantially with pH and concentration. The pH MRI precision decreased with pH and concentration. The standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and 20 mM iopamidol solution of pH 6, and it improved to be less than 0.1 unit for pH above 7. Moreover, we determined base-catalyzed chemical exchange for 2-hydrooxypropanamido (k(sw) = 1.2*10(pH-4.1)) and amide (k(sw) = 1.2*10(pH-4.6)) protons that are statistically different from each other (P < 0.01, ANCOVA), understanding of which should help guide in vivo translation of iopamidol pH imaging. C1 [Sun, Phillip Zhe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02114 USA. [Sun, Phillip Zhe] Harvard Univ, Sch Med, Charlestown, MA USA. [Longo, Dario Livio] Univ Turin, Ctr Mol Biotechnol, Inst Biostruct & Bioimages CNR, Turin, Italy. [Longo, Dario Livio] Univ Turin, Mol Imaging Ctr, Turin, Italy. [Hu, Wei; Xiao, Gang; Wu, Renhua] Shantou Univ, Coll Med, Affiliated Hosp 2, Dept Radiol, Shantou, Peoples R China. [Xiao, Gang] Hanshan Normal Univ, Dept Math & Appl Math, Chaozhou, Peoples R China. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02114 USA. EM pzhesun@nmr.mgh.harvard.edu; rhwu@stu.edu.cn OI Longo, Dario/0000-0002-6906-9925 FU NIH/NIBIB [1K01EB009771]; NIH/NINDS [1R01NS083654]; Regione Piemonte [NanoIGT-CIPE2007, FIRB08-RBFR08R7OU]; NSFC [30930027] FX This study was supported in part by grants from NIH/NIBIB 1K01EB009771, NIH/NINDS 1R01NS083654, Regione Piemonte (NanoIGT-CIPE2007), FIRB08-RBFR08R7OU and NSFC 30930027. The authors would like to thank Dr Chongzhao Ran for helpful discussions and Bracco Imaging, S.p.A., Milan, Italy for generously providing iopamidol samples. NR 56 TC 6 Z9 7 U1 2 U2 25 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 AUG 21 PY 2014 VL 59 IS 16 BP 4493 EP 4504 DI 10.1088/0031-9155/59/16/4493 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AO5JH UT WOS:000341379900005 PM 25054859 ER PT J AU Wu, B Peisley, A Tetrault, D Li, ZL Egelman, EH Magor, KE Walz, T Penczek, PA Hur, S AF Wu, Bin Peisley, Alys Tetrault, David Li, Zongli Egelman, Edward H. Magor, Katharine E. Walz, Thomas Penczek, Pawel A. Hur, Sun TI Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-I SO MOLECULAR CELL LA English DT Article ID STRUCTURAL BASIS; DSRNA RECOGNITION; MDA5 FILAMENTS; OLIGOMERIZATION; TRANSDUCTION; SUPERFAMILY; RECEPTORS; DOMAIN AB RIG-I activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Assembly of the MAVS filament is mediated by its CARD domain (CARD(MAVS)), and requires its interaction with the tandem CARDs of RIG-I (2CARD(RIG-I)). However, the precise nature of the interaction between 2CARD(RIG-I) and CARD(MAVS), and how this interaction leads to CARD(MAVS) filament assembly, has been unclear. Here we report a 3.6 angstrom electron microscopy structure of the CARD(MAVS) filament and a 3.4 angstrom crystal structure of the 2CARD(RIG-I):CARD(MAVS) complex, representing 2CARD(RIG-I) "caught in the act" of nucleating the CARD MAVS filament. These structures, together with functional analyses, show that 2CARD(RIG-I) acts as a template for the CARD(MAVS) filament assembly, by forming a helical tetrameric structure and recruiting CARD(MAVS) along its helical trajectory. Our work thus reveals that signal activation by RIG-I occurs by imprinting its helical assembly architecture on MAVS, a previously uncharacterized mechanism of signal transmission. C1 [Wu, Bin; Peisley, Alys; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Li, Zongli; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Wu, Bin; Peisley, Alys; Hur, Sun] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Tetrault, David; Magor, Katharine E.] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada. [Tetrault, David; Magor, Katharine E.] Univ Alberta, Li Ka Shing Inst Virol, Edmonton, AB T6G 2E9, Canada. [Egelman, Edward H.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. [Li, Zongli; Walz, Thomas] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Penczek, Pawel A.] Univ Texas Houston, Houston Med Sch, Dept Biochem & Mol Biol, Houston, TX 77030 USA. RP Hur, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM sun.hur@childrens.harvard.edu RI Wu, Bin/C-4715-2015; OI Egelman, Edward/0000-0003-4844-5212; Tetrault, David/0000-0002-4301-8134; Magor, Katharine/0000-0002-9331-1486 FU Canadian Institutes of Health Research [MOP 125865]; Howard Hughes Medical Institute; NCI NIH HHS [P30 CA044579]; NIAID NIH HHS [R01 AI106912]; NIBIB NIH HHS [R01 EB001567, EB001567]; NIGMS NIH HHS [GM R01 60635, GM U54 094598, R01 GM060635, U54 GM094598] NR 33 TC 51 Z9 52 U1 2 U2 19 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 AUG 21 PY 2014 VL 55 IS 4 BP 511 EP 523 DI 10.1016/j.molcel.2014.06.010 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AN5EK UT WOS:000340612700003 PM 25018021 ER PT J AU Joukov, V Walter, JC De Nicolo, A AF Joukov, Vladimir Walter, Johannes C. De Nicolo, Arcangela TI The Cep192-Organized Aurora A-Plk1 Cascade Is Essential for Centrosome Cycle and Bipolar Spindle Assembly SO MOLECULAR CELL LA English DT Article ID GAMMA-TUBULIN COMPLEXES; PERICENTRIOLAR MATERIAL; MICROTUBULE NUCLEATION; CENTRIOLE DUPLICATION; CAENORHABDITIS-ELEGANS; NEDD1 PHOSPHORYLATION; MITOTIC CENTROSOMES; DROSOPHILA SPD-2; PROTEIN SPD-2; KINASE AURORA AB As cells enter mitosis, the two centrosomes separate and grow dramatically, each forming a nascent spindle pole that nucleates a radial array of microtubules. Centrosome growth (and associated microtubule nucleation surge), termed maturation, involves the recruitment of pericentriolar material components via an as-yet unknown mechanism. Here, we show that Cep192 binds Aurora A and Plk1, targets them to centrosomes in a pericentrin-dependent manner, and promotes sequential activation of both kinases via T-loop phosphorylation. The Cep192-bound Plk1 then phosphorylates Cep192 at several residues to generate the attachment sites for the g-tubulin ring complex and, possibly, other pericentriolar material components, thus promoting their recruitment and subsequent microtubule nucleation. We further found that the Cep192-dependent Aurora A-Plk1 activity is essential for kinesin-5-mediated centrosome separation, bipolar spindle formation, and equal centrosome/centriole segregation into daughter cells. Thus, our study identifies a Cep192-organized signaling cascade that underlies both centrosome maturation and bipolar spindle assembly. C1 [Joukov, Vladimir; De Nicolo, Arcangela] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Joukov, Vladimir; Walter, Johannes C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Walter, Johannes C.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [De Nicolo, Arcangela] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Joukov, V (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM vladimir_joukov@hms.harvard.edu FU NIH [GM080676] FX We thank D. M. Livingston for his support and comments on the manuscript; M. Budzowska, A. Groen, C. D. Hu, J. Maller, A. Merdes, and T. Mitchison for providing reagents; M. Eck for providing the baculovirus expression facility; S. Gygi and R. Tomaino for mass spectrometry analysis; E. Parisini for help with sequence alignments; and J. Higgins for critical reading of the manuscript. We also thank L. Piedmont, J. Waters, and the Nikon Imaging Center at Harvard Medical School for help with light microscopy. J.C.W. was supported by the NIH grant GM080676. NR 48 TC 23 Z9 23 U1 0 U2 14 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 AUG 21 PY 2014 VL 55 IS 4 BP 578 EP 591 DI 10.1016/j.molcel.2014.06.016 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AN5EK UT WOS:000340612700008 PM 25042804 ER PT J AU Wang, F Chen, X Li, C Sun, Q Chen, Y Wang, Y Peng, H Liu, Z Chen, R Liu, K Yan, H Ye, BH Kwiatkowski, DJ Zhang, H AF Wang, F. Chen, X. Li, C. Sun, Q. Chen, Y. Wang, Y. Peng, H. Liu, Z. Chen, R. Liu, K. Yan, H. Ye, B. H. Kwiatkowski, D. J. Zhang, H. TI Pivotal role of augmented alpha B-crystallin in tumor development induced by deficient TSC1/2 complex SO ONCOGENE LA English DT Article DE alpha B-crystallin; mTOR; NF kappa B; TSC; tumor ID TUBEROUS SCLEROSIS COMPLEX; SUPPRESSOR GENE-PRODUCT; NF-KAPPA-B; MAMMALIAN TARGET; INDUCED APOPTOSIS; BINDING PARTNER; CELL-ADHESION; UP-REGULATION; CANCER-CELLS; MTOR AB Tuberous sclerosis complex 1 (TSC1) and TSC2 are suppressors of mechanistic target of rapamycin (mTOR). mTOR is the major component of two protein complexes: mTOR complex 1 (mTORC1) and mTORC2. Inactive mutation of either TSC1 or TSC2 unleashes mTOR signaling and consequently causes TSC, a benign tumor syndrome affecting multiple organs. We report here that expression of alpha B-crystallin was upregulated in Tsc1-/- or Tsc2-/- mouse embryonic fibroblasts, Eker rat uterine leiomyoma-derived Tsc2-deficient ELT3 cells, mutant Tsc2-associated mouse kidney tumors, and human lung lymphangioleiomyomatosis nodules. alpha B-crystallin was transcriptionally activated by mTOR complex 2 (mTORC2): nuclear factor-kappa B (NF kappa B) signaling cascade. The augmented alpha B-crystallin was critical for the migration, invasion and apoptotic resistance of Tsc2-defective cells. Disruption of alpha B-crystallin suppressed Tsc2-null cell proliferation and tumorigenesis. Therefore, enhanced alpha B-crystallin has an essential role in TSC1/2 complex deficiency-mediated tumorigenesis, and inhibition of alpha B-crystallin may complement the current therapy for TSC. C1 [Wang, F.; Chen, X.; Li, C.; Wang, Y.; Liu, Z.; Chen, R.; Zhang, H.] Peking Union Med Coll, Grad Sch, Inst Basic Med Sci, State Key Lab Med Mol Biol,Dept Physiol & Pathoph, Beijing 100005, Peoples R China. [Wang, F.; Chen, X.; Li, C.; Wang, Y.; Liu, Z.; Chen, R.; Zhang, H.] Peking Union Med Coll, Grad Sch, Sch Basic Med, Beijing 100005, Peoples R China. [Wang, F.; Chen, X.; Li, C.; Chen, Y.; Wang, Y.; Liu, Z.; Chen, R.; Yan, H.; Zhang, H.] Chinese Acad Med Sci, Beijing 100730, Peoples R China. [Sun, Q.] Tianjin Med Univ, Tianjin Canc Inst & Hosp, Dept Immunol, Tianjin, Peoples R China. [Chen, Y.; Yan, H.] Peking Union Med Coll, Cardiovasc Inst, Ctr Coronary Heart Dis, Beijing 100005, Peoples R China. [Chen, Y.; Yan, H.] Peking Union Med Coll, Fu Wai Hosp, Beijing 100005, Peoples R China. [Peng, H.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. [Liu, K.] Zhengzhou Univ, Sch Basic Med Sci, Dept Pathophysiol, Zhengzhou 450052, Henan, Peoples R China. [Ye, B. H.] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. [Kwiatkowski, D. J.] Brigham & Womens Hosp, Div Translat Med, Boston, MA 02115 USA. [Kwiatkowski, D. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhang, H (reprint author), Peking Union Med Coll, Grad Sch, Inst Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100005, Peoples R China. EM hbzhang@ibms.pumc.edu.cn RI Peng, Haiyong/S-8045-2016 FU National Basic Research Program of China 973 Program [2009CB522203, 2011CB965002]; National Natural Science Foundation of China [81130085, 81101516] FX This study was supported by National Basic Research Program of China 973 Program Grants 2009CB522203 and 2011CB965002 and National Natural Science Foundation of China Grants 81130085 and 81101516. NR 49 TC 3 Z9 3 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD AUG 21 PY 2014 VL 33 IS 34 BP 4352 EP 4358 DI 10.1038/onc.2013.401 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AO2MK UT WOS:000341156900008 PM 24077282 ER PT J AU Woo, JH Wang, SM Melhem, ER Gee, JC Cucchiara, A McCluskey, L Elman, L AF Woo, John H. Wang, Sumei Melhem, Elias R. Gee, James C. Cucchiara, Andrew McCluskey, Leo Elman, Lauren TI Linear Associations between Clinically Assessed Upper Motor Neuron Disease and Diffusion Tensor Imaging Metrics in Amyotrophic Lateral Sclerosis SO PLOS ONE LA English DT Article ID CORTICOSPINAL TRACT; WHITE-MATTER; MRI; ALS; REGISTRATION; TRACTOGRAPHY; INVOLVEMENT; ATLAS; TOOL AB Objective: To assess the relationship between clinically assessed Upper Motor Neuron (UMN) disease in Amyotrophic Lateral Sclerosis (ALS) and local diffusion alterations measured in the brain corticospinal tract (CST) by a tractography-driven template-space region-of-interest (ROI) analysis of Diffusion Tensor Imaging (DTI). Methods: This cross-sectional study included 34 patients with ALS, on whom DTI was performed. Clinical measures were separately obtained including the Penn UMN Score, a summary metric based upon standard clinical methods. After normalizing all DTI data to a population-specific template, tractography was performed to determine a region-of-interest (ROI) outlining the CST, in which average Mean Diffusivity (MD) and Fractional Anisotropy (FA) were estimated. Linear regression analyses were used to investigate associations of DTI metrics (MD, FA) with clinical measures (Penn UMN Score, ALSFRS-R, duration-of-disease), along with age, sex, handedness, and El Escorial category as covariates. Results: For MD, the regression model was significant (p = 0.02), and the only significant predictors were the Penn UMN Score (p = 0.005) and age (p = 0.03). The FA regression model was also significant (p = 0.02); the only significant predictor was the Penn UMN Score (p = 0.003). Conclusions: Measured by the template-space ROI method, both MD and FA were linearly associated with the Penn UMN Score, supporting the hypothesis that DTI alterations reflect UMN pathology as assessed by the clinical examination. C1 [Woo, John H.; Wang, Sumei; Gee, James C.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cucchiara, Andrew] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [McCluskey, Leo; Elman, Lauren] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Woo, John H.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Melhem, Elias R.] Univ Maryland, Dept Radiol, Baltimore, MD 21201 USA. RP Woo, JH (reprint author), Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM john.woo@uphs.upenn.edu FU National Institutes of Health [NS063111, NS065347, DA022807, NS045839, AG032953]; Greater Philadelphia Chapter of the ALS Association; Philadelphia Veterans Affairs Medical Center; National Center for Advancing Translational Sciences (NCATS) of the NIH [UL1TR000003] FX The authors acknowledge the financial support of the following institutions: National Institutes of Health (NS063111, NS065347, DA022807, NS045839, AG032953), the Greater Philadelphia Chapter of the ALS Association, and the Philadelphia Veterans Affairs Medical Center. This project was also supported by Grant Number UL1TR000003 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official view of NCATS or the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 3 Z9 3 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 21 PY 2014 VL 9 IS 8 AR e105753 DI 10.1371/journal.pone.0105753 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO1WL UT WOS:000341106100118 PM 25144708 ER PT J AU Naito, T Nosho, K Ito, M Igarashi, H Mitsuhashi, K Yoshii, S Aoki, H Nomura, M Sukawa, Y Yamamoto, E Adachi, Y Takahashi, H Hosokawa, M Fujita, M Takenouchi, T Maruyama, R Suzuki, H Baba, Y Imai, K Yamamoto, H Ogino, S Shinomura, Y AF Naito, Takafumi Nosho, Katsuhiko Ito, Miki Igarashi, Hisayoshi Mitsuhashi, Kei Yoshii, Shinji Aoki, Hironori Nomura, Masafumi Sukawa, Yasutaka Yamamoto, Eiichiro Adachi, Yasushi Takahashi, Hiroaki Hosokawa, Masao Fujita, Masahiro Takenouchi, Toshinao Maruyama, Reo Suzuki, Hiromu Baba, Yoshifumi Imai, Kohzoh Yamamoto, Hiroyuki Ogino, Shuji Shinomura, Yasuhisa TI IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE BRAF; Colon polyp; Colorectal neoplasia; Colorectum; Genome; Insulin-like growth factor; Long interspersed nucleotide element-1; Microsatellite instability; Serrated pathway ID EARLY NEOPLASTIC PROGRESSION; COLORECTAL-CANCER; COLON-CANCER; LINE-1 HYPOMETHYLATION; PROXIMAL COLON; BRAF MUTATION; POLYPOSIS SYNDROME; POOR-PROGNOSIS; ADENOMAS; PATHWAY AB AIM: To investigate insulin-like growth factor 2 (IGF2) differentially methylated region (DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions. METHODS: To accurately analyze the association between the histological types and molecular features of each type of serrated lesion, we consecutively collected 1386 formalin-fixed paraffin-embedded tissue specimens that comprised all histological types [hyperplastic polyps (HPs, n = 121), sessile serrated adenomas (SSAs, n = 132), traditional serrated adenomas (TSAs, n = 111), non-serrated adenomas (n = 195), and colorectal cancers (CRCs, n = 827)]. We evaluated the methylation levels of IGF2 DMR0 and long interspersed nucleotide element-1 (LINE-1) in HPs (n = 115), SSAs (n = 120), SSAs with cytological dysplasia (n = 10), TSAs (n = 91), TSAs with high-grade dysplasia (HGD) (n = 15), non-serrated adenomas (n = 80), non-serrated adenomas with HGD (n = 105), and CRCs (n = 794). For the accurate quantification of the relative methylation levels (scale 0%-100%) of IGF2 DMR0 and LINE-1, we used bisulfite pyrosequencing method. Tumor specimens were analyzed for microsatellite instability, KRAS (codons 12 and 13), BRAF (V600E), and PIK3CA (exons 9 and 20) mutations; MLH1 and MGMT methylation; and IGF2 expression by immunohistochemistry. RESULTS: The distribution of the IGF2 DMR0 methylation level in 351 serrated lesions and 185 non-serrated adenomas (with or without HGD) was as follows: mean 61.7, median 62.5, SD 18.0, range 5.0-99.0, interquartile range 49.5-74.4. The IGF2 DMR0 methylation level was divided into quartiles (Q1 >= 74.5, Q2 62.6-74.4, Q3 49.6-62.5, Q4 <= 49.5) for further analysis. With regard to the histological type, the IGF2 DMR0 methylation levels of SSAs (mean +/- SD, 73.1 +/- 12.3) were significantly higher than those of HPs (61.9 +/- 20.5), TSAs (61.6 +/- 19.6), and non-serrated adenomas (59.0 +/- 15.8) (P < 0.0001). The IGF2 DMR0 methylation level was inversely correlated with the IGF2 expression level (r = -0.21, P = 0.0051). IGF2 DMR0 hypomethylation was less frequently detected in SSAs compared with HPs, TSAs, and non-serrated adenomas (P < 0.0001). Multivariate logistic regression analysis also showed that IGF2 DMR0 hypomethylation was inversely associated with SSAs (P < 0.0001). The methylation levels of IGF2 DMR0 and LINE-1 in TSAs with HGD (50.2 +/- 18.7 and 55.7 +/- 5.4, respectively) were significantly lower than those in TSAs (61.6 +/- 19.6 and 58.8 +/- 4.7, respectively) (IGF2 DMR0, P = 0.038; LINE-1, P = 0.024). CONCLUSION: IGF2 DMR0 hypomethylation may be an infrequent epigenetic alteration in the SSA pathway. Hypomethylation of IGF2 DMR0 and LINE-1 may play a role in TSA pathway progression. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. C1 [Naito, Takafumi; Nosho, Katsuhiko; Ito, Miki; Igarashi, Hisayoshi; Mitsuhashi, Kei; Yamamoto, Eiichiro; Adachi, Yasushi; Shinomura, Yasuhisa] Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido 0608543, Japan. [Yoshii, Shinji; Takahashi, Hiroaki] Keiyukai Sapporo Hosp, Dept Gastroenterol, Sapporo, Hokkaido 0030027, Japan. [Aoki, Hironori; Nomura, Masafumi] Teine Keijinkai Hosp, Ctr Gastroenterol, Sapporo, Hokkaido 0060811, Japan. [Sukawa, Yasutaka; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hosokawa, Masao] Keiyukai Sapporo Hosp, Dept Surg, Sapporo, Hokkaido 0030027, Japan. [Fujita, Masahiro; Takenouchi, Toshinao] Keiyukai Sapporo Hosp, Dept Pathol, Sapporo, Hokkaido 0030027, Japan. [Maruyama, Reo; Suzuki, Hiromu] Sapporo Med Univ, Sch Med, Dept Mol Biol, Sapporo, Hokkaido 0608543, Japan. [Baba, Yoshifumi] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto 8600862, Japan. [Imai, Kohzoh] Univ Tokyo, Inst Med Sci, Div Canc Res, Tokyo 1088639, Japan. [Yamamoto, Hiroyuki] St Marianna Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Kawasaki, Kanagawa 2168511, Japan. RP Nosho, K (reprint author), Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Chou Ku, S-1,W-16, Sapporo, Hokkaido 0608543, Japan. EM nosho@sapmed.ac.jp FU Japan Society for the Promotion of Science (JSPS); A-STEP (Adaptable and Seamless Technology Transfer Program through Target-driven R and D); Daiwa Securities Health Foundation; Kobayashi Foundation for Cancer Research; Sagawa Foundation for Promotion of Cancer Research; Suzuken Memorial Foundation; Takeda Science Foundation; USA National Institute of Health [R01 CA151993]; [23790800]; [23390200] FX Supported by The Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant No. 23790800 (to Nosho K) and 23390200 (to Shinomura Y); A-STEP (Adaptable and Seamless Technology Transfer Program through Target-driven R and D) (to Nosho K); Daiwa Securities Health Foundation (to Nosho K); Kobayashi Foundation for Cancer Research (to Nosho K); Sagawa Foundation for Promotion of Cancer Research (to Nosho K); Suzuken Memorial Foundation (to Nosho K), and Takeda Science Foundation (to Nosho K); and USA National Institute of Health, grant number R01 CA151993 (to Ogino S) NR 55 TC 8 Z9 8 U1 0 U2 3 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD AUG 21 PY 2014 VL 20 IS 29 BP 10050 EP 10061 DI 10.3748/wjg.v20.i29.10050 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AN6TK UT WOS:000340730300029 PM 25110432 ER PT J AU Jamuar, SS Lam, ATN Kircher, M D'Gama, AM Wang, J Barry, BJ Zhang, XC Hill, RS Partlow, JN Rozzo, A Servattalab, S Mehta, BK Topcu, M Amrom, D Andermann, E Dan, B Parrini, E Guerrini, R Scheffer, IE Berkovic, SF Leventer, RJ Shen, YP Wu, BL Barkovich, AJ Sahin, M Chang, BS Bamshad, M Nickerson, DA Shendure, J Poduri, A Yu, TW Walsh, CA AF Jamuar, Saumya S. Lam, Anh-Thu N. Kircher, Martin D'Gama, Alissa M. Wang, Jian Barry, Brenda J. Zhang, Xiaochang Hill, Robert Sean Partlow, Jennifer N. Rozzo, Aldo Servattalab, Sarah Mehta, Bhaven K. Topcu, Meral Amrom, Dina Andermann, Eva Dan, Bernard Parrini, Elena Guerrini, Renzo Scheffer, Ingrid E. Berkovic, Samuel F. Leventer, Richard J. Shen, Yiping Wu, Bai Lin Barkovich, A. James Sahin, Mustafa Chang, Bernard S. Bamshad, Michael Nickerson, Deborah A. Shendure, Jay Poduri, Annapurna Yu, Timothy W. Walsh, Christopher A. TI Somatic Mutations in Cerebral Cortical Malformations SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SEVERE INTELLECTUAL DISABILITY; EXOME; MOSAICISM; DISEASE; DYNC1H1; TUBB2B; AKT3 AB BACKGROUND Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. METHODS Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, = 200x) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. RESULTS Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. CONCLUSIONS Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.) C1 [Jamuar, Saumya S.; Lam, Anh-Thu N.; D'Gama, Alissa M.; Barry, Brenda J.; Zhang, Xiaochang; Hill, Robert Sean; Partlow, Jennifer N.; Rozzo, Aldo; Servattalab, Sarah; Mehta, Bhaven K.; Yu, Timothy W.; Walsh, Christopher A.] Boston Childrens Hosp, Div Genet & Gen, Manton Ctr Orphan Dis Res, Howard Hughes Med Inst, Boston, MA USA. [Wang, Jian; Shen, Yiping; Wu, Bai Lin] Boston Childrens Hosp, Dept Lab Med, Boston, MA USA. [Sahin, Mustafa; Poduri, Annapurna] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Jamuar, Saumya S.; Lam, Anh-Thu N.; D'Gama, Alissa M.; Barry, Brenda J.; Zhang, Xiaochang; Hill, Robert Sean; Partlow, Jennifer N.; Rozzo, Aldo; Servattalab, Sarah; Mehta, Bhaven K.; Yu, Timothy W.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Jamuar, Saumya S.; Lam, Anh-Thu N.; D'Gama, Alissa M.; Barry, Brenda J.; Zhang, Xiaochang; Hill, Robert Sean; Partlow, Jennifer N.; Rozzo, Aldo; Servattalab, Sarah; Mehta, Bhaven K.; Sahin, Mustafa; Poduri, Annapurna; Yu, Timothy W.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Shen, Yiping; Wu, Bai Lin] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chang, Bernard S.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Yu, Timothy W.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jamuar, Saumya S.] KK Womens & Childrens Hosp, Dept Paediat, Singapore, Singapore. [Kircher, Martin; Bamshad, Michael; Nickerson, Deborah A.; Shendure, Jay] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Wang, Jian; Shen, Yiping] Shanghai Childrens Med Ctr, Dept Lab Med, Shanghai, Peoples R China. [Topcu, Meral] Hacettepe Univ, Sch Med, Dept Pediat, Div Neurol, TR-06100 Ankara, Turkey. [Amrom, Dina; Andermann, Eva] McGill Univ, Montreal Neurol Hosp & Inst, Neurogenet Unit, Montreal, PQ, Canada. [Andermann, Eva] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Dan, Bernard] Univ Libre Brussels, Hop Univ Enfants Reine Fabiola, Dept Neurol, Brussels, Belgium. [Parrini, Elena; Guerrini, Renzo] Univ Florence, Childrens Hosp A Meyer, Pediat Neurol Unit & Labs, Florence, Italy. [Scheffer, Ingrid E.; Berkovic, Samuel F.] Univ Melbourne, Austin Hlth, Dept Med, Heidelberg, Vic, Australia. [Scheffer, Ingrid E.] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic 3010, Australia. [Scheffer, Ingrid E.] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia. [Leventer, Richard J.] Univ Melbourne, Murdoch Childrens Res Inst, Royal Childrens Hosp, Dept Neurol, Parkville, Vic 3052, Australia. [Shen, Yiping; Wu, Bai Lin] Claritas Genom, Cambridge, MA USA. [Walsh, Christopher A.] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Walsh, Christopher A.] Harvard, Cambridge, MA USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Barkovich, A. James] USCF, Benioff Childrens Hosp, San Francisco, CA USA. RP Walsh, CA (reprint author), Boston Childrens Hosp, Ctr Life Sci, Div Genet & Gen, 15062-2,3 Blackfan Circle, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu RI Scheffer, Ingrid/G-1668-2013; Parrini, Elena/K-5283-2016; OI Scheffer, Ingrid/0000-0002-2311-2174; Parrini, Elena/0000-0001-8933-7694; Berkovic, Samuel/0000-0003-4580-841X; Dan, Bernard/0000-0002-2051-9876; Shendure, Jay/0000-0002-1516-1865; Kircher, Martin/0000-0001-9278-5471; Yu, Timothy/0000-0003-2988-7701 FU National Institute of Neurological Disorders and Stroke FX Funded by the National Institute of Neurological Disorders and Stroke and others. NR 27 TC 63 Z9 66 U1 3 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 AUG 21 PY 2014 VL 371 IS 8 BP 733 EP 743 DI 10.1056/NEJMoa1314432 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AN3SV UT WOS:000340509900008 PM 25140959 ER PT J AU Foo, J Michor, F AF Foo, Jasmine Michor, Franziska TI Evolution of acquired resistance to anti-cancer therapy SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Review DE Drug resistance; Cancer; Evolution; Mathematical modeling; Optimal dosing strategies ID LURIA-DELBRUCK DISTRIBUTION; CHRONIC MYELOID-LEUKEMIA; CELL LUNG-CANCER; DRUG-RESISTANCE; MATHEMATICAL-MODEL; CLONAL EXPANSION; TUMOR-GROWTH; COMBINATION CHEMOTHERAPY; MULTIDRUG-RESISTANCE; FLUCTUATION ANALYSIS AB Acquired drug resistance is a major limitation for the successful treatment of cancer. Resistance can emerge due to a variety of reasons including host environmental factors as well as genetic or epigenetic alterations in the cancer cells. Evolutionary theory has contributed to the understanding of the dynamics of resistance mutations in a cancer cell population, the risk of resistance pre-existing before the initiation of therapy, the composition of drug cocktails necessary to prevent the emergence of resistance, and optimum drug administration schedules for patient populations at risk of evolving acquired resistance. Here we review recent advances towards elucidating the evolutionary dynamics of acquired drug resistance and outline how evolutionary thinking can contribute to outstanding questions in the field. Published by Elsevier Ltd. C1 [Foo, Jasmine] Univ Minnesota, Sch Math, Minneapolis, MN 55455 USA. [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM jyfoo@umn.edu; michor@jimmy.harvard.edu FU NCI NIH HHS [U54 CA143798] NR 119 TC 31 Z9 32 U1 3 U2 60 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 EI 1095-8541 J9 J THEOR BIOL JI J. Theor. Biol. PD AUG 21 PY 2014 VL 355 BP 10 EP 20 DI 10.1016/j.jtbi.2014.02.025 PG 11 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA AJ7GL UT WOS:000337865100002 PM 24681298 ER PT J AU Yuan, YS Wang, Y Chi, FL AF Yuan Yasheng Wang Yang Chi Fanglu TI Reinnervation of hair cells by neural stem cell-derived neurons SO CHINESE MEDICAL JOURNAL LA English DT Article DE neural stem cells; hair cells; reinnervation; synapse ID LONG-TERM POTENTIATION; INNER-EAR; GANGLION NEURONS; AUDITORY NEURONS; SENSORY NEURONS; DIFFERENTIATION; TRANSPLANTATION; PLASTICITY; PROMOTE; MODEL AB Background Replacement of spiral ganglion neurons would be one prioritized step in an attempt to restore sensory neuronal hearing loss. However, the possibility that transplanted neurons could regenerate new synaptic connections to hair cells has not been explored. The objective of this study was to test whether neural stem cell (NSC)-derived neurons can form synaptic connections with hair cells in vitro. Methods NSCs were mechanically separated from the hippocampus in SD rat embryos (E12-E14) and cultured in a serum-free medium containing basic fibroblast growth factor and epidermal growth factor. Rat NSCs were co-cultured with explants of cochlea sensory epithelia obtained from postnatal Day 3 rats under transway filter membrane. Results At Day 3, the NSCs began to show chemotactic differentiation and grew toward cochlea sensory epithelia. After 9-day co-culture, neurites of NSC-derived neurons predominantly elongated toward hair cells. lmmunohistochemical analyses revealed the fibers overlapped with synapsin and hair cells, indicating the formation of new synaptic connections. After 14-day culture, triple staining revealed the fibers overlapped with PSD95 (postsynaptic density) which is juxtaposed with CtBP2 (presynaptic vesicle), indicating the formation of new ribbon synapse. Conclusions NSC-derived neurons can make synaptic connections with hair cells and provide a model for studying synaptic plasticity and regeneration. Whether the newly forming synapse is functional merits further electrophysiological study. C1 [Yuan Yasheng; Chi Fanglu] Eye Ear Nose & Throat Hosp, Dept ENT Head & Neck Surg, Shanghai 200031, Peoples R China. [Yuan Yasheng; Chi Fanglu] Fudan Univ, Shanghai Med Sch, Shanghai 210029, Peoples R China. [Wang Yang] Fudan Univ, Shanghai Med Sch, Dept Anat, Shanghai 210029, Peoples R China. [Yuan Yasheng] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Chi, FL (reprint author), Fudan Univ, Eye Ear Nose & Throat Hosp, Dept ENT Head & Neck Surg, Shanghai 200031, Peoples R China. EM chifanglu@126.com FU National Institute on Deafness; NSFC [81028003/H1305, 30973303]; Key Basic Research Project of Shanghai Committee of Science and Technology [10JC1402500]; Ministry of Education [20090071120072]; Innovation Program of Shanghai Committee of Science and Technology [11411952300] FX This work was supported by grants from the National Institute on Deafness, the NSFC grant (No. 81028003/H1305); the NSFC grant (No. 30973303), Key Basic Research Project of Shanghai Committee of Science and Technology (No. 10JC1402500), the Ministry of Education Grant (No. 20090071120072), and Innovation Program of Shanghai Committee of Science and Technology (No. 11411952300). NR 20 TC 3 Z9 3 U1 0 U2 3 PU CHINESE MEDICAL ASSOC PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD AUG 20 PY 2014 VL 127 IS 16 BP 2972 EP 2976 DI 10.3760/cma.j.issn.0366-6999.20140585 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AY3OD UT WOS:000347491900017 PM 25131237 ER PT J AU Toussaint, RJ Bergeron, SG Weaver, MJ Tornetta, P Vrahas, MS Harris, MB AF Toussaint, Rull James Bergeron, Stephane G. Weaver, Michael J. Tornetta, Paul, III Vrahas, Mark S. Harris, Mitchel B. TI The Effect of the Massachusetts Healthcare Reform on the Uninsured Rate of the Orthopaedic Trauma Population SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID COVERAGE AB Background: The 2006 Massachusetts Healthcare Reform (MHR) has resulted in health coverage for 98.1% of residents in Massachusetts. The purpose of this study was to evaluate the effect of MHR on the actual rate of uninsured individuals in the orthopaedic trauma population in the largest metropolitan area of Massachusetts. We also sought to measure the change in uncompensated care following the implementation of MHR. Methods: We performed a retrospective review of all patients treated by the orthopaedic trauma services at three of the four level-I trauma centers in Boston from 2003 to 2010. The primary study cohort consisted of all uninsured patients, while the remaining patients were considered to have insurance. The study population was divided into two groups to compare the uninsured rate before and after MHR. Patients from 2006 to 2007 were excluded from the analysis to allow for an enrollment period in subsidized health insurance. Results: A total of 16,338 patients with extremity and pelvic fractures and dislocations were treated from 2003 to 2010. There was a significant decrease in the uninsured rate from 23.8% to 14.4% following MHR (p < 0.001). The post-MHR risk of being uninsured is approximately 0.6 times the pre-MHR risk, with a 95% confidence interval of 0.56 to 0.65. There was also a reduction in the proportion of uncompensated care from 16.7% to 11.5% after MHR. Conclusions: There was an estimated 40% reduction in risk of uninsured individuals in the orthopaedic trauma population in the metropolitan Boston area following MHR. Despite a significant improvement, these results reveal a rate of uninsured individuals fivefold greater than currently reported by the state of Massachusetts and the U.S. government. C1 [Toussaint, Rull James] Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Boston, MA 02115 USA. [Bergeron, Stephane G.] Jewish Gen Hosp, Dept Orthopaed Surg, Montreal, PQ H3T 1E2, Canada. [Weaver, Michael J.; Harris, Mitchel B.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Tornetta, Paul, III] Boston Med Ctr, Dept Orthopaed Surg, Boston, MA 02118 USA. [Vrahas, Mark S.] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Toussaint, RJ (reprint author), Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, 55 Fruit St,White 535, Boston, MA 02115 USA. NR 21 TC 5 Z9 5 U1 0 U2 0 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 AUG 20 PY 2014 VL 96A IS 16 AR e141 DI 10.2106/JBJS.M.00740 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AR8BB UT WOS:000343799400006 PM 25143509 ER PT J AU Michel, SG La Muraglia, GM Madariaga, MLL Titus, JS Selig, MK Farkash, EA Allan, JS Anderson, LM Madsen, JC AF Michel, Sebastian G. La Muraglia, Glenn M., II Madariaga, Maria Lucia L. Titus, James S. Selig, Martin K. Farkash, Evan A. Allan, James S. Anderson, Lisa M. Madsen, Joren C. TI Preservation of Donor Hearts Using Hypothermic Oxygenated Perfusion SO ANNALS OF TRANSPLANTATION LA English DT Article DE Heart Transplantation; Organ Preservation; Pulsatile Flow ID CARDIAC ALLOGRAFT PRESERVATION; MACHINE PERFUSION; CARDIOPULMONARY BYPASS; INTERNATIONAL SOCIETY; ENDOTHELIAL FUNCTION; NONPULSATILE FLOW; TRANSPLANTATION; DEATH; PULSATILE; RECOVERY AB Background: Hypothermic machine perfusion of donor hearts enables continuous aerobic metabolism and washout of toxic metabolic byproducts. We evaluated the effect of machine perfusion on cardiac myocyte integrity in hearts preserved for 4 h in a novel device that provides pulsatile oxygenated hypothermic perfusion (Paragonix Sherpa Perfusion T Cardiac Transport System). Material/Methods: Pig hearts were harvested and stored in Celsior (R) solution for 4 h using either conventional cold storage on ice (4-h CS, n=6) or the Sherpa device (4-h pulsatile perfusion (PP), n=6). After cold preservation, hearts were evaluated using a non-working heart Langendorff system. Controls (n=3) were reperfused immediately after organ harvest. Biopsies were taken from the apex of the left ventricle before storage, after storage, and after reperfusion to measure ATP content and endothelin-1 in the tissue. Ultrastructural analysis using electron microscopy was performed. Results: Four-hour CS, 4-h PP, and control group did not show any significant differences in systolic or diastolic function (+dP/dt, -dP/dt, EDP). Four-hour PP hearts showed significantly more weight gain than 4-h CS after preservation, which shows that machine perfusion led to myocardial edema. Four-hour CS led to higher endothelin-1 levels after preservation, suggesting more endothelial dysfunction compared to 4-h PP. Electron microscopy revealed endothelial cell rupture and damaged muscle fibers in the 4-h CS group after reperfusion, but the cell structures were preserved in the 4-h PP group. Conclusions: Hypothermic pulsatile perfusion of donor hearts leads to a better-preserved cell structure compared to the conventional cold storage method. This may lead to less risk of primary graft failure after orthotopic heart transplantation. C1 [Michel, Sebastian G.; La Muraglia, Glenn M., II; Madariaga, Maria Lucia L.; Allan, James S.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Michel, Sebastian G.; La Muraglia, Glenn M., II; Madariaga, Maria Lucia L.; Allan, James S.; Madsen, Joren C.] Harvard Univ, Sch Med, Boston, MA USA. [Michel, Sebastian G.] Univ Munich, Klinikum Grosshadern, Dept Cardiac Surg, D-80539 Munich, Germany. [Titus, James S.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. [Selig, Martin K.; Farkash, Evan A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Allan, James S.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Anderson, Lisa M.] Paragonix Technol Inc, Braintree, MA USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM jcmadsen@partners.org FU SBIR [1R43HL115852-01] FX Sebastian G. Michel, Glenn M. La Muraglia II, Maria Lucia L. Madariaga, James S. Titus, Martin K. Selig, Evan A. Farkash and James S. Allan: nothing to disclose. Joren C. Madsen received grant support from Paragonix Technologies, Inc. to perform this study as part of a Phase I SBIR grant (1R43HL115852-01) awarded to Paragonix Technologies, Inc. (Braintree, MA). Lisa M. Anderson is an employee at Paragonix Technologies, Inc. NR 30 TC 0 Z9 0 U1 0 U2 0 PU INT SCIENTIFIC LITERATURE, INC PI SMITHTOWN PA 361 FOREST LANE, SMITHTOWN, NY 11787 USA SN 1425-9524 J9 ANN TRANSPL JI Ann. Transpl. PD AUG 20 PY 2014 VL 19 AR 890797 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA AQ8HJ UT WOS:000343065000002 ER PT J AU Jackson, JW Schneeweiss, S VanderWeele, TJ Blacker, D AF Jackson, John W. Schneeweiss, Sebastian VanderWeele, Tyler J. Blacker, Deborah TI Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis SO PLOS ONE LA English DT Article ID NURSING-HOME RESIDENTS; INTENSIVE-CARE-UNIT; TORSADE-DE-POINTES; VENOUS THROMBOEMBOLISM; CEREBROVASCULAR EVENTS; RETROSPECTIVE COHORT; ELDERLY-PATIENTS; ISCHEMIC-STROKE; SUDDEN-DEATH; NONDIFFERENTIAL MISCLASSIFICATION AB Background: Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture. Objectives: 1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs. Data sources: Pubmed and Science Citation Index. Study eligibility criteria, participants, and interventions: Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a "new user" design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events. Study appraisal and synthesis methods: For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference-comparing FGAs to SGAs-mediated by their difference in risk for the medical event. Results: We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference. Conclusions: The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs. C1 [Jackson, John W.; Schneeweiss, Sebastian] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Jackson, John W.; Schneeweiss, Sebastian; Blacker, Deborah] Harvard Univ, Sch Med, Boston, MA USA. [Jackson, John W.; Schneeweiss, Sebastian; VanderWeele, Tyler J.; Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02114 USA. RP Jackson, JW (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. EM john.jackson@mail.harvard.edu RI Schneeweiss, Sebastian/C-2125-2013 FU NIMH Training Grant in Training in Psychiatric Genetics and Translational Research [T32 MH017119]; Horace W. Goldsmith Fellowship at Harvard University; NIA [P50 AG005134] FX John W. Jackson was supported by NIMH Training Grant in Training in Psychiatric Genetics and Translational Research (T32 MH017119) and the Horace W. Goldsmith Fellowship at Harvard University. Sebastian Schneeweiss had no relevant funding. Tyler J. VanderWeele: NIH R01 ES 0178876. Deborah Blacker was supported by NIA P50 AG005134. The funders had no role in the motivation for the study or the study design, data collection and analysis, interpretation of results, decision to publish, or preparation of the manuscript. NR 75 TC 6 Z9 6 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 AUG 20 PY 2014 VL 9 IS 8 AR e105376 DI 10.1371/journal.pone.0105376 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AQ3JB UT WOS:000342687200081 PM 25140533 ER PT J AU McDougal, SJ Alexander, J Dhanireddy, S Harrington, RD Stekler, JD AF McDougal, Sarah J. Alexander, Jeremiah Dhanireddy, Shireesha Harrington, Robert D. Stekler, Joanne D. TI Non-Occupational Post-Exposure Prophylaxis for HIV: 10-Year Retrospective Analysis in Seattle, Washington SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG EXPOSURE; SEXUAL EXPOSURE; COST-EFFECTIVENESS; ZIDOVUDINE TREATMENT; UNITED-STATES; INFECTION; RISK; MEN; TRANSMISSION AB Despite treatment guidelines in place since 2005, non-occupational post-exposure HIV prophylaxis (nPEP) remains an underutilized prevention strategy. We conducted a retrospective chart review of patients presenting to a publicly-funded HIV clinic in Seattle, Washington for nPEP between 2000 and 2010 (N = 360). nPEP prescriptions were provided for 324 (90%) patients; 83% of prescription decisions were appropriate according to Centers for Disease Control and Prevention guidelines, but only 31% (N = 111/360) of patients were considered "high risk.'' In order to use limited resources most efficiently, public health agencies should target messaging for this high-cost intervention to individuals with high-risk HIV exposures. C1 [McDougal, Sarah J.; Alexander, Jeremiah; Dhanireddy, Shireesha; Harrington, Robert D.; Stekler, Joanne D.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Stekler, Joanne D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Alexander, Jeremiah] Vet Affairs Puget Sound, Gen Med Serv, Seattle, WA USA. RP McDougal, SJ (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM sjmcd13@uw.edu NR 36 TC 4 Z9 4 U1 3 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 AUG 20 PY 2014 VL 9 IS 8 AR e105030 DI 10.1371/journal.pone.0105030 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AQ3JB UT WOS:000342687200048 PM 25140868 ER PT J AU Qureshi, AY Mueller, S Snyder, AZ Mukherjee, P Berman, JI Roberts, TPL Nagarajan, SS Spiro, JE Chung, WK Sherr, EH Buckner, RL AF Qureshi, Abid Y. Mueller, Sophia Snyder, Abraham Z. Mukherjee, Pratik Berman, Jeffrey I. Roberts, Timothy P. L. Nagarajan, Srikantan S. Spiro, John E. Chung, Wendy K. Sherr, Elliott H. Buckner, Randy L. CA Simons VIP Consortium TI Opposing Brain Differences in 16p11.2 Deletion and Duplication Carriers SO JOURNAL OF NEUROSCIENCE LA English DT Article DE 16p11.2; ASD; CNV; copy number variation; morphometry; structural MRI ID AUTISM SPECTRUM DISORDER; SURFACE-BASED ANALYSIS; WHITE-MATTER; CORTICAL THICKNESS; HEAD CIRCUMFERENCE; NORMAL INDIVIDUALS; COSTELLO SYNDROME; HUMAN NEOCORTEX; CHILDREN; VOLUME AB Deletions and duplications of the recurrent similar to 600 kb chromosomal BP4-BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development. C1 [Qureshi, Abid Y.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Qureshi, Abid Y.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Qureshi, Abid Y.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller, Sophia; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mueller, Sophia] Univ Munich, Inst Clin Radiol, D-81377 Munich, Germany. [Snyder, Abraham Z.] Washington Univ, Sch Med St Louis, Dept Neurol, St Louis, MO 63110 USA. [Snyder, Abraham Z.] Washington Univ, Sch Med St Louis, Dept Radiol, St Louis, MO 63110 USA. [Mukherjee, Pratik; Nagarajan, Srikantan S.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94158 USA. [Sherr, Elliott H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Berman, Jeffrey I.; Roberts, Timothy P. L.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Spiro, John E.] Simons Fdn, New York, NY 10010 USA. [Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Pediat & Med, New York, NY 10032 USA. RP Buckner, RL (reprint author), Harvard Univ, Northwest Bldg,Room 280-06,52 Oxford St, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu OI Mukherjee, Pratik/0000-0001-7473-7409 FU Simons Foundation (SFARI) [219193]; NIH/NINDS [5R25NS065743] FX This work was supported by a Grant from the Simons Foundation (SFARI no. 219193 to R.B.). We thank all of the families at the participating Simons Variation in Individuals Project (VIP) sites, as well as the Simons VIP Consortium. We appreciate obtaining access to phenotypic data on SFARI Base. Approved researchers can obtain the Simons VIP population dataset described in this study by contacting the Simons Foundation Autism Research Initiative. A.Q. was supported by NIH/NINDS 5R25NS065743. We thank Avram Holmes for helpful advice on data analysis and Dr Nicholas Katsanis for insightful discussion. NR 63 TC 31 Z9 33 U1 4 U2 14 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 AUG 20 PY 2014 VL 34 IS 34 BP 11199 EP 11211 DI 10.1523/JNEUROSCI.1366-14.2014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AO4MI UT WOS:000341312600005 PM 25143601 ER PT J AU Lee, CN Wetschler, MH Chang, YC Belkora, JK Moy, B Partridge, A Sepucha, KR AF Lee, Clara N. Wetschler, Matthew H. Chang, Yuchiao Belkora, Jeffrey K. Moy, Beverly Partridge, Ann Sepucha, Karen R. TI Measuring decision quality: psychometric evaluation of a new instrument for breast cancer chemotherapy SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Decision; Regret; Breast cancer; Shared decision making; Quality of care; Decision quality; Chemotherapy; Adjuvant therapy ID ADJUVANT THERAPY; RISK COMMUNICATION; MEDICAL DECISIONS; INFORMED CHOICES; WOMEN; PREFERENCES; PERCEPTIONS; WORTHWHILE; PROGNOSIS; KNOWLEDGE AB Background: Women diagnosed with early stage (I or II) breast cancer face a highly challenging decision - whether or not to undergo adjuvant chemotherapy. We developed a decision quality instrument for chemotherapy for early stage breast cancer and sought to evaluate its performance. Methods: Cross-sectional, mailed survey of recent breast cancer survivors, providers, and healthy controls and a retest survey of survivors. The decision quality instrument includes questions on knowledge and personal goals. It results in a knowledge score and concordance score, which reflects the percentage of patients who received treatments that match their goals. Hypotheses related to acceptability, feasibility, validity, and reliability of the survey instrument were examined. Results: Responses were received from 352 patients, 89 providers and 35 healthy controls. The decision quality instrument was feasible to implement with few missing data. The knowledge scores had good retest reliability (intraclass correlation coefficient (ICC) = 0.75). Knowledge scores discriminated between providers and patients (mean difference 31.1%, 95% CI 26.9, 35.3) and between patients and healthy controls (mean difference 11.2, 95% CI 5.4, 17.1). Most providers reported that the knowledge items covered essential content. Two of the five goal items had a ceiling effect, and one goal had low content validity. The goal items had moderate retest reliability (ICC's 0.57 to 0.78). In the multivariable model of treatment, none of the patient goals was associated with receipt of chemotherapy. Age and hormone receptor status were the only variables independently associated with chemotherapy. Most patients (77.6%) had treatment concordant with that predicted by the model. Patients who had concordant treatment had similar levels of confidence and regret as those who did not. Conclusions: The Decision Quality Instrument is a reliable and valid measure of patient knowledge about chemotherapy, but its ability to measure concordance with patient goals is limited. In this sample, patient goals were not associated with treatment, and most patients reported they were not asked their preference, suggesting that goals were not adequately considered in decision making. C1 [Lee, Clara N.] Univ N Carolina, Sheps Ctr Hlth Serv Res, Lineberger Comprehens Canc Ctr, Dept Surg, Chapel Hill, NC 27599 USA. [Wetschler, Matthew H.] Stanford Univ, Dept Emergency Med, Palo Alto, CA 94304 USA. [Chang, Yuchiao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. [Belkora, Jeffrey K.] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA USA. [Moy, Beverly] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Partridge, Ann] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Sepucha, Karen R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Boston, MA USA. RP Lee, CN (reprint author), Univ N Carolina, Sheps Ctr Hlth Serv Res, Lineberger Comprehens Canc Ctr, Dept Surg, UNC Plast Surg CB 7195, Chapel Hill, NC 27599 USA. EM cnlee@med.unc.edu FU Informed Medical Decision Foundation (IMDF); IMDF; National Institutes of Health [KL2RR025746, 5K07CA154850-02] FX The study was funded by the Informed Medical Decision Foundation (IMDF). The IMDF contributed to the study design. Karen Sepucha received salary support from the IMDF. Clara Lee received salary support from IMDF and National Institutes of Health KL2RR025746 and 5K07CA154850-02. NR 36 TC 1 Z9 1 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD AUG 20 PY 2014 VL 14 AR 73 DI 10.1186/1472-6947-14-73 PG 11 WC Medical Informatics SC Medical Informatics GA AO1FA UT WOS:000341056500002 ER PT J AU Sepucha, KR Feibelmann, S Cosenza, C Levin, CA Pignone, M AF Sepucha, Karen R. Feibelmann, Sandra Cosenza, Carol Levin, Carrie A. Pignone, Michael TI Development and evaluation of a new survey instrument to measure the quality of colorectal cancer screening decisions SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Colon cancer screening; Decision quality; Shared decision making; Quality measurement; Survey research; Psychometrics ID PSYCHOMETRIC EVALUATION; CONTROLLED-TRIAL; PREFERENCES; POPULATION; KNOWLEDGE; LITERACY; BELIEFS; AID AB Background: Guidelines for colorectal cancer screening recommend that patients be informed about options and be able to select preferred method of screening; however, there are no existing measures available to assess whether this happens. Methods: Colorectal Cancer Screening Decision Quality Instrument (CRC-DQI) includes knowledge items and patients' goals and concerns. Items were generated through literature review and qualitative work with patients and providers. Hypotheses relating to the acceptability, feasibility, discriminant validity and retest reliability of the survey were examined using data from three studies: (1) 2X2 randomized study of participants recruited online, (2) cross-sectional sample of patients recruited in community health clinics, and (3) cross-sectional sample of providers recruited from American Medical Association Master file. Results: 338 participants were recruited online, 94 participants were recruited from community health centers, and 115 physicians were recruited. The CRC-DQI was feasible and acceptable with low missing data and high response rates for both online and paper-based administrations. The knowledge score was able to discriminate between those who had seen a decision aid or not (84% vs. 64%, p < 0.001) and between providers, online patients and clinic patients (89% vs. 74% vs. 41%, p < 0.001 for all comparisons). The knowledge score and most of the goals had adequate retest reliability. About half of the participants received a test that matched their goals (47% and 51% in online and clinic samples respectively). Many respondents who had never been screened had goals that indicated a preference for colonoscopy. A minority of respondents in the online (21%) and in clinic (2%) samples were both well informed and received a test that matched their goals. Conclusions: The CRC-DQI demonstrated good psychometric properties in diverse samples, and across different modes of administration. Few respondents made high quality decisions about colon cancer screening. C1 [Sepucha, Karen R.; Feibelmann, Sandra] Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Div Gen Internal Med, Boston, MA 02114 USA. [Sepucha, Karen R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cosenza, Carol] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. [Levin, Carrie A.] Informed Med Decis Fdn, Boston, MA 02108 USA. [Pignone, Michael] Univ N Carolina, UNC Div Gen Internal Med, Chapel Hill, NC 27599 USA. [Pignone, Michael] Univ N Carolina, UNC Inst Healthcare Qual Improvement, Chapel Hill, NC 27599 USA. RP Sepucha, KR (reprint author), Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Div Gen Internal Med, 50 Staniford St,8th Floor, Boston, MA 02114 USA. EM ksepucha@partners.org FU Informed Medical Decisions Foundation (IMDF) FX The authors would like to acknowledge the participation of the many patients and providers in these studies. The funding for the study was provided from the Informed Medical Decisions Foundation (IMDF). The decision aid used in the online sample was developed by the IMDF in collaboration with Health Dialog, Inc. The AMA is the source of the data used to identify the providers surveyed in this research study. NR 21 TC 5 Z9 5 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD AUG 20 PY 2014 VL 14 AR 72 DI 10.1186/1472-6947-14-72 PG 9 WC Medical Informatics SC Medical Informatics GA AO1FA UT WOS:000341056500001 PM 25138444 ER PT J AU Rigotti, NA Regan, S Levy, DE Japuntich, S Chang, YC Park, ER Viana, JC Kelley, JHI Reyen, M Singer, DE AF Rigotti, Nancy A. Regan, Susan Levy, Douglas E. Japuntich, Sandra Chang, Yuchiao Park, Elyse R. Viana, Joseph C. Kelley, Jennifer H. I. Reyen, Michele Singer, Daniel E. TI Sustained Care Intervention and Postdischarge Smoking Cessation Among Hospitalized Adults A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VOICE RESPONSE SYSTEM; NICOTINE DEPENDENCE; POPULATION HEALTH; FOLLOW-UP; SMOKERS; OUTCOMES AB IMPORTANCE Health care systems need effective models to manage chronic diseases like tobacco dependence across transitions in care. Hospitalizations provide opportunities for smokers to quit, but research suggests that hospital-delivered interventions are effective only if treatment continues after discharge. OBJECTIVE To determine whether an intervention to sustain tobacco treatment after hospital discharge increases smoking cessation rates compared with standard care. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial compared sustained care (a postdischarge tobacco cessation intervention) with standard care among 397 hospitalized daily smokers (mean age, 53 years; 48% were males; 81% were non-Hispanic whites) who wanted to quit smoking after discharge and received a tobacco dependence intervention in the hospital; 92% of eligible patients and 44% of screened patients enrolled. The study was conducted from August 2010 through November 2012 at Massachusetts General Hospital. INTERVENTIONS Sustained care participants received automated interactive voice response telephone calls and their choice of free smoking cessation medication (any type approved by the US Food and Drug Administration) for up to 90 days. The automated telephone calls promoted cessation, provided medication management, and triaged smokers for additional counseling. Standard care participants received recommendations for postdischarge pharmacotherapy and counseling. MAIN OUTCOMES AND MEASURES The primary outcome was biochemically confirmed past 7-day tobacco abstinence at 6-month follow-up after discharge from the hospital; secondary outcomes included self-reported tobacco abstinence. RESULTS Smokers randomly assigned to sustained care (n = 198) used more counseling and more pharmacotherapy at each follow-up assessment than those assigned to standard care (n = 199). Biochemically validated 7-day tobacco abstinence at 6 months was higher with sustained care (26%) than with standard care (15%) (relative risk [RR], 1.71 [95% CI, 1.14-2.56], P = .009; number needed to treat, 9.4 [95% CI, 5.4-35.5]). Using multiple imputation for missing outcomes, the RR for 7-day tobacco abstinence was 1.55 (95% CI, 1.03-2.21; P = .04). Sustained care also resulted in higher self-reported continuous abstinence rates for 6 months after discharge (27% vs 16% for standard care; RR, 1.70 [95% CI, 1.15-2.51]; P = .007). CONCLUSIONS AND RELEVANCE Among hospitalized adult smokers who wanted to quit smoking, a postdischarge intervention providing automated telephone calls and free medication resulted in higher rates of smoking cessation at 6 months compared with a standard recommendation to use counseling and medication after discharge. These findings, if replicated, suggest an approach to help achieve sustained smoking cessation after a hospital stay. C1 [Rigotti, Nancy A.; Regan, Susan; Levy, Douglas E.; Japuntich, Sandra; Park, Elyse R.; Viana, Joseph C.; Kelley, Jennifer H. I.; Reyen, Michele] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.; Regan, Susan; Chang, Yuchiao; Reyen, Michele; Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, Med Serv, Boston, MA 02114 USA. [Rigotti, Nancy A.; Levy, Douglas E.; Park, Elyse R.; Kelley, Jennifer H. I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Rigotti, Nancy A.; Levy, Douglas E.; Park, Elyse R.; Kelley, Jennifer H. I.] Partners HealthCare, Boston, MA USA. [Rigotti, Nancy A.; Regan, Susan; Levy, Douglas E.; Chang, Yuchiao; Singer, Daniel E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Japuntich, Sandra] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Japuntich, Sandra] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Park, Elyse R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Viana, Joseph C.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Los Angeles, CA USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St, Boston, MA 02114 USA. EM nrigotti@partners.org FU National Institutes of Health/National Heart, Lung, and Blood Institute [RC1 HL099668, K24 HL004440]; National Heart, Lung, and Blood Institute; National Cancer Institute; National Institute on Drug Abuse; National Institutes of Health Office of Behavioral and Social Science Research; US Department of Veterans Affairs Clinical Sciences Research and Development Service [11K2CX000918-01A1] FX This study was supported by grants RC1 HL099668 and K24 HL004440 from the National Institutes of Health/National Heart, Lung, and Blood Institute. This study is part of the Consortium of Hospitals Advancing Research on Tobacco initiative, jointly sponsored by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the National Institute on Drug Abuse, and the National Institutes of Health Office of Behavioral and Social Science Research. TelAsk Technologies (Ottawa, Ontario, Canada) developed and provided the interactive voice response services and was compensated for this work by the National Heart, Lung, and Blood Institute grants that funded the project. This work was supported in part by career development award 11K2CX000918-01A1 (Dr Japuntich) from the US Department of Veterans Affairs Clinical Sciences Research and Development Service. NR 32 TC 24 Z9 25 U1 0 U2 4 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 AUG 20 PY 2014 VL 312 IS 7 BP 719 EP 728 DI 10.1001/jama.2014.9237 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AN2TR UT WOS:000340438700020 PM 25138333 ER PT J AU Kwan, A Abraham, RS Currier, R Brower, A Andruszewski, K Abbott, JK Baker, M Ballow, M Bartoshesky, LE Bonilla, FA Brokopp, C Brooks, E Caggana, M Celestin, J Church, JA Comeau, AM Connelly, JA Cowan, MJ Cunningham-Rundles, C Dasu, T Dave, N De La Morena, MT Duffner, U Fong, CT Forbes, L Freedenberg, D Gelfand, EW Hale, JE Hanson, IC Hay, BN Hu, D Infante, A Johnson, D Kapoor, N Kay, DM Kohn, DB Lee, R Lehman, H Lin, ZL Lorey, F Abdel-Mageed, A Manning, A McGhee, S Moore, TB Naides, SJ Notarangelo, LD Orange, JS Pai, SY Porteus, M Rodriguez, R Romberg, N Routes, J Ruehle, M Rubenstein, A Saavedra-Matiz, CA Scott, G Scott, PM Secord, E Seroogy, C Shearer, WT Siegel, S Silvers, SK Stiehm, ER Sugerman, RW Sullivan, JL Tanksley, S Tierce, ML Verbsky, J Vogel, B Walker, R Walkovich, K Walter, JE Wasserman, RL Watson, MS Weinberg, GA Weiner, LB Wood, H Yates, AB Puck, JM AF Kwan, Antonia Abraham, Roshini S. Currier, Robert Brower, Amy Andruszewski, Karen Abbott, Jordan K. Baker, Mei Ballow, Mark Bartoshesky, Louis E. Bonilla, Francisco A. Brokopp, Charles Brooks, Edward Caggana, Michele Celestin, Jocelyn Church, Joseph A. Comeau, Anne Marie Connelly, James A. Cowan, Morton J. Cunningham-Rundles, Charlotte Dasu, Trivikram Dave, Nina De La Morena, Maria T. Duffner, Ulrich Fong, Chin-To Forbes, Lisa Freedenberg, Debra Gelfand, Erwin W. Hale, Jaime E. Hanson, I. Celine Hay, Beverly N. Hu, Diana Infante, Anthony Johnson, Daisy Kapoor, Neena Kay, Denise M. Kohn, Donald B. Lee, Rachel Lehman, Heather Lin, Zhili Lorey, Fred Abdel-Mageed, Aly Manning, Adrienne McGhee, Sean Moore, Theodore B. Naides, Stanley J. Notarangelo, Luigi D. Orange, Jordan S. Pai, Sung-Yun Porteus, Matthew Rodriguez, Ray Romberg, Neil Routes, John Ruehle, Mary Rubenstein, Arye Saavedra-Matiz, Carlos A. Scott, Ginger Scott, Patricia M. Secord, Elizabeth Seroogy, Christine Shearer, William T. Siegel, Subhadra Silvers, Stacy K. Stiehm, E. Richard Sugerman, Robert W. Sullivan, John L. Tanksley, Susan Tierce, Millard L. Verbsky, James Vogel, Beth Walker, Rosalyn Walkovich, Kelly Walter, Jolan E. Wasserman, Richard L. Watson, Michael S. Weinberg, Geoffrey A. Weiner, Leonard B. Wood, Heather Yates, Anne B. Puck, Jennifer M. TI Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID T-CELL LYMPHOPENIA; 1ST 2 YEARS; IMMUNE-DEFICIENCY; OMENN SYNDROME; CHILDREN; TRANSPLANTATION; EXPERIENCE; MUTATIONS; PHENOTYPES; TTC7A AB IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95% CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58 000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined. C1 [Kwan, Antonia; Cowan, Morton J.; Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Kwan, Antonia; Cowan, Morton J.; Puck, Jennifer M.] Univ Calif San Francisco, Benioff Childrens Hosp, San Francisco, CA USA. [Abraham, Roshini S.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Currier, Robert; Lorey, Fred] Calif Dept Publ Hlth, Genet Dis Screening Program, Richmond, CA USA. [Brower, Amy; Watson, Michael S.] Amer Coll Med Genet & Genom, Newborn Screening Translat Res Network, Bethesda, MD USA. [Andruszewski, Karen; Wood, Heather] Michigan Dept Community Hlth, Lansing, MI USA. [Abbott, Jordan K.; Gelfand, Erwin W.] Natl Jewish Hlth, Div Allergy & Immunol, Dept Pediat, Denver, CO USA. [Baker, Mei] Wisconsin State Lab Hyg, Newborn Screening Lab, Madison, WI USA. [Baker, Mei] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Ballow, Mark; Lehman, Heather] Women & Childrens Hosp Buffalo, Buffalo, NY USA. [Bartoshesky, Louis E.] Christiana Care Hlth Syst, Dept Pediat, Wilmington, DE USA. [Bonilla, Francisco A.; Notarangelo, Luigi D.; Pai, Sung-Yun] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Bonilla, Francisco A.; Notarangelo, Luigi D.; Pai, Sung-Yun] Harvard Univ, Sch Med, Boston, MA USA. [Brokopp, Charles] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Brooks, Edward; Infante, Anthony] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Caggana, Michele; Kay, Denise M.; Saavedra-Matiz, Carlos A.; Vogel, Beth] New York State Dept Hlth, Newborn Screening Program, Wadsworth Ctr, Albany, NY 12237 USA. [Celestin, Jocelyn] Albany Med Coll, Div Allergy & Immunol, Albany, NY 12208 USA. [Church, Joseph A.; Kapoor, Neena] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Church, Joseph A.; Kapoor, Neena] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Comeau, Anne Marie; Hale, Jaime E.] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Jamaica Plain, MA USA. [Connelly, James A.; Walkovich, Kelly] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Cunningham-Rundles, Charlotte] Mt Sinai Med Ctr, New York, NY 10029 USA. [Dasu, Trivikram] Med Coll Wisconsin, Clin Immunodiagnost & Res Lab, Milwaukee, WI 53226 USA. [Dave, Nina; Rodriguez, Ray; Walker, Rosalyn; Yates, Anne B.] Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS USA. [De La Morena, Maria T.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Duffner, Ulrich; Abdel-Mageed, Aly] Helen DeVos Childrens Hosp, Div Blood & Bone Marrow Transplantat, Grand Rapids, MI USA. [Fong, Chin-To; Weinberg, Geoffrey A.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Forbes, Lisa; Hanson, I. Celine; Orange, Jordan S.; Shearer, William T.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Forbes, Lisa; Hanson, I. Celine; Orange, Jordan S.; Shearer, William T.] Texas Childrens Hosp, Houston, TX 77030 USA. [Freedenberg, Debra; Johnson, Daisy; Scott, Ginger; Tanksley, Susan] Texas Dept State Hlth Serv, Austin, TX USA. [Comeau, Anne Marie; Hay, Beverly N.; Sullivan, John L.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Hu, Diana] Tuba City Reg Hlth Care, Tuba City, AZ USA. [Kohn, Donald B.; Moore, Theodore B.; Stiehm, E. Richard] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Lin, Zhili] PerkinElmer Genet, Bridgeville, PA USA. [Manning, Adrienne] Connecticut Dept Publ Hlth Lab, Rocky Hill, CT USA. [McGhee, Sean; Porteus, Matthew] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. [McGhee, Sean; Porteus, Matthew] Lucille Packard Childrens Hosp, Palo Alto, CA USA. [Naides, Stanley J.] Quest Diagnost Nichols Inst, Dept Immunol, San Juan Capistrano, CA USA. [Romberg, Neil] Yale Univ, Sch Med, Dept Pediat, Div Allergy & Clin Immunol, New Haven, CT 06510 USA. [Routes, John; Verbsky, James] Med Coll Wisconsin, Dept Pediat, Childrens Res Inst, Milwaukee, WI 53226 USA. [Ruehle, Mary; Secord, Elizabeth; Tierce, Millard L.] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Rubenstein, Arye] Montefiore Med Pk, Div Allergy & Immunol, Bronx, NY USA. [Scott, Patricia M.] Delaware Publ Hlth Lab, Newborn Screening Program, Smyrna, DE USA. [Seroogy, Christine] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53706 USA. [Siegel, Subhadra] New York Med Coll, Westchester Med Ctr, Valhalla, NY 10595 USA. [Silvers, Stacy K.; Sugerman, Robert W.; Wasserman, Richard L.] Med City Childrens Hosp, Dallas, TX USA. [Walter, Jolan E.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Walter, Jolan E.] Harvard Univ, Sch Med, Boston, MA USA. [Weiner, Leonard B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. RP Puck, JM (reprint author), Univ Calif San Francisco, Dept Pediat, HSE-301A,513 Parnassus Ave, San Francisco, CA 94143 USA. EM puckj@peds.ucsf.edu RI Notarangelo, Luigi/F-9718-2016; Abbott, Jordan/P-2509-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Abbott, Jordan/0000-0001-6334-5266; Kay, Denise/0000-0002-9928-2698; orange, jordan/0000-0001-7117-7725; Bonagura, Vincent/0000-0002-0681-2099 FU California: National Institutes of Health (NIH) [HHSN267200603430C]; National Institutes of Health (NIH) through New York [R01 FD003005-01, U01 AI1087628, RO1 AI078248, AI105776]; HCA International Foundation Travelling Scholarship; Jeffrey Modell Foundation; Perkin Elmer Genetics; Colorado: Colorado Department of Public Heath and Environment; Delaware: Centers for Disease Control and Prevention (CDC) [U01 EH000454]; Massachusetts: CDC [UO1 EH000362]; New England Newborn Screening Program funds; Michigan: CDC [U01 EH000936]; Mississippi: Mississippi State Department of Health; Navajo Nation: NIH [RO3HD060311]; New York: NIH [HHSN26720060343OC]; New York State Department of Health; Texas: CDC through New England Newborn Screening Program; Texas: Jeffery Modell Foundation; Children's Hospital of Wisconsin; Wisconsin State Laboratory of Hygiene; CDC [U01 EH000365]; Primary Immunodeficiency Treatment Consortium [U54 A1082973, R13-A1094943]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH [HHSN27520080001C] FX This study received support from the following institutions: in California: National Institutes of Health (NIH) (HHSN267200603430C through New York, R01 FD003005-01, U01 AI1087628 [D. B. K.]; RO1 AI078248, AI105776 [J. M.P.]); HCA International Foundation Travelling Scholarship (A. K.); Jeffrey Modell Foundation; and Perkin Elmer Genetics. In Colorado: Colorado Department of Public Heath and Environment. In Connecticut: state appropriation, pursuant to Public Act 11-48, Sections 38 and 39, which mandated the inclusion of testing for severe combined immunodeficiency (SCID) in the Connecticut Newborn Screening Disorders Panel and provided increased agency funding to accomplish this mandate. In Delaware: Centers for Disease Control and Prevention (CDC) (U01 EH000454) and state funding. In Massachusetts: CDC (UO1 EH000362) and New England Newborn Screening Program funds. In Michigan: CDC (U01 EH000936). In Mississippi: Mississippi State Department of Health. In the Navajo Nation: NIH (RO3HD060311 [J. M. P.]) and a gift to Navajo-area delivering hospitals from PerlkinElmer Genetics, Bridgeville, Pennsylvania. In New York: NIH (HHSN26720060343OC), Jeffrey Modell Foundation, and New York State Department of Health. In Texas: CDC grant through New England Newborn Screening Program (pilot phase), Jeffrey Modell Foundation, and the Texas Department of State Health Services. In Wisconsin: Jeffery Modell Foundation, Children's Hospital of Wisconsin, Wisconsin State Laboratory of Hygiene, CDC (U01 EH000365), and Primary Immunodeficiency Treatment Consortium (U54 A1082973 [M. J. C.], R13-A1094943 [M. J. C., L.D.N.]). The Newborn Screening Translational Research Network (NBSTRN) is a contract to the American College of Medical Genetics and Genomics by Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH (HHSN27520080001C). NR 47 TC 91 Z9 96 U1 2 U2 12 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 AUG 20 PY 2014 VL 312 IS 7 BP 729 EP 738 DI 10.1001/jama.2014.9132 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AN2TR UT WOS:000340438700021 PM 25138334 ER PT J AU McCleary, NJ Dotan, E Browner, I AF McCleary, Nadine J. Dotan, Efrat Browner, Ilene TI Refining the Chemotherapy Approach for Older Patients With Colon Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID METASTATIC COLORECTAL-CANCER; RANDOMIZED CONTROLLED-TRIAL; BRITE OBSERVATIONAL COHORT; POPULATION-BASED COHORT; PHASE-III TRIAL; ELDERLY-PATIENTS; ADJUVANT CHEMOTHERAPY; CLINICAL-TRIALS; 1ST-LINE TREATMENT; POOLED ANALYSIS AB Population studies support an increased incidence of most cancers among older adults. Colorectal cancer has high prevalence in the aging population, with a median age of 69 years at diagnosis and 74 years at death. The vast majority of patients with colon cancer (CC) will require chemotherapy treatments during their disease course, challenging oncologists with the task of tailoring therapy for older patients with CC in the face of limited evidence-based data to guide them. Factors such as comorbidity, performance status, cognitive function, and social support may affect decision making and complicate tolerance of any recommended therapy. In recent years, attention to the specific needs of the aging population with cancer has given rise to the field of geriatric oncology in general, and has generated an increasing fund of knowledge on which to base chemotherapy delivery for this specific population of patients with CC. This article will review the available data specifically for chemotherapy management of older patients with CC in the postoperative and metastatic settings. (C) 2014 by American Society of Clinical Oncology C1 [McCleary, Nadine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dotan, Efrat] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Browner, Ilene] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP McCleary, NJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM nj_mccleary@dfci.harvard.edu NR 74 TC 14 Z9 14 U1 0 U2 5 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 AUG 20 PY 2014 VL 32 IS 24 BP 2570 EP 2580 DI 10.1200/JCO.2014.55.1960 PG 11 WC Oncology SC Oncology GA AN6TQ UT WOS:000340731100007 PM 25071118 ER PT J AU Finci, LI Kruger, N Sun, XQ Zhang, J Chegkazi, M Wu, Y Schenk, G Mertens, HDT Svergun, DI Zhang, Y Wang, JH Meijers, R AF Finci, Lorenzo I. Krueger, Nina Sun, Xiaqin Zhang, Jie Chegkazi, Magda Wu, Yu Schenk, Gundolf Mertens, Haydyn D. T. Svergun, Dmitri I. Zhang, Yan Wang, Jia-huai Meijers, Rob TI The Crystal Structure of Netrin-1 in Complex with DCC Reveals the Bifunctionality of Netrin-1 As a Guidance Cue SO NEURON LA English DT Article ID AXON GUIDANCE; SCATTERING DATA; RECEPTOR; FAMILY; BINDING; GROWTH; DOMAIN; IDENTIFICATION; ATTRACTION; HEPARIN AB Netrin-1 is a guidance cue that can trigger either attraction or repulsion effects on migrating axons of neurons, depending on the repertoire of receptors available on the growth cone. How a single chemotropic molecule can act in such contradictory ways has long been a puzzle at the molecular level. Here wepresent the crystal structure of netrin-1 in complex with the Deleted in Colorectal Cancer (DCC) receptor. We show that one netrin-1 molecule can simultaneously bind to two DCC molecules through a DCC-specific site and through a unique generic receptor binding site, where sulfate ions staple together positively charged patches on both DCC and netrin-1. Furthermore, we demonstrate that UNC5A can replace DCC on the generic receptor binding site to switch the response from attraction to repulsion. We propose that the modularity of binding allows for the association of other netrin receptors at the generic binding site, eliciting alternative turning responses. C1 [Finci, Lorenzo I.; Sun, Xiaqin; Zhang, Jie; Wu, Yu; Zhang, Yan; Wang, Jia-huai] Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. [Finci, Lorenzo I.; Wang, Jia-huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Krueger, Nina; Chegkazi, Magda; Schenk, Gundolf; Mertens, Haydyn D. T.; Svergun, Dmitri I.; Meijers, Rob] EMBL, Hamburg Outstn, D-22607 Hamburg, Germany. [Zhang, Yan] Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China. RP Zhang, Y (reprint author), Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. EM yanzhang@pku.edu.cn; jwang@red.dfci.harvard.edu; r.meijers@embl-hamburg.de RI Meijers, Rob/D-5521-2011; OI Mertens, Haydyn/0000-0002-5664-744X; Svergun, Dmitri/0000-0003-0830-5696; Meijers, Rob/0000-0003-2872-6279 FU Ministry of Education of China; National Science Foundation of China (NSFC) [91132718]; Beijing Natural Science Foundation [7142085]; NIH [HL48675]; Peking-Tsinghua Center for Life Sciences; short-term EMBO postdoctoral fellowship; European Commission [283570, 261572] FX We thank Yi Rao, Matthias Wilmanns, and Steve Harrison for critical reading of the manuscript; the staff of the EMBL beamlines P12 and P14; and the sample preparation and characterization (SPC) facility of EMBL at PETRA3 (DESY, Hamburg) for assistance. We also thank Jonathan Rapley and Liya Xu for early exploration of the project and Rebecca Spoerl and Alexandra Koetter for technical support. Work was funded by the Ministry of Education of China to J.-H.W. and Y.Z., the National Science Foundation of China (NSFC) Major Research Grant (91132718) and the Beijing Natural Science Foundation (7142085) to Y.Z., an NIH grant (HL48675) and funds from the Peking-Tsinghua Center for Life Sciences to J.-H.W., and a short-term EMBO postdoctoral fellowship to L. I. F. The authors G. S., H. D. T. M, and D. S. acknowledge support by the European Commission (the 7th Framework Program) projects Bio-Struct-X (contract number 283570) and WeNMR (contract number 261572). NR 45 TC 23 Z9 24 U1 2 U2 11 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 AUG 20 PY 2014 VL 83 IS 4 BP 839 EP 849 DI 10.1016/j.neuron.2014.07.010 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AN3ID UT WOS:000340479600012 PM 25123307 ER PT J AU Uchida, M Faraone, SV Martelon, M Kenworthy, T Woodworth, KY Spencer, TJ Wozniak, JR Biederman, J AF Uchida, Mai Faraone, Stephen V. Martelon, MaryKate Kenworthy, Tara Woodworth, K. Yvonne Spencer, Thomas J. Wozniak, Janet R. Biederman, Joseph TI Further evidence that severe scores in the aggression/anxiety-depression/attention subscales of child behavior checklist (severe dysregulation profile) can screen for bipolar disorder symptomatology: a conditional probability analysis SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Mood disorders; Severity of illness index; Screening instrument; CBCL; Bipolar disorder ID DEFICIT HYPERACTIVITY DISORDER; I DISORDER; DIAGNOSTIC-ACCURACY; CONTROLLED FAMILY; CONDUCT DISORDER; JUVENILE MANIA; CBCL; ADHD; METAANALYSIS; COMORBIDITY AB Background: Previous work shows that children with high scores (2SD, combined score >= 210) on the Attention Problems, Aggressive Behavior, and Anxious-Depressed (A-A-A) subscales of the Child Behavior Checklist (CBCL) are more likely than other children to meet criteria for bipolar (BP)-I disorder. However, the utility of this profile as a screening tool has remained unclear. Methods: We compared 140 patients with pediatric BP-I disorder, 83 with attention deficit hyperactivity disorder (ADHD), and 114 control subjects. We defined the CBCL-Severe Dysregulation profile as an aggregate cutoff score of >= 210 on the A-A-A scales. Patients were assessed with structured diagnostic interviews and functional measures. Results: Patients with BP-I disorder were significantly more likely than both control subjects (Odds Ratio [OR]: 173.2; 95% Confidence Interval [CI], 21.2 to 1413.8; P < 0.001) and those with ADHD (OR: 14.6; 95% CI, 6.2 to 34.3; P < 0.001) to have a positive CBCL-Severe Dysregulation profile. Receiver Operating Characteristics analyses showed that the area under the curve for this profile comparing children with BP-I disorder against control subjects and those with ADHD was 99% and 85%, respectively. The corresponding positive predictive values for this profile were 99% and 92% with false positive rates of < 0.2% and 8% for the comparisons with control subjects and patients with ADHD, respectively. Limitations: Non-clinician raters administered structured diagnostic interviews, and the sample was referred and largely Caucasian. Conclusions: The CBCL-Severe Dysregulation profile can be useful as a screen for BP-I disorder in children in clinical practice. (C) 2014 Elsevier B.V. All rights reserved. C1 [Uchida, Mai; Martelon, MaryKate; Kenworthy, Tara; Woodworth, K. Yvonne; Spencer, Thomas J.; Wozniak, Janet R.; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Uchida, Mai; Martelon, MaryKate; Kenworthy, Tara; Woodworth, K. Yvonne; Spencer, Thomas J.; Wozniak, Janet R.; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program ADHD, Boston, MA 02114 USA. [Uchida, Mai; Spencer, Thomas J.; Wozniak, Janet R.; 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 Biederman, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Health (NIH) [R01 HD36317, R01 MH50657]; Pediatric Psychopharmacology Research Council Fund FX This manuscript was supported in part by grants to J. Biederman from the National Institute of Health (NIH) Nos. (R01 HD36317; R01 MH50657) and the Pediatric Psychopharmacology Research Council Fund. NR 37 TC 10 Z9 10 U1 2 U2 15 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 AUG 20 PY 2014 VL 165 BP 81 EP 86 DI 10.1016/j.jad.2014.04.021 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AJ7FF UT WOS:000337861900013 PM 24882182 ER PT J AU Tsai, J Elhai, JD Pietrzak, RH Hoff, RA Harpaz-Rotem, I AF Tsai, Jack Elhai, Jon D. Pietrzak, Robert H. Hoff, Rani A. Harpaz-Rotem, Ilan TI Comparing four competing models of depressive symptomatology: A confirmatory factor analytic study of 986,647 US veterans SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Veterans; Confirmatory factor analyses ID SPINAL-CORD-INJURY; PATIENT HEALTH QUESTIONNAIRE-9; NATIONAL-COMORBIDITY-SURVEY; OF-FIT INDEXES; MAJOR DEPRESSION; PRIMARY-CARE; SYMPTOMS; EPIDEMIOLOGY; ANXIETY; INVARIANCE AB Background: Few rigorous studies have examined the factor structure of major depression symptoms as assessed by current diagnostic systems. This study evaluated four competing models of depressive symptomatology among a large, heterogeneous sample of U.S. veterans. Methods: To determine the best fitting model of major depressive symptoms among four competing models, this study conducted a series of confirmatory factor analyses on a national sample of 986,647 U.S. veterans. Results: A two-factor model first reported by Krause, Reed, and McArdle (2010) provided superior fit to symptom-level data compared to three other models. The optimal model consists of a somatic factor including anhedonia, sleep difficulties, fatigue, appetite changes, concentration difficulties, and psychomotor agitation; and a non-somatic factor including depressed mood, feelings of worthlessness, and thoughts of death. Factorial invariance testing found this model to be invariant by gender and major depression diagnosis. Limitations: A widely used self-report measure of depression was used and the sample consisted solely of veterans so further study is needed with clinician-administered measures and non-veteran samples. Conclusions: Together, these findings support separating symptoms of major depression into somatic and non-somatic factors which may have clinical relevance, and help clarify debates about the factor structure of depressive symptoms. Published by Elsevier B.V. C1 [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT 06516 USA. [Tsai, Jack; Pietrzak, Robert H.; Hoff, Rani A.; Harpaz-Rotem, Ilan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Elhai, Jon D.] Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. [Elhai, Jon D.] Univ Toledo, Dept Psychiat, Toledo, OH 43606 USA. [Pietrzak, Robert H.; Harpaz-Rotem, Ilan] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT 06516 USA. [Hoff, Rani A.] Vet Affairs Northeast Program Evaluat Ctr, West Haven, CT 06516 USA. RP Tsai, J (reprint author), US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM Jack.Tsai@yale.edu OI Tsai, Jack/0000-0002-0329-648X FU Bristol Meyers Squibb Foundation; United States Department of Veterans Affairs, Office of Research and Development FX None of the authors report any conflicts of interest related to this work. Dr. Tsai has received funding from the Bristol Meyers Squibb Foundation, which had no influence on this work. This work was supported by the United States Department of Veterans Affairs, Office of Research and Development. The views presented here are those of the authors alone and do not represent the position of any federal agency or of the United States Government. NR 24 TC 6 Z9 6 U1 0 U2 4 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 AUG 20 PY 2014 VL 165 BP 166 EP 169 DI 10.1016/j.jad.2014.04.075 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AJ7FF UT WOS:000337861900026 PM 24882195 ER PT J AU Frank, DA Marrazzo, J AF Frank, David A. Marrazzo, Jeanne TI Self-collected samples are less accurate for HPV testing than clinician-collected samples SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Frank, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marrazzo, Jeanne] Univ Washington, Seattle, WA 98195 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2014 VL 161 IS 4 AR JC11 DI 10.7326/0003-4819-161-4-201408190-02011 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AP8RU UT WOS:000342347300010 PM 25133378 ER PT J AU Kansagara, D Papak, J Pasha, AS O'Neil, M Freeman, M Relevo, R Quinones, A Motu'apuaka, M Jou, JH AF Kansagara, Devan Papak, Joel Pasha, Amirala S. O'Neil, Maya Freeman, Michele Relevo, Rose Quinones, Ana Motu'apuaka, Makalapua Jou, Janice H. TI Screening for Hepatocellular Carcinoma in Chronic Liver Disease A Systematic Review SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC VIRAL-HEPATITIS; CIRRHOTIC-PATIENTS; PATIENT SURVIVAL; NATURAL-HISTORY; SURVEILLANCE PROGRAM; COST-EFFECTIVENESS; CLINICAL-PRACTICE; CANCER INCIDENCE; EARLY-DIAGNOSIS AB Background: Guidelines recommend routine screening for hepatocellular carcinoma (HCC) in high-risk patients, but the strength of evidence supporting these recommendations is unclear. Purpose: To review the benefits and harms of HCC screening in patients with chronic liver disease. Data Sources: MEDLINE, PsycINFO, and ClinicalTrials.gov from inception to April 2014; Cochrane databases to June 2013; reference lists; and technical advisors. Study Selection: English-language trials and observational studies comparing screening versus no screening, studies of harms, and trials comparing different screening intervals. Data Extraction: Mortality and adverse events were the outcomes of interest. Individual-study quality and the overall strength of evidence were dual-reviewed using published criteria. Data Synthesis: Of 13 801 citations, 22 studies met inclusion criteria. The overall strength of evidence on the effects of screening was very low. One large trial of patients with hepatitis B found decreased HCC mortality with periodic ultrasonographic screening (rate ratio, 0.63 [95% CI, 0.41 to 0.98]), but the study was limited by methodological flaws. Another trial in patients with hepatitis B found no survival benefit with periodic alpha-fetoprotein screening. In 18 observational studies, screened patients had earlier-stage HCC than clinically diagnosed patients, but lead- and length-time biases confounded the effects on mortality. Two trials found no survival differences between shorter (3- to 4-month) and longer (6- to 12-month) screening intervals. Harms of screening were not well-studied. Limitations: Only English-language studies were included. The evidence base is limited by methodological issues and a paucity of trials. Conclusion: There is very-low-strength evidence about the effects of HCC screening on mortality in patients with chronic liver disease. Screening tests can identify early-stage HCC, but whether systematic screening leads to a survival advantage over clinical diagnosis is uncertain. C1 [Kansagara, Devan; O'Neil, Maya; Freeman, Michele; Relevo, Rose] Portland VA Med Ctr, Portland, OR 97239 USA. [Papak, Joel; Jou, Janice H.] Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. [Pasha, Amirala S.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Quinones, Ana] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Motu'apuaka, Makalapua] Oregon Evidence Based Practice Ctr, Portland, OR 97233 USA. RP Kansagara, D (reprint author), Portland VA Med Ctr, RD71,3710 SW US Veterans Hosp Rd, Portland, OR 97239 USA. EM kansagar@ohsu.edu FU U.S. Department of Veterans Affairs Quality Enhancement Research Initiative FX U.S. Department of Veterans Affairs Quality Enhancement Research Initiative. NR 56 TC 37 Z9 38 U1 2 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2014 VL 161 IS 4 BP 261 EP + DI 10.7326/M14-0558 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AP8RU UT WOS:000342347300016 PM 24934699 ER PT J AU Zipkin, DA Umscheid, CA Keating, NL Allen, E Aung, K Beyth, R Kaatz, S Mann, DM Sussman, JB Korenstein, D Schardt, C Nagi, A Sloane, R Feldstein, DA AF Zipkin, Daniella A. Umscheid, Craig A. Keating, Nancy L. Allen, Elizabeth Aung, Koko Beyth, Rebecca Kaatz, Scott Mann, Devin M. Sussman, Jeremy B. Korenstein, Deborah Schardt, Connie Nagi, Avishek Sloane, Richard Feldstein, David A. TI Evidence-Based Risk Communication A Systematic Review SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER RISKS; DECISION-MAKING; PRESENTING RISK; DIFFERENT FORMATS; RELATIVE RISK; QUANTITATIVE INFORMATION; FRAMING INFORMATION; INFORMING PATIENTS; TREATMENT CHOICES AB Background: Effective communication of risks and benefits to patients is critical for shared decision making. Purpose: To review the comparative effectiveness of methods of communicating probabilistic information to patients that maximize their cognitive and behavioral outcomes. Data Sources: PubMed (1966 to March 2014) and CINAHL, EMBASE, and the Cochrane Central Register of Controlled Trials (1966 to December 2011) using several keywords and structured terms. Study Selection: Prospective or cross-sectional studies that recruited patients or healthy volunteers and compared any method of communicating probabilistic information with another method. Data Extraction: Two independent reviewers extracted study characteristics and assessed risk of bias. Data Synthesis: Eighty-four articles, representing 91 unique studies, evaluated various methods of numerical and visual risk display across several risk scenarios and with diverse outcome measures. Studies showed that visual aids (icon arrays and bar graphs) improved patients' understanding and satisfaction. Presentations including absolute risk reductions were better than those including relative risk reductions for maximizing accuracy and seemed less likely than presentations with relative risk reductions to influence decisions to accept therapy. The presentation of numbers needed to treat reduced understanding. Comparative effects of presentations of frequencies (such as 1 in 5) versus event rates (percentages, such as 20%) were inconclusive. Limitation: Most studies were small and highly variable in terms of setting, context, and methods of administering interventions. Conclusion: Visual aids and absolute risk formats can improve patients' understanding of probabilistic information, whereas numbers needed to treat can lessen their understanding. Due to study heterogeneity, the superiority of any single method for conveying probabilistic information is not established, but there are several good options to help clinicians communicate with patients. C1 [Zipkin, Daniella A.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Umscheid, Craig A.] Univ Penn, Ctr Evidence Based Practice, Philadelphia, PA 19104 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Allen, Elizabeth] Portland VA Med Ctr, Portland, OR 97207 USA. [Aung, Koko] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Beyth, Rebecca] North Florida South Georgia Vet Hlth Syst, Geriatric Res Educ & Clin Ctr T2 182, Gainesville, FL 32608 USA. [Kaatz, Scott] Hurley Med Ctr, Flint, MI 48503 USA. [Mann, Devin M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sussman, Jeremy B.] Ctr Clin Management Res, Ann Arbor, MI 48109 USA. [Korenstein, Deborah] Amer Coll Physicians, Philadelphia, PA 19106 USA. [Schardt, Connie] Univ N Carolina, Sch Lib & Informat Sci, Chapel Hill, NC 27599 USA. [Nagi, Avishek] Vet Affairs Med Ctr, Durham, NC 27705 USA. [Sloane, Richard] Duke Univ, Med Ctr, Ctr Study Aging, Durham, NC 27710 USA. [Feldstein, David A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. RP Zipkin, DA (reprint author), Duke Univ, Med Ctr, Box 2992, Durham, NC 27710 USA. EM daniella.zipkin@duke.edu OI Mann, Devin/0000-0002-2099-0852 NR 103 TC 39 Z9 39 U1 5 U2 31 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2014 VL 161 IS 4 BP 270 EP + DI 10.7326/M14-0295 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AP8RU UT WOS:000342347300017 PM 25133362 ER PT J AU Nikolaou, P Coffey, AM Barlow, MJ Rosen, MS Goodson, BM Chekmenev, EY AF Nikolaou, Panayiotis Coffey, Aaron M. Barlow, Michael J. Rosen, Matthew S. Goodson, Boyd M. Chekmenev, Eduard Y. TI Temperature-Ramped Xe-129 Spin-Exchange Optical Pumping SO ANALYTICAL CHEMISTRY LA English DT Article ID VOLUME HOLOGRAPHIC GRATINGS; POLARIZED NOBLE-GASES; LASER-DIODE ARRAYS; VERY-LOW-FIELD; HYPERPOLARIZED XE-129; MAGNETIC-RESONANCE; HUMAN LUNG; OPEN-ACCESS; MRI; SYSTEM AB We describe temperature-ramped spin-exchange optical pumping (TR-SEOP) in an automated high-throughput batch-mode Xe-129 hyperpolarizer utilizing three key temperature regimes: (i) "hot" where the Xe-129 hypeipolarization rate is maximal, (ii) "warm" where the Xe-129 hyperpolarization approaches unity, and (iii) "cool" where hyperpolarized Xe-129 gas is transferred into a Tedlar bag with low Rb content (<5 ng per similar to 1. L dose) suitable for human imaging applications. Unlike with the conventional approach of batch-mode SEOP, here all three temperature regimes may be operated under continuous high-power (170 W) laser irradiation, and hypetpolarized Xe-129 gas is delivered without the need for a cryocollection step. The variable-temperature approach increased the SEOP rate by more than 2-fold compared to the constant-temperature polarization rate (e.g., giving effective values for the exponential buildup constant gamma(SEOP) of 62.5 +/- 3.7 x 10(-3) min(-1) vs 29.9 +/- 1.2 x 10-3 min-1) while achieving nearly the same maximum %P-xe value (88.0 +/- 0.8% vs 90.1% +/- 0.8%, for a 500 Torr (67 kPa) Xe cell loading corresponding to nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI) enhancements of similar to 3.1 x 10(5) and similar to 2.32 x 10(8) at the relevant fields for clinical imaging and HP Xe-129 production of 3 T and 4 mT, respectively); moreover, the intercycle "dead" time was also significantly decreased. The higher-throughput TR-SEOP approach can be implemented without sacrificing the level of Xe-129 hyperpolarization or the experimental stability for automation making this approach beneficial for improving the overall Xe-129 production rate in clinical settings. C1 [Nikolaou, Panayiotis; Coffey, Aaron M.; Chekmenev, Eduard Y.] Vanderbilt Univ, Inst Imaging Sci, Dept Radiol, Nashville, TN 37232 USA. [Barlow, Michael J.] Univ Nottingham, Sir Peter Mansfield Magnet Resonance Ctr, Nottingham NG7 2RD, England. [Rosen, Matthew S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Rosen, Matthew S.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Goodson, Boyd M.] So Illinois Univ, Dept Chem & Biochem, Carbondale, IL 62901 USA. [Coffey, Aaron M.; Chekmenev, Eduard Y.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37205 USA. [Chekmenev, Eduard Y.] Vanderbilt Univ, Dept Biochem, Nashville, TN 37205 USA. [Chekmenev, Eduard Y.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37205 USA. RP Nikolaou, P (reprint author), Vanderbilt Univ, Inst Imaging Sci, Dept Radiol, Nashville, TN 37232 USA. EM peter.nikolaou@vanderbilt.edu; eduard.chekmenev@vanderbilt.edu RI Coffey, Aaron/Q-3921-2016; OI Chekmenev, Eduard/0000-0002-8745-8801; Goodson, Boyd/0000-0001-6079-5077 FU DoD CDMRP Era of Hope Award [W81XWH-12-1-0159/BC112431]; SIU Office of Sponsored Projects Administration (OSPA); NIH [2R15EB007074-02, 3R00CA134749-03]; School of Medicine, University of Nottingham, U.K.; Department of Defense, Defense Medical Research and Development Program, Applied Research and Advanced Technology Development Award [W81XWH-11-2-0076 (DM09094)] FX We thank the anonymous reviewers for helpful suggestions. Work at Vanderbilt and SIUC is supported by a DoD CDMRP Era of Hope Award W81XWH-12-1-0159/BC112431. Portions of this work were supported by SIU Office of Sponsored Projects Administration (OSPA). B.M.G. is supported in part by the NIH (2R15EB007074-02). E.Y.C. is supported in part by the NIH (3R00CA134749-03). M.J.B. acknowledges the support of the School of Medicine, University of Nottingham, U.K. M.S.R. acknowledges the support of Department of Defense, Defense Medical Research and Development Program, Applied Research and Advanced Technology Development Award: Grant No. W81XWH-11-2-0076 (DM09094). NR 39 TC 11 Z9 11 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD AUG 19 PY 2014 VL 86 IS 16 BP 8206 EP 8212 DI 10.1021/ac501537w PG 7 WC Chemistry, Analytical SC Chemistry GA AN6JT UT WOS:000340701500027 PM 25008290 ER PT J AU Kilarski, LL Achterberg, S Devan, WJ Traylor, M Malik, R Lindgren, A Pare, G Sharma, P Slowik, A Thijs, V Walters, M Worrall, BB Sale, MM Algra, A Kappelle, LJ Wijmenga, C Norrving, B Sandling, JK Ronnblom, L Goris, A Franke, A Sudlow, C Rothwell, PM Levi, C Holliday, EG Fornage, M Psaty, B Gretarsdottir, S Thorsteinsdottir, U Seshadri, S Mitchell, BD Kittner, S Clarke, R Hopewell, JC Bis, JC Boncoraglio, GB Meschia, J Ikram, MA Hansen, BM Montaner, J Thorleifsson, G Stefanson, K Rosand, J de Bakker, PIW Farrall, M Dichgans, M Markus, HS Bevan, S AF Kilarski, Laura L. Achterberg, Sefanja Devan, William J. Traylor, Matthew Malik, Rainer Lindgren, Arne Pare, Guillame Sharma, Pankaj Slowik, Agniesczka Thijs, Vincent Walters, Matthew Worrall, Bradford B. Sale, Michele M. Algra, Ale Kappelle, L. Jaap Wijmenga, Cisca Norrving, Bo Sandling, Johanna K. Roennblom, Lars Goris, An Franke, Andre Sudlow, Cathie Rothwell, Peter M. Levi, Christopher Holliday, Elizabeth G. Fornage, Myriam Psaty, Bruce Gretarsdottir, Solveig Thorsteinsdottir, Unnar Seshadri, Sudha Mitchell, Braxton D. Kittner, Steven Clarke, Robert Hopewell, Jemma C. Bis, Joshua C. Boncoraglio, Giorgio B. Meschia, James Ikram, M. Arfan Hansen, Bjorn M. Montaner, Joan Thorleifsson, Gudmar Stefanson, Kari Rosand, Jonathan de Bakker, Paul I. W. Farrall, Martin Dichgans, Martin Markus, Hugh S. Bevan, Steve CA Garnet Collaborative Res Grp Wellcome Trust Case Australian Stroke Metastroke Consortium Int Stroke Genetics Consortium TI Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12 SO NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; INTRACEREBRAL HEMORRHAGE; RISK-FACTORS; IMPUTATION; RATIONALE; VARIANTS; ALLELES; DESIGN; BURDEN; LOCI AB Objectives: To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. Results: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 x 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695). Conclusion: Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage. C1 [Kilarski, Laura L.; Traylor, Matthew] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Achterberg, Sefanja; Algra, Ale; Kappelle, L. Jaap] Univ Med Ctr, Utrecht Stroke Ctr, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Algra, Ale; de Bakker, Paul I. W.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Thorleifsson, Gudmar; de Bakker, Paul I. W.] Univ Med Ctr, Dept Med Genet, Utrecht, Netherlands. [Devan, William J.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Devan, William J.; Rosand, Jonathan; de Bakker, Paul I. W.; Dichgans, Martin] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Malik, Rainer] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Munich, Germany. [Lindgren, Arne; Norrving, Bo; Hansen, Bjorn M.] Lund Univ, Dept Clin Sci Lund, Lund, Sweden. [Lindgren, Arne; Norrving, Bo; Hansen, Bjorn M.] Skane Univ Hosp, Dept Neurol, Lund, Sweden. [Pare, Guillame] McMaster Univ, Dept Pathol & Mol Med, Populat Hlth Res Inst, Hamilton, ON, Canada. [Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London SW7 2AZ, England. [Slowik, Agniesczka] Jagiellonian Univ, Dept Neurol, Krakow, Poland. [Thijs, Vincent] VIB, Vesalius Res Ctr, Neurobiol Lab, Leuven, Belgium. [Thijs, Vincent] Univ Leuven KU Leuven, Louvain, Belgium. [Thijs, Vincent] Univ Leuven KU Leuven, Leuven Res Inst Neurodegenerat Dis LIND, Louvain, Belgium. [Goris, An] Univ Leuven KU Leuven, Lab Neuroimmunol, Sect Expt Neurol, Dept Neurosci, Louvain, Belgium. [Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium. [Walters, Matthew] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 AB Groningen, Netherlands. [Sandling, Johanna K.] Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, S-75105 Uppsala, Sweden. [Roennblom, Lars] Uppsala Univ, S-75105 Uppsala, Sweden. [Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh EH8 9YL, Midlothian, Scotland. [Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Rothwell, Peter M.] Univ Oxford, Stroke Prevent Res Unit, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England. [Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, Clin Trial Serv Unit, Oxford OX1 2JD, England. [Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, Epidemiol Studies Unit, Oxford OX1 2JD, England. [Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. [Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford OX1 2JD, England. [Levi, Christopher] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth Res, Callaghan, NSW 2308, Australia. [Levi, Christopher; Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. Hunter Med Res Inst, Newcastle, NSW, Australia. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Psaty, Bruce] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce] Univ Washington, Dept Hlth Serv, Seattle, WA USA. [Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Gretarsdottir, Solveig; Thorsteinsdottir, Unnar; Stefanson, Kari] DeCODE Genet, Reykjavik, Iceland. [Thorsteinsdottir, Unnar; Stefanson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Kittner, Steven] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Kittner, Steven] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD USA. [Boncoraglio, Giorgio B.] IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy. [Meschia, James] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Montaner, Joan] Univ Barcelona, Dept Neurol, Neurovasc Res Lab, VHIR, Barcelona, Spain. [Montaner, Joan] Hosp Barcelona, Barcelona, Spain. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Markus, Hugh S.; Bevan, Steve] Univ Cambridge, Cambridge CB2 1TN, England. RP Bevan, S (reprint author), Univ Cambridge, Cambridge CB2 1TN, England. EM snb31@medschl.cam.ac.uk RI de Bakker, Paul/B-8730-2009; Boncoraglio, Giorgio/B-8647-2011; Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015; Wijmenga, Cisca/D-2173-2009; Goris, An/F-2943-2010; Franke, Andre/B-2151-2010; Sandling, Johanna/B-2973-2016; OI de Bakker, Paul/0000-0001-7735-7858; Goris, An/0000-0002-1276-6682; Franke, Andre/0000-0003-1530-5811; Norrving, Bo/0000-0002-8024-5096; Kilarski, Laura/0000-0003-0645-3134; Sandling, Johanna/0000-0003-1382-2321; Mitchell, Braxton/0000-0003-4920-4744 FU Wellcome Trust FX Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the Wellcome Trust as funders of this study. NR 22 TC 36 Z9 37 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 19 PY 2014 VL 83 IS 8 BP 678 EP 685 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AN6SR UT WOS:000340727800007 PM 25031287 ER PT J AU Ahola, S Isohanni, P Euro, L Brilhante, V Palotie, A Pihko, H Lonnqvist, T Lehtonen, T Laine, J Tyynismaa, H Suomalainen, A AF Ahola, Sofia Isohanni, Pirjo Euro, Liliya Brilhante, Virginia Palotie, Aarno Pihko, Helena Lonnqvist, Tuula Lehtonen, Tanita Laine, Jukka Tyynismaa, Henna Suomalainen, Anu TI Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy SO NEUROLOGY LA English DT Article ID SIDEROBLASTIC ANEMIA-MLASA; RNA SYNTHETASE MUTATIONS; SPINAL-CORD INVOLVEMENT; ELONGATION-FACTOR EFTS; BRAIN-STEM; LACTATE ELEVATION; PROTEIN-SYNTHESIS; LACTIC-ACIDOSIS; TRANSLATION; CARDIOMYOPATHY AB Objective: We report novel defects of mitochondrial translation elongation factor Ts (EFTs), with high carrier frequency in Finland and expand the manifestations of this disease group from infantile cardiomyopathy to juvenile neuropathy/encephalopathy disorders. Methods: DNA analysis, whole-exome analysis, protein biochemistry, and protein modeling. Results: We used whole-exome sequencing to find the genetic cause of infantile-onset mitochondrial cardiomyopathy, progressing to juvenile-onset Leigh syndrome, neuropathy, and optic atrophy in 2 siblings. We found novel compound heterozygous mutations, c.944G>A [p.C315Y] and c.856C>T [p.Q286X], in the TSFM gene encoding mitochondrial EFTs. The same p.Q286X variant was found as compound heterozygous with a splice site change in a patient from a second family, with juvenile-onset optic atrophy, peripheral neuropathy, and ataxia. Our molecular modeling predicted the coding-region mutations to cause protein instability, which was experimentally confirmed in cultured patient cells, with mitochondrial translation defect and lacking EFTs. Only a single TSFM mutation has been previously described in different populations, leading to an infantile fatal multisystem disorder with cardiomyopathy. Sequence data from 35,000 Finnish population controls indicated that the heterozygous carrier frequency of p.Q286X change was exceptionally high in Finland, 1: 80, but no homozygotes were found in the population, in our mitochondrial disease patient collection, or in an intrauterine fetal death material, suggesting early developmental lethality of the homozygotes. Conclusions: We show that in addition to early-onset cardiomyopathy, TSFM mutations should be considered in childhood and juvenile encephalopathies with optic and/or peripheral neuropathy, ataxia, or Leigh disease. C1 [Ahola, Sofia; Isohanni, Pirjo; Euro, Liliya; Brilhante, Virginia; Tyynismaa, Henna; Suomalainen, Anu] Univ Helsinki, Biomedicum Helsinki, Res Programs Unit, FIN-00014 Helsinki, Finland. [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Tyynismaa, Henna] Univ Helsinki, Haartman Inst, Dept Med Genet, FIN-00014 Helsinki, Finland. [Suomalainen, Anu] Univ Helsinki, Neurosci Ctr, FIN-00014 Helsinki, Finland. [Isohanni, Pirjo; Pihko, Helena; Lehtonen, Tanita] Univ Helsinki, Cent Hosp, Childrens Hosp, Dept Child Neurol, FIN-00014 Helsinki, Finland. [Suomalainen, Anu] Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Lehtonen, Tanita; Laine, Jukka] Univ Turku, Dept Pathol, SF-20500 Turku, Finland. RP Suomalainen, A (reprint author), Univ Helsinki, Biomedicum Helsinki, Res Programs Unit, FIN-00014 Helsinki, Finland. EM anu.wartiovaara@helsinki.fi RI Euro, Liliya/F-3808-2015; OI Euro, Liliya/0000-0001-9705-3886; Tyynismaa, Henna/0000-0002-2493-2422 FU Jane and Aatos Erkko Foundation; Academy of Finland; Sigrid Juselius Foundation; University of Helsinki; Helsinki Biomedical Graduate Program; Biomedicum Helsinki Foundation; Finnish Medical Foundation; European Commission EU [FP7-242167]; Wellcome Trust Sanger Institute [091310/D/10/Z] FX Supported by the Jane and Aatos Erkko Foundation, Academy of Finland, Sigrid Juselius Foundation, the University of Helsinki (to A. S.), the Helsinki Biomedical Graduate Program and the Biomedicum Helsinki Foundation (to S. A.), and the Finnish Medical Foundation (to P. I.). A. P. is funded by European Commission EU FP7-242167 and by Wellcome Trust Sanger Institute 091310/D/10/Z. None of the funding sources were involved in conception or design of the study, acquisition, or analysis or interpretation of the data; neither did any of the funding sources have insight in the statistical analysis or drafting or revising the article. NR 40 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 19 PY 2014 VL 83 IS 8 BP 743 EP 751 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AN6SR UT WOS:000340727800015 PM 25037205 ER PT J AU Kellis, M Wold, B Snyder, MP Bernstein, BE Kundaje, A Marinov, GK Ward, LD Birney, E Crawford, GE Dekker, J Dunham, I Elnitski, LL Farnham, PJ Feingold, EA Gerstein, M Giddings, MC Gilbert, DM Gingeras, TR Green, ED Guigo, R Hubbard, T Kent, J Lieb, JD Myers, RM Pazin, MJ Ren, B Stamatoyannopoulos, J Weng, Z White, KP Hardison, RC AF Kellis, Manolis Wold, Barbara Snyder, Michael P. Bernstein, Bradley E. Kundaje, Anshul Marinov, Georgi K. Ward, Lucas D. Birney, Ewan Crawford, Gregory E. Dekker, Job Dunham, Ian Elnitski, Laura L. Farnham, Peggy J. Feingold, Elise A. Gerstein, Mark Giddings, Morgan C. Gilbert, David M. Gingeras, Thomas R. Green, Eric D. Guigo, Roderic Hubbard, Tim Kent, Jim Lieb, Jason D. Myers, Richard M. Pazin, Michael J. Ren, Bing Stamatoyannopoulos, John Weng, Zhiping White, Kevin P. Hardison, Ross C. TI Reply to Brunet and Doolittle: Both selected effect and causal role elements can influence human biology and disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID GENOME C1 [Kellis, Manolis; Kundaje, Anshul; Ward, Lucas D.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Kellis, Manolis; Bernstein, Bradley E.; Kundaje, Anshul; Ward, Lucas D.] Broad Inst, Cambridge, MA 02139 USA. [Wold, Barbara; Marinov, Georgi K.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Snyder, Michael P.; Kundaje, Anshul] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Birney, Ewan; Dunham, Ian] European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England. [Crawford, Gregory E.] Duke Univ, Durham, NC 27708 USA. [Dekker, Job; Weng, Zhiping] Univ Massachusetts, Sch Med, Program Syst Biol, Worcester, MA 01605 USA. [Elnitski, Laura L.; Feingold, Elise A.; Green, Eric D.; Pazin, Michael J.] NIH, NHGRI, Bethesda, MD 20892 USA. [Farnham, Peggy J.] Univ So Calif, Los Angeles, CA 90089 USA. [Gerstein, Mark] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Giddings, Morgan C.] LLC, Marketing Your Sci, Boise, ID 83702 USA. [Gilbert, David M.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. [Gingeras, Thomas R.] Cold Spring Harbor Lab, Funct Genom Grp, Cold Spring Harbor, NY 11724 USA. [Guigo, Roderic] Ctr Genome Regulat, Bioinformat & Genom Program, E-08003 Barcelona, Catalonia, Spain. [Hubbard, Tim] Kings Coll London, Cambridge CB10 1SD, England. [Hubbard, Tim] Wellcome Trust Sanger Inst, Cambridge CB10 1SD, England. [Kent, Jim] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Lieb, Jason D.; White, Kevin P.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Ren, Bing] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Stamatoyannopoulos, John] Univ Washington, Seattle, WA 98195 USA. [Hardison, Ross C.] Penn State Univ, University Pk, PA 16802 USA. RP Kellis, M (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM manoli@mit.edu; rch8@psu.edu RI Guigo, Roderic/D-1303-2010; Hubbard, Tim/C-2567-2008; OI Guigo, Roderic/0000-0002-5738-4477; Hubbard, Tim/0000-0002-1767-9318; Ward, Lucas/0000-0002-8017-809X; Farnham, Peggy/0000-0003-4469-7914; Gerstein, Mark/0000-0002-9746-3719; Dunham, Ian/0000-0003-2525-5598; Birney, Ewan/0000-0001-8314-8497; Pazin, Michael/0000-0002-7561-3640 FU NHGRI NIH HHS [U41 HG007234, U54 HG007004]; NIGMS NIH HHS [P01 GM085354, R01 GM083337] NR 4 TC 1 Z9 1 U1 1 U2 22 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 AUG 19 PY 2014 VL 111 IS 33 BP E3366 EP E3366 DI 10.1073/pnas.1410434111 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN2TS UT WOS:000340438800004 PM 25275169 ER EF