FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Nishino, M Brais, LK Brooks, NV Hatabu, H Kulke, MH Ramaiya, NH AF Nishino, Mizuki Brais, Lauren K. Brooks, Nichole V. Hatabu, Hiroto Kulke, Matthew H. Ramaiya, Nikhil H. TI Drug-related pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors: a radiographic pattern-based approach SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE mTOR inhibitor; Pneumonitis; Drug toxicity; Computed tomography; Neuroendocrine tumours ID RENAL-CELL CARCINOMA; LUNG-DISEASE; WALDENSTROM MACROGLOBULINEMIA; EVEROLIMUS; TEMSIROLIMUS; TEMOZOLOMIDE; MANAGEMENT; EFFICACY; TRIAL AB Purpose: The purpose of this study was to investigate the incidence of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in patients with neuroendocrine tumours (NET) and characterise radiographic patterns of pneumonitis. Methods: Sixty-six patients (39 males, 27 females, age: 22-79 years) with advanced NET treated with mTOR inhibitor, everolimus, were retrospectively studied. Chest computed tomography scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by an independent review of two radiologists. Extent, distributions, and specific findings were evaluated in cases positive for pneumonitis. Radiographic patterns of pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia. Results: Drug-related pneumonitis was radiographically detected in 14 patients (21%). Time from the initiation of therapy to pneumonitis was within 6 months of therapy in 10 patients (71%), while it ranged from 1.0 to 27.7 months. Pneumonitis was more common in patients who had never smoked (p = 0.03). Lower lungs were more extensively involved than upper and middle lungs. Peripheral and lower distributions were most common (n = 8), followed by peripheral and multifocal distributions (n = 3). Ground glass and reticular opacities were present in all cases, with consolidation in eight cases. The radiographic pattern of pneumonitis was classified as cryptogenic organising pneumonia (COP) pattern in eight patients, non-specific interstitial pneumonia (NSIP) pattern in five, and hypersensitivity pneumonitis pattern in one patient. Conclusion: Drug-related pneumonitis was noted in 21% of the advanced NET patients treated with everolimus. Radiographic pattern of pneumonitis was most commonly COP pattern, followed by NSIP pattern. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Nishino, Mizuki; Hatabu, Hiroto; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. [Nishino, Mizuki; Hatabu, Hiroto; Ramaiya, Nikhil H.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Brais, Lauren K.; Brooks, Nichole V.; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Brais, Lauren K.; Brooks, Nichole V.; Kulke, Matthew H.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02215 USA. RP Nishino, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA.; Nishino, M (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@DFCI.HARVARD.EDU FU NCI NIH HHS [K23 CA157631, 5K23CA157631] NR 26 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2016 VL 53 BP 163 EP 170 DI 10.1016/j.ejca.2015.10.015 PG 8 WC Oncology SC Oncology GA DB8TI UT WOS:000368789100018 PM 26760924 ER PT J AU Lokko, HN Ongur, D Gunderson, JG Chen, JA AF Lokko, Hermioni N. Oenguer, Dost Gunderson, John G. Chen, Justin A. TI Ambivalence About Recovery in a Case of Psychotic Illness: Diagnostic, Treatment, and Cultural Challenges SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE ambivalence; cross-cultural; depression; negative symptoms; psychosis; psychotherapy; resistance ID DEPRESSION; PSYCHIATRY; STIGMA C1 [Lokko, Hermioni N.; Chen, Justin A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lokko, Hermioni N.; Oenguer, Dost; Gunderson, John G.] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. RP Lokko, HN (reprint author), Care Of Steven Gans, McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 2016 VL 24 IS 1 BP 61 EP 68 DI 10.1097/HRP.0000000000000107 PG 8 WC Psychiatry SC Psychiatry GA DB8JR UT WOS:000368763500005 PM 26735323 ER PT J AU Sarinana, J Tonegawa, S AF Sarinana, Joshua Tonegawa, Susumu TI Differentiation of forebrain and hippocampal dopamine 1-class receptors, D1R and D5R, in spatial learning and memory SO HIPPOCAMPUS LA English DT Article DE dopamine-1 receptor; dopamine-5 receptor; water-maze; conditional KO; neuromodulator ID PREFRONTAL CORTEX; NMDA RECEPTORS; SYNAPTIC PLASTICITY; NUCLEUS-ACCUMBENS; MOUSE HIPPOCAMPUS; DEPENDENT MEMORY; VENTRAL STRIATUM; MESSENGER-RNA; KNOCKOUT MICE; CA1 REGION AB Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R-specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory. (c) 2015 Wiley Periodicals, Inc. C1 [Sarinana, Joshua; Tonegawa, Susumu] MIT, RIKEN, Ctr Neural Circuit Genet, Picower Inst Learning & Memory,Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Sarinana, Joshua; Tonegawa, Susumu] MIT, RIKEN, Picower Inst Learning & Memory, Ctr Neural Circuit Genet,Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Tonegawa, Susumu] MIT, Howard Hughes Med Inst, Cambridge, MA USA. RP Tonegawa, S (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Inst Neurodegenerat Dis, Charlestown Navy Yard, Bldg 114,Mail Code CNY B114-2-2003,114 16th St,Ro, Charlestown, MA 02129 USA. EM tonegawa@mit.edu FU RIKEN Brain Science Institute; Howard Hughes Medical Institute FX Grant sponsor: RIKEN Brain Science Institute and the Howard Hughes Medical Institute. NR 53 TC 2 Z9 3 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD JAN PY 2016 VL 26 IS 1 BP 76 EP 86 DI 10.1002/hipo.22492 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DC3ZD UT WOS:000369158200008 PM 26174222 ER PT J AU Miller, DR Hayes, JP Lafleche, G Salat, DH Verfaellie, M AF Miller, Danielle R. Hayes, Jasmeet P. Lafleche, Ginette Salat, David H. Verfaellie, Mieke TI White Matter Abnormalities are Associated With Chronic Postconcussion Symptoms in Blast-Related Mild Traumatic Brain Injury SO HUMAN BRAIN MAPPING LA English DT Article DE diffusion tensor imaging; OEF/OIF; PTSD; loss of consciousness ID POSTTRAUMATIC-STRESS-DISORDER; HIPPOCAMPAL VOLUME; WAR VETERANS; HEAD-INJURY; COMBAT; CONCUSSION; IRAQ; PTSD; PERSISTENT; AFGHANISTAN AB Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no - TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI - LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no - TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. C1 [Miller, Danielle R.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Miller, Danielle R.; Lafleche, Ginette; Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, 151A,150 South,Huntington Ave, Boston, MA 02130 USA. [Hayes, Jasmeet P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Hayes, Jasmeet P.; Lafleche, Ginette; Verfaellie, Mieke] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Hayes, Jasmeet P.; Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. [Salat, David H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Salat, David H.] Harvard Univ, Sch Med, Boston, MA USA. RP Miller, DR (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, 151A,150 South,Huntington Ave, Boston, MA 02130 USA. EM dmiller3@bu.edu FU VA Rehabilitation Research Development [RX000216]; NIH [K23MH084013]; National Center for PTSD; VA Clinical Science Research and Development Service FX Contract grant sponsor: VA Rehabilitation Research & Development; Contract grant number: RX000216; Contract grant sponsor: NIH; Contract grant number: K23MH084013; Contract grant sponsor: National Center for PTSD; Contract grant sponsor: VA Clinical Science Research and Development Service. NR 61 TC 4 Z9 4 U1 4 U2 5 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 JAN PY 2016 VL 37 IS 1 BP 220 EP 229 DI 10.1002/hbm.23022 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DC3WU UT WOS:000369150500015 PM 26497829 ER PT J AU Smucny, J Olincy, A Rojas, DC Tregellas, JR AF Smucny, Jason Olincy, Ann Rojas, Donald C. Tregellas, Jason R. TI Neuronal Effects of Nicotine During Auditory Selective Attention in Schizophrenia SO HUMAN BRAIN MAPPING LA English DT Article DE attention; fMRI; hippocampus; nicotine; schizophrenia; ventral parietal cortex ID BRAIN ACTIVATION PATTERNS; PURSUIT EYE-MOVEMENT; SUSTAINED-ATTENTION; ACETYLCHOLINE-RECEPTORS; HIPPOCAMPAL-FORMATION; HEMODYNAMIC-RESPONSE; ALPHA-BUNGAROTOXIN; ANTERIOR CINGULATE; HEALTHY-VOLUNTEERS; PREFRONTAL CORTEX AB Although nicotine has been shown to improve attention deficits in schizophrenia, the neurobiological mechanisms underlying this effect are poorly understood. We hypothesized that nicotine would modulate attention-associated neuronal response in schizophrenia patients in the ventral parietal cortex (VPC), hippocampus, and anterior cingulate based on previous findings in control subjects. To test this hypothesis, the present study examined response in these regions in a cohort of nonsmoking patients and healthy control subjects using an auditory selective attention task with environmental noise distractors during placebo and nicotine administration. In agreement with our hypothesis, significant diagnosis (Control vs. Patient) X drug (Placebo vs. Nicotine) interactions were observed in the VPC and hippocampus. The interaction was driven by task-associated hyperactivity in patients (relative to healthy controls) during placebo administration, and decreased hyperactivity in patients after nicotine administration (relative to placebo). No significant interaction was observed in the anterior cingulate. Task-associated hyperactivity of the VPC predicted poor task performance in patients during placebo. Poor task performance also predicted symptoms in patients as measured by the Brief Psychiatric Rating Scale. These results are the first to suggest that nicotine may modulate brain activity in a selective attention-dependent manner in schizophrenia. (C) 2015 Wiley Periodicals, Inc. C1 [Smucny, Jason; Tregellas, Jason R.] Univ Colorado, Neurosci Program, Anschutz Med Campus, Aurora, CO USA. [Smucny, Jason; Olincy, Ann; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Anschutz Med Campus, Aurora, CO USA. [Olincy, Ann; Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO USA. [Rojas, Donald C.] Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. RP Smucny, J (reprint author), Univ Colorado, Neurosci Program, Anschutz Med Campus, Aurora, CO USA. EM jason.smucny@ucdenver.edu OI Smucny, Jason/0000-0001-5656-7987 FU VA Biomedical Laboratory and Clinical Science Research and Development Service [CX000459]; NIH [MH-089095, DK-103691, MH-102224, MH-102879]; Brain and Behavior Research Foundation FX Contract grant sponsor: VA Biomedical Laboratory and Clinical Science Research and Development Service; Contract grant number: CX000459; Contract grant sponsor: NIH; Contract grant numbers: MH-089095, DK-103691, MH-102224, MH-102879; Contract grant sponsor: the Brain and Behavior Research Foundation. NR 77 TC 3 Z9 3 U1 1 U2 4 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 JAN PY 2016 VL 37 IS 1 BP 410 EP 421 DI 10.1002/hbm.23040 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DC3WU UT WOS:000369150500029 PM 26518728 ER PT J AU Charidimou, A Pantoni, L Love, S AF Charidimou, Andreas Pantoni, Leonardo Love, Seth TI The concept of sporadic cerebral small vessel disease: A road map on key definitions and current concepts SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE Cerebral microbleeds; cerebral small vessel disease; cerebral amyloid angiopathy; intracerebral hemorrhage; antithrombotics; leukoaraiosis ID VIRCHOW-ROBIN SPACES; WHITE-MATTER LESIONS; AMYLOID ANGIOPATHY; COGNITIVE IMPAIRMENT; LACUNAR STROKE; SUPERFICIAL SIDEROSIS; POSTMORTEM ASSESSMENT; PERIVASCULAR SPACES; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA AB Sporadic cerebral small vessel disease is considered to be among the most common known neuropathological processes and has an important role in stroke, cognitive impairment, and functional loss in elderly persons. The term is now commonly used to describe a range of neuroimaging, neuropathological, and associated clinical features, the pathogenesis of which is largely unclear but that are thought to arise from disease affecting the perforating cerebral arterioles, capillaries, and venules. Modern neuroimaging has revolutionized our understanding of the consequences of small vessels disease on the brain parenchyma, even though small arteries, arterioles, capillaries, and venules are difficult to be directly visualized with current techniques used in clinical practice. In this short review, we focus on histopathological and neuroimaging perspectives, basic definitions, and recent advances in the field. C1 [Charidimou, Andreas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Stroke Res,Dept Neurol,Hemorrhag Stroke Res P, Boston, MA USA. [Charidimou, Andreas] UCL Inst Neurol, Queen Sq, London WC1N 3BG, England. [Charidimou, Andreas] Natl Hosp Neurol & Neurosurg, Queen Sq, London WC1N 3BG, England. [Pantoni, Leonardo] Univ Florence, NEUROFARBA Dept, Florence, Italy. [Pantoni, Leonardo] Azienda Osped Univ Careggi, Stroke Unit & Neurol, Florence, Italy. [Love, Seth] Univ Bristol, Southmead Hosp, Inst Clin Neurosci, Dementia Res Grp, Learning & Res Level 2, Bristol, Avon, England. RP Charidimou, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Stroke Res,Dept Neurol,Hemorrhag Stroke Res P, Boston, MA USA.; Charidimou, A (reprint author), UCL Inst Neurol, Queen Sq, London WC1N 3BG, England.; Charidimou, A (reprint author), Natl Hosp Neurol & Neurosurg, Queen Sq, London WC1N 3BG, England. EM andreas.charidimou.09@ucl.ac.uk NR 77 TC 6 Z9 6 U1 1 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD JAN PY 2016 VL 11 IS 1 BP 6 EP 18 DI 10.1177/1747493015607485 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DB7NV UT WOS:000368703300013 PM 26763016 ER PT J AU Cadilhac, DA Kim, J Lannin, NA Kapral, MK Schwamm, LH Dennis, MS Norrving, B Meretoja, A AF Cadilhac, Dominique A. Kim, Joosup Lannin, Natasha A. Kapral, Moira K. Schwamm, Lee H. Dennis, Martin S. Norrving, Bo Meretoja, Atte TI National stroke registries for monitoring and improving the quality of hospital care: A systematic review SO INTERNATIONAL JOURNAL OF STROKE LA English DT Review DE Stroke; outcome assessment; quality assurance; health care; registries ID ISCHEMIC-STROKE; INTERNATIONAL EXPERIENCE; GUIDELINES-STROKE; RISK-FACTORS; RIKS-STROKE; PART 1; MULTICENTER; INDICATORS; MANAGEMENT; DATABASE AB Background: Routine monitoring of the quality of stroke care is becoming increasingly important since patient outcomes could be improved with better access to proven treatments. It remains unclear how many countries have established a national registry for monitoring stroke care. Aims: To describe the current status of national, hospital-based stroke registries that have a focus on monitoring access to evidence-based care and patient outcomes and to summarize the main features of these registries. Summary of review: We undertook a systematic search of the published literature to identify the registries that are considered in their country to represent a national standardized dataset for acute stroke care and outcomes. Our initial keyword search yielded 5002 potential papers, of which we included 316 publications representing 28 national stroke registries from 26 countries. Where reported, data were most commonly collected with a waiver of patient consent (70%). Most registries used web-based systems for data collection (57%) and 25% used data linkage. Few variables were measured consistently among the registries reflecting their different local priorities. Funding, resource requirements, and coverage also varied. Conclusions: This review provides an overview of the current use of national stroke registries, a description of their common features relevant to monitoring stroke care in hospitals. Formal registration and description of registries would facilitate better awareness of efforts in this field. C1 [Cadilhac, Dominique A.; Kim, Joosup] Monash Univ, Sch Clin Sci Monash Hlth, Stroke & Ageing Res, Clayton, Vic, Australia. [Cadilhac, Dominique A.; Kim, Joosup; Meretoja, Atte] Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia. [Lannin, Natasha A.] La Trobe Univ, Coll Sci Hlth & Engn, Bundoora, Vic, Australia. [Lannin, Natasha A.] Alfred Hlth, Prahran, Vic, Australia. [Kapral, Moira K.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv Div, Boston, MA 02114 USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Boston, MA USA. [Dennis, Martin S.] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Norrving, Bo] Lund Univ, Dept Clin Neurol Sci, S-22100 Lund, Sweden. [Meretoja, Atte] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic 3052, Australia. [Meretoja, Atte] Univ Helsinki, Dept Neurol, Cent Hosp, Helsinki, Finland. RP Cadilhac, DA (reprint author), Monash Univ, Sch Clin Sci Monash Hlth, Stroke & Ageing Res, Clayton, Vic, Australia.; Cadilhac, DA (reprint author), Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia. EM dominique.cadilhac@monash.edu OI Lannin, Natasha/0000-0002-2066-8345; Cadilhac, Dominique/0000-0001-8162-682X FU National Health and Medical Research Council (NHMRC) [1063761]; National Heart Foundation; NHMRC [1034415]; Heart and Stroke Foundation, Ontario Provincial Office FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dominique Cadilhac was supported by a fellowship from the National Health and Medical Research Council (NHMRC; 1063761 co-funded by National Heart Foundation) and Joosup Kim receives salary support from a partnership project grant funded by the NHMRC (1034415). Moira Kapral was supported by a Career Investigator Award from the Heart and Stroke Foundation, Ontario Provincial Office. NR 42 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD JAN PY 2016 VL 11 IS 1 BP 28 EP 40 DI 10.1177/1747493015607523 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DB7NV UT WOS:000368703300015 PM 26763018 ER PT J AU Marra, G Sturch, P Oderda, M Tabatabaei, S Muir, G Gontero, P AF Marra, Giancarlo Sturch, Paul Oderda, Marco Tabatabaei, Shahin Muir, Gordon Gontero, Paolo TI Systematic review of lower urinary tract symptoms/benign prostatic hyperplasia surgical treatments on men's ejaculatory function: Time for a bespoke approach? SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Review DE benign prostatic hyperplasia; decreased ejaculation; ejaculatory dysfunction; lower urinary tract symptoms; painful ejaculation; retrograde ejaculation ID PROSPECTIVE RANDOMIZED-TRIAL; STANDARD TRANSURETHRAL RESECTION; 2-YEAR FOLLOW-UP; HOLMIUM LASER ENUCLEATION; SMALL BENIGN PROSTATE; MALE SEXUAL FUNCTION; MICROWAVE THERMOTHERAPY; CLINICAL-TRIAL; NEEDLE ABLATION; THULIUM LASER AB Although ejaculatory dysfunction is common for patients undergoing benign prostatic hyperplasia surgery, no clear evidence is present to counsel men seeking to preserve ejaculation. Our aim was to evaluate ejaculatory dysfunction in relation to benign prostatic hyperplasia surgery. We carried out a web and manual search using MEDLINE and Embase including randomized controlled trials reporting ejaculatory dysfunction after benign prostatic hyperplasia surgery: 42 randomized controlled trials comprising a total of 3857 patients were included. Only one study had ejaculatory dysfunction as a primary outcome, and just 10 evaluated ejaculatory dysfunction before and after surgery. The definition of ejaculatory dysfunction was not standardized. Similarly, just seven studies used internationally validated questionnaires to address ejaculatory dysfunction. The reported rates of ejaculatory dysfunction after resectional elecrosurgery, laser procedures, coagulation, ablation and implant techniques were assessed and compared. Transurethral resection of the prostate and recent laser procedures including holmium, thulium and GreenLight cause similar rates of ejaculatory dysfunction, occurring in almost three out of four to five men. Although providing less symptomatic benefit compared with transurethral resection of the prostate, transurethral incision of the prostate, transurethral needle ablation and transurethral microwave thermotherapy should be considered for men aiming to maintain normal ejaculation. UroLift is also a recent promising option for this category of patients. The vast majority of studies reporting ejaculatory dysfunction after benign prostatic hyperplasia surgery used poor methodology to investigate this complication. Future studies able to address clear hypothesis and considering ejaculatory dysfunction anatomical and pathophysiological features are required to develop ejaculation preserving techniques and to increase the evidence to counsel men aiming to preserve ejaculation. C1 [Marra, Giancarlo; Oderda, Marco; Gontero, Paolo] Univ Turin, Urol Clin, Citta Salute & Sci, Corso Bramante 88-90, I-10126 Turin, Italy. [Sturch, Paul; Muir, Gordon] Kings Coll Hosp London, Dept Urol, London, England. [Tabatabaei, Shahin] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Gontero, P (reprint author), Univ Turin, Urol Clin, Citta Salute & Sci, Corso Bramante 88-90, I-10126 Turin, Italy.; Gontero, P (reprint author), Univ Turin, AOU San Giovanni Battista, Dept Urol, Corso Bramante 88-90, I-10126 Turin, Italy. EM paolo.gontero@unito.it OI Marra, Giancarlo/0000-0003-2363-026X FU Fondazione di Ricerca Molinette Onlus FX This work received funds from the Fondazione di Ricerca Molinette Onlus. NR 67 TC 10 Z9 11 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-8172 EI 1442-2042 J9 INT J UROL JI Int. J. Urol. PD JAN PY 2016 VL 23 IS 1 BP 22 EP 35 DI 10.1111/iju.12866 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA DC3YE UT WOS:000369155200004 PM 26177667 ER PT J AU Contractor, AA Armour, C Shea, MT Mota, N Pietrzak, RH AF Contractor, Ateka A. Armour, Cherie Shea, M. Tracie Mota, Natalie Pietrzak, Robert H. TI Latent profiles of DSM-5 PTSD symptoms and the "Big Five" personality traits SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE DSM-5 PTSD; Big-five personality dimensions; Latent profile analyses; Coping; Mental health treatment ID POSTTRAUMATIC-STRESS-DISORDER; INTERNALIZING SUBTYPES; BRIEF COPE; MODEL; VETERANS; PSYCHOPATHOLOGY; TRAUMA; QUESTIONNAIRE; HETEROGENEITY; VALIDATION AB Typologies of DSM-5 PTSD symptoms and personality traits were evaluated in regard to coping styles and treatment preferences using data from 1266 trauma-exposed military veterans of which the majority were male (n = 1097; weighted 89.6%). Latent profile analyses indicated a best-fitting 5-class solution; PTSD asymptomatic and emotionally stable (Cl); predominant re-experiencing and avoidance symptoms and less emotionally stable (C2); subsyndromal PTSD (C3); predominant negative alterations in mood/cognitions and combined internalizing-externalizing traits (C4); and high PTSD severity and combined internalizing-externalizing traits (C5). Compared to C5, Cl members were less likely to use self-distraction, denial, and substance use and more likely to use active coping; C2 and C4 members were less likely to use denial and more likely to use behavioral disengagement; C3 members were less likely to use denial and instrumental coping and more likely to use active coping; most classes were less likely to seek mental health treatment. Compared to Cl, C2 members were more likely to use self-distraction, substance use, behavioral disengagement and less likely to use active coping; C3 members were more likely to use self-distraction, and substance use, and less likely to use positive reframing, and acceptance; and C4 members were more likely to use denial, substance use, emotional support, and behavioral disengagement, and less likely to use active coping, positive reframing, and acceptance; all classes were more likely to seek mental health treatment. Emotional stability was most distinguishing of the typologies. Other implications are discussed. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Contractor, Ateka A.] Univ Toledo, Dept Psychol, 2801 W Bancroft St, Toledo, OH 43606 USA. [Contractor, Ateka A.; Shea, M. Tracie] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Box Box G BH, Providence, RI 02912 USA. [Armour, Cherie] Univ Ulster, Sch Psychol, Cromore Rd, Coleraine BT52 1SA, Londonderry, North Ireland. [Shea, M. Tracie] Vet Affairs Med Ctr, 830 Chalkstone Ave, Providence, RI 02908 USA. [Mota, Natalie; Pietrzak, Robert H.] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT USA. [Mota, Natalie; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Contractor, Ateka A.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. RP Contractor, AA (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Box Box G BH, Providence, RI 02912 USA. EM ateka.c@gmail.com OI Armour, Cherie/0000-0001-7649-3874 FU U.S. Department of Veteran Affairs National Center for Posttraumatic Stress Disorder FX The NHRVS was funded by the U.S. Department of Veteran Affairs National Center for Posttraumatic Stress Disorder. NR 48 TC 1 Z9 1 U1 9 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN PY 2016 VL 37 BP 10 EP 20 DI 10.1016/j.janxdis.2015.10.005 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DC1IK UT WOS:000368969800002 PM 26561734 ER PT J AU Luke, B Stern, JE Hornstein, MD Kotelchuck, M Diop, H Cabral, H Declercq, ER AF Luke, Barbara Stern, Judy E. Hornstein, Mark D. Kotelchuck, Milton Diop, Hafsatou Cabral, Howard Declercq, Eugene R. TI Is the wrong question being asked in infertility research? SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE Assisted reproductive technology; Adverse pregnancy outcomes; Women's health; Child health ID ASSISTED REPRODUCTIVE TECHNOLOGY; IN-VITRO FERTILIZATION; CONCEPTION PREGNANCY OUTCOMES; EARLY FETAL LOSSES; UNDERLYING INFERTILITY; PERINATAL OUTCOMES; ADVERSE PREGNANCY; SINGLETONS; CHILDREN; SWEDEN AB A persistent finding is that assisted reproductive technology (ART) is associated with compromised birth outcomes, including higher risks for prematurity, low birthweight, and congenital malformations, even among singletons. Over the past decade, our research group, the Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART), has evaluated pregnancy and birth outcomes among three groups of women, those women treated with ART, those with indicators of subfertility but without ART treatment, and fertile women. We have also explored the influence of infertility-related diagnoses on outcomes for women and infants. Over the course of our research, we have changed our perspective from an original focus on ART treatment parameters as the primary cause of excess morbidity to one centered instead on the underlying infertility-related diagnoses. This paper summarizes the research findings from our group that support this change in focus for infertility-based research from a primary emphasis on ART treatment to greater attention to the contribution of preexisting pathology underlying the infertility and suggests directions for future analyses. C1 [Luke, Barbara] Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, 965 Fee Rd,East Fee Hall,Room 628, E Lansing, MI 48824 USA. [Stern, Judy E.] Geisel Sch Med Dartmouth, Dept Obstet & Gynecol, Lebanon, NH USA. [Hornstein, Mark D.] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Sch Med, Boston, MA 02115 USA. [Kotelchuck, Milton] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. [Diop, Hafsatou] Massachusetts Dept Publ Hlth, Boston, MA USA. [Cabral, Howard] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Declercq, Eugene R.] Boston Univ, Dept Community Hlth Sci, Sch Publ Hlth, Boston, MA USA. RP Luke, B (reprint author), Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, 965 Fee Rd,East Fee Hall,Room 628, E Lansing, MI 48824 USA. EM lukeb@msu.edu OI Luke, Barbara/0000-0002-0405-8133 FU National Institute of Child Health and Human Development [R01HD064595, R01HD067270] FX The project described was supported by Award Numbers R01HD064595 and R01HD067270 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development or the National Institutes of Health. NR 35 TC 1 Z9 1 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 EI 1573-7330 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD JAN PY 2016 VL 33 IS 1 BP 3 EP 8 DI 10.1007/s10815-015-0610-3 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA DB7HW UT WOS:000368686400002 PM 26634257 ER PT J AU Christophersen, IE Ellinor, PT AF Christophersen, Ingrid E. Ellinor, Patrick T. TI Genetics of atrial fibrillation: from families to genomes SO JOURNAL OF HUMAN GENETICS LA English DT Review ID OF-FUNCTION MUTATION; SHORT QT SYNDROME; SINGLE NUCLEOTIDE POLYMORPHISM; ANTIARRHYTHMIC-DRUG THERAPY; CHROMOSOME 4Q25 VARIANTS; DEFECTIVE HCN4 MUTATION; GATED SODIUM-CHANNEL; I-KS CHANNELS; EARLY-ONSET; KCNQ1 MUTATION AB Atrial fibrillation (AF) is the most common cardiac rhythm disorder and the prevalence is increasing. The disease confers an increased risk of severe complications such as heart failure, stroke and death, yet the treatment options available are insufficient. AF can develop secondary to other diseases, but there is also evidence of a heritable component. The molecular basis for the heritability of AF has been explored in depth over the past decade. Rare variants have been identified in ion channels, transcription factors and a wide range of other genes. More recently, common variant analyses have identified 14 genetic loci associated with AF. Thus, the genetics of AF is complex and heterogeneous. In this review, we describe the common and rare variants identified for AF, the potential clinical implications of these variants and the future directions in this field. Increasing our understanding of the pathophysiology of AF will aid the development of new and improved treatment strategies and risk prediction of AF, the first steps toward a more individualized treatment of the arrhythmia. C1 [Christophersen, Ingrid E.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Christophersen, Ingrid E.] Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Rud, Norway. [Christophersen, Ingrid E.; Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Broad Inst Harvard & MIT, Cardiovasc Res Ctr, 55 Fruit St,Gray 109, Boston, MA 02129 USA. EM ellinor@mgh.harvard.edu FU Research Council of Norway; National Institutes of Health [1RO1HL092577, 1K24HL105780]; American Heart Association [13EIA14220013]; Fondation Leducq [14CVD01] FX IEC is supported by a mobility grant from the Research Council of Norway. PTE is supported by grants from the National Institutes of Health (1RO1HL092577, 1K24HL105780), an Established Investigator Award from the American Heart Association (13EIA14220013) and the Fondation Leducq (14CVD01). NR 161 TC 3 Z9 3 U1 3 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 EI 1435-232X J9 J HUM GENET JI J. Hum. Genet. PD JAN PY 2016 VL 61 IS 1 SI SI BP 61 EP 70 DI 10.1038/jhg.2015.44 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA DC2GB UT WOS:000369034100011 PM 25994868 ER PT J AU Dirice, E Kulkarni, RN AF Dirice, Ercument Kulkarni, Rohit N. TI Harnessing immune cells to enhance beta-cell mass in type 1 diabetes SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE type 1 diabetes; immune cells; beta cells; proliferation ID INSULIN MICROSECRETORS; INDUCIBLE PROTEIN-10; PLACENTAL-LACTOGEN; PANCREATIC-ISLETS; ADULT RATS; ROAD MAP; IN-VIVO; PROLIFERATION; MICE; EXPRESSION AB Type 1 diabetes is characterized by early -cell loss leading to insulin dependence in virtually all patients with the disease in order to maintain glucose homeostasis. Most studies over the past few decades have focused on limiting the autoimmune attack on the cells. However, emerging data from patients with long-standing diabetes who continue to harbor functional insulin-producing cells in their diseased pancreas have prompted scientists to examine whether proliferation of existing cells can be enhanced to promote better glycemic control. In support of this concept, several studies indicate that mononuclear cells that infiltrate the islets have the capacity to trigger proliferation of islet cells including cells. These observations indicate the exciting possibility of identifying those mononuclear cell types and their soluble factors and harnessing their ability to promote -cell growth concomitant with autoimmune therapy to prevent the onset and/or halt the progression of the disease. C1 [Dirice, Ercument; Kulkarni, Rohit N.] Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Dirice, Ercument; Kulkarni, Rohit N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kulkarni, RN (reprint author), Islet Cell & Regenerat Biol, Rm 410,One Joslin Pl, Boston, MA 02215 USA. RI Dirice, Ercument/B-2825-2017 FU NIDDK NIH HHS [R01 DK103215, R01 DK67536]; PHS HHS [R01 55523] NR 43 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2016 VL 64 IS 1 BP 14 EP 20 DI 10.1136/jim-d-15-00196 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DB7MM UT WOS:000368699600004 PM 26755809 ER PT J AU Hinchcliff, M Routson, R Segal, A Suri, P Czerniecki, J Aubin, P AF Hinchcliff, M. Routson, R. Segal, A. Suri, P. Czerniecki, J. Aubin, P. TI A BIOFEEDBACK SMART CANE TO REDUCE KNEE LOADING ASSOCIATED WITH OSTEOARTHRITIS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-30, 2016 CL Carmel, CA SP Amer Federat Med Res C1 [Hinchcliff, M.; Routson, R.; Segal, A.; Suri, P.; Czerniecki, J.; Aubin, P.] VA Puget Sound, Seattle, WA USA. [Hinchcliff, M.; Routson, R.; Suri, P.; Czerniecki, J.; Aubin, P.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2016 VL 64 IS 1 MA 24 BP 144 EP 145 DI 10.1136/jim-d-15-00013.24 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DB7MM UT WOS:000368699600034 ER PT J AU Tsoi, S Vasti, E Moin, T AF Tsoi, S. Vasti, E. Moin, T. TI PRIMARY CARE PROVIDERS' PERCEPTIONS OF LIFESTYLE MODIFICATION AND MANAGEMENT FOR OBESITY AND PREDIABETES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-30, 2016 CL Carmel, CA SP Amer Federat Med Res C1 [Tsoi, S.; Moin, T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Vasti, E.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Vasti, E.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Moin, T.] HSR&D Ctr Study Healthcare Innovat Implementat &, Los Angeles, CA USA. [Moin, T.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2016 VL 64 IS 1 MA 170 BP 209 EP 209 DI 10.1136/jim-d-15-00013.170 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DB7MM UT WOS:000368699600180 ER PT J AU Szkudlinska, MA Neuhouser, ML Utzschneider, KM AF Szkudlinska, M. A. Neuhouser, M. L. Utzschneider, K. M. TI RELATIONSHIP BETWEEN GLYCEMIC VARIABILITY AND B-CELL FUNCTION IN ADULTS AT HIGH RISK OF TYPE 2 DIABETES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-30, 2016 CL Carmel, CA SP Amer Federat Med Res C1 [Szkudlinska, M. A.] Univ Washington, Seattle, WA 98195 USA. [Neuhouser, M. L.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Utzschneider, K. M.] VA Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2016 VL 64 IS 1 MA 248 BP 241 EP 242 DI 10.1136/jim-d-15-00013.248 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DB7MM UT WOS:000368699600257 ER PT J AU Vasti, EC Tsoi, S Moin, T AF Vasti, E. C. Tsoi, S. Moin, T. TI PRIMARY CARE PROVIDERS' PERCEPTIONS OF DIABETES PREVENTION PROGRAMS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-30, 2016 CL Carmel, CA SP Amer Federat Med Res C1 [Vasti, E. C.; Tsoi, S.; Moin, T.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Tsoi, S.; Moin, T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moin, T.] HSR&D Ctr Study Healthcare Innovat Implementat &, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2016 VL 64 IS 1 MA 449 BP 329 EP 330 DI 10.1136/jim-d-15-00013.449 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DB7MM UT WOS:000368699600456 ER PT J AU Ryan, JS Wang, Q Wu, D Dong, Z Wu, P AF Ryan, J. S. Wang, Q. Wu, D. Dong, Z. Wu, P. TI CHARACTERIZATION OF A CUSTOM MONOCLONAL ANTIBODY AS A NOVEL TUMOR BIOMARKER IN HUMAN GASTROINTESTINAL CANCERS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-30, 2016 CL Carmel, CA SP Amer Federat Med Res C1 [Ryan, J. S.; Wu, D.; Dong, Z.; Wu, P.] Univ Washington, Sch Med, Seattle, WA USA. [Wang, Q.; Wu, D.; Dong, Z.; Wu, P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2016 VL 64 IS 1 MA 450 BP 330 EP 330 DI 10.1136/jim-d-15-00013.450 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DB7MM UT WOS:000368699600457 ER PT J AU Liu, MA Hshieh, T Condron, N Wadleigh, M Armand, P Abel, G Driver, JA AF Liu, M. A. Hshieh, T. Condron, N. Wadleigh, M. Armand, P. Abel, G. Driver, J. A. TI PHYSICIAN-PATIENT DISAGREEMENT ON EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS IS ASSOCIATED WITH INCREASED MORTALITY IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-30, 2016 CL Carmel, CA SP Amer Federat Med Res C1 [Liu, M. A.] Univ Arizona, Coll Med, Tucson, AZ USA. [Hshieh, T.; Driver, J. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Hshieh, T.; Condron, N.; Wadleigh, M.; Armand, P.; Abel, G.; Driver, J. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Driver, J. A.] Boston VA Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2016 VL 64 IS 1 MA 452 BP 331 EP 331 DI 10.1136/jim-d-15-00013.452 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DB7MM UT WOS:000368699600459 ER PT J AU Pan, P Huang, J Morioka, C Hathout, G El-Saden, SM AF Pan, P. Huang, J. Morioka, C. Hathout, G. El-Saden, S. M. TI Cost analysis of vestibular schwannoma screening with contrast-enhanced magnetic resonance imaging in patients with asymmetrical hearing loss SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article DE Vestibular Schwannoma; Screening; Magnetic Resonance Imaging; Hearing Loss; Cost Analysis ID FAST SPIN-ECHO; ACOUSTIC NEUROMA; RADIOSURGERY; MANAGEMENT; SURGERY; MR; MICROSURGERY; PRESERVATION; EXPERIENCE AB Background: Vestibular schwannomas are a rare cause of asymmetrical hearing loss, and routine screening with magnetic resonance imaging can be costly. This paper reports results on vestibular schwannoma screening at our institution and compares the cost of screening to a utility of hearing benefit. Method: All screening examinations with magnetic resonance imaging performed for asymmetrical hearing loss between 2006 and 2011 were retrospectively reviewed. The cost per new vestibular schwannoma diagnosis was calculated. The cost per patient for those who benefitted from intervention was estimated based on rates of hearing preservation reported in the literature. Results: Forty-five (4.3 per cent) of 1050 screening examinations with magnetic resonance imaging performed for asymmetrical hearing loss were positive for vestibular schwannoma, and the cost per new diagnosis was $11 436. The estimated screening cost per patient for those who benefitted from surgery or radiation was $147 030, while US federal compensation for unilateral hearing loss was $44 888. Conclusion: Although we achieved a lower screening cost per new diagnosis than reported in the current literature, there remains disparity between the screening cost per benefitted patient and the benefit' of hearing. C1 [Pan, P.] Univ Calif Los Angeles, Med Ctr, Dept Radiol, 757 Westwood Blvd, Los Angeles, CA 90095 USA. [Huang, J.; Morioka, C.; Hathout, G.; El-Saden, S. M.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Radiol, Los Angeles, CA USA. RP Pan, P (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Radiol, 757 Westwood Blvd, Los Angeles, CA 90095 USA. EM ppan@mednet.ucla.edu NR 30 TC 1 Z9 1 U1 4 U2 4 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0022-2151 EI 1748-5460 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD JAN PY 2016 VL 130 IS 1 BP 21 EP 24 DI 10.1017/S0022215115002431 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA DB8RI UT WOS:000368783900005 PM 26365591 ER PT J AU Herrington, TM Cheng, JJ Eskandar, EN AF Herrington, Todd M. Cheng, Jennifer J. Eskandar, Emad N. TI Mechanisms of deep brain stimulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review DE deep brain stimulation; basic science of clinical practice; Parkinson's disease; tremor; dystonia; obsessive-compulsive disorder ID HIGH-FREQUENCY STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; TREATMENT-RESISTANT DEPRESSION; OBSESSIVE-COMPULSIVE DISORDER; PRIMARY MOTOR CORTEX; ADVANCED PARKINSONS-DISEASE; GLOBUS-PALLIDUS INTERNUS; LOCAL-FIELD POTENTIALS; RANDOMIZED CONTROLLED-TRIAL; NIGRA PARS RETICULATA AB Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS. C1 [Herrington, Todd M.; Cheng, Jennifer J.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nayef Al Rodhan Labs,Dept Neurosurg, Boston, MA USA. [Herrington, Todd M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cheng, Jennifer J.] Johns Hopkins Univ Hosp, Dept Neurosurg, Baltimore, MD 21287 USA. RP Herrington, TM (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Wang Bldg,Suite 720, Boston, MA 02114 USA. EM therrington@mgh.harvard.edu FU Anne Young Fellowship in Movement Disorders; Bachman-Strauss Dystonia & Parkinson Foundation Fellowship; Defense Advanced Research Projects Agency (DARPA); National Institute of Neurological Disorders and Stroke; DARPA FX T. M. Herrington has received support from the Anne Young Fellowship in Movement Disorders, the Bachman-Strauss Dystonia & Parkinson Foundation Fellowship, and the Defense Advanced Research Projects Agency (DARPA). E. N. Eskandar has received support from National Institute of Neurological Disorders and Stroke and DARPA. NR 325 TC 13 Z9 13 U1 18 U2 57 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN 1 PY 2016 VL 115 IS 1 BP 19 EP 38 DI 10.1152/jn.00281.2015 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DC2QR UT WOS:000369061900004 PM 26510756 ER PT J AU Merfeld, DM Clark, TK Lu, YM Karmali, F AF Merfeld, Daniel M. Clark, Torin K. Lu, Yue M. Karmali, Faisal TI Dynamics of individual perceptual decisions SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review DE drift diffusion; signal detection; threshold ID SELF-MOTION PERCEPTION; INNERVATING SEMICIRCULAR CANALS; COMPETING ACCUMULATOR MODEL; SPEED-ACCURACY TRADEOFF; EARTH-VERTICAL AXIS; SPATIAL ORIENTATION; REACTION-TIME; VELOCITY STORAGE; RESPONSE-TIME; WHOLE-BODY AB Perceptual decision making is fundamental to a broad range of fields including neurophysiology, economics, medicine, advertising, law, etc. Although recent findings have yielded major advances in our understanding of perceptual decision making, decision making as a function of time and frequency (i.e., decision-making dynamics) is not well understood. To limit the review length, we focus most of this review on human findings. Animal findings, which are extensively reviewed elsewhere, are included when beneficial or necessary. We attempt to put these various findings and data sets, which can appear to be unrelated in the absence of a formal dynamic analysis, into context using published models. Specifically, by adding appropriate dynamic mechanisms (e.g., high-pass filters) to existing models, it appears that a number of otherwise seemingly disparate findings from the literature might be explained. One hypothesis that arises through this dynamic analysis is that decision making includes phasic (high pass) neural mechanisms, an evidence accumulator and/or some sort of midtrial decision-making mechanism (e.g., peak detector and/or decision boundary). C1 [Merfeld, Daniel M.; Clark, Torin K.; Karmali, Faisal] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Merfeld, Daniel M.; Clark, Torin K.; Karmali, Faisal] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lu, Yue M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Merfeld, DM (reprint author), Mass Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Rm 421, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu OI Karmali, Faisal/0000-0002-1140-4954 FU National Institute on Deafness and Other Communication Disorders [R01 DC04158, R03 DC013635]; National Space Biomedical Research Institute [NCC9-58] FX This work was supported by National Institute on Deafness and Other Communication Disorders Grants R01 DC04158 (to D. M. Merfeld) and R03 DC013635 (to F. Karmali) as well as National Space Biomedical Research Institute Grant NCC9-58 (to T. K. Clark). NR 157 TC 1 Z9 1 U1 6 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN 1 PY 2016 VL 115 IS 1 BP 39 EP 59 DI 10.1152/jn.00225.2015 PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DC2QR UT WOS:000369061900005 PM 26467513 ER PT J AU Becerra, L Bishop, J Barmettler, G Xie, Y Navratilova, E Porreca, F Borsook, D AF Becerra, L. Bishop, J. Barmettler, G. Xie, Y. Navratilova, E. Porreca, F. Borsook, D. TI Triptans disrupt brain networks and promote stress-induced CSD-like responses in cortical and subcortical areas SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE sumatriptan; fMRI; pain; chronic dosing; cortical spreading depression ID MEDICATION-OVERUSE HEADACHE; CENTRAL TRIGEMINOVASCULAR NEURONS; INDEPENDENT COMPONENT ANALYSIS; STATE FUNCTIONAL CONNECTIVITY; DEFAULT MODE NETWORK; SPREADING DEPRESSION; CEREBRAL-CORTEX; BASAL GANGLIA; MIGRAINE; AURA AB A number of drugs, including triptans, promote migraine chronification in susceptible individuals. In rats, a period of triptan administration over 7 days can produce "latent sensitization" (14 days after discontinuation of drug) demonstrated as enhanced sensitivity to presumed migraine triggers such as environmental stress and lowered threshold for electrically induced cortical spreading depression (CSD). Here we have used fMRI to evaluate the early changes in brain networks at day 7 of sumatriptan administration that may induce latent sensitization as well as the potential response to stress. After continuous infusion of sumatriptan, rats were scanned to measure changes in resting state networks and the response to bright light environmental stress. Rats receiving sumatriptan, but not saline infusion, showed significant differences in default mode, autonomic, basal ganglia, salience, and sensorimotor networks. Bright light stress produced CSD-like responses in sumatriptan-treated but not control rats. Our data show the first brain-related changes in a rat model of medication overuse headache and suggest that this approach could be used to evaluate the multiple brain networks involved that may promote this condition. C1 [Becerra, L.; Bishop, J.; Barmettler, G.; Borsook, D.] Boston Childrens Hosp, PAIN Grp, Waltham, MA USA. [Becerra, L.; Borsook, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Xie, Y.; Navratilova, E.; Porreca, F.] Univ Arizona, Dept Pharmacol, Tucson, AZ USA. RP Becerra, L (reprint author), Boston Childrens Hosp, Ctr Pain & Brain, 9 Hope Ave, Waltham, MA 02453 USA. EM lino.becerra@childrens.harvard.edu FU Herlands Fund for Pain Research; National Institute of Neurological Disorders and Stroke [K24 NS-064050] FX This work was supported by the Herlands Fund for Pain Research (D. Borsook, L. Becerra) and the National Institute of Neurological Disorders and Stroke (K24 NS-064050, D. Borsook). NR 82 TC 4 Z9 4 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN 1 PY 2016 VL 115 IS 1 BP 208 EP 217 DI 10.1152/jn.00632.2015 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DC2QR UT WOS:000369061900018 PM 26490291 ER PT J AU Johnson, DB Estrada, MV Salgado, R Sanchez, V Doxie, DB Opalenik, SR Vilgelm, AE Feld, E Johnson, AS Greenplate, AR Sanders, ME Lovly, CM Frederick, DT Kelley, MC Richmond, A Irish, JM Shyr, Y Sullivan, RJ Puzanov, I Sosman, JA Balko, JM AF Johnson, Douglas B. Estrada, Monica V. Salgado, Roberto Sanchez, Violeta Doxie, Deon B. Opalenik, Susan R. Vilgelm, Anna E. Feld, Emily Johnson, Adam S. Greenplate, Allison R. Sanders, Melinda E. Lovly, Christine M. Frederick, Dennie T. Kelley, Mark C. Richmond, Ann Irish, Jonathan M. Shyr, Yu Sullivan, Ryan J. Puzanov, Igor Sosman, Jeffrey A. Balko, Justin M. TI Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy SO NATURE COMMUNICATIONS LA English DT Article ID CELL LUNG-CANCER; T-CELLS; UNTREATED MELANOMA; CLINICAL-RESPONSE; NRAS MUTATIONS; PD-1 BLOCKADE; BREAST-CANCER; NIVOLUMAB; SAFETY; IPILIMUMAB AB Anti-PD-1 therapy yields objective clinical responses in 30-40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFN gamma-stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of 'PD-1 signalling', 'allograft rejection' and 'T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1-treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4(+) and CD8(+) tumour infiltrate. MHC-II+ tumours can be identified by melanoma-specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection. C1 [Johnson, Douglas B.; Opalenik, Susan R.; Feld, Emily; Lovly, Christine M.; Puzanov, Igor; Sosman, Jeffrey A.; Balko, Justin M.] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. [Estrada, Monica V.; Sanchez, Violeta; Johnson, Adam S.; Greenplate, Allison R.; Sanders, Melinda E.; Irish, Jonathan M.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Salgado, Roberto] Inst Jules Bordet, Dept Pathol, Breast Canc Translat Res Lab, Blvd Waterloo 121, B-1000 Brussels, Belgium. [Doxie, Deon B.; Vilgelm, Anna E.; Greenplate, Allison R.; Lovly, Christine M.; Richmond, Ann; Irish, Jonathan M.; Balko, Justin M.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA. [Vilgelm, Anna E.; Richmond, Ann; Sullivan, Ryan J.] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Nashville, TN 37232 USA. [Frederick, Dennie T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kelley, Mark C.] Vanderbilt Univ, Dept Surg Oncol, Nashville, TN 37232 USA. [Shyr, Yu] Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA. RP Johnson, DB; Balko, JM (reprint author), Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. EM douglas.b.johnson@vanderbilt.edu; justin.balko@vanderbilt.edu OI Irish, Jonathan/0000-0001-9428-8866 FU Vanderbilt Ingram Cancer Center [P30 CA68485]; Vanderbilt Digestive Disease Research Center [DK058404]; Damon Runyon Clinical Investigator Award; LUNGevity Career Development Award [T32CA009592, R00CA143231-03]; [4R00CA181491]; [K12CA0906525]; [5R01CA121210-07]; [5P01CA129243-06] FX Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource. The VMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30 CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). Study support was provided by 4R00CA181491 (J.M.B.), K12CA0906525 (D.B.J.), 5R01CA121210-07 (C.M.L.) 5P01CA129243-06 (C.M.L.), Damon Runyon Clinical Investigator Award (C.M.L.) and a LUNGevity Career Development Award (C.M.L.), T32CA009592 (D.B.D.) and R00CA143231-03 (J.M.I.). NR 48 TC 23 Z9 23 U1 5 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10582 DI 10.1038/ncomms10582 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2FU UT WOS:000369033400001 PM 26822383 ER PT J AU Kimmerling, RJ Szeto, GL Li, JW Genshaft, AS Kazer, SW Payer, KR Borrajo, JD Blainey, PC Irvine, DJ Shalek, AK Manalis, SR AF Kimmerling, Robert J. Szeto, Gregory Lee Li, Jennifer W. Genshaft, Alex S. Kazer, Samuel W. Payer, Kristofor R. Borrajo, Jacob de Riba Blainey, Paul C. Irvine, Darrell J. Shalek, Alex K. Manalis, Scott R. TI A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages SO NATURE COMMUNICATIONS LA English DT Article ID STEM-CELLS; HEMATOPOIETIC STEM; GENE-EXPRESSION; GENOME-WIDE; HETEROGENEITY; DIVISION; DIVERSIFICATION; PROLIFERATION; SYSTEM; FATES AB We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multi-generational lineage tracking under controlled culture conditions. We use this platform to generate whole-transcriptome profiles of primary, activated murine CD8+ T-cell and lymphocytic leukemia cell line lineages. Here we report that both cell types have greater intra-than inter-lineage transcriptional similarity. For CD8+ T-cells, genes with functional annotation relating to lymphocyte differentiation and function-including Granzyme B-are enriched among the genes that demonstrate greater intra-lineage expression level similarity. Analysis of gene expression covariance with matched measurements of time since division reveals cell type-specific transcriptional signatures that correspond with cell cycle progression. We believe that the ability to directly measure the effects of lineage and cell cycle-dependent transcriptional profiles of single cells will be broadly useful to fields where heterogeneous populations of cells display distinct clonal trajectories, including immunology, cancer, and developmental biology. C1 [Kimmerling, Robert J.; Szeto, Gregory Lee; Irvine, Darrell J.; Manalis, Scott R.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Kimmerling, Robert J.; Szeto, Gregory Lee; Li, Jennifer W.; Borrajo, Jacob de Riba; Blainey, Paul C.; Irvine, Darrell J.; Manalis, Scott R.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Szeto, Gregory Lee; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Szeto, Gregory Lee; Genshaft, Alex S.; Kazer, Samuel W.; Irvine, Darrell J.; Shalek, Alex K.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA. [Genshaft, Alex S.; Kazer, Samuel W.; Shalek, Alex K.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Genshaft, Alex S.; Kazer, Samuel W.; Shalek, Alex K.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Genshaft, Alex S.; Kazer, Samuel W.; Borrajo, Jacob de Riba; Blainey, Paul C.; Shalek, Alex K.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Payer, Kristofor R.] MIT, Microsyst Technol Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Shalek, Alex K.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Shalek, Alex K.] Massachusetts Gen Hosp, Dept Immunol, Boston, MA 02114 USA. [Manalis, Scott R.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Szeto, Gregory Lee] Univ Maryland Baltimore Cty, Dept Chem Biochem & Environm Engn, Engn Bldg Room 314,1000 Hilltop Circle, Baltimore, MD 21250 USA. RP Manalis, SR (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Manalis, SR (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Shalek, AK (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA.; Shalek, AK (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA.; Shalek, AK (reprint author), MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Shalek, AK (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Shalek, AK (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.; Shalek, AK (reprint author), Massachusetts Gen Hosp, Dept Immunol, Boston, MA 02114 USA.; Manalis, SR (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM shalek@mit.edu; srm@mit.edu OI , /0000-0003-3079-5134; Blainey, Paul/0000-0002-4889-8783; Szeto, Gregory/0000-0001-7604-1333 FU US National Institutes of Health [R21AI110787]; Physical Sciences Oncology Center from the National Cancer Institute [U54CA143874]; Koch Institute Support (core) grant from the National Cancer Institute [P30-CA14051]; National Science Foundation GRFP fellowships; National Institutes of Health under Ruth L. Kirchstein National Research Service Award [F32CA1800586]; Searle Scholars Program; Beckman Young Investigator Program; NIH New Innovator Award [DP2 OD020839] FX This work was supported by contract R21AI110787 from the US National Institutes of Health, the Physical Sciences Oncology Center U54CA143874 from the National Cancer Institute and the Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute. This work was carried out in part through the use of MIT's Microsystems Technology Laboratories. R.J.K and S.W.K were supported by National Science Foundation GRFP fellowships. G.L.S. was supported by the National Institutes of Health under Ruth L. Kirchstein National Research Service Award #F32CA1800586. D.J.I. is an investigator of the Howard Hughes Medical Institute. A.K.S. was supported by the Searle Scholars Program, Beckman Young Investigator Program, and the NIH New Innovator Award (DP2 OD020839). NR 22 TC 6 Z9 7 U1 8 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10220 DI 10.1038/ncomms10220 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2EG UT WOS:000369029400001 PM 26732280 ER PT J AU Nizamoglu, S Gather, MC Humar, M Choi, M Kim, S Kim, KS Hahn, SK Scarcelli, G Randolph, M Redmond, RW Yun, SH AF Nizamoglu, Sedat Gather, Malte C. Humar, Matjaz Choi, Myunghwan Kim, Seonghoon Kim, Ki Su Hahn, Sei Kwang Scarcelli, Giuliano Randolph, Mark Redmond, Robert W. Yun, Seok Hyun TI Bioabsorbable polymer optical waveguides for deep-tissue photomedicine SO NATURE COMMUNICATIONS LA English DT Article ID IN-VIVO; PHOTODYNAMIC THERAPY; SILK FIBROIN; HAIR REMOVAL; ENDOMICROSCOPY; NANOPARTICLES; SKIN; FABRICATION; ENDOSCOPY; HYDROGELS AB Advances in photonics have stimulated significant progress in medicine, with many techniques now in routine clinical use. However, the finite depth of light penetration in tissue is a serious constraint to clinical utility. Here we show implantable light-delivery devices made of bio-derived or biocompatible, and biodegradable polymers. In contrast to conventional optical fibres, which must be removed from the body soon after use, the biodegradable and biocompatible waveguides may be used for long-term light delivery and need not be removed as they are gradually resorbed by the tissue. As proof of concept, we demonstrate this paradigm-shifting approach for photochemical tissue bonding (PTB). Using comb-shaped planar waveguides, we achieve a full thickness ( 410 mm) wound closure of porcine skin, which represents similar to 10-fold extension of the tissue area achieved with conventional PTB. The results point to a new direction in photomedicine for using light in deep tissues. C1 [Nizamoglu, Sedat; Gather, Malte C.; Humar, Matjaz; Choi, Myunghwan; Kim, Ki Su; Scarcelli, Giuliano; Randolph, Mark; Redmond, Robert W.; Yun, Seok Hyun] Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med, 65 Landsdowne St UP-5, Cambridge, MA 02139 USA. [Nizamoglu, Sedat] Koc Univ, Dept Elect & Elect Engn, TR-34450 Istanbul, Turkey. [Gather, Malte C.] Univ St Andrews, Sch Phys & Astron, SUPA, St Andrews KY16 9SS, Fife, Scotland. [Humar, Matjaz] Jozef Stefan Inst, Condensed Matter Dept, Jamova 39, SI-1000 Ljubljana, Slovenia. [Choi, Myunghwan] Sungkyunkwan Univ, Inst Basic Sci, Ctr Neurosci & Imaging Res, Global Biomed Engn, 2066 Seoburo, Suwon 440746, Gyeonggi, South Korea. [Kim, Seonghoon] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, 291 Daehakro, Yuseong 305701, Daejeon, South Korea. [Hahn, Sei Kwang] Pohang Univ Sci & Technol, Dept Mat Sci & Engn, San 31, Pohang 790784, Kyungbuk, South Korea. [Scarcelli, Giuliano] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. [Randolph, Mark] Div Plast Surg, 40 Blossom St, Boston, MA 02114 USA. [Randolph, Mark] Harvard Univ, Sch Med, Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA. [Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Yun, SH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med, 65 Landsdowne St UP-5, Cambridge, MA 02139 USA.; Yun, SH (reprint author), Harvard MIT Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM syun@mgh.harvard.edu RI Humar, Matjaz/I-8862-2012; OI Humar, Matjaz/0000-0003-3338-6723; Choi, Myunghwan/0000-0002-4235-7003; Gather, Malte/0000-0002-4857-5562 FU U.S. National Institutes of Health [R21EB013761, P41EB015903, R01CA192878]; Department of Defense [FA9550-13-1-0068]; Bullock-Wellman Fellowships; Marie Curie Career Integration Grant [631679]; Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme [627274]; Human Frontier Science Program (Young Investigator Grant) [RGY0074/2013]; Bio & Medical Technology Development Program of the National Research Foundation of Korea [2012M3A9C6049791]; IT Consilience Creative Program of MKE [IITP-2015-R0346-15-1007]; IT Consilience Creative Program of NIPA [IITP-2015-R0346-15-1007] FX We thank Orhan Celiker for help in numerical simulation. This work was funded by the U.S. National Institutes of Health (R21EB013761, P41EB015903, R01CA192878), Department of Defense (FA9550-13-1-0068), Bullock-Wellman Fellowships, Marie Curie Career Integration Grant (631679), Marie Curie International Outgoing Fellowship No627274 within the 7th European Community Framework Programme, Human Frontier Science Program (Young Investigator Grant RGY0074/2013), the Bio & Medical Technology Development Program of the National Research Foundation of Korea (2012M3A9C6049791) and the IT Consilience Creative Program of MKE and NIPA (IITP-2015-R0346-15-1007). NR 38 TC 9 Z9 9 U1 13 U2 56 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10374 DI 10.1038/ncomms10374 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2BL UT WOS:000369022100011 PM 26783091 ER PT J AU Ohguchi, H Hideshima, T Bhasin, MK Gorgun, GT Santo, L Cea, M Samur, MK Mimura, N Suzuki, R Tai, YT Carrasco, RD Raje, N Richardson, PG Munshi, NC Harigae, H Sanda, T Sakai, J Anderson, KC AF Ohguchi, Hiroto Hideshima, Teru Bhasin, Manoj K. Gorgun, Gullu T. Santo, Loredana Cea, Michele Samur, Mehmet K. Mimura, Naoya Suzuki, Rikio Tai, Yu-Tzu Carrasco, Ruben D. Raje, Noopur Richardson, Paul G. Munshi, Nikhil C. Harigae, Hideo Sanda, Takaomi Sakai, Juro Anderson, Kenneth C. TI The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival SO NATURE COMMUNICATIONS LA English DT Article ID KRUPPEL-LIKE FACTOR-2; HISTONE DEMETHYLASE JMJD1A; EMBRYONIC STEM-CELLS; MULTIPLE-MYELOMA; GENE-EXPRESSION; CHROMOSOMAL TRANSLOCATION; PLASMA-CELLS; BONE-MARROW; GENOME-WIDE; TRANSCRIPTION AB KDM3A is implicated in tumorigenesis; however, its biological role in multiple myeloma ( MM) has not been elucidated. Here we identify KDM3A-KLF2-IRF4 axis dependence in MM. Knockdown of KDM3A is toxic to MM cells in vitro and in vivo. KDM3A maintains expression of KLF2 and IRF4 through H3K9 demethylation, and knockdown of KLF2 triggers apoptosis. Moreover, KLF2 directly activates IRF4 and IRF4 reciprocally upregulates KLF2, forming a positive autoregulatory circuit. The interaction of MM cells with bone marrow milieu mediates survival of MM cells. Importantly, silencing of KDM3A, KLF2 or IRF4 both decreases MM cell adhesion to bone marrow stromal cells and reduces MM cell homing to the bone marrow, in association with decreased ITGB7 expression in MAF-translocated MM cell lines. Our results indicate that the KDM3A-KLF2-IRF4 pathway plays an essential role in MM cell survival and homing to the bone marrow, and therefore represents a therapeutic target. C1 [Ohguchi, Hiroto; Hideshima, Teru; Gorgun, Gullu T.; Cea, Michele; Mimura, Naoya; Suzuki, Rikio; Tai, Yu-Tzu; Carrasco, Ruben D.; Richardson, Paul G.; Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bhasin, Manoj K.] Beth Israel Deaconess Med Ctr, BIDMC Gen Prote Bioinformat & Syst Biol Ctr, Boston, MA 02115 USA. [Santo, Loredana; Raje, Noopur] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Samur, Mehmet K.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury Div, West Roxbury, MA 02132 USA. [Harigae, Hideo] Tohoku Univ, Grad Sch Med, Dept Hematol & Rheumatol, Sendai, Miyagi 9808574, Japan. [Sanda, Takaomi] Natl Univ Singapore, Dept Med, Canc Sci Inst Singapore, Singapore 117599, Singapore. [Sakai, Juro] Univ Tokyo, Res Ctr Adv Sci & Technol, Div Metab Med, Tokyo 1538904, Japan. [Cea, Michele] Univ Genoa, IRCCS AOU San Martino IST, Dept Internal Med DiMI, Chair Hematol, I-16100 Genoa, Italy. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu FU NIH [P50 100707, PO-1 78378, PO-1 155258, RO-1 50947]; Uehara Memorial Foundation FX We thank Dr James E. Bradner for helpful suggestions and discussions, Dr Takashi Minami for providing the KLF2 antibody (N2212), Drs Bjoern Chapuy and Margaret A. Shipp for providing HBL-1 and SU-DHL4 cell lines and Dr Shinsuke Iida for providing KIS-1 cell line. This research was supported by NIH grants SPORE P50 100707 (N.C.M. and K.C.A.), PO-1 78378 (N.C.M. and K.C.A.), PO-1 155258 (M.K.S., N.C.M., and K.C.A.), and RO-1 50947 (K.C.A.). K.C.A. is an American Cancer Society Clinical Research Professor. H.O. was supported in part by a fellowship from the Uehara Memorial Foundation. NR 65 TC 3 Z9 3 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10258 DI 10.1038/ncomms10258 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2AU UT WOS:000369020400001 PM 26728187 ER PT J AU Pattaro, C Teumer, A Gorski, M Chu, AY Li, M Mijatovic, V Garnaas, M Tin, A Sorice, R Li, Y Taliun, D Olden, M Foster, M Yang, Q Chen, MH Pers, TH Johnson, AD Ko, YA Fuchsberger, C Tayo, B Nalls, M Feitosa, MF Isaacs, A Dehghan, A d'Adamo, P Adeyemo, A Dieffenbach, AK Zonderman, AB Nolte, IM van der Most, PJ Wright, AF Shuldiner, AR Morrison, AC Hofman, A Smith, AV Dreisbach, AW Franke, A Uitterlinden, AG Metspalu, A Tonjes, A Lupo, A Robino, A Johansson, A Demirkan, A Kollerits, B Freedman, BI Ponte, B Oostra, BA Paulweber, B Kramer, BK Mitchell, BD Buckley, BM Peralta, CA Hayward, C Helmer, C Rotimi, CN Shaffer, CM Muller, C Sala, C van Duijn, CM Saint-Pierre, A Ackermann, D Shriner, D Ruggiero, D Toniolo, D Lu, YC Cusi, D Czamara, D Ellinghaus, D Siscovick, DS Ruderfer, D Gieger, C Grallert, H Rochtchina, E Atkinson, EJ Holliday, EG Boerwinkle, E Salvi, E Bottinger, EP Murgia, F Rivadeneira, F Ernst, F Kronenberg, F Hu, FB Navis, GJ Curhan, GC Ehret, GB Homuth, G Coassin, S Thun, GA Pistis, G Gambaro, G Malerba, G Montgomery, GW Eiriksdottir, G Jacobs, G Li, G Wichmann, HE Campbell, H Schmidt, H Wallaschofski, H Volzke, H Brenner, H Kroemer, HK Kramer, H Lin, HH Leach, IM Ford, I Guessous, I Rudan, I Prokopenko, I Borecki, I Heid, IM Kolcic, I Persico, I Jukema, JW Wilson, JF Felix, JF Divers, J Lambert, JC Stafford, JM Gaspoz, JM Smith, JA Faul, JD Wang, JJ Ding, JZ Hirschhorn, JN Attia, J Whitfield, JB Chalmers, J Viikari, J Coresh, J Denny, JC Karjalainen, J Fernandes, JK Endlich, K Butterbach, K Keene, KL Lohman, K Portas, L Launer, LJ Lyytikainen, LP Yengo, L Franke, L Ferrucci, L Rose, LM Kedenko, L Rao, M Struchalin, M Kleber, ME Cavalieri, M Haun, M Cornelis, MC Ciullo, M Pirastu, M de Andrade, M McEvoy, MA Woodward, M Adam, M Cocca, M Nauck, M Imboden, M Waldenberger, M Pruijm, M Metzger, M Stumvoll, M Evans, MK Sale, MM Kahonen, M Boban, M Bochud, M Rheinberger, M Verweij, N Bouatia-Naji, N Martin, NG Hastie, N Probst-Hensch, N Soranzo, N Devuyst, O Raitakari, O Gottesman, O Franco, OH Polasek, O Gasparini, P Munroe, PB Ridker, PM Mitchell, P Muntner, P Meisinger, C Smit, JH Kovacs, P Wild, PS Froguel, P Rettig, R Magi, R Biffar, R Schmidt, R Middelberg, RPS Carroll, RJ Penninx, BW Scott, RJ Katz, R Sedaghat, S Wild, SH Kardia, SLR Ulivi, S Hwang, SJ Enroth, S Kloiber, S Trompet, S Stengel, B Hancock, SJ Turner, ST Rosas, SE Stracke, S Harris, TB Zeller, T Zemunik, T Lehtimaki, T Illig, T Aspelund, T Nikopensius, T Esko, T Tanaka, T Gyllensten, U Volker, U Emilsson, V Vitart, V Aalto, V Gudnason, V Chouraki, V Chen, WM Igl, W Marz, W Koenig, W Lieb, W Loos, RJF Liu, YM Snieder, H Pramstaller, PP Parsa, A O'Connell, JR Susztak, K Hamet, P Tremblay, J de Boer, IH Boger, CA Goessling, W Chasman, DI Kottgen, A Kao, WHL Fox, CS AF Pattaro, Cristian Teumer, Alexander Gorski, Mathias Chu, Audrey Y. Li, Man Mijatovic, Vladan Garnaas, Maija Tin, Adrienne Sorice, Rossella Li, Yong Taliun, Daniel Olden, Matthias Foster, Meredith Yang, Qiong Chen, Ming-Huei Pers, Tune H. Johnson, Andrew D. Ko, Yi-An Fuchsberger, Christian Tayo, Bamidele Nalls, Michael Feitosa, Mary F. Isaacs, Aaron Dehghan, Abbas d'Adamo, Pio Adeyemo, Adebowale Dieffenbach, Aida Karina Zonderman, Alan B. Nolte, Ilja M. van der Most, Peter J. Wright, Alan F. Shuldiner, Alan R. Morrison, Alanna C. Hofman, Albert Smith, Albert V. Dreisbach, Albert W. Franke, Andre Uitterlinden, Andre G. Metspalu, Andres Tonjes, Anke Lupo, Antonio Robino, Antonietta Johansson, Asa Demirkan, Ayse Kollerits, Barbara Freedman, Barry I. Ponte, Belen Oostra, Ben A. Paulweber, Bernhard Kraemer, Bernhard K. Mitchell, Braxton D. Buckley, Brendan M. Peralta, Carmen A. Hayward, Caroline Helmer, Catherine Rotimi, Charles N. Shaffer, Christian M. Mueller, Christian Sala, Cinzia van Duijn, Cornelia M. Saint-Pierre, Aude Ackermann, Daniel Shriner, Daniel Ruggiero, Daniela Toniolo, Daniela Lu, Yingchang Cusi, Daniele Czamara, Darina Ellinghaus, David Siscovick, David S. Ruderfer, Douglas Gieger, Christian Grallert, Harald Rochtchina, Elena Atkinson, Elizabeth J. Holliday, Elizabeth G. Boerwinkle, Eric Salvi, Erika Bottinger, Erwin P. Murgia, Federico Rivadeneira, Fernando Ernst, Florian Kronenberg, Florian Hu, Frank B. Navis, Gerjan J. Curhan, Gary C. Ehret, George B. Homuth, Georg Coassin, Stefan Thun, Gian-Andri Pistis, Giorgio Gambaro, Giovanni Malerba, Giovanni Montgomery, Grant W. Eiriksdottir, Gudny Jacobs, Gunnar Li, Guo Wichmann, H-Erich Campbell, Harry Schmidt, Helena Wallaschofski, Henri Voelzke, Henry Brenner, Hermann Kroemer, Heyo K. Kramer, Holly Lin, Honghuang Leach, I. Mateo Ford, Ian Guessous, Idris Rudan, Igor Prokopenko, Inga Borecki, Ingrid Heid, Iris M. Kolcic, Ivana Persico, Ivana Jukema, J. Wouter Wilson, James F. Felix, Janine F. Divers, Jasmin Lambert, Jean-Charles Stafford, Jeanette M. Gaspoz, Jean-Michel Smith, Jennifer A. Faul, Jessica D. Wang, Jie Jin Ding, Jingzhong Hirschhorn, Joel N. Attia, John Whitfield, John B. Chalmers, John Viikari, Jorma Coresh, Josef Denny, Joshua C. Karjalainen, Juha Fernandes, Jyotika K. Endlich, Karlhans Butterbach, Katja Keene, Keith L. Lohman, Kurt Portas, Laura Launer, Lenore J. Lyytikaeinen, Leo-Pekka Yengo, Loic Franke, Lude Ferrucci, Luigi Rose, Lynda M. Kedenko, Lyudmyla Rao, Madhumathi Struchalin, Maksim Kleber, Marcus E. Cavalieri, Margherita Haun, Margot Cornelis, Marilyn C. Ciullo, Marina Pirastu, Mario de Andrade, Mariza McEvoy, Mark A. Woodward, Mark Adam, Martin Cocca, Massimiliano Nauck, Matthias Imboden, Medea Waldenberger, Melanie Pruijm, Menno Metzger, Marie Stumvoll, Michael Evans, Michele K. Sale, Michele M. Kaehoenen, Mika Boban, Mladen Bochud, Murielle Rheinberger, Myriam Verweij, Niek Bouatia-Naji, Nabila Martin, Nicholas G. Hastie, Nick Probst-Hensch, Nicole Soranzo, Nicole Devuyst, Olivier Raitakari, Olli Gottesman, Omri Franco, Oscar H. Polasek, Ozren Gasparini, Paolo Munroe, Patricia B. Ridker, Paul M. Mitchell, Paul Muntner, Paul Meisinger, Christa Smit, Johannes H. Kovacs, Peter Wild, Philipp S. Froguel, Philippe Rettig, Rainer Maegi, Reedik Biffar, Reiner Schmidt, Reinhold Middelberg, Rita P. S. Carroll, Robert J. Penninx, Brenda W. Scott, Rodney J. Katz, Ronit Sedaghat, Sanaz Wild, Sarah H. Kardia, Sharon L. R. Ulivi, Sheila Hwang, Shih-Jen Enroth, Stefan Kloiber, Stefan Trompet, Stella Stengel, Benedicte Hancock, Stephen J. Turner, Stephen T. Rosas, Sylvia E. Stracke, Sylvia Harris, Tamara B. Zeller, Tanja Zemunik, Tatijana Lehtimaeki, Terho Illig, Thomas Aspelund, Thor Nikopensius, Tiit Esko, Tonu Tanaka, Toshiko Gyllensten, Ulf Voelker, Uwe Emilsson, Valur Vitart, Veronique Aalto, Ville Gudnason, Vilmundur Chouraki, Vincent Chen, Wei-Min Igl, Wilmar Maerz, Winfried Koenig, Wolfgang Lieb, Wolfgang Loos, Ruth J. F. Liu, Yongmei Snieder, Harold Pramstaller, Peter P. Parsa, Afshin O'Connell, Jeffrey R. Susztak, Katalin Hamet, Pavel Tremblay, Johanne de Boer, Ian H. Boeger, Carsten A. Goessling, Wolfram Chasman, Daniel I. Koettgen, Anna Kao, W. H. Linda Fox, Caroline S. CA ICBP Consortium AGEN Consortium CARDIOGRAM CHARGe-Heart Failure Grp ECHOGen Consortium TI Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; FALSE DISCOVERY RATES; STAGE RENAL-DISEASE; SERUM CREATININE; METAANALYSIS; VARIANTS; INDIVIDUALS; POPULATION; RISK; HYPERTENSION AB Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. C1 [Pattaro, Cristian; Taliun, Daniel; Fuchsberger, Christian; Saint-Pierre, Aude; Pramstaller, Peter P.] Med Univ Lubeck, European Acad Bozen Bolzano EURAC, Ctr Biomed, Via Galvani 31, I-39100 Bolzano, Italy. 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[Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. [Wichmann, H-Erich] Klinikum Grosshadern, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. [Campbell, Harry; Rudan, Igor; Wilson, James F.; Wild, Sarah H.] Univ Edinburgh, Ctr Populat Hlth Sci, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland. [Schmidt, Helena] Med Univ Graz, Dept Neurol, Inst Mol Biol & Biochem, Austrian Stroke Prevent Study, Harrachgasse 21, A-8010 Graz, Austria. [Wallaschofski, Henri; Nauck, Matthias] Univ Med Greifswald, Inst Clin Chem & Lab Med, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany. [Wallaschofski, Henri; Voelzke, Henry; Nauck, Matthias; Voelker, Uwe] German Ctr Cardiovasc Res DZHK, Partner Site Greifswald,Ferdinand Sauerbruch St, D-17475 Greifswald, Germany. 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[Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London W12 0NN, England. [Kolcic, Ivana; Boban, Mladen; Polasek, Ozren; Zemunik, Tatijana] Univ Split, Sch Med, Croatian Ctr Global Hlth, Soltanska 2, Split 21000, Croatia. [Jukema, J. Wouter; Trompet, Stella] Leiden Univ, Med Ctr, Dept Cardiol, POB 9600, NL-2300 RC Leiden, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands ICIN, Moreelsepk 1, NL-3511 EP Utrecht, Netherlands. [Jukema, J. Wouter] Einthoven Lab Expt Vasc Med, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Divers, Jasmin; Stafford, Jeanette M.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Div Publ Hlth Sci, 2326 Med Ctr Blvd, Winston Salem, NC 27157 USA. [Lambert, Jean-Charles; Stracke, Sylvia; Chouraki, Vincent] Inst Pasteur, INSERM, U744, 1 Rue Pr, F-59019 Lille, France. [Smith, Jennifer A.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA. [Faul, Jessica D.] Univ Michigan, Inst Social Res, Survey Res Ctr, 426 Thompson St,3456, Ann Arbor, MI 48104 USA. [Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst, Ctr Vis Res, Westmead Hosp C24, Sydney, NSW 2145, Australia. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med Geriatr, Med Ctr Blvd, Winston Salem, NC 27157 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur,NRB 0330, Boston, MA 02115 USA. [Chalmers, John; Woodward, Mark] Univ Sydney, George Inst Global Hlth, Level 10,King George V Bldg,83-117 Missenden Rd, Camperdown, NSW 2050, Australia. [Viikari, Jorma; Woodward, Mark] Univ Turku, Turku Univ Hosp, Dept Med, POB 52, Turku 20521, Finland. [Coresh, Josef; Kao, W. H. Linda] Welch Ctr Prevent Epidemiol & Clin Res, 2024 East Monument St,Suite 2-600, Baltimore, MD 21287 USA. [Denny, Joshua C.; Carroll, Robert J.] Vanderbilt Univ, Sch Med, Eskind Biomed Lib 448, 2209 Garland Ave, Nashville, TN 37212 USA. [Karjalainen, Juha; Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, POB 72, NL-9700 AB Groningen, Netherlands. [Fernandes, Jyotika K.] Med Univ S Carolina, Div Endocrinol, 171 Ashley Ave, Charleston, SC 29425 USA. [Endlich, Karlhans] Ernst Moritz Arndt Univ Greifswald, Inst Anat & Cell Biol, Friedrich Loeffler Str 23c, D-17487 Greifswald, Germany. [Keene, Keith L.] E Carolina Univ, Dept Biol, Ctr Hlth Dispar, 1001 East 10th St,N209 Howell Sci Complex, Greenville, NC 27858 USA. [Launer, Lenore J.; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Gateway Bldg,3C309,7201 Winsconsin Ave, Bethesda, MD 20892 USA. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, Fimlab Labs, Tampere 33520, Finland. [Yengo, Loic; Froguel, Philippe] CNRS, UMR 8199, 1 Rue Prof Calmette, F-59000 Lille, France. [Yengo, Loic; Froguel, Philippe] Lille Pasteur Inst, 1 Rue Prof Calmette, F-59000 Lille, France. [Yengo, Loic; Froguel, Philippe] Univ Lille 2, 42 Rue Paul Duez, F-59000 Lille, France. [Ferrucci, Luigi; Tanaka, Toshiko] NIA, Clin Res Branch, 251 Bayview Blvd, Baltimore, MD 21250 USA. [Struchalin, Maksim] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, Dr Molewaterpl, NL-3000 DR Rotterdam, Netherlands. [Struchalin, Maksim] Erasmus Univ, Med Ctr, Dept Forens Mol Biol, Dr Molewaterpl, Rotterdam, Netherlands. [Kleber, Marcus E.] Heidelberg Univ, Med Fac Mannheim, Med Clin 5, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. [Cavalieri, Margherita; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Austrian Stroke Prevent Study, Div Special Neurol, Auenbruggerpl 22, A-8036 Graz, Austria. [McEvoy, Mark A.] Univ Newcastle, John Hunter Hosp, Hunter Med Res Inst, Ctr Clin Epidemiol & Biostat,HRMC, Locked Bag 1, Newcastle, NSW 2310, Australia. [Woodward, Mark] Univ Oxford, Nuffield Dept Populat Hlth, George Inst Global Hlth, Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England. [Pruijm, Menno] Univ Lausanne Hosp, Serv Nephrol, Rue Bugnon 17, CH-1005 Lausanne, Switzerland. [Metzger, Marie; Stengel, Benedicte] Univ Paris 11, INSERM, UMRS 1018, CESP Team 10, 16 Ave Paul Vaillant Couturier, F-94807 Villejuif, France. [Evans, Michele K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH,Biomed Ctr, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. [Sale, Michele M.; Chen, Wei-Min] Univ Virginia, Dept Med Cardiovasc Med, Ctr Publ Hlth Genom, POB 800717, Charlottesville, VA 22908 USA. [Kaehoenen, Mika] Univ Tampere, Sch Med, Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland. [Bochud, Murielle] Univ Lausanne, CHU Vaudois, Univ Inst Social & Prevent Med, Route Corniche 2, CH-1066 Epalinges, Switzerland. [Bouatia-Naji, Nabila] Paris Cardiovasc Res Ctr PARCC, INSERM, UMR970, 56 Rue Leblanc, F-75015 Paris, France. [Bouatia-Naji, Nabila] Paris Descartes Univ, Fac Med, Sorbonne Paris Cite, 12 Rue Ecole Med, F-75006 Paris, France. [Martin, Nicholas G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. [Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton CB10 1HH, England. [Devuyst, Olivier] Univ Zurich, Inst Physiol, Mech Inherited Kidney Disorders Grp, Winterthurerstr 190, CH-8057 Zurich, Switzerland. [Raitakari, Olli; Aalto, Ville] Univ Turku, Turku Univ Hosp, Dept Clin Physiol, Res Ctr Appl & Prevent Cardiovasc Med, POB 52, Turku 20521, Finland. [Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Dept Clin Pharmacol, London EC1M 6BQ, England. [Munroe, Patricia B.] Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London EC1M 6BQ, England. [Ridker, Paul M.; Chasman, Daniel I.] Harvard Univ, Sch Med, 900 Commonwealth Ave Eeast, Boston, MA 02115 USA. [Muntner, Paul] Univ Alabama Birmingham, Dept Med, 1530 3rd Ave, South Birmingham, AL 35294 USA. [Muntner, Paul] Univ Alabama Birmingham, Dept Epidemiol, 1530 3rd Ave, South Birmingham, AL 35294 USA. [Smit, Johannes H.; Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, AJ Ernststr 1187, NL-1081 HL Amsterdam, Netherlands. [Smit, Johannes H.; Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, AJ Ernststr 1187, NL-1081 HL Amsterdam, Netherlands. [Kovacs, Peter] Univ Leipzig, IFB AdiposityDis, Liebigstr 21, D-04103 Leipzig, Germany. [Wild, Philipp S.] Med Univ Ctr Mainz, Langenbeckstr 1, D-55131 Mainz, Germany. [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, D-17487 Greifswald, Germany. [Biffar, Reiner] Ernst Moritz Arndt Univ Greifswald, Clin Prosthodont Dent Gerostomatol & Mat Sci, Rotgerberstr 8, D-17475 Greifswald, Germany. [Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Hunter Med Res Inst, John Hunter Hosp,HRMC, Locked Bag 1, Newcastle, NSW 2310, Australia. [Katz, Ronit; de Boer, Ian H.] Univ Washington, Kidney Res Inst, Box 359606,325 9th Ave, Seattle, WA 98104 USA. [Ulivi, Sheila] Inst Maternal & Child Health IRCCS Burlo Garofolo, Via Istria 65, I-34137 Trieste, Italy. [Turner, Stephen T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, 200 First St SW, Rochester, MN 55905 USA. [Stracke, Sylvia] Ernst Moritz Arndt Univ Greifswald, Clin Internal Med A, Friedrich Loeffler Str 23a, D-17475 Greifswald, Germany. [Emilsson, Valur] Univ Iceland, Fac Pharmaceut Sci, Saemundargata 2, IS-101 Reykjavik, Iceland. [Maerz, Winfried] Synlab Serv GmbH, Synlab Acad, Oberer Eselsberg 45, D-89081 Ulm, Germany. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Albert Einstein Allee 23, D-89081 Ulm, Germany. [Loos, Ruth J. F.] Ichan Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Via Lorenz Bohler 5, I-39100 Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. [Parsa, Afshin] Univ Maryland, Sch Med, Div Nephrol, 685 W Baltimore St,MSTF 314, Baltimore, MD 21201 USA. [Hamet, Pavel; Tremblay, Johanne] Univ Montreal, CHUM Res Ctr, CRCHUM, Technopole Angus, 900 St Denis, Montreal, PQ H2X 0A9, Canada. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol, 221 Longwood Ave, Boston, MA 02115 USA. RP Pattaro, C (reprint author), Med Univ Lubeck, European Acad Bozen Bolzano EURAC, Ctr Biomed, Via Galvani 31, I-39100 Bolzano, Italy.; Kottgen, A (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.; Kottgen, A (reprint author), Univ Hosp Freiburg, Dept Internal Med 4, Berliner Allee 29, D-79110 Freiburg, Germany.; Fox, CS (reprint author), NHLBIs Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.; Fox, CS (reprint author), Ctr Populat Studies, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.; Fox, CS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol, 221 Longwood Ave, Boston, MA 02115 USA. EM cristian.pattaro@eurac.edu; anna.koettgen@uniklinik-freiburg.de; foxca@nhlbi.nih.gov RI Ellinghaus, David/G-4467-2012; Deloukas, Panos/B-2922-2013; Colaus, PsyColaus/K-6607-2013; Verweij, Niek/A-4499-2017; HELMER, Catherine/I-6581-2015; Brenner, Hermann/B-4627-2017; Franke, Andre/B-2151-2010; Lieb, Wolfgang/C-1990-2012; Yengo, Loic/D-2692-2017; Palmer, Lyle/K-3196-2014; Polasek, Ozren/B-6002-2011; Boban, Mladen/E-2777-2017; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Li, Yong/A-6283-2011; Lyytikainen, Leo-Pekka/C-8544-2016; Woodward, Mark/D-8492-2015; Mitchell, Paul/P-1498-2014; Grallert, Harald/B-3424-2013; Waldenberger, Melanie/B-5355-2014; Wang, Jie Jin/P-1499-2014; Singleton, Andrew/C-3010-2009; Kronenberg, Florian/B-1736-2008; Aulchenko, Yurii/M-8270-2013; Stengel, Benedicte/G-5730-2015; Cossette, Suzanne/I-8008-2016; Lambert, jean-charles/A-9553-2014; ruggiero, daniela/K-5638-2016; Matullo, Giuseppe/K-6383-2016; Onland-Moret, N. Charlotte/G-9185-2011; Bochud, Murielle/A-3981-2010; van der Schouw, Yvonne/F-8327-2014; Ruderfer, Douglas/M-5795-2016; BOUATIA-NAJI, NABILA/D-5863-2013; d'Adamo, Adamo Pio/G-4064-2011; Schwarz, Peter/B-5127-2013; Johnson, Andrew/G-6520-2013; Franke, Lude/P-7036-2016; Karjalainen, Juha/P-8624-2016; Laan, Maris/A-4100-2011; Erdmann, Jeanette/P-7513-2014; Smith, Albert Vernon/K-5150-2015; OI Deloukas, Panos/0000-0001-9251-070X; HELMER, Catherine/0000-0002-5169-7421; Brenner, Hermann/0000-0002-6129-1572; Franke, Andre/0000-0003-1530-5811; Yengo, Loic/0000-0002-4272-9305; Palmer, Lyle/0000-0002-1628-3055; Polasek, Ozren/0000-0002-5765-1862; Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Waldenberger, Melanie/0000-0003-0583-5093; Wang, Jie Jin/0000-0001-9491-4898; Kronenberg, Florian/0000-0003-2229-1120; Aulchenko, Yurii/0000-0002-7899-1575; Lambert, jean-charles/0000-0003-0829-7817; ruggiero, daniela/0000-0003-3898-7827; Bochud, Murielle/0000-0002-5727-0218; van der Schouw, Yvonne/0000-0002-4605-435X; Ruderfer, Douglas/0000-0002-2365-386X; d'Adamo, Adamo Pio/0000-0001-9367-4909; Schwarz, Peter/0000-0001-6317-7880; Franke, Lude/0000-0002-5159-8802; Laan, Maris/0000-0002-8519-243X; Humphries, Stephen E/0000-0002-8221-6547; Verweij, Niek/0000-0002-4303-7685; Kloiber, Stefan/0000-0002-6838-4114; Cooper, Matthew/0000-0003-1139-3682; Org, Elin/0000-0003-1451-9375; Gieger, Christian/0000-0001-6986-9554; Beckmann, Jacques S /0000-0002-9741-1900; ELOSUA, ROBERTO/0000-0001-8235-0095; Cocca, Massimiliano/0000-0002-1127-7596; Erdmann, Jeanette/0000-0002-4486-6231; Smith, Albert Vernon/0000-0003-1942-5845; Ramachandran, Vasan/0000-0001-7357-5970; Goessling, Wolfram/0000-0001-9972-1569; Enroth, Stefan/0000-0002-5056-9137; Soranzo, Nicole/0000-0003-1095-3852; Chen, Wei-Min/0000-0002-2643-2333; Kumari, Meena/0000-0001-9716-1035; Meisinger, Christa/0000-0002-9026-6544; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Salvi, Erika/0000-0002-2724-2291; Marmot, Michael/0000-0002-2431-6419; Prabhakaran, Dorairaj/0000-0002-3172-834X; Zonderman, Alan B/0000-0002-6523-4778; Mitchell, Braxton/0000-0003-4920-4744; Smith, Jennifer/0000-0002-3575-5468; Lawlor, Debbie A/0000-0002-6793-2262; Tai, E Shyong/0000-0003-2929-8966; Johansson, Asa/0000-0002-2915-4498; Morris, Richard/0000-0001-7240-4563; Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Peters, Annette/0000-0001-6645-0985; Wain, Louise/0000-0003-4951-1867 FU NIH [R01DK090311, R24OD017870] FX Study-specific acknowledgements and funding sources for participating studies are reported in Supplementary Note. Zebrafish work was supported by NIH R01DK090311 and R24OD017870 to W.G. NR 48 TC 22 Z9 22 U1 16 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10023 DI 10.1038/ncomms10023 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2FO UT WOS:000369032800001 PM 26831199 ER PT J AU Shi, YJ Zhang, LL Pu, HJ Mao, LL Hu, XM Jiang, XY Xu, N Stetler, RA Zhang, F Liu, XR Leak, RK Keep, RF Ji, XM Chen, J AF Shi, Yejie Zhang, Lili Pu, Hongjian Mao, Leilei Hu, Xiaoming Jiang, Xiaoyan Xu, Na Stetler, R. Anne Zhang, Feng Liu, Xiangrong Leak, Rehana K. Keep, Richard F. Ji, Xunming Chen, Jun TI Rapid endothelial cytoskeletal reorganization enables early blood-brain barrier disruption and long-term ischaemic reperfusion brain injury SO NATURE COMMUNICATIONS LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; TIGHT JUNCTION PROTEINS; APPARENT DIFFUSION-COEFFICIENT; ACTIN STRESS FIBERS; MATRIX METALLOPROTEINASES; HSP27 PROTECTS; NEURONAL DEATH; STROKE; PERMEABILITY; BREAKDOWN AB The mechanism and long-term consequences of early blood-brain barrier (BBB) disruption after cerebral ischaemic/reperfusion (I/R) injury are poorly understood. Here we discover that I/R induces subtle BBB leakage within 30-60 min, likely independent of gelatinase B/MMP-9 activities. The early BBB disruption is caused by the activation of ROCK/MLC signalling, persistent actin polymerization and the disassembly of junctional proteins within microvascular endothelial cells (ECs). Furthermore, the EC alterations facilitate subsequent infiltration of peripheral immune cells, including MMP-9-producing neutrophils/macrophages, resulting in late-onset, irreversible BBB damage. Inactivation of actin depolymerizing factor (ADF) causes sustained actin polymerization in ECs, whereas EC-targeted overexpression of constitutively active mutant ADF reduces actin polymerization and junctional protein disassembly, attenuates both early-and late-onset BBB impairment, and improves long-term histological and neurological outcomes. Thus, we identify a previously unexplored role for early BBB disruption in stroke outcomes, whereby BBB rupture may be a cause rather than a consequence of parenchymal cell injury. C1 [Shi, Yejie; Zhang, Lili; Pu, Hongjian; Mao, Leilei; Hu, Xiaoming; Jiang, Xiaoyan; Stetler, R. Anne; Zhang, Feng; Liu, Xiangrong; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Shi, Yejie; Liu, Xiangrong; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, China Amer Inst Neurosci, Beijing 100053, Peoples R China. [Zhang, Lili; Pu, Hongjian; Mao, Leilei; Hu, Xiaoming; Jiang, Xiaoyan; Xu, Na; Stetler, R. Anne; Zhang, Feng; Chen, Jun] Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Zhang, Lili; Pu, Hongjian; Mao, Leilei; Hu, Xiaoming; Jiang, Xiaoyan; Xu, Na; Stetler, R. Anne; Chen, Jun] Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200032, Peoples R China. [Zhang, Lili; Hu, Xiaoming; Stetler, R. Anne; Zhang, Feng; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Keep, Richard F.] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA.; Ji, XM (reprint author), Capital Med Univ, Xuanwu Hosp, China Amer Inst Neurosci, Beijing 100053, Peoples R China.; Chen, J (reprint author), Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China.; Chen, J (reprint author), Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200032, Peoples R China.; Chen, J (reprint author), Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. EM jixm@ccmu.edu.cn; chenj2@upmc.edu OI Shi, Yejie/0000-0001-7502-9201 FU US National Institutes of Health [NS089534, NS045048, NS056118, NS092810]; US Department of Veterans Affairs Research Career Scientist Award; VA Merit Review Award [BX002495]; American Heart Association [15POST22260011]; Chinese Natural Science Foundation Outstanding Young Investigator Award [81325007]; Chang Jiang Scholars Program from the Chinese Ministry of Education [T2014251] FX This project was supported by the US National Institutes of Health grants NS089534, NS045048 and NS056118 (to J.C.), the US Department of Veterans Affairs Research Career Scientist Award and VA Merit Review Award BX002495 (to J.C.). Y.S. was supported by the American Heart Association grant 15POST22260011. X.Ji was supported by the Chinese Natural Science Foundation Outstanding Young Investigator Award (#81325007) and the Chang Jiang Scholars Program (#T2014251) from the Chinese Ministry of Education. F.Z. was supported by the US National Institutes of Health grant NS092810. We are indebted to Pat Strickler for excellent administrative support. NR 67 TC 11 Z9 11 U1 7 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10523 DI 10.1038/ncomms10523 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2CJ UT WOS:000369024500002 PM 26813496 ER PT J AU Tang, Q Moore, JC Ignatius, MS Tenente, IM Hayes, MN Garcia, EG Yordan, NT Bourque, C He, SN Blackburn, JS Look, AT Houvras, Y Langenau, DM AF Tang, Qin Moore, John C. Ignatius, Myron S. Tenente, Ines M. Hayes, Madeline N. Garcia, Elaine G. Yordan, Nora Torres Bourque, Caitlin He, Shuning Blackburn, Jessica S. Look, A. Thomas Houvras, Yariv Langenau, David M. TI Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish SO NATURE COMMUNICATIONS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CANCER STEM-CELL; IN-VIVO; CLONAL EVOLUTION; EMBRYONAL RHABDOMYOSARCOMA; TRANSGENIC ZEBRAFISH; PANCREATIC-CANCER; PROPAGATING CELLS; MUTANT ZEBRAFISH; DRUG-RESISTANCE AB Cancers contain a wide diversity of cell types that are defined by differentiation states, genetic mutations and altered epigenetic programmes that impart functional diversity to individual cells. Elevated tumour cell heterogeneity is linked with progression, therapy resistance and relapse. Yet, imaging of tumour cell heterogeneity and the hallmarks of cancer has been a technical and biological challenge. Here we develop optically clear immune-compromised rag2(E450fs) (casper) zebrafish for optimized cell transplantation and direct visualization of fluorescently labelled cancer cells at single-cell resolution. Tumour engraftment permits dynamic imaging of neovascularization, niche partitioning of tumour-propagating cells in embryonal rhabdomyosarcoma, emergence of clonal dominance in T-cell acute lymphoblastic leukaemia and tumour evolution resulting in elevated growth and metastasis in BRAF(V600E)-driven melanoma. Cell transplantation approaches using optically clear immune-compromised zebrafish provide unique opportunities to uncover biology underlying cancer and to dynamically visualize cancer processes at single-cell resolution in vivo. C1 [Tang, Qin; Moore, John C.; Ignatius, Myron S.; Tenente, Ines M.; Hayes, Madeline N.; Garcia, Elaine G.; Yordan, Nora Torres; Blackburn, Jessica S.; Langenau, David M.] Massachusetts Gen Hosp East, Mol Pathol, Ctr Canc, Boston, MA 02129 USA. [Tang, Qin; Moore, John C.; Ignatius, Myron S.; Tenente, Ines M.; Hayes, Madeline N.; Garcia, Elaine G.; Yordan, Nora Torres; Blackburn, Jessica S.; Langenau, David M.] Massachusetts Gen Hosp East, Regenerat Med, Boston, MA 02129 USA. [Tang, Qin; Moore, John C.; Ignatius, Myron S.; Tenente, Ines M.; Hayes, Madeline N.; Garcia, Elaine G.; Yordan, Nora Torres; He, Shuning; Blackburn, Jessica S.; Look, A. Thomas; Langenau, David M.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02139 USA. [Tenente, Ines M.] Univ Porto, Abel Salazar Biomed Sci Inst, P-4099003 Oporto, Portugal. [Bourque, Caitlin; Houvras, Yariv] Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA. [Bourque, Caitlin; Houvras, Yariv] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [He, Shuning; Look, A. Thomas] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Blackburn, Jessica S.] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40506 USA. RP Langenau, DM (reprint author), Massachusetts Gen Hosp East, Mol Pathol, Ctr Canc, Boston, MA 02129 USA.; Langenau, DM (reprint author), Massachusetts Gen Hosp East, Regenerat Med, Boston, MA 02129 USA.; Langenau, DM (reprint author), Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02139 USA. EM dlangenau@mgh.harvard.edu FU Alex's Lemonade Stand Foundation; Live Like Bella Foundation for Childhood Cancer; American Cancer Society; MGH Howard Goodman Fellowship; NIH [R24OD016761, R01CA154923, U54CA168512]; China Scholarship Council; Fundacao para a Cienca e Tecnologia, Portugal [SFRH/BD/51288/2010] FX This work was supported by Alex's Lemonade Stand Foundation (J.S.B., M.S.I., D.M.L.), the Live Like Bella Foundation for Childhood Cancer (D.M.L.), American Cancer Society (D.M.L.), the MGH Howard Goodman Fellowship (D.M.L.) and NIH grants R24OD016761, R01CA154923 and U54CA168512. Q.T. is funded by the China Scholarship Council. I.M.T. is funded by Fundacao para a Cienca e Tecnologia, Portugal (SFRH/BD/51288/2010). We thank the Specialized Histopathology Services at Massachusetts General Hospital and the Dana-Farber/Harvard Cancer Center (P30 CA06516), Massachusetts General Hospital Cancer Center/Molecular Pathology Confocal Core and the Harvard Center for Biological Imaging for technical support; Drs Fabrice Laroche and Hui Feng for helpful suggestions; Brian Millet and Anthony Sinagra for helpful statistical advice. NR 68 TC 10 Z9 10 U1 6 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10358 DI 10.1038/ncomms10358 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2AF UT WOS:000369018900004 PM 26790525 ER PT J AU Wani, AH Boettiger, AN Schorderet, P Ergun, A Munger, C Sadreyev, RI Zhuang, X Kingston, RE Francis, NJ AF Wani, Ajazul H. Boettiger, Alistair N. Schorderet, Patrick Ergun, Ayla Muenger, Christine Sadreyev, Ruslan I. Zhuang, Xiaowei Kingston, Robert E. Francis, Nicole J. TI Chromatin topology is coupled to Polycomb group protein subnuclear organization SO NATURE COMMUNICATIONS LA English DT Article ID CHROMOSOME CONFORMATION CAPTURE; GROUP RESPONSE ELEMENTS; BITHORAX COMPLEX; SAM DOMAIN; FLUORESCENCE MICROSCOPY; DROSOPHILA-MELANOGASTER; NUCLEAR-ORGANIZATION; GENOME ORGANIZATION; REPRESSIVE COMPLEX; JAK/STAT PATHWAY AB The genomes of metazoa are organized at multiple scales. Many proteins that regulate genome architecture, including Polycomb group (PcG) proteins, form subnuclear structures. Deciphering mechanistic links between protein organization and chromatin architecture requires precise description and mechanistic perturbations of both. Using super-resolution microscopy, here we show that PcG proteins are organized into hundreds of nanoscale protein clusters. We manipulated PcG clusters by disrupting the polymerization activity of the sterile alpha motif (SAM) of the PcG protein Polyhomeotic (Ph) or by increasing Ph levels. Ph with mutant SAM disrupts clustering of endogenous PcG complexes and chromatin interactions while elevating Ph level increases cluster number and chromatin interactions. These effects can be captured by molecular simulations based on a previously described chromatin polymer model. Both perturbations also alter gene expression. Organization of PcG proteins into small, abundant clusters on chromatin through Ph SAM polymerization activity may shape genome architecture through chromatin interactions. C1 [Wani, Ajazul H.; Schorderet, Patrick; Ergun, Ayla; Sadreyev, Ruslan I.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Wani, Ajazul H.; Schorderet, Patrick; Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Boettiger, Alistair N.; Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Boettiger, Alistair N.; Zhuang, Xiaowei] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Boettiger, Alistair N.; Zhuang, Xiaowei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Muenger, Christine; Francis, Nicole J.] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. [Sadreyev, Ruslan I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sadreyev, Ruslan I.] Harvard Univ, Sch Med, Boston, MA USA. [Francis, Nicole J.] Univ Montreal, Dept Biochim & Med Mol, Montreal, PQ, Canada. [Wani, Ajazul H.; Muenger, Christine] Univ Kashmir, Dept Biotechnol, Srinagar 190006, Jammu & Kashmir, India. RP Francis, NJ (reprint author), Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada.; Francis, NJ (reprint author), Univ Montreal, Dept Biochim & Med Mol, Montreal, PQ, Canada. EM Nicole.Francis@ircm.qc.ca FU Damon Runyon Foundation; NIGMS; CIHR FX The authors thank Dr Nicole Follmer for help in the early phases of the project, B. Bintu of the Zhuang lab for assistance with the polymer modelling and implementation of the 'pivot algorithm', Drs J. Mueller and R. Jones for antisera and the Genomics Platform at the University of Geneve for prioritized sequencing and data processing. ANB is supported by a postdoctoral fellowship from the Damon Runyon Foundation. Work in the lab of REK is supported by NIGMS and in the lab of NJF by NIGMS and CIHR. NR 67 TC 19 Z9 19 U1 10 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10291 DI 10.1038/ncomms10291 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2BB UT WOS:000369021100008 PM 26759081 ER PT J AU Evans, M Moy, B AF Evans, Michele Moy, Beverly TI Announcing a New Journal Section: Community Outreach SO ONCOLOGIST LA English DT Editorial Material C1 [Evans, Michele] NIA, Hlth Dispar Res Sect, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Moy, Beverly] Massachusetts Gen Hosp, Breast Oncol Program, 55 Fruit St,Lawrence House,LRH 304, Boston, MA 02114 USA. RP Moy, B (reprint author), Massachusetts Gen Hosp, Breast Oncol Program, 55 Fruit St,Lawrence House,LRH 304, Boston, MA 02114 USA.; Evans, M (reprint author), NIH, Hlth Dispar Res Sect, Lab Epidemiol & Populat Sci, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 04C222, Baltimore, MD 21224 USA. EM me42v@nih.gov; bmoy@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2016 VL 21 IS 1 BP 1 EP 1 DI 10.1634/theoncologist.2015-0494 PG 1 WC Oncology SC Oncology GA DC3RV UT WOS:000369137300001 PM 26712959 ER PT J AU Kumar, P Gareen, IF Lathan, C Sicks, JD Perez, GK Hyland, KA Park, ER AF Kumar, Pallavi Gareen, Ilana F. Lathan, Christopher Sicks, Jorean D. Perez, Giselle K. Hyland, Kelly A. Park, Elyse R. TI Racial Differences in Tobacco Cessation and Treatment Usage After Lung Screening: An Examination of the National Lung Screening Trial SO ONCOLOGIST LA English DT Article DE Smoking cessation; Tobacco cessation; Lung cancer; Cancer screening ID NICOTINE REPLACEMENT THERAPY; SERVICES TASK-FORCE; AFRICAN-AMERICAN SMOKERS; SMOKING-CESSATION; COMPUTED-TOMOGRAPHY; ETHNIC DISPARITIES; CANCER-MORTALITY; RISK-FACTORS; PREDICTORS; SURGERY AB Background. Black smokers have demonstrated greater lung cancer disease burden and poorer smoking cessation outcomes compared with whites. Lung cancer screening represents a unique opportunity to promote cessation among smokers; however, little is known about the differential impact of screening on smoking behaviors among black and white smokers. Using data from the National Lung Screening Trial (NLST), we examined the racial differences in smoking behaviors after screening. Methods. We examined racial differences in smoking behavior and cessation activity among 6,316 white and 497 black (median age, 60 and 59 years, respectively) NLST participants who were current smokers at screening using a follow-up survey on 24 -hour and 7 -day quit attempts, 6 -month continuous abstinence, and the use of smoking cessation programs and aids at 12 months after screening. Using multiple regression analyses, we examined the predictors of 24 -hour and 7 -day quit attempts and 6 -month continuous abstinence. Results. At 12 months after screening, blacks were more likely to report a 74 -hour (57.7% vs. 41.7%, p <.0001) or 7 -day (33.6% vs. 77.2%, p =.002) quit attempt. However, no significant racial differences were found in 6 -month continuous abstinence (5.6% blacks vs. 7.7% whites). In multiple regression, black race was predictive of a higher likelihood of a 24 -hour (odds ratio [OR], 1.6, 95% confidence interval [Cl], 1.2-2.0) and 7 -day (OR, 1.5, 95% CI, 1.1-1.8) quit attempt; however, race was not associated with 6 -month continuous abstinence. Onlya positive screening result for lung cancer was significantly predictive of successful 6 -month continuous abstinence (OR, 7.3, 95% CI, 1.8-2.9). Conclusion. Although blacks were more likely than whites to have 24 -hour and 7 -day quit attempts, the rates of 6 -month continuous abstinence did not differ. Targeted interventions are needed at the time of lung cancer screening to promote abstinence among all smokers. C1 [Kumar, Pallavi] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gareen, Ilana F.; Sicks, Jorean D.] Brown Univ, Sch Publ Hlth, Ctr Stat Sci, Providence, RI 02912 USA. [Gareen, Ilana F.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Lathan, Christopher] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA. [Perez, Giselle K.; Hyland, Kelly A.; Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Perez, Giselle K.; Hyland, Kelly A.; Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr,Dept Med, Boston, MA USA. [Hyland, Kelly A.] Univ S Florida, Tampa, FL USA. [Hyland, Kelly A.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. RP Kumar, P (reprint author), Univ Penn, Med Oncol & Palliat Med, Abramson Canc Ctr, 3400 Civ Ctr Blvd,6 PCAM South, Philadelphia, PA 19104 USA. EM pallavi.kumar@uphs.upenn.edu RI Gareen, Ilana/I-2816-2014 OI Gareen, Ilana/0000-0002-0457-5595 FU American Cancer Society's Mentored Research Scholar Award [MRSG-005-05-CPPB]; ACRIN/NLSTTrial Grants [U01 CA079778, U01 CA080098] FX This project was funded by a grant from the American Cancer Society's Mentored Research Scholar Award (Grant MRSG-005-05-CPPB) and ACRIN/NLSTTrial Grants U01 CA079778 and U01 CA080098. NR 53 TC 2 Z9 2 U1 1 U2 1 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 JAN PY 2016 VL 21 IS 1 BP 40 EP 49 DI 10.1634/theoncologist.2015-0325 PG 10 WC Oncology SC Oncology GA DC3RV UT WOS:000369137300009 PM 26712960 ER PT J AU Nipp, RD Greer, JA El-Jawahri, A Traeger, L Gallagher, ER Park, ER Jackson, VA Pirl, WF Temel, JS AF Nipp, Ryan D. Greer, Joseph A. El-Jawahri, Areej Traeger, Lara Gallagher, Emily R. Park, Elyse R. Jackson, Vicki A. Pirl, William F. Temel, Jennifer S. TI Age and Gender Moderate the Impact of Early Palliative Care in Metastatic Non-Small Cell Lung Cancer SO ONCOLOGIST LA English DT Article DE Palliative care; Quality of life; Mood; Advanced cancer; Gender; Geriatrics ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; COMMUNICATION SUPPORT INTERVENTION; LATE-STAGE CANCER; MULTIDISCIPLINARY INTERVENTION; GERIATRIC ASSESSMENT; OLDER PATIENTS; BREAST-CANCER; DEPRESSION; PREDICTORS AB Background. Studies demonstrate that early palliative care (EPC) improves advanced cancer patients' quality of life (QOL) and mood. However, it remains unclear whether the role of palliative care differs based upon patients' demographic characteristics. We explored whether age and gender moderate the improvements in QOL and mood seen with EPC. Methods. We performed a secondary analysis of data from a randomized controlled trial of patients with metastatic non small cell lung cancer. Patients received either EPC integrated with oncology care or oncology care alone. We assessed the degree to which QOL (Trial Outcome Index [T01]) and mood (Hospital Anxiety and Depression Scale [HADS] and Patient Health Questionnaire 9 [PHQ-9]) outcomes at week 12 varied by patient age (<65) and gender. The week 12 data of 107 patients are included in this analysis. Results. At 17 weeks, younger patients receiving EPC reported better 00L (TOImean = 62.04 vs. 49.43,p =. 0 0 1) and I ower rates of depression (HADS Depression = 4.0% vs. 52.4%, p.001; PHQ-9 = 0.0% vs. 28.6%, p =.0 0 6) than younger patients receiving oncology care alone. Males receiving EPC reported better QOL (TOImean = 58.81 vs. 48.30,p =.001) and lower rates of depression (HADS Depression = 18.5% vs. 60.9%, p =.0 0 2; PHQ-9 = 3.8% vs. 34.8%, p =. 0 0 8) than males receiving oncology care alone. At 12 weeks, QOL and mood did not differ between study groups for females and older patients. Conclusion. Males and younger patients who received [PC had better 00L and mood than those who received oncology care alone. However, these outcomes did not differ significantly between treatment groups for females or older patients. C1 [Nipp, Ryan D.; El-Jawahri, Areej; Gallagher, Emily R.; Temel, Jennifer S.] Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. [Greer, Joseph A.; Traeger, Lara; Park, Elyse R.; Pirl, William F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Jackson, Vicki A.] Massachusetts Gen Hosp, Dept Med, Div Palliat Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nipp, RD (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM RNipp@MGH.Harvard.edu FU American Society of Clinical Oncology Career Development Award; National Institutes of Health [5T32CA071345-18]; National Cancer Institute Career Development Award [K24CA181253] FX This work was supported by an American Society of Clinical Oncology Career Development Award and philanthropic gifts from the Joanne Hill Monahan Cancer Fund and Golf Fights Cancer. Ryan D. Nipp is supported by Training Grant 5T32CA071345-18 from the National Institutes of Health. Jennifer S. Temel is supported by National Cancer Institute Career Development Award K24CA181253. NR 55 TC 3 Z9 3 U1 3 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2016 VL 21 IS 1 BP 119 EP 126 DI 10.1634/theoncologist.2015-0232 PG 8 WC Oncology SC Oncology GA DC3RV UT WOS:000369137300018 PM 26621041 ER PT J AU Fairweather, M Keung, E Raut, CP AF Fairweather, Mark Keung, Emily Raut, Chandrajit P. TI Neoadjuvant Therapy for Soft-Tissue Sarcomas SO ONCOLOGY-NEW YORK LA English DT Review ID RESECTED RETROPERITONEAL SARCOMA; BEAM RADIATION-THERAPY; HIGH-GRADE; HIGH-RISK; LOCAL-CONTROL; BODY-WALL; PHASE-II; CHEMOTHERAPY; RADIOTHERAPY; EXTREMITY AB Soft-tissue sarcomas encompass a diverse group of rare neoplasms that can occur in any compartment of the body. They provide a therapeutic challenge to clinicians because of their typically large size at presentation, as well as their potentially close proximity to critical structures (ie, blood vessels, nerves). Even when a macroscopically complete resection with negative microscopic margins is achieved, local and distant recurrence rates are significant. Optimal management of patients with soft-tissue sarcomas should involve a multidisciplinary approach, with involvement of a surgical oncologist in addition to medical and radiation oncologists. Utilization of neoadjuvant therapies potentially provides local and distant control. The use of neoadjuvant therapy is influenced by the tumor biology (histologic subtype and grade), as well as the tumor location, and remains an area of controversy. The aim of this review is to discuss current neoadjuvant treatment options for soft-tissue sarcomas. C1 [Fairweather, Mark; Keung, Emily; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Fairweather, Mark; Keung, Emily; Raut, Chandrajit P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Raut, Chandrajit P.] Brigham & Womens Canc Ctr, Ctr Sarcoma & Bone Oncol, Boston, MA USA. [Fairweather, Mark; Keung, Emily; Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA. RP Fairweather, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. NR 31 TC 1 Z9 1 U1 1 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2016 VL 30 IS 1 BP 99 EP 106 PG 8 WC Oncology SC Oncology GA DB9XS UT WOS:000368871600014 PM 26791852 ER PT S AU Sweadner, KJ AF Sweadner, Kathleen J. BE Bublitz, M TI Colorimetric Assays of Na,K-ATPase SO P-TYPE ATPASES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Na,K-ATPase; Activity assay; Cardiac glycosides; Drug assay; ATP hydrolysis ID SODIUM DODECYL-SULFATE; ATPASE ACTIVITY; NA+,K+-ATPASE; SUBUNIT; PATHWAY; KIDNEY AB The Na,K-ATPase is a plasma membrane enzyme that catalyzes active ion transport by the hydrolysis of ATP. Its activity in vivo is determined by many factors, particularly the concentration of intracellular sodium ions. It is the target of the cardiac glycoside class of drugs and of endogenous regulators. Its assay is often an endpoint in the investigation of physiological processes, and it is a promising drug target. As described in this unit, its enzymatic activity can be determined in extracts from tissues by test tube assay using a spectrophotometer or P-32-ATP. The protocols in this chapter measure inorganic phosphate as the end product of hydrolysis of ATP. C1 [Sweadner, Kathleen J.] Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. FU NEI NIH HHS [EY014390]; NHLBI NIH HHS [HL036271]; NINDS NIH HHS [NS045283, NS050696, NS081558] NR 9 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3179-8; 978-1-4939-3178-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1377 BP 89 EP 104 DI 10.1007/978-1-4939-3179-8_10 D2 10.1007/978-1-4939-3179-8 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BE1ZX UT WOS:000368839300011 PM 26695025 ER PT S AU Arystarkhova, E Sweadner, KJ AF Arystarkhova, Elena Sweadner, Kathleen J. BE Bublitz, M TI Functional Studies of Na+,K+-ATPase Using Transfected Cell Cultures SO P-TYPE ATPASES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Gamma subunit; FXYD; Stable transfectants; Na,K-ATPase activity; Affinity; Cell growth ID NA-K-ATPASE; SODIUM-POTASSIUM PUMP; GAMMA-SUBUNIT; RENAL NA,K-ATPASE; CRYSTAL-STRUCTURE; REGULATORS; KIDNEY AB The properties of different combinations of Na,K-ATPase subunits or their mutations can be studied in stably transfected mammalian cells. As a specific example, the methods here are for transfection of a modulatory subunit into cells with endogenous alpha and beta subunits. Renal Na,K-ATPase is tightly bound to a small single-span membrane protein, the. subunit, or FXYD2. The protein co-localizes and co-immunoprecipitates with the alpha/beta complex, however it is not required for basic enzyme properties. Functional consequences of association with FXYD2 were investigated in stably transfected cells. The outcome was that FXYD2 reduced activity of Na,K-ATPase at the level of apparent affi nity for Na+ and to a smaller extent for K+. Moreover, expression of FXYD2 reduced cell growth. Here we describe the methodologies as well as potential pitfalls. C1 [Arystarkhova, Elena; Sweadner, Kathleen J.] Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. RP Arystarkhova, E (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. FU NEI NIH HHS [EY014390]; NHLBI NIH HHS [HL036271]; NINDS NIH HHS [NS045283, NS050696, NS081558] NR 12 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3179-8; 978-1-4939-3178-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1377 BP 321 EP 332 DI 10.1007/978-1-4939-3179-8_28 D2 10.1007/978-1-4939-3179-8 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BE1ZX UT WOS:000368839300029 PM 26695043 ER PT J AU Birtolo, C Go, VLW Ptasznik, A Eibl, G Pandol, SJ AF Birtolo, Chiara Go, Vay Liang W. Ptasznik, Andrzej Eibl, Guido Pandol, Stephen J. TI Phosphatidylinositol 3-Kinase A Link Between Inflammation and Pancreatic Cancer SO PANCREAS LA English DT Review DE PI3K; pancreatic cancer; chronic pancreatitis; inflammation ID ALCOHOLIC CHRONIC-PANCREATITIS; KEY PATHOLOGICAL RESPONSES; STELLATE CELLS; DUCTAL ADENOCARCINOMA; TUMOR PROGRESSION; ACINAR-CELLS; PHOSPHOINOSITIDE 3-KINASE; MACROPHAGE POLARIZATION; BREAST-CANCER; SIGNAL-TRANSDUCTION AB Even though a strong association between inflammation and cancer has been widely accepted, the underlying precise molecular mechanisms are still largely unknown. A complex signaling network between tumor and stromal cells is responsible for the infiltration of inflammatory cells into the cancer microenvironment. Tumor stromal cells such as pancreatic stellate cells (PSCs) and immune cells create a microenvironment that protects cancer cells through a complex interaction, ultimately facilitating their local proliferation and their migration to different sites. Furthermore, PSCs have multiple functions related to local immunity, angiogenesis, inflammation, and fibrosis. Recently, many studies have shown that members of the phosphoinositol-3-phosphate kinase (PI3K) family are activated in tumor cells, PSCs, and tumor-infiltrating inflammatory cells to promote cancer growth. Proinflammatory cytokines and chemokines secreted by immune cells and fibroblasts within the tumor environment can activate the PI3K pathway both in cancer and inflammatory cells. In this review, we focus on the central role of the PI3K pathway in regulating the cross talk between immune/stromal cells and cancer cells. Understanding the role of the PI3K pathway in the development of chronic pancreatitis and cancer is crucial for the discovery of novel and efficacious treatment options. C1 [Birtolo, Chiara; Ptasznik, Andrzej; Pandol, Stephen J.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Birtolo, Chiara] Univ Bologna, S Orsola M Malpighi Hosp, Dept Internal Med, Bologna, Italy. [Go, Vay Liang W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Eibl, Guido] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Pandol, Stephen J.] VA Greater Angeles Hlth Care Syst, Los Angeles, CA USA. RP Pandol, SJ (reprint author), Cedars Sinai Med Ctr, Basic & Translat Pancreas Res, Gastroenterol, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM stephen.pandol@cshs.org FU Department of Veterans Affairs; [P50 AA11999]; [P01 CA163200]; [P01 DK098108]; [P01AT3960] FX The study was partly supported by P50 AA11999, P01 CA163200, P01 DK098108, and P01AT3960 grants, as well as the Department of Veterans Affairs. NR 148 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD JAN PY 2016 VL 45 IS 1 BP 21 EP 31 DI 10.1097/MPA.0000000000000531 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB6AZ UT WOS:000368596800004 PM 26658038 ER PT J AU Morales-Oyarvide, V Mino-Kenudson, M AF Morales-Oyarvide, Vicente Mino-Kenudson, Mari TI Tumor islands and spread through air spaces: Distinct patterns of invasion in lung adenocarcinoma SO PATHOLOGY INTERNATIONAL LA English DT Review DE air space invasion; lung adenocarcinoma; micropapillay; spread through air spaces; tumor islands ID HISTOLOGIC SUBTYPE; IASLC/ATS/ERS CLASSIFICATION; PROGNOSTIC-SIGNIFICANCE; INTERNATIONAL ASSOCIATION; MICROPAPILLARY PATTERN; LIMITED RESECTION; POOR-PROGNOSIS; RECURRENCE; CARCINOMA; EGFR AB Lung adenocarcinoma is a highly heterogeneous disease and the heterogeneity is associated with various patient outcomes even in early-stage tumors. In order to improve prognostic and predictive values, the IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification was put forth in 2011 and it has been adopted in the recently published World Health Organization (WHO) classification of Tumours of the Lung, Pleura, Thymus and Heart 4th edition 2015, and lung adenocarcinomas are classified based on the predominant pattern. The performance of the classification in stratifying patient outcomes after resection of Stage I tumors and predicting molecular alterations has been confirmed by several studies. It also includes the category of minimally invasive adenocarcinoma (MIA) that predicts 100% 5-year recurrence free survival after curative resection similar to adenocarcinoma in situ. The diagnosis of MIA is based on not only size of the invasive component but also the absence of aggressive morphologic features such as pleural and/or lymphovascular invasion. Importantly, the WHO 2015 classification has introduced the concept of air space invasion and includes it as the exclusion criteria for MIA. The air space invasion consists of tumor islands and spread through air spaces (STAS). In this review, we will discuss the two entities and their clinical implications. C1 [Morales-Oyarvide, Vicente] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Morales-Oyarvide, Vicente; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Mino-Kenudson, M (reprint author), 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org NR 32 TC 4 Z9 4 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5463 EI 1440-1827 J9 PATHOL INT JI Pathol. Int. PD JAN PY 2016 VL 66 IS 1 BP 1 EP 7 DI 10.1111/pin.12368 PG 7 WC Pathology SC Pathology GA DC3VC UT WOS:000369146000001 PM 26642845 ER PT J AU Vital, P Castro, P Ittmann, M AF Vital, Paz Castro, Patricia Ittmann, Michael TI Oxidative Stress Promotes Benign Prostatic Hyperplasia SO PROSTATE LA English DT Article DE oxidative stress; benign prostatic hyperplasia; Nox4; oxidative DNA damage; transgenic ID EPITHELIAL GROWTH-FACTOR; URINARY-TRACT SYMPTOMS; CANCER PROGRESSION; PARACRINE INDUCER; NAD(P)H OXIDASE; GENE-EXPRESSION; RAT PROSTATE; CELLS; BPH; FIBROSIS AB BACKGROUND. Benign prostatic hyperplasia (BPH) is characterized by increased tissue mass in the transition zone of the prostate, which leads to obstruction of urine outflow and significant morbidity in the majority of older men. Plasma markers of oxidative stress are increased in men with BPH but it is unclear whether oxidative stress and/or oxidative DNA damage are causal in the pathogenesis of BPH. METHODS. Levels of 8-OH deoxyguanosine (8-OH dG), a marker of oxidative stress, were measured in prostate tissues from normal transition zone and BPH by ELISA. 8-OH dG was also detected in tissues by immunohistochemistry and staining quantitated by image analysis. Nox4 promotes the formation of reactive oxygen species. We therefore created and characterized transgenic mice with prostate specific expression of Nox4 under the control of the prostate specific ARR2PB promoter. RESULTS. Human BPH tissues contained significantly higher levels of 8-OH dG than control transition zone tissues and the levels of 8-OH dG were correlated with prostate weight. Cells with 8-OH dG staining were predominantly in the epithelium and were present in a patchy distribution. The total fraction of epithelial staining with 8-OH dG was significantly increased in BPH tissues by image analysis. The ARR2PB-Nox4 mice had increased oxidative DNA damage in the prostate, increased prostate weight, increased epithelial proliferation, and histological changes including epithelial proliferation, stromal thickening, and fibrosis when compared to wild type controls. CONCLUSIONS. Oxidative stress and oxidative DNA damage are important in the pathogenesis of BPH. Prostate 76: 58-67, 2016. (C) 2015 Wiley Periodicals, Inc. C1 [Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, One Baylor Plaza Houston, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol & Immunol, One Baylor Plaza Houston, Houston, TX 77030 USA. EM mittmann@bcm.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK083244, P20 DK097775 T32-DK007763]; National Institute on Aging [T32-AG000183]; National Cancer Institute P30 Cancer Center [P30 CA125123] FX Grant sponsor: National Institute of Diabetes and Digestive and Kidney Diseases; Grant numbers: R01 DK083244; P20 DK097775 T32-DK007763; Grant sponsor: National Institute on Aging; Grant number: T32-AG000183; Grant sponsor: National Cancer Institute P30 Cancer Center; Grant number: P30 CA125123. NR 33 TC 9 Z9 9 U1 4 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD JAN 1 PY 2016 VL 76 IS 1 BP 58 EP 67 DI 10.1002/pros.23100 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA DB9AZ UT WOS:000368809600007 PM 26417670 ER PT J AU Lokko, HN Gatchel, JR Becker, MA Stern, TA AF Lokko, Hermioni N. Gatchel, Jennifer R. Becker, Madeleine A. Stern, Theodore A. TI The Art and Science of Learning, Teaching, and Delivering Feedback in Psychosomatic Medicine SO PSYCHOSOMATICS LA English DT Article ID CLINICAL SETTINGS; EDUCATION; MODEL; TRAINEES; SKILLS; TIPS AB Background: The teaching and learning of psychosomatic medicine has evolved with the better understanding of effective teaching methods and feedback delivery in medicine and psychiatry. Objectives: We sought to review the variety of teaching methods used in psychosomatic medicine, to present principles of adult learning (and how these theories can be applied to students of psychosomatic medicine), and to discuss the role of effective feedback delivery in the process of teaching and learning psychosomatic medicine. Methods: In addition to drawing on the clinical and teaching experiences of the authors of the paper, we reviewed the literature on teaching methods, adult learning theories, and effective feedback delivery methods in medicine to draw parallels for psychosomatic medicine education. Results: We provide a review of teaching methods that have been employed to teach psychosomatic medicine over the past few decades. We outline examples of educational methods using the affective, behavioral, and cognitive domains. We provide examples of learning styles together with the principles of adult learning theory and how they can be applied to psychosomatic medicine learners. We discuss barriers to feedback delivery and offer suggestions as to how to give feedback to trainees on a psychosomatic medicine service. Conclusions: The art of teaching psychosomatic medicine is dynamic and will continue to evolve with advances in the field. Psychosomatic medicine educators must familiarize themselves with learning domains, learning styles, and principles of adult learning in order to be iinpactful. Effective feedback delivery methods are critical to fostering a robust learning environment for psychosomatic medicine. C1 [Lokko, Hermioni N.; Stern, Theodore A.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Gatchel, Jennifer R.] McLean Hosp, Psychiat, 115 Mill St, Belmont, MA 02178 USA. [Becker, Madeleine A.] Thomas Jefferson Univ Hosp, Psychiat, Philadelphia, PA 19107 USA. RP Lokko, HN (reprint author), Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. EM hlokko@partners.org NR 42 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2016 VL 57 IS 1 BP 31 EP 40 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA DC2JB UT WOS:000369041900004 PM 26683348 ER PT J AU Claessen, FMAP Mellema, JJ Stoop, N Lubberts, B Ring, D Poolman, RW AF Claessen, Femke M. A. P. Mellema, Jos J. Stoop, Nicky Lubberts, Bart Ring, David Poolman, Rudolf W. TI Influence of Priming on Patient-Reported Outcome Measures: A Randomized Controlled Trial SO PSYCHOSOMATICS LA English DT Article ID PAIN INTENSITY; INFORMATION; DEPRESSION; ANXIETY; MEMORY AB Background: Patient-reported outcome measures (PROMs) are influenced by psychosocial factors, but it is unknown whether we can influence PROM scores by modifying the mindset of the patient. Purpose: We assessed whether priming affects scores on PROMs. Methods: In all, 168 patients with musculoskeletal illness participated in this double-blinded, randomized, controlled, parallel study between July 2014 and October 2014 in a level I trauma center. Inclusion criteria were patients aged 18 years or older with English fluency and literacy and the ability to provide informed consent. Priming was performed by means of the Pain Catastrophizing Scale (PCS). The patients were randomized (1:1:1) into 3 groups: intervention group I was negatively primed with the original PCS, intervention group II was positively primed with a positively phrased PCS group; and control group III was not primed. Assessments were performed using PROMS on the domain of physical function, depression, and pain. Bivariate and multivariable regression analyses were conducted. Results: The intervention and control groups were well balanced in demographic and condition-specific characteristics. The positive PCS was independently associated with higher PROM scores in the physical function domain (Patient-Reported Outcome Measurement Information System Upper Extremity Function: coefficient = 4.7, partial R-2 = 0.042; CI: 1.2-8.2; p < 0.010). Conclusions: Patients primed with a positively phrased version of the PCS reported less functional disability as compared with patients who were either negatively primed or not primed at all. This suggests that by influencing the mindset, PROMs can be influenced, resulting in better outcome if positively primed. Level of evidence: Level 1 therapeutic study. C1 [Claessen, Femke M. A. P.; Mellema, Jos J.; Stoop, Nicky; Lubberts, Bart; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Poolman, Rudolf W.] Dept Orthopaed Surg, Oosterpk 9, NL-1091 AC Amsterdam, Netherlands. [Poolman, Rudolf W.] Joint Res Onze Lieve Vrouwe Gasthuis, Oosterpk 9, NL-1091 AC Amsterdam, Netherlands. RP Poolman, RW (reprint author), Dept Orthopaed Surg, Oosterpk 9, NL-1091 AC Amsterdam, Netherlands.; Poolman, RW (reprint author), Joint Res Onze Lieve Vrouwe Gasthuis, Oosterpk 9, NL-1091 AC Amsterdam, Netherlands. EM r.w.poolman@olvg.nl NR 25 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2016 VL 57 IS 1 BP 47 EP 56 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA DC2JB UT WOS:000369041900006 PM 26683347 ER PT J AU Phillips, CT Gavin, MC Luptakova, K Reynolds, EE Stern, TA Tapper, EB AF Phillips, Colin T. Gavin, Michael C. Luptakova, Katarina Reynolds, Eileen E. Stern, Theodore A. Tapper, Elliot B. TI Chest Pain Suggestive of a Life-Threatening Condition: A Department of Medicine Morbidity and Mortality Conference SO PSYCHOSOMATICS LA English DT Article ID ACUTE AORTIC DISSECTION; MUNCHAUSEN-SYNDROME; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; DIAGNOSIS; MANAGEMENT; DISEASE; UPDATE; IMPACT C1 [Phillips, Colin T.; Gavin, Michael C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiol, Sch Med, Boston, MA 02115 USA. [Luptakova, Katarina] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Oncol, Sch Med, Boston, MA 02115 USA. [Reynolds, Eileen E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02115 USA. [Stern, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Consultat Serv, Boston, MA 02115 USA. [Tapper, Elliot B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Liver Transplant Ctr, Sch Med, Boston, MA 02115 USA. RP Tapper, EB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Ctr Liver, Sch Med, 330 Brookline Ave, Boston, MA 02115 USA. EM etapper@bidmc.harvard.edu NR 27 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2016 VL 57 IS 1 BP 89 EP 96 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA DC2JB UT WOS:000369041900011 PM 26791516 ER PT J AU Eshel, N Marcovitz, DE Stern, TA AF Eshel, Neir Marcovitz, David E. Stern, Theodore A. TI Psychiatric Consultations in Less-Than-Private Places: Challenges and Unexpected Benefits of Hospital Roommates SO PSYCHOSOMATICS LA English DT Article ID CARE ENVIRONMENTS; FELLOW PATIENTS; SINGLE ROOMS; HEALTH; PREFERENCES C1 [Eshel, Neir] Harvard Univ, Sch Med, 260 Longwood Ave,Suite 168, Boston, MA 02115 USA. [Marcovitz, David E.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Eshel, N (reprint author), Massachusetts Gen Hosp, 260 Longwood Ave,Suite 168, Boston, MA 02115 USA. EM Neir_Eshel@hms.harvard.edu FU NIGMS NIH HHS [T32 GM007753]; NIMH NIH HHS [F30 MH100729] NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2016 VL 57 IS 1 BP 97 EP 101 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA DC2JB UT WOS:000369041900012 PM 26671624 ER PT J AU Merideth, FL Quinn, DK AF Merideth, Flannery L. Quinn, Davin K. TI "Walking the Walk": Decisional Capacity Deficits After Right Hemisphere Subdural Hematoma SO PSYCHOSOMATICS LA English DT Article ID TRAUMATIC BRAIN-INJURY; EXECUTIVE INTERVIEW; OLDER-ADULTS; CHALLENGES; COMPETENCE; ILLNESS; LESIONS; IMPACT C1 [Merideth, Flannery L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Quinn, Davin K.] Univ New Mexico, Dept Psychiat, 2600 Marble Ave NE Albuquerque, Albuquerque, NM 87131 USA. RP Quinn, DK (reprint author), Univ New Mexico, Dept Psychiat, 2600 Marble Ave NE Albuquerque, Albuquerque, NM 87131 USA. EM dquinn@salud.unm.edu NR 22 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2016 VL 57 IS 1 BP 102 EP 106 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA DC2JB UT WOS:000369041900013 PM 26481960 ER PT J AU Gakis, G Morgan, TM Efstathiou, JA Keegan, KA Mischinger, J Todenhoefer, T Schubert, T Zaid, HB Hrbacek, J Ali-El-Dein, B Clayman, RH Galland, S Olugbade, K Rink, M Fritsche, HM Burger, M Chang, SS Babjuk, M Thalmann, GN Stenzl, A Daneshmand, S AF Gakis, Georgios Morgan, Todd M. Efstathiou, Jason A. Keegan, Kirk A. Mischinger, Johannes Todenhoefer, Tilman Schubert, Tina Zaid, Harras B. Hrbacek, Jan Ali-El-Dein, Bedeir Clayman, Rebecca H. Galland, Sigolene Olugbade, Kola, Jr. Rink, Michael Fritsche, Hans-Martin Burger, Maximilian Chang, Sam S. Babjuk, Marko Thalmann, George N. Stenzl, Arnulf Daneshmand, Siamak TI Prognostic factors and outcomes in primary urethral cancer: results from the international collaboration on primary urethral carcinoma SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Clinical; Nodal stage; Primary urethral carcinoma; Prognostic; Risk factors; Survival AB Purpose To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC). Methods A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death. Results Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026). Conclusions These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC. C1 [Gakis, Georgios; Mischinger, Johannes; Todenhoefer, Tilman; Schubert, Tina; Stenzl, Arnulf] Univ Tubingen, Dept Urol, Tubingen, Germany. [Morgan, Todd M.; Olugbade, Kola, Jr.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Efstathiou, Jason A.; Clayman, Rebecca H.; Galland, Sigolene] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Keegan, Kirk A.; Zaid, Harras B.; Chang, Sam S.] Vanderbilt Univ, Ctr Med, Dept Urol Surg, Nashville, TN 37232 USA. [Hrbacek, Jan; Babjuk, Marko] Charles Univ Prague, Dept Urol, Fac Med 2, Prague, Czech Republic. [Ali-El-Dein, Bedeir] Mansoura Clin, Urol & Nephrol Ctr, Mansoura, Egypt. [Rink, Michael] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Fritsche, Hans-Martin; Burger, Maximilian] Univ Hosp Regensburg, Dept Urol, Regensburg, Germany. [Thalmann, George N.] Univ Hosp Bern, Dept Urol, CH-3010 Bern, Switzerland. [Daneshmand, Siamak] USC Norris Comprehens Canc Ctr, Inst Urol, Los Angeles, CA USA. RP Gakis, G (reprint author), Univ Tubingen, Dept Urol, Tubingen, Germany. EM georgios.gakis@web.de NR 13 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD JAN PY 2016 VL 34 IS 1 BP 97 EP 103 DI 10.1007/s00345-015-1583-7 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DC1XJ UT WOS:000369011200015 PM 25981402 ER PT J AU Park, J Koh, M Koo, JY Lee, S Park, SB AF Park, Jongmin Koh, Minseob Koo, Ja Young Lee, Sanghee Park, Seung Bum TI Investigation of Specific Binding Proteins to Photoaffinity Linkers for Efficient Deconvolution of Target Protein SO ACS CHEMICAL BIOLOGY LA English DT Article ID SMALL-MOLECULE PROBES; PHOTO-CROSS-LINKERS; IDENTIFICATION; DISCOVERY; MECHANISM; CELL; INHIBITORS; DESIGN AB Photoaffinity-based target identification has received recent attention as an efficient research tool for chemical biology and drug discovery. The major obstacle of photoaffinity-based target identification is the nonspecific interaction between target identification probes and nontarget proteins. Consequently, the rational design of photoaffinity linkers has been spotlighted for successful target identification. These nonspecific interactions have been considered as random events, and therefore no systematic investigation has been conducted regarding nonspecific interactions between proteins and photoaffinity linkers. Herein, we report the protein-labeling analysis of photoaffinity linkers containing three photoactivatable moieties: benzophenone, diazirine, and arylazide. Each photoaffinity linker binds to a different set of proteins in a structure-dependent manner, in contrast to the previous conception. The list of proteins labeled by each photoaffinity linker was successfully used to eliminate the nonspecific binding proteins from target candidates, thereby increasing the success rate of target identification. C1 [Park, Jongmin; Koh, Minseob; Koo, Ja Young; Lee, Sanghee; Park, Seung Bum] Seoul Natl Univ, Dept Biophys & Chem Biol, N Bio Inst, Seoul 151747, South Korea. [Park, Seung Bum] Seoul Natl Univ, Dept Chem, Seoul 151747, South Korea. [Park, Jongmin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. [Koh, Minseob] Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA. [Koh, Minseob] Scripps Res Inst, Skaggs Inst Mol Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA. [Lee, Sanghee] Novartis Inst Biomed Res, Dev & Mol Pathways, 250 Massachusetts Ave, Cambridge, MA 02139 USA. RP Park, J; Park, SB (reprint author), Seoul Natl Univ, Dept Biophys & Chem Biol, N Bio Inst, Seoul 151747, South Korea.; Park, SB (reprint author), Seoul Natl Univ, Dept Chem, Seoul 151747, South Korea.; Park, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM sbpark@snu.ac.kr; pls6443@snu.ac.kr OI Park, Jongmin/0000-0001-8338-9346 FU Creative Research Initiative Grant [2014R1A3A2030423]; Bio & Medical Technology Development Program - National Research Foundation of Korea (NRF) [2012M3A9C4048780] FX This work was supported by the Creative Research Initiative Grant (2014R1A3A2030423) and the Bio & Medical Technology Development Program (2012M3A9C4048780), funded by the National Research Foundation of Korea (NRF). NR 35 TC 6 Z9 6 U1 9 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2016 VL 11 IS 1 BP 44 EP 52 DI 10.1021/acschembio.5b00671 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DB5OC UT WOS:000368562500005 PM 26502221 ER PT J AU Wang, L Yui, J Wang, QF Zhang, YD Mori, W Shimoda, Y Fujinaga, M Kumata, K Yamasaki, T Hatori, A Rotstein, BH Collier, TL Ran, CZ Vasdev, N Zhang, MR Liang, SH AF Wang, Lu Yui, Joji Wang, Qifan Zhang, Yiding Mori, Wakana Shimoda, Yoko Fujinaga, Masayuki Kumata, Katsushi Yamasaki, Tomoteru Hatori, Akiko Rotstein, Benjamin H. Collier, Thomas Lee Ran, Chongzhao Vasdev, Neil Zhang, Ming-Rong Liang, Steven H. TI Synthesis and Preliminary PET Imaging Studies of a FAAH Radiotracer ([C-11]MPPO) Based on alpha-Ketoheterocyclic Scaffold SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE PET; fatty acid amide hydrolase; FAAH; [C-11]MPPO; radiotracer ID ACID AMIDE HYDROLASE; IN-VIVO EVALUATION; ANANDAMIDE HYDROLYSIS; CANNABINOID RECEPTOR; NERVOUS-SYSTEM; BRAIN; INHIBITORS; DISCOVERY; ENZYME; RAT AB Fatty acid amide hydrolase (FAAH) is one of the principle enzymes for metabolizing endogenous cannabinoid neurotransmitters such as anandamide, and thus regulates endocannabinoid (eCB) signaling. Selective pharmacological blockade of FAAH has emerged as a potential therapy to discern the endogenous functions of anandamide-mediated eCB pathways in anxiety, pain, and addiction. Quantification of FAAH in the living brain by positron emission tomography (PET) would help our understanding of the endocannabinoid system in these conditions. While most FAAH radiotracers operate by an irreversible ("suicide") binding mechanism, a FAAH tracer with reversibility would facilitate quantitative analysis. We have identified and radiolabeled a reversible FAAH inhibitor, 7-(2-[C-11]methoxyphenyl)-1- (5-(pyridin-2-yl)oxazol-2-yl)heptan-1-one ([C-11]MPPO) in 13% radiochemical yield (nondecay corrected) with >99% radiochemical purity and 2 Ci/mu mol (74 GBq/mu mol) specific activity. The tracer showed moderate brain uptake (0.8 SUV) with heterogeneous brain distribution. However, blocking studies with a potent FAAH inhibitor URB597 demonstrated a low to modest specificity to the target. Measurement of lipophilicity, metabolite, and efflux pathway analysis were also performed to study the pharmacokinetic profile of [C-11]MPPO. In all, we reported an efficient radiolabeling and preliminary evaluation of the first-in-class FAAH inhibitor [C-11]MPPO with alpha-ketoheterocyclic scaffold. C1 [Wang, Lu; Wang, Qifan; Rotstein, Benjamin H.; Collier, Thomas Lee; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Wang, Lu; Wang, Qifan; Rotstein, Benjamin H.; Collier, Thomas Lee; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Yui, Joji; Zhang, Yiding; Mori, Wakana; Shimoda, Yoko; Fujinaga, Masayuki; Kumata, Katsushi; Yamasaki, Tomoteru; Hatori, Akiko; Zhang, Ming-Rong] Natl Inst Radiol Sci, Mol Imaging Ctr, Chiba 2638555, Japan. [Collier, Thomas Lee] Advion BioSyst, 10 Brown Rd,Suite 101, Ithaca, NY 14850 USA. [Ran, Chongzhao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ran, Chongzhao] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. RP Liang, SH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.; Liang, SH (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA.; Zhang, MR (reprint author), Natl Inst Radiol Sci, Mol Imaging Ctr, Chiba 2638555, Japan. EM zhang@nirs.go.jp; liang.steven@mgh.harvard.edu FU NIH [NIH/NIDA K01DA038000] FX S.H.L. is a recipient of an NIH career development award (NIH/NIDA K01DA038000). NR 54 TC 0 Z9 0 U1 6 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD JAN PY 2016 VL 7 IS 1 BP 109 EP 118 DI 10.1021/acs.chemneuro.5b00248 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA DB5PX UT WOS:000368567200014 PM 26505525 ER PT J AU Butler, CR O'Hare, AM AF Butler, Catherine R. O'Hare, Ann M. TI Considerations in Applying the Results of Randomized Controlled Clinical Trials to the Care of Older Adults With Kidney Disease in the Clinical Setting: The SHARP Trial SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Lipids; Cholesterol; Statin; Ezetimibe; Clinical trials; SHARP; Older adults; Kidney disease; Guidelines ID PRIMARY CARDIOVASCULAR PREVENTION; DENSITY-LIPOPROTEIN CHOLESTEROL; UNITED-STATES; PRACTICE GUIDELINE; COST-EFFECTIVENESS; RENAL PROTECTION; STATINS; CKD; HEART; DEATH AB The Study of Heart and Renal Protection (SHARP) found that treatment with ezetemibe and low-dose simvastatin reduced the incidence of major atherosclerotic events in patients with kidney disease. Due to the paucity of evidence-based interventions that lower cardiovascular morbidity in this high-risk population, the SHARP trial will likely have a large impact on clinical practice. However, applying the results of clinical trials conducted in select populations to the care of individual patients in real world settings can be fraught with difficulty. This is especially true when caring for older adults with complex comorbidity and limited life expectancy. These patients are often excluded from clinical trials, frequently have competing health priorities, and may be less likely to benefit and more likely to be harmed by medications. We discuss key considerations in applying the results of the SHARP trial to the care of older adults with CKD in real-world clinical settings using guiding principles set forth by the American Geriatrics Society's Expert Panel on the Care of Older Adults with Multimorbidity. Using this schema, we emphasize the importance of evaluating trial results in the unique context of each patient's goals, values, priorities, and circumstances. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. C1 Dept Med, Seattle, WA USA. Univ Washington, Harborview Med Ctr, Div Hospitalist Med, 325 9Th Ave, Seattle, WA 98104 USA. VA Puget Sound Healthcare Syst, Hosp & Specialty Med Serv, Nephrol Sect, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. RP O'Hare, AM (reprint author), VA Puget Sound Healthcare Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM ann.ohare@va.gov FU NIH; CDC; VA FX A.M.O'H. receives research funding from NIH, CDC, and VA. She has received honoraria from UpToDate and the American Society of Nephrology, The Japanese Society of Dialysis, and Transplantation and Henry Ford Hospital System. NR 52 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 EI 1548-5609 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD JAN PY 2016 VL 23 IS 1 BP 29 EP 35 DI 10.1053/j.ackd.2015.11.004 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DB6UW UT WOS:000368652200006 PM 26709060 ER PT J AU Nimptsch, K Zhang, XH Cassidy, A Song, MY O'Reilly, EJ Lin, JH Pischon, T Rimm, EB Willett, WC Fuchs, CS Ogino, S Chan, AT Giovannucci, EL Wu, KN AF Nimptsch, Katharina Zhang, Xuehong Cassidy, Aedin Song, Mingyang O'Reilly, Eilis J. Lin, Jennifer H. Pischon, Tobias Rimm, Eric B. Willett, Walter C. Fuchs, Charles S. Ogino, Shuji Chan, Andrew T. Giovannucci, Edward L. Wu, Kana TI Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE flavonoids; flavonols; flavones; flavanones; flavan-3-ols; anthocyanins; colorectal cancer ID NATIONAL DEATH INDEX; TOTAL-ENERGY-INTAKE; IOWA WOMENS HEALTH; DIETARY FLAVONOIDS; POSTMENOPAUSAL WOMEN; NETHERLANDS COHORT; NURSES HEALTH; HEART-DISEASE; COLON-CANCER; MEN AB Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results. Objective: In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer. Design: Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses' Health Study. Results: During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk. Conclusion: Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer. C1 [Nimptsch, Katharina; Pischon, Tobias] Max Delbruck Ctr Mol Med, Mol Epidemiol Res Grp, Berlin, Germany. [Nimptsch, Katharina; Song, Mingyang; O'Reilly, Eilis J.; Rimm, Eric B.; Willett, Walter C.; Giovannucci, Edward L.; Wu, Kana] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Rimm, Eric B.; Willett, Walter C.; Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Zhang, Xuehong; O'Reilly, Eilis J.; Rimm, Eric B.; Willett, Walter C.; Fuchs, Charles S.; Ogino, Shuji; Chan, Andrew T.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Cassidy, Aedin] Univ E Anglia, Dept Nutr, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Lin, Jennifer H.] Takeda Dev Ctr Amer Inc, Quantitat Sci, Safety Stat & Observat Res Analyt, Deerfield, IL USA. [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Nimptsch, K (reprint author), Max Delbruck Ctr Mol Med, Mol Epidemiol Res Grp, Berlin, Germany. EM katharina.nimptsch@mdc-berlin.de OI Pischon, Tobias/0000-0003-1568-767X; Nimptsch, Katharina/0000-0001-7877-205X FU NIH [P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, R01 CA151993, R35 CA197735, R01 CA137178, P50 CA127003]; Biotechnology and Biological Sciences Research Council, United Kingdom [BB/J004545/1]; SDA Agricultural Research Service [58-1950-0-0141]; Royal Society Wolfson Research Merit Award FX Supported by NIH grants P01 CA87969, UM1 CA186107, P01 CA55075 and UM1 CA167552 (to WCW), R01 CA151993 and R35 CA197735 (to SO), R01 CA137178 (to ATC), and P50 CA127003 (to CSF); Biotechnology and Biological Sciences Research Council, United Kingdom (REF: BB/J004545/1 to AC); SDA Agricultural Research Service (agreement 58-1950-0-0141 to AC); and Royal Society Wolfson Research Merit Award (to AC). This is an open access article distributed under the CC-BY license (http://creativecommons.org/licenses/by/3.0/). NR 49 TC 8 Z9 8 U1 1 U2 6 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 JAN PY 2016 VL 103 IS 1 BP 184 EP 191 DI 10.3945/ajcn.115.117507 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DA5VA UT WOS:000367869500022 PM 26537935 ER PT J AU Starling, RC Stehlik, J Baran, DA Armstrong, B Stone, JR Ikle, D Morrison, Y Bridges, ND Putheti, P Strom, TB Bhasin, M Guleria, I Chandraker, A Sayegh, M Daly, KP Briscoe, DM Heeger, PS AF Starling, R. C. Stehlik, J. Baran, D. A. Armstrong, B. Stone, J. R. Ikle, D. Morrison, Y. Bridges, N. D. Putheti, P. Strom, T. B. Bhasin, M. Guleria, I. Chandraker, A. Sayegh, M. Daly, K. P. Briscoe, D. M. Heeger, P. S. CA CTOT-05 Consortium TI Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID CARDIAC ALLOGRAFT VASCULOPATHY; CORONARY-ARTERY-DISEASE; ANTIBODY-MEDIATED REJECTION; ENDOTHELIAL GROWTH-FACTOR; INTRAVASCULAR ULTRASOUND ASSESSMENT; ACUTE CELLULAR REJECTION; ALLOMAP GENE-EXPRESSION; LONG-TERM SURVIVAL; REACTIVE T-CELLS; INTERNATIONAL SOCIETY AB Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA-and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation. C1 [Starling, R. C.] Cleveland Clin, Kaufman Ctr Heart Failure, Cleveland, OH 44106 USA. [Starling, R. C.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Stehlik, J.] Univ Utah, Hlth Sci Ctr, Div Cardiovasc Med, Salt Lake City, UT USA. [Baran, D. A.] Newark Beth Israel Med Ctr, Transplant Ctr, Newark, NJ USA. [Armstrong, B.; Ikle, D.] Rho, Chapel Hill, NC USA. [Stone, J. R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Morrison, Y.; Bridges, N. D.] NIAID, Transplantat Branch, NIH, Rockville, MD USA. [Putheti, P.; Strom, T. B.; Bhasin, M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02115 USA. [Bhasin, M.] Beth Israel Deaconess Med Ctr, Genom Prot Bioinformat & Syst Biol Ctr, Boston, MA 02215 USA. [Guleria, I.; Chandraker, A.; Sayegh, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Schuster Family Transplantat Res Ctr,Dept Med, Boston, MA 02115 USA. [Guleria, I.; Briscoe, D. M.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Med, Boston, MA USA. [Guleria, I.; Daly, K. P.; Briscoe, D. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Daly, K. P.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. [Heeger, P. S.] Icahn Sch Med Mt Sinai, Inst Immunol, Translat Transplant Res Ctr, Dept Med, New York, NY 10029 USA. [Heeger, P. S.] Icahn Sch Med Mt Sinai, Recanati Miller Transplant Inst, New York, NY 10029 USA. RP Heeger, PS (reprint author), Icahn Sch Med Mt Sinai, Inst Immunol, Translat Transplant Res Ctr, Dept Med, New York, NY 10029 USA.; Heeger, PS (reprint author), Icahn Sch Med Mt Sinai, Recanati Miller Transplant Inst, New York, NY 10029 USA. EM peter.heeger@mssm.edu OI Daly, Kevin/0000-0003-4327-1532 FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [U01AI063594, AI063623] FX This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under U01AI063594 awarded to P.H. and AI063623 awarded to M. S. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 85 TC 6 Z9 6 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2016 VL 16 IS 1 BP 121 EP 136 DI 10.1111/ajt.13422 PG 16 WC Surgery; Transplantation SC Surgery; Transplantation GA DB4TW UT WOS:000368507300017 PM 26260101 ER PT J AU Villani, V Yamada, K Scalea, JR Gillon, BC Arn, JS Sekijima, M Tasaki, M Cormack, TA Moran, SG Torabi, R Shimizu, A Sachs, DH AF Villani, V. Yamada, K. Scalea, J. R. Gillon, B. C. Arn, J. S. Sekijima, M. Tasaki, M. Cormack, T. A. Moran, S. G. Torabi, R. Shimizu, A. Sachs, D. H. TI Adoptive Transfer of Renal Allograft Tolerance in a Large Animal Model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; MINIATURE SWINE; TRANSPLANTATION TOLERANCE; CLASS-I; CELLS; INDUCTION; TRANSFUSION; ANTIGEN AB Our recent studies in an inbred swine model demonstrated that both peripheral and intra-graft regulatory cells were required for the adoptive transfer of tolerance to a second, naive donor-matched kidney. Here, we have asked whether both peripheral and intra-graft regulatory elements are required for adoptive transfer of tolerance when only a long-term tolerant (LTT) kidney is transplanted. Nine highly-inbred swine underwent a tolerance-inducing regimen to prepare LTT kidney grafts which were then transplanted to histocompatible recipients, with or without the peripheral cell populations required for adoptive transfer of tolerance to a naive kidney. In contrast to our previous studies, tolerance of the LTT kidney transplants alone was achieved without transfer of additional peripheral cells and without strategies to increase the number/potency of regulatory T cells in the donor. This tolerance was systemic, since most subsequent, donor-matched challenge kidney grafts were accepted. These results confirm the presence of a potent tolerance-inducing and/or tolerance-maintaining cell population within LTT renal allografts. They suggest further that additional peripheral tolerance mechanisms, required for adoptive transfer of tolerance to a naive donor-matched kidney, depend on peripheral cells that, if not transferred with the LTT kidney, require time to develop in the adoptive host. C1 [Villani, V.; Yamada, K.; Scalea, J. R.; Gillon, B. C.; Arn, J. S.; Sekijima, M.; Tasaki, M.; Cormack, T. A.; Moran, S. G.; Torabi, R.; Shimizu, A.; Sachs, D. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CTS,TBRC Labs, Boston, MA USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CTS,TBRC Labs, Boston, MA USA. EM david.sachs@tbrc.mgh.harvard.edu FU NIH [R37AI031046-24, C06RR020135-01]; American Society of Transplantation FX This work was supported by NIH grants R37AI031046-24 and C06RR020135-01. Cyclosporine A was kindly provided by Novartis. J.R.S. is a recipient of a Basic Science Fellowship Grant from the American Society of Transplantation. We thank Drs. Maria Lucia Madariaga and Isabel M. Hanekamp for critical review of the paper, and Rebecca Brophy for her expert editorial assistance. NR 19 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2016 VL 16 IS 1 BP 317 EP 324 DI 10.1111/ajt.13424 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA DB4TW UT WOS:000368507300037 PM 26260215 ER PT J AU Lan, CW Fiellin, DA Barry, DT Bryant, KJ Gordon, AJ Edelman, EJ Gaither, JR Maisto, SA Marshall, BDL AF Lan, Chiao-Wen Fiellin, David A. Barry, Declan T. Bryant, Kendall J. Gordon, Adam J. Edelman, E. Jennifer Gaither, Julie R. Maisto, Stephen A. Marshall, Brandon D. L. TI The Epidemiology of Substance Use Disorders in US Veterans: A Systematic Review and Analysis of Assessment Methods SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VA HEALTH-CARE; RANDOMIZED CLINICAL-TRIAL; MAJOR DEPRESSIVE DISORDER; AMERICAN-INDIAN VETERANS; HAZARDOUS ALCOHOL-USE; SPINAL-CORD-INJURY; PSYCHIATRIC-DISORDERS; BIPOLAR DISORDER; DRUG-USE AB Background: Substance use disorders (SUDs), which encompass alcohol and drug use disorders (AUDs, DUDs), constitute a major public health challenge among US veterans. SUDs are among the most common and costly of all health conditions among veterans. Objectives: This study sought to examine the epidemiology of SUDs among US veterans, compare the prevalence of SUDs in studies using diagnostic and administrative criteria assessment methods, and summarize trends in the prevalence of SUDs reported in studies sampling US veterans over time. Methods: Comprehensive electronic database searches were conducted. A total of 3,490 studies were identified. We analyzed studies sampling US veterans and reporting prevalence, distribution, and examining AUDs and DUDs. Results: Of the studies identified, 72 met inclusion criteria. The studies were published between 1995 and 2013. Studies using diagnostic criteria reported higher prevalence of AUDs (32% vs. 10%) and DUDs (20% vs. 5%) than administrative criteria, respectively. Regardless of assessment method, both the lifetime and past year prevalence of AUDs in studies sampling US veterans has declined gradually over time. Conclusion: The prevalence of SUDs reported in studies sampling US veterans are affected by assessment method. Given the significant public health problems of SUDs among US veterans, improved guidelines for clinical screening using validated diagnostic criteria to assess AUDs and DUDs in US veteran populations are needed. Scientific Significance: These findings may inform VA and other healthcare systems in prevention, diagnosis, and intervention for SUDs among US veterans. C1 [Lan, Chiao-Wen] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA USA. [Fiellin, David A.; Edelman, E. Jennifer] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Barry, Declan T.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Barry, Declan T.] APT Fdn Inc, Pain Treatment Serv, New Haven, CT USA. [Bryant, Kendall J.] NIAAA, NIH, Bethesda, MD USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Hlth Res Educ & Clin Ctr, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Gaither, Julie R.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Maisto, Stephen A.] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Marshall, Brandon D. L.] Brown Univ, Dept Epidemiol, Sch Publ Hlth, 121 South Main St,Box G-S-121-2, Providence, RI 02912 USA. RP Marshall, BDL (reprint author), Brown Univ, Dept Epidemiol, 121 South Main St,Box G-S-121-2, Providence, RI 02912 USA. EM brandon_marshall@brown.edu OI Fiellin, David/0000-0002-4006-010X FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U24-AA022000]; Yale Drug Abuse, Addiction and HIV Research Scholars (DAHRS) Program [K12-DA-33312-03]; Brown University; [K05-AA16928] FX This work was supported in part by grant U24-AA022000 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Dr. Edelman is funded by the Yale Drug Abuse, Addiction and HIV Research Scholars (DAHRS) Program (K12-DA-33312-03). Dr. Maisto is supported by grant K05-AA16928 (NIAAA). Dr. Marshall is supported by a Richard B. Salomon Faculty Research Award from Brown University. NR 113 TC 1 Z9 1 U1 2 U2 7 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 JAN PY 2016 VL 25 IS 1 BP 7 EP 24 DI 10.1111/ajad.12319 PG 18 WC Substance Abuse SC Substance Abuse GA DB4TS UT WOS:000368506900001 PM 26693830 ER PT J AU McRae-Clark, AL Baker, NL Gray, KM Killeen, T Hartwell, KJ Simonian, SJ AF McRae-Clark, Aimee L. Baker, Nathaniel L. Gray, Kevin M. Killeen, Therese Hartwell, Karen J. Simonian, Susan J. TI Vilazodone for Cannabis Dependence: A Randomized, Controlled Pilot Trial SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; 5-HT1A RECEPTORS; FLUOXETINE; SMOKERS AB Background and Objectives: The purpose of this study was to evaluate the efficacy of vilazodone, a selective serotonin receptor inhibitor and partial 5-HT1A agonist, for treatment of cannabis dependence. Methods: Seventy-six cannabis-dependent adults were randomized to receive either up to 40 mg/day of vilazodone (n = 41) or placebo (n = 35) for 8 weeks combined with a brief motivational enhancement therapy intervention and contingency management to encourage study retention. Cannabis use outcomes were assessed via weekly urine cannabinoid tests; secondary outcomes included cannabis use self-report and cannabis craving. Results: Participants in both groups reported reduced self-reported cannabis use over the course of the study; however, vilazodone provided no advantage over placebo in reducing cannabis use. Men had significantly lower creatinine-adjusted cannabinoid levels and a trend for increased negative urine cannabinoid tests than women. Discussion and Conclusions: Vilazodone was not more efficacious than placebo in reducing cannabis use. Important gender differences were noted, with women having worse cannabis use outcomes than men. Scientific Significance: Further medication development efforts for cannabis use disorders are needed, and gender should be considered as an important variable in future trials. C1 [McRae-Clark, Aimee L.; Gray, Kevin M.; Killeen, Therese; Hartwell, Karen J.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Baker, Nathaniel L.] Med Univ S Carolina, Dept Publ Hlth Sci, 125 Doughty St,Suite 190, Charleston, SC 29403 USA. [Hartwell, Karen J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Simonian, Susan J.] Coll Charleston, Dept Psychol, Charleston, SC 29401 USA. RP McRae-Clark, AL (reprint author), Med Univ S Carolina, 125 Doughty St,Suite 190, Charleston, SC 29403 USA. EM mcraeal@musc.edu FU NIH [R21DA34089] FX Support for this project was provided by NIH grant R21DA34089 (McRae-Clark). NR 27 TC 3 Z9 3 U1 1 U2 2 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 JAN PY 2016 VL 25 IS 1 BP 69 EP 75 DI 10.1111/ajad.12324 PG 7 WC Substance Abuse SC Substance Abuse GA DB4TS UT WOS:000368506900010 PM 26685701 ER PT S AU Bobbin, ML Rossi, JJ AF Bobbin, Maggie L. Rossi, John J. BE Insel, PA TI RNA Interference (RNAi)-Based Therapeutics: Delivering on the Promise? SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 56 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE clinical trials; siRNA; miRNA; shRNA; dsiRNA ID DOUBLE-STRANDED-RNA; CHRONIC HEPATITIS-B; NONHUMAN-PRIMATES; SIRNA DELIVERY; RIG-I; STRATEGIES; INFECTION; EFFICACY; MICE AB A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although there were initial difficulties in achieving efficacious results with RNAi without toxic side effects, advances in delivery and improved chemistry made this resurgence possible. More than 20 RNAi-based therapeutics are currently in clinical trials, and several of these are Phase III trials. Continued positive results from these trials have helped bolster further attempts to develop clinically relevant RNAi therapies. With a wide variety of disease targets to choose from, the first RNAi therapeutic to be clinically approved is not far off. This review covers recently established and completed clinical trials. C1 [Bobbin, Maggie L.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Bobbin, Maggie L.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Rossi, John J.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. RP Bobbin, ML (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.; Bobbin, ML (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.; Rossi, JJ (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. EM mlbobbin@mgh.harvard.edu; jrossi@coh.org FU NHLBI NIH HHS [R01 HL074704]; NIAID NIH HHS [R01 AI029329, R01 AI042552] NR 64 TC 29 Z9 29 U1 17 U2 45 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0456-0 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2016 VL 56 BP 103 EP 122 DI 10.1146/annurev-pharmtox-010715-103633 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BE1PJ UT WOS:000368345700007 PM 26738473 ER PT S AU Whitaker, RM Corum, D Beeson, CC Schnellmann, RG AF Whitaker, Ryan M. Corum, Daniel Beeson, Craig C. Schnellmann, Rick G. BE Insel, PA TI Mitochondrial Biogenesis as a Pharmacological Target: A New Approach to Acute and Chronic Diseases SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 56 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE mitochondrial homeostasis; tissue bioenergetics; drug screening; high-throughput respirometry ID ISCHEMIA-REPERFUSION INJURY; ACUTE KIDNEY INJURY; THROUGHPUT RESPIROMETRIC ASSAY; ACTIVATED RECEPTOR-GAMMA; PROTEIN-QUALITY CONTROL; HIGH-FAT DIET; OXIDATIVE STRESS; MYOCARDIAL-INFARCTION; TRANSCRIPTION FACTOR; PARKINSONS-DISEASE AB Mitochondrial dysfunction is a key pathophysiological component of many acute and chronic diseases. Maintenance of mitochondrial homeostasis through the balance of mitochondrial turnover, fission and fusion, and generation of new mitochondria via mitochondrial biogenesis is critical for tissue health. Pharmacological activation of mitochondrial biogenesis can enhance oxidative metabolism and tissue bioenergetics, and improve organ function in conditions characterized by mitochondrial dysfunction. However, owing to the complexity of mitochondrial assembly and maintenance, identification of specific activators of mitochondrial biogenesis has been difficult. This review provides an overview of the role of mitochondrial dysfunction in acute and chronic diseases, details the current state of therapeutics for the stimulation of mitochondrial biogenesis and their effects on disease outcomes, describes new screening methodologies to identify novel stimulators and noncanonical pathways of mitochondrial biogenesis, and discusses potential hurdles of mitochondrial biogenesis as a therapeutic strategy. C1 [Whitaker, Ryan M.; Corum, Daniel; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Whitaker, RM; Corum, D; Beeson, CC; Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA.; Schnellmann, RG (reprint author), Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. EM rmw3@musc.edu; corumd@musc.edu; beesonc@musc.edu; schnell@musc.edu FU NIDDK NIH HHS [F30 DK096964]; NIGMS NIH HHS [R01 GM084147] NR 142 TC 9 Z9 10 U1 8 U2 20 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0456-0 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2016 VL 56 BP 229 EP 249 DI 10.1146/annurev-pharmtox-010715-103155 PG 21 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BE1PJ UT WOS:000368345700013 PM 26566156 ER PT S AU Sharma, S Powers, A Bradley, B Ressler, KJ AF Sharma, Sumeet Powers, Abigail Bradley, Bekh Ressler, Kerry J. BE Fiske, ST TI Gene x Environment Determinants of Stress- and Anxiety-Related Disorders SO ANNUAL REVIEW OF PSYCHOLOGY, VOL 67 SE Annual Review of Psychology LA English DT Review; Book Chapter DE anxiety; depression; posttraumatic stress disorder; stress; trauma; epigenetics; gene-by-environment interaction; genome-wide association study ID GENOME-WIDE ASSOCIATION; SEROTONIN TRANSPORTER GENE; LINKED POLYMORPHIC REGION; MAJOR DEPRESSIVE DISORDER; COPY-NUMBER VARIATION; EARLY-LIFE STRESS; POSTTRAUMATIC-STRESS; CHILDHOOD-TRAUMA; PSYCHIATRIC-DISORDERS; 5-HTTLPR GENOTYPE AB The burgeoning field of gene-by-environment (G x E) interactions has revealed fascinating biological insights, particularly in the realm of stress-, anxiety-, and depression-related disorders. In this review we present an integrated view of the study of GxE interactions in stress and anxiety disorders, including the evolution of genetic association studies from genetic epidemiology to contemporary large-scale genome-wide association studies and GxE studies. We convey the importance of consortia efforts and collaboration to gain the large sample sizes needed to move the field forward. Finally, we discuss several robust and well-reproduced GxE interactions and demonstrate how epidemiological identification of GxE interactions has naturally led to a plethora of basic research elucidating the mechanisms of high-impact genetic variants. C1 [Sharma, Sumeet; Powers, Abigail; Bradley, Bekh; Ressler, Kerry J.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Sharma, Sumeet; Ressler, Kerry J.] Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA. [Bradley, Bekh] US Dept Vet Affairs, Atlanta VA Med Ctr, Decatur, GA 30033 USA. RP Ressler, KJ (reprint author), Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.; Ressler, KJ (reprint author), Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA. EM kressler@mclean.harvard.edu FU Howard Hughes Medical Institute; NCRR NIH HHS [M01RR00039]; NICHD NIH HHS [HD071982]; NIMH NIH HHS [MH071537, MH096764, MH102890] NR 80 TC 4 Z9 4 U1 12 U2 38 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4308 BN 978-0-8243-0267-2 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol PY 2016 VL 67 BP 239 EP 261 DI 10.1146/annurev-psych-122414-033408 PG 23 WC Psychology; Psychology, Multidisciplinary SC Psychology GA BE1PH UT WOS:000368344500011 PM 26442668 ER PT J AU Klyuchnikov, E Bacher, U Ahn, KW Carreras, J Kroger, NM Hari, PN Ku, GH Ayala, E Chen, A Chen, YB Cohen, JB Freytes, CO Gale, RP Kamble, RT Kharfan-Dabaja, MA Lazarus, HM Martino, R Mussetti, A Savani, BN Schouten, HC Usmani, SZ Wiernik, PH Wirk, B Smith, SM Sureda, A Hamadani, M AF Klyuchnikov, E. Bacher, U. Ahn, K. Woo Carreras, J. Kroeger, N. M. Hari, P. N. Ku, G. H. Ayala, E. Chen, Al Chen, Y-B Cohen, J. B. Freytes, C. O. Gale, R. P. Kamble, R. T. Kharfan-Dabaja, M. A. Lazarus, H. M. Martino, R. Mussetti, A. Savani, B. N. Schouten, H. C. Usmani, S. Z. Wiernik, P. H. Wirk, B. Smith, S. M. Sureda, A. Hamadani, M. TI Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma SO BONE MARROW TRANSPLANTATION LA English DT Article ID STEM-CELL TRANSPLANTATION; NON-HODGKIN-LYMPHOMA; HIGH-DOSE THERAPY; FOLLOW-UP; HISTOLOGIC GRADE; PREDICT SURVIVAL; RITUXIMAB; CHEMOTHERAPY; GRAFT; CYCLOPHOSPHAMIDE AB Grade 3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade 3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs autologous hematopoietic cell transplantation (auto-HCT) in the rituximab era. A total of 197 patients undergoing first reduced-intensity conditioning (RIC) allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naive patients were excluded. Allo-HCT recipients were younger, more heavily pretreated and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, PFS and overall survival (OS) for auto-HCT vs allo-HCT groups were 4% vs 27% (P < 0.001), 61% vs 20% (P < 0.001), 36% vs 51% (P=0.07) and 59% vs 54% (P=0.7), respectively. On multivariate analysis, auto-HCT was associated with reduced risk of NRM (relative risk (RR) = 0.20; P=0.001). Within the first 11 months post HCT, auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11 months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; P=0.003) and inferior PFS (RR = 3.2; P=0.005). In the first 24 months post HCT, auto-HCT was associated with improved OS (RR = 0.42; P=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; P=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors. C1 [Klyuchnikov, E.; Kroeger, N. M.] Univ Canc Ctr Hamburg, Dept Stem Cell Transplantat, Hamburg, Germany. [Bacher, U.] Univ Gottingen, Dept Hematol Oncol, D-37073 Gottingen, Germany. [Ahn, K. Woo; Carreras, J.; Hari, P. N.; Hamadani, M.] Med Coll Wisconsin, Dept Med, CIBMTR, 9200 West Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. [Ahn, K. Woo] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Ku, G. H.] Univ Calif San Diego, Dept Med, Div Blood & Marrow Transplantat, San Diego, CA 92103 USA. [Ayala, E.; Kharfan-Dabaja, M. A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Chen, Al] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chen, Y-B] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Cohen, J. B.] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA. [Freytes, C. O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, C. O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, R. P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England. [Kamble, R. T.] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Lazarus, H. M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Martino, R.] Hosp Santa Creu & Sant Pau, Div Clin Hematol, Barcelona, Spain. [Mussetti, A.] Fdn IRCCS Ist Nazl Tumori, SC Ematol & Trapianto Midollo Osseo, Milan, Italy. [Mussetti, A.] Univ Milan, Milan, Italy. [Savani, B. N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Schouten, H. C.] Acad Ziekenhuis, Dept Hematol, Maastricht, Netherlands. [Usmani, S. Z.] Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Med Oncol, Charlotte, NC USA. [Wiernik, P. H.] Our Lady Mercy Med Ctr, Bronx, NY USA. [Wirk, B.] Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA. [Smith, S. M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Sureda, A.] Hosp Duran & Reynals, Inst Catala Oncol, Serv Hematol, Barcelona, Spain. [Sureda, A.] European Grp Blood & Marrow Transplantat, Barcelona, Spain. RP Hamadani, M (reprint author), Med Coll Wisconsin, Dept Med, CIBMTR, 9200 West Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM mhamadani@mcw.edu RI Mussetti, Alberto/C-9500-2017; OI Mussetti, Alberto/0000-0002-4088-036X; Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) [U24-CA076518]; National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics Inc.; Amgen 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 We would like to acknowledge the following working committee members for their contributions to the manuscript: Mahmoud D Aljurf, Siddhartha Ganguly, Mark S Hertzberg, Leona A Holmberg, Andreas Klein, Taiga Nishihori, Richard F Olsson and Nishitha M Reddy. Also, Maggie Simaytis for administrative assistance. 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 No. HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two grants (N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics Inc.; *Amgen 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 US Government. NR 38 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2016 VL 51 IS 1 BP 58 EP 66 DI 10.1038/bmt.2015.223 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA DB4FV UT WOS:000368469800009 PM 26437062 ER PT J AU Bensinger, WI Becker, PS Gooley, TA Chauncey, TR Maloney, DG Gopal, AK Green, DJ Press, OW Lill, M Ifthikharuddin, JJ Vescio, R Holmberg, LA Phillips, GL AF Bensinger, W. I. Becker, P. S. Gooley, T. A. Chauncey, T. R. Maloney, D. G. Gopal, A. K. Green, D. J. Press, O. W. Lill, M. Ifthikharuddin, J. J. Vescio, R. Holmberg, L. A. Phillips, G. L. TI A randomized study of melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative regimen for patients with multiple myeloma undergoing auto-SCT SO BONE MARROW TRANSPLANTATION LA English DT Article ID STEM-CELL TRANSPLANTATION; HIGH-DOSE MELPHALAN; ORAL MUCOSITIS; MARROW-TRANSPLANTATION; STANDARD CHEMOTHERAPY; CONDITIONING REGIMENS; INDUCTION TREATMENT; TRIAL; BORTEZOMIB; AMIFOSTINE AB We aimed to examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m(2) (mel200) vs 280 mg/m(2) (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (>= nCR). No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 vs mel280, respectively, >= nCR 22 vs 39%, P=0.03, >= PR 57 vs 74%, P=0.04. The hazard of mortality was not statistically significantly different between groups (mel200 vs mel280; hazard ratio (HR) = 1.15 (95% confidence interval (CI), 0.62-2.13, P=0.66)) nor was the rate of progression/mortality (HR = 0.81 (0.52-1.27, P=0.36)). The estimated PFS at 1 and 3 years were 83 and 46%, respectively, for mel200 and 78 and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade 4 regimen-related toxicities and only one grade 3 mucositis (none with mel200) and three grade 3 gastrointestinal (GI) toxicities (two in mel200). Hospitalization rates were more frequent in the mel280 group (59 vs 43%, P=0.08). Mel280 resulted in a higher major response rate (CR+nCR) and should be evaluated in larger studies. C1 [Bensinger, W. I.; Gooley, T. A.; Maloney, D. G.; Gopal, A. K.; Green, D. J.; Press, O. W.; Holmberg, L. A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Bensinger, W. I.; Becker, P. S.; Gooley, T. A.; Chauncey, T. R.; Maloney, D. G.; Gopal, A. K.; Green, D. J.; Press, O. W.; Holmberg, L. A.] Univ Washington, Seattle, WA 98195 USA. [Chauncey, T. R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lill, M.; Vescio, R.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Ifthikharuddin, J. J.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Phillips, G. L.] Wake Forest Baptist Med Ctr, Winston Salem, NC USA. [Bensinger, W. I.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-390, Seattle, WA 98109 USA. RP Bensinger, WI (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-390, Seattle, WA 98109 USA. EM wbensing@fhcrc.org FU NIH/NCI [R21 CA155911-01, P01 CA18029-28]; VA Puget Sound Health Care System, Seattle, WA FX This study was supported in part by research funds supplied by Astra-Zeneca, R21 CA155911-01, and by P01 CA18029-28 both from NIH/NCI. Previously published at the 2012 ASH Annual Meeting, Atlanta, GA December 2012. This study was supported in part by resources of the VA Puget Sound Health Care System, Seattle, WA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2016 VL 51 IS 1 BP 67 EP 71 DI 10.1038/bmt.2015.211 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA DB4FV UT WOS:000368469800010 PM 26367217 ER PT J AU Dretsch, MN Williams, K Emmerich, T Crynen, G Ait-Ghezala, G Chaytow, H Mathura, V Crawford, FC Iverson, GL AF Dretsch, Michael N. Williams, Kathy Emmerich, Tanja Crynen, Gogce Ait-Ghezala, Ghania Chaytow, Helena Mathura, Venkat Crawford, Fiona C. Iverson, Grant L. TI Brain-derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress SO BRAIN AND BEHAVIOR LA English DT Article DE BDNF; deployment; genetics; military; posttraumatic stress disorder; psychological health; traumatic brain injury ID DOPAMINE-RECEPTOR GENE; ALZHEIMERS-DISEASE; DRD2 GENE; BINDING CHARACTERISTICS; HEALTHY-VOLUNTEERS; COGNITIVE RESERVE; APOE GENOTYPE; USE DISORDERS; ALCOHOL-USE; A1 ALLELE AB Background In addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute to the development of posttraumatic stress disorder (PTSD) in military service members. This study explored the contribution of genetics, childhood environment, prior trauma, psychological, cognitive, and deployment factors to the development of traumatic stress following deployment. Methods Both pre- and postdeployment data on 231 of 458 soldiers were analyzed. Postdeployment assessments occurred within 30days from returning stateside and included a battery of psychological health, medical history, and demographic questionnaires; neurocognitive tests; and blood serum for the D2 dopamine receptor (DRD2), apolipoprotein E (APOE), and brain-derived neurotropic factor (BDNF) genes. Results Soldiers who screened positive for traumatic stress at postdeployment had significantly higher scores in depression (d=1.91), anxiety (d=1.61), poor sleep quality (d=0.92), postconcussion symptoms (d=2.21), alcohol use (d=0.63), traumatic life events (d=0.42), and combat exposure (d=0.91). BDNF Val66 Met genotype was significantly associated with risk for sustaining a mild traumatic brain injury (mTBI) and screening positive for traumatic stress. Predeployment traumatic stress, greater combat exposure and sustaining an mTBI while deployed, and the BDNF Met/Met genotype accounted for 22% of the variance of postdeployment PTSD scores (R-2=0.22, P<0.001). However, predeployment traumatic stress, alone, accounted for 17% of the postdeployment PTSD scores. Conclusion These findings suggest predeployment traumatic stress, genetic, and environmental factors have unique contributions to the development of combat-related traumatic stress in military service members. C1 [Dretsch, Michael N.] US Army, Aeromed Res Lab, 6901 Farrel Rd, Ft Rucker, AL USA. [Dretsch, Michael N.; Williams, Kathy] Walter Reed Natl Mil Med Ctr, Natl Intrepid Ctr Excellence, 4860 South Palmer Rd, Bethesda, MD 20889 USA. [Dretsch, Michael N.] Headquarters Army Training & Doctrine Command HQ, Human Dimens Div, 950 Jefferson Ave, Ft Eustis, VA 23604 USA. [Emmerich, Tanja; Crynen, Gogce; Ait-Ghezala, Ghania; Chaytow, Helena; Mathura, Venkat; Crawford, Fiona C.] Roskamp Inst, 2040 Whitfield Ave, Sarasota, FL 34243 USA. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Iverson, Grant L.] Def & Vet Brain Injury Ctr, Bethesda, MD USA. [Iverson, Grant L.] Harvard Univ, Sch Med, Ctr Hlth & Rehabil, Dept Phys Med & Rehabil, 79-96 Thirteenth St, Charlestown, MA 02129 USA. RP Dretsch, MN (reprint author), HQ TRADOC, Human Dimens Div, 950 Jefferson Ave, Ft Eustis, VA USA. EM michael.n.dretsch.mil@mail.mil FU US Army Medical Research and Materiel Command FX Funding for this study was provided by the US Army Medical Research and Materiel Command. NR 65 TC 2 Z9 2 U1 3 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2162-3279 J9 BRAIN BEHAV JI Brain Behav. PD JAN PY 2016 VL 6 IS 1 AR e00392 DI 10.1002/brb3.392 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DB8OV UT WOS:000368777200006 PM 27110438 ER PT J AU Caplan, D Michaud, J Hufford, R Makris, N AF Caplan, David Michaud, Jennifer Hufford, Rebecca Makris, Nikos TI Deficit-lesion correlations in syntactic comprehension in aphasia SO BRAIN AND LANGUAGE LA English DT Article DE Aphasia; Syntactic comprehension; Localization ID VERBAL WORKING-MEMORY; HUMAN CEREBRAL-CORTEX; SPOKEN-LANGUAGE COMPREHENSION; REAL-TIME COMPREHENSION; INFERIOR FRONTAL-CORTEX; MOVING-WINDOW TECHNIQUE; SURFACE-BASED ANALYSIS; SENTENCE COMPREHENSION; LEFT-HEMISPHERE; AGRAMMATIC APHASIA AB The effects of lesions on syntactic comprehension were studied in thirty-one people with aphasia (PWA). Participants were tested for the ability to parse and interpret four types of syntactic structures and elements - passives, object extracted relative clauses, reflexives and pronouns - in three tasks - object manipulation, sentence picture matching with full sentence presentation and sentence picture matching with self-paced listening presentation. Accuracy, end-of-sentence RT and self-paced listening times for each word were measured. MR scans were obtained and analyzed for total lesion volume and for lesion size in 48 cortical areas. Lesion size in several areas of the left hemisphere was related to accuracy in particular sentence types in particular tasks and to self-paced listening times for critical words in particular sentence types. The results support a model of brain organization that includes areas that are specialized for the combination of particular syntactic and interpretive operations and the use of the meanings produced by those operations to accomplish task-related operations. (C) 2015 Elsevier Inc. All rights reserved. C1 [Caplan, David; Michaud, Jennifer; Hufford, Rebecca; Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. [Caplan, David] Neuropsychol Lab, 175 Cambridge St,Suite 340,Fruit St, Boston, MA 02114 USA. RP Caplan, D (reprint author), Neuropsychol Lab, 175 Cambridge St,Suite 340,Fruit St, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIDCD [DC00942] FX This research was supported by NIDCD grant DC00942 to David Caplan. NR 68 TC 2 Z9 2 U1 5 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD JAN PY 2016 VL 152 BP 14 EP 27 DI 10.1016/j.bandl.2015.10.005 PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA DB4FK UT WOS:000368468700002 PM 26688433 ER PT J AU Tang, R Saksena, M Coopey, SB Fernandez, L Buckley, JM Lei, L Aftreth, O Koerner, F Michaelson, J Rafferty, E Brachtel, E Smith, BL AF Tang, Rong Saksena, Mansi Coopey, Suzanne B. Fernandez, Leopoldo Buckley, Julliette M. Lei, Lan Aftreth, Owen Koerner, Frederick Michaelson, James Rafferty, Elizabeth Brachtel, Elena Smith, Barbara L. TI Intraoperative micro-computed tomography (micro-CT): a novel method for determination of primary tumour dimensions in breast cancer specimens SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID NEOADJUVANT CHEMOTHERAPY; PHYSICAL-EXAMINATION; SIZE; MAMMOGRAPHY; MRI; PATHOLOGY; ULTRASOUND; SONOGRAPHY; ACCURACY; ULTRASONOGRAPHY AB Objectives: Micro-CT is a promising modality to determine breast tumour size in three dimensions in intact lumpectomy specimens. We compared the accuracy of tumour size measurements using specimen micro-CT with measurements using multimodality pre-operative imaging. Methods: A tabletop micro-CT was used to image breast lumpectomy specimens. The largest tumour dimension on three-dimensional reconstructed micro-CT images of the specimen was compared with the measurements determined by pre-operative mammography, ultrasound and MRI. The largest dimension of pathologic invasive cancer size was used as the gold standard reference to assess the accuracy of imaging assessments. Results: 50 invasive breast cancer specimens in 50 patients had micro-CT imaging. 42 were invasive ductal carcinoma, 6 were invasive lobular carcinoma and 2 were other invasive cancer. Median patient age was 63 years (range 33-82 years). When compared with the largest pathologic tumour dimension, micro-CT measurements had the best correlation coefficient (r = 0.82, p < 0.001) followed by MRI (r = 0.78, p < 0.001), ultrasound (r = 0.61, p < 0.001) and mammography (r = 0.40, p < 0.01). When compared with preoperative modalities, micro-CT had the best correlation coefficient (r = 0.86, p < 0.001) with MRI, followed by ultrasound (r = 0.60, p < 0.001) and mammography (r = 0.54, p < 0.001). Overall, mammography and ultrasound tended to underestimate the largest tumour dimension, while MRI and micro-CT overestimated the largest tumour dimension more frequently. Conclusion: Micro-CT is a potentially useful tool for accurate assessment of tumour dimensions within a lumpectomy specimen. Future studies need to be carried out to see if this technology could have a role in margin assessment. Advances in knowledge: Micro-CT is a promising new technique which could potentially be used for rapid assessment of breast cancer dimensions in an intact lumpectomy specimen in order to guide surgical excision. C1 [Tang, Rong; Coopey, Suzanne B.; Fernandez, Leopoldo; Buckley, Julliette M.; Lei, Lan; Aftreth, Owen; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Tang, Rong] Cent S Univ, Affiliated Canc Hosp, Div Breast Surg, Hunan Canc Hosp,Xiangya Med Sch, Changsha, Hunan, Peoples R China. [Saksena, Mansi; Rafferty, Elizabeth] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Koerner, Frederick; Michaelson, James; Brachtel, Elena] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM blsmith1@partners.org NR 28 TC 0 Z9 0 U1 0 U2 3 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. PY 2016 VL 89 IS 1058 AR 20150581 DI 10.1259/bjr.20150581 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB3OX UT WOS:000368422100022 PM 26568439 ER PT J AU Golestanirad, L Elahi, B Graham, SJ Das, S Wald, LL AF Golestanirad, Laleh Elahi, Behzad Graham, Simon J. Das, Sunit Wald, Lawrence L. TI Efficacy and Safety of Pedunculopontine Nuclei (PPN) Deep Brain Stimulation in the Treatment of Gait Disorders: A Meta-Analysis of Clinical Studies SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article DE Deep Brain Stimulation (DBS); Parkinson's disease; Pedunculopontine Nucleus (PPN); systematic reviews ID LOW-FREQUENCY STIMULATION; PROGRESSIVE SUPRANUCLEAR PALSY; PARKINSONS-DISEASE; TEGMENTAL NUCLEUS; SUBTHALAMIC NUCLEUS; FOLLOW-UP; MOVEMENT-DISORDERS; BASAL GANGLIA; TARGET; SLEEP AB Background: Pedunculopontine nucleus (PPN) has complex reciprocal connections with basal ganglia, especially with internal globus pallidus and substantia nigra, and it has been postulated that PPN stimulation may improve gait instability and freezing of gait. In this meta-analysis, we will assess the evidence for PPN deep brain stimulation in treatment of gait and motor abnormalities especially focusing on Parkinson disease patients. Methods: PubMed and Scopus electronic databases were searched for related studies published before February 2014. Medline (1966-2014), Embase (1974-2010), CINAHL, Web of Science, Scopus bibliographic, and Google Scholar databases (1960-2014) were also searched for studies investigating effect of PPN deep brain stimulation in treatment of postural and postural instability and total of ten studies met the inclusion criteria for this analysis. Results: Our findings showed a significant improvement in postural instability (p<0.001) and motor symptoms of Parkinson disease on and off medications (p<0.05), but failed to show improvement in freezing of gait. Conclusions: Despite significant improvement in postural instability observed in included studies, evidence from current literature is not sufficient to generalize these findings to the majority of patients. C1 [Golestanirad, Laleh; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 32 Fruit St, Boston, MA 02114 USA. [Golestanirad, Laleh; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Elahi, Behzad] Tufts Med Ctr, Div Neurol, 800 Washington St, Boston, MA 02111 USA. [Graham, Simon J.] Univ Toronto, Dept Med Biophys, Fac Med, Toronto, ON, Canada. [Das, Sunit] Univ Toronto, Fac Med, Div Neurosurg, Toronto, ON, Canada. RP Elahi, B (reprint author), Tufts Med Ctr, Div Neurol, 800 Washington St, Boston, MA 02111 USA. EM BElahi@tuftsmedicalcenter.org RI Wald, Lawrence/D-4151-2009 NR 54 TC 3 Z9 3 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0317-1671 EI 2057-0155 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD JAN PY 2016 VL 43 IS 1 BP 120 EP 126 DI 10.1017/cjn.2015.318 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DB5FW UT WOS:000368541000017 PM 26786642 ER PT J AU Phipps, AI Passarelli, MN Chan, AT Harrison, TA Jeon, J Hutter, CM Berndt, SI Brenner, H Caan, BJ Campbell, PT Chang-Claude, J Chanock, SJ Cheadle, JP Curtis, KR Duggan, D Fisher, D Fuchs, CS Gala, M Giovannucci, EL Hayes, RB Hoffmeister, M Hsu, L Jacobs, EJ Jansen, L Kaplan, R Kap, EJ Maughan, TS Potter, JD Schoen, RE Seminara, D Slattery, ML West, H White, E Peters, U Newcomb, PA AF Phipps, Amanda I. Passarelli, Michael N. Chan, Andrew T. Harrison, Tabitha A. Jeon, Jihyoun Hutter, Carolyn M. Berndt, Sonja I. Brenner, Hermann Caan, Bette J. Campbell, Peter T. Chang-Claude, Jenny Chanock, Stephen J. Cheadle, Jeremy P. Curtis, Keith R. Duggan, David Fisher, David Fuchs, Charles S. Gala, Manish Giovannucci, Edward L. Hayes, Richard B. Hoffmeister, Michael Hsu, Li Jacobs, Eric J. Jansen, Lina Kaplan, Richard Kap, Elisabeth J. Maughan, Timothy S. Potter, John D. Schoen, Robert E. Seminara, Daniela Slattery, Martha L. West, Hannah White, Emily Peters, Ulrike Newcomb, Polly A. TI Common genetic variation and survival after colorectal cancer diagnosis: a genome-wide analysis SO CARCINOGENESIS LA English DT Article ID FATTY LIVER-DISEASE; INTESTINAL-CELL KINASE; SUSCEPTIBILITY LOCI; COLON-CANCER; NURSES HEALTH; ASSOCIATION; RISK; METAANALYSIS; POLYMORPHISMS; TRIAL AB Genome-wide association studies have identified several germline single nucleotide polymorphisms (SNPs) significantly associated with colorectal cancer (CRC) incidence. Common germline genetic variation may also be related to CRC survival. We used a discovery-based approach to identify SNPs related to survival outcomes after CRC diagnosis. Genome-wide genotyping arrays were conducted for 3494 individuals with invasive CRC enrolled in six prospective cohort studies (median study-specific follow-up = 4.2-8.1 years). In pooled analyses, we used Cox regression to assess SNP-specific associations with CRC-specific and overall survival, with additional analyses stratified by stage at diagnosis. Top findings were followed-up in independent studies. A P value threshold of P < 5x10(-8) in analyses combining discovery and follow-up studies was required for genome-wide significance. Among individuals with distant-metastatic CRC, several SNPs at 6p12.1, nearest the LOVL5 gene, were statistically significantly associated with poorer survival, with the strongest associations noted for rs209489 [hazard ratio (HR) = 1.8, P = 7.6x10(-10) and HR = 1.8, P = 3.7x10(-9) for CRC-specific and overall survival, respectively). No SNPs were statistically significantly associated with survival among all cases combined or in cases without distant-metastases. SNPs in 6p12.1/ELOVL5 were associated with survival outcomes in individuals with distant-metastatic CRC, and merit further follow-up for functional significance. Findings from this genome-wide association study highlight the potential importance of genetic variation in CRC prognosis and provide clues to genomic regions of potential interest. C1 [Phipps, Amanda I.; Passarelli, Michael N.; Potter, John D.; White, Emily; Peters, Ulrike; Newcomb, Polly A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Phipps, Amanda I.; Passarelli, Michael N.; Harrison, Tabitha A.; Jeon, Jihyoun; Hutter, Carolyn M.; Curtis, Keith R.; Hsu, Li; Potter, John D.; White, Emily; Peters, Ulrike; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Brenner, Hermann; Jansen, Lina] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Brenner, Hermann; Hoffmeister, Michael] German Canc Consortium DKTK, D-69120 Heidelberg, Germany. [Caan, Bette J.] Kaiser Permanente Med Care Program Northern Calif, Div Res, Oakland, CA 94612 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA. [Chang-Claude, Jenny; Jacobs, Eric J.; Kap, Elisabeth J.] German Canc Res Ctr, Div Canc Epidemiol, Unit Genet Epidemiol, D-69120 Heidelberg, Germany. [Cheadle, Jeremy P.; West, Hannah] Cardiff Univ, Sch Med, Inst Canc & Genet, Cardiff CF14 4XN, S Glam, Wales. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ 85004 USA. [Fisher, David] UCL, MRC Clin Trials Unit, London WC2B 6NH, England. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Gala, Manish; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY 10016 USA. [Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Maughan, Timothy S.] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford OX3 7DQ, England. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington 6140, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA 15213 USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT 84132 USA. RP Phipps, AI (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.; Phipps, AI (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. EM aiphipps@u.washington.edu RI Jansen, Lina/D-7255-2016; Brenner, Hermann/B-4627-2017; OI Jansen, Lina/0000-0001-8004-4940; Brenner, Hermann/0000-0002-6129-1572; Hayes, Richard/0000-0002-0918-661X; Hoffmeister, Michael/0000-0002-8307-3197 FU National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01CA137088, R01CA059045, R25CA094880, T32CA009168, K07CA172298, K05CA152715, R01 CA176272]; Cancer Research UK; Medical Research Council; Bobby Moore Fund from Cancer Research UK, Tenovus; Kidani Trust; National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit; CORECT: National Cancer Institute, National Institutes of Health [CA-09-002, U19CA148107]; CPS-II: The American Cancer Society; DACHS: German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; DALS: National Institutes of Health [R01 CA48998]; HPFS: National Institutes of Health [P01CA055075, UM1CA167552, R01CA137178, P50CA127003, K24DK098311]; NHS: National Institutes of Health [R01CA137178, P50CA127003, K24DK098311, P01CA087969]; PHS: National Institutes of Health [K24DK098311, R01CA42182]; PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; WHI: National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C] FX National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01CA137088 to U.P., R01CA059045 to U.P., R25CA094880, T32CA009168, K07CA172298 to A.I.P., K05CA152715 to P.A.N., R01 CA176272 to P.A.N. and A.T.C.). The COIN trial was funded by Cancer Research UK and the Medical Research Council, and its associated translational studies are supported by the Bobby Moore Fund from Cancer Research UK, Tenovus, the Kidani Trust and the National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit. Additional funding support for individual studies is provided below:; CORECT: National Cancer Institute, National Institutes of Health under RFA # CA-09-002 (U19CA148107). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in CORECT, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or CORECT.; CPS-II: The American Cancer Society funds the creation, maintenance and updating of the Cancer Prevention Study-II (CPS-II) cohort. This study was conducted with Institutional Review Board approval.; DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1) and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; DALS: National Institutes of Health (R01 CA48998 to M.L.S).; HPFS: National Institutes of Health (P01CA055075, UM1CA167552, R01CA137178, P50CA127003, K24DK098311).; NHS: National Institutes of Health (R01CA137178, P01CA087969, P50CA127003, K24DK098311).; PHS: National Institutes of Health (R01CA42182, K24DK098311).; PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS.; VITAL: National Institutes of Health (K05CA154337 to E.W.).; WHI: National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C. Supplementary Tables 1-4 and Figures 1-8 can be found at http://carcin.oxfordjournals.org/ NR 50 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2016 VL 37 IS 1 BP 87 EP 95 DI 10.1093/carcin/bgv161 PG 9 WC Oncology SC Oncology GA DB3LK UT WOS:000368412900012 PM 26586795 ER PT J AU Kachuri, L Amos, CI Mckay, JD Johansson, M Vineis, P Bueno-De-Mesquita, HB Boutron-Ruault, MC Johansson, M Quiros, JR Sieri, S Travis, RC Weiderpass, E Le Marchand, L Henderson, BE Wilkens, L Goodman, GE Chen, C Doherty, JA Christiani, DC Wei, YY Su, L Tworoger, S Zhang, XH Kraft, P Zaridze, D Field, JK Marcus, MW Davies, MPA Hyde, R Caporaso, NE Landi, MT Severi, G Giles, GG Liu, G McLaughlin, JR Li, YF Xiao, XJ Fehringer, G Zong, XC Denroche, RE Zuzarte, PC McPherson, JD Brennan, P Hung, RJ AF Kachuri, Linda Amos, Christopher I. Mckay, James D. Johansson, Mattias Vineis, Paolo Bueno-de-Mesquita, H. Bas Boutron-Ruault, Marie-Christine Johansson, Mikael Quiros, J. Ramon Sieri, Sabina Travis, Ruth C. Weiderpass, Elisabete Le Marchand, Loic Henderson, Brian E. Wilkens, Lynne Goodman, Gary E. Chen, Chu Doherty, Jennifer A. Christiani, David C. Wei, Yongyue Su, Li Tworoger, Shelley Zhang, Xuehong Kraft, Peter Zaridze, David Field, John K. Marcus, Michael W. Davies, Michael P. A. Hyde, Russell Caporaso, Neil E. Landi, Maria Teresa Severi, Gianluca Giles, Graham G. Liu, Geoffrey McLaughlin, John R. Li, Yafang Xiao, Xiangjun Fehringer, Gord Zong, Xuchen Denroche, Robert E. Zuzarte, Philip C. McPherson, John D. Brennan, Paul Hung, Rayjean J. TI Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci SO CARCINOGENESIS LA English DT Article ID GENOME-WIDE ASSOCIATION; TELOMERE LENGTH; NEVER-SMOKERS; LYSOPHOSPHATIDYLCHOLINE ACYLTRANSFERASE; GENETIC-VARIATION; PROSTATE-CANCER; RISK; POPULATION; VARIANTS; EXPRESSION AB Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000x) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73x10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64x10(-6)), rs112290073 (OR = 1.85, P = 1.27x10(-5)), rs138895564 (OR = 2.16, P = 2.06x10(-5); among young cases, OR = 3.77, P = 8.41x10(-4)). In addition, we found that rs139852726 (P = 1.44x10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84x10(-7)) and lung cancer (P = 2.37x10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism. C1 [Kachuri, Linda; McLaughlin, John R.; Fehringer, Gord; Zong, Xuchen; Hung, Rayjean J.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5T 3L9, Canada. [Kachuri, Linda; Liu, Geoffrey; Hung, Rayjean J.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5T 3M7, Canada. [Amos, Christopher I.; Severi, Gianluca; Xiao, Xiangjun] Dartmouth Coll, Geisel Sch Med, Ctr Genom Med, Dept Community & Family Med, Lebanon, NH 03766 USA. [Mckay, James D.; Johansson, Mattias; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Vineis, Paolo; Severi, Gianluca] Human Genet Fdn HuGeF, I-10126 Turin, Italy. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Norfolk Pl, London W2 1PG, England. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, NL-3721 MA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, NL-3584 CX Utrecht, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England. [Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur 50603, Malaysia. [Boutron-Ruault, Marie-Christine; Severi, Gianluca] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Lifestyle Genes & Hth Integrat Trans Generat Epid, U1018, F-94805 Villejuif, France. [Boutron-Ruault, Marie-Christine; Severi, Gianluca] Univ Paris 11, UMRS 1018 94805, Villejuif, France. [Boutron-Ruault, Marie-Christine; Severi, Gianluca] Inst Gustave Roussy, F-94805 Villejuif, France. [Johansson, Mikael] Umea Univ, Dept Radiat Sci, SE-90187 Umea, Sweden. [Quiros, J. Ramon] Publ Hlth Directorate Asturias, Oviedo 33006, Spain. [Sieri, Sabina] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, I-20133 Milan, Italy. [Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England. [Weiderpass, Elisabete] Univ Tromso, Fac Hlth Sci, Dept Community Med, Arctic Univ Norway, N-9037 Tromso, Norway. [Weiderpass, Elisabete] Canc Registry Norway, Dept Res, N-0379 Oslo, Norway. [Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Le Marchand, Loic; Henderson, Brian E.; Wilkens, Lynne] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA. [Goodman, Gary E.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Christiani, David C.; Wei, Yongyue; Su, Li; Tworoger, Shelley] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, David C.; Wei, Yongyue; Su, Li] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tworoger, Shelley; Zhang, Xuehong] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Tworoger, Shelley; Zhang, Xuehong] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Zaridze, David] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Zaridze, David] Russian Canc Res Ctr, Moscow 115478, Russia. [Field, John K.; Marcus, Michael W.; Davies, Michael P. A.; Hyde, Russell] Univ Liverpool, Canc Res Ctr Inst Translat Med Univ, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England. [Caporaso, Neil E.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Severi, Gianluca; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Severi, Gianluca; Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Liu, Geoffrey] Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON M5G 0A3, Canada. [McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON M5G 1V2, Canada. [Denroche, Robert E.; Zuzarte, Philip C.; McPherson, John D.] Ontario Inst Canc Res, Genome Technol, Toronto, ON M5G 0A3, Canada. RP Hung, RJ (reprint author), Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5T 3L9, Canada.; Hung, RJ (reprint author), Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5T 3M7, Canada. EM rayjean.hung@lunenfeld.ca RI Hung, Rayjean/A-7439-2013; Sieri, Sabina/K-4667-2016; Weiderpass, Elisabete/M-4029-2016; Liu, Geoffrey/N-4421-2016; McPherson, John/D-2633-2017; OI Sieri, Sabina/0000-0001-5201-172X; Weiderpass, Elisabete/0000-0003-2237-0128; McPherson, John/0000-0001-8049-9347; Giles, Graham/0000-0003-4946-9099 FU National Institutes of Health [U19CA148127, CA092824, CA074386, CA090578, UM1 CA164973]; Cancer Care Ontario Research Chair of Population Studies; Canadian Cancer Society Research Institute [020214]; CIHR Research Doctoral Award-Frederick Banting; Charles Best Canada Graduate Scholarships FX This work was supported by: the National Institutes of Health grant U19CA148127 (PI: Amos), the data harmonization was supported by Cancer Care Ontario Research Chair of Population Studies to Rayjean J. Hung. The MSH-PMH study was supported by Canadian Cancer Society Research Institute (no. 020214, PI: Hung). The Harvard Lung Cancer Study was funded by the National Institutes of Health grants: CA092824, CA074386, CA090578 (PI: Christiani). The Multiethnic Cohort Study was supported by the National Institutes of Health grant UM1 CA164973. Linda Kachuri is a trainee in the Canadian Institutes of Health Research (CIHR) Strategic Training for Advanced Genetic Epidemiology (STAGE) Program, and is supported by the CIHR Research Doctoral Award-Frederick Banting and Charles Best Canada Graduate Scholarships. NR 48 TC 3 Z9 3 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2016 VL 37 IS 1 BP 96 EP 105 DI 10.1093/carcin/bgv165 PG 10 WC Oncology SC Oncology GA DB3LK UT WOS:000368412900013 PM 26590902 ER PT J AU Jaffer, FA AF Jaffer, Farouc A. TI High-Risk Stents Harboring Neoatherosclerosis Light From Near-Infrared Spectroscopy? SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE Editorials; autopsy; acute coronary syndrome; drug-eluting stents; macrophages; neoatherosclerosis; restenosis ID DRUG-ELUTING STENTS; IN-VIVO; THROMBOSIS; PATHOLOGY; PLAQUES C1 [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Sch Med,Cardiovasc Res Ctr,Wellman Ctr Photomed, Boston, MA USA. RP Jaffer, FA (reprint author), MGH Cardiovasc Res Ctr, Simches Res Bldg,Room 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2016 VL 9 IS 1 AR e004354 DI 10.1161/CIRCIMAGING.115.004354 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DB6FN UT WOS:000368609600001 ER PT J AU Ong, DS Lee, JS Soeda, T Higuma, T Minami, Y Wang, Z Lee, H Yokoyama, H Yokota, T Okumura, K Jang, IK AF Ong, Daniel S. Lee, Jay S. Soeda, Tsunenari Higuma, Takumi Minami, Yoshiyasu Wang, Zhao Lee, Hang Yokoyama, Hiroaki Yokota, Takashi Okumura, Ken Jang, Ik-Kyung TI Coronary Calcification and Plaque Vulnerability An Optical Coherence Tomographic Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; calcium; cross-sectional studies; myocardial infarction; tomography; optical coherence ID BEAM COMPUTED-TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; SPOTTY CALCIFICATION; ARTERY CALCIFICATION; CALCIUM DEPOSITS; CULPRIT PLAQUE; RUPTURE; LESIONS; MICROCALCIFICATIONS AB Background Spotty superficial calcium deposits have been implicated in plaque vulnerability based on previous intravascular imaging studies. Biomechanical models suggest that microcalcifications between 5 and 65 mu m in diameter can intensify fibrous cap stress, promoting plaque rupture. However, the 100- to 200-mu m resolution of intravascular ultrasound limits its ability to discriminate single calcium deposits from clusters of smaller deposits, and a previous optical coherence tomographic investigation evaluated calcifications within a long segment of artery, which may not truly reflect the mechanics involved in potentiating focal plaque rupture. Methods and Results Detailed optical coherence tomographic assessment of coronary calcification at the culprit plaque (10-mm length) was performed in 53 patients with acute ST-segment-elevation myocardial infarction mediated by plaque rupture and 55 patients with stable angina pectoris. The number and longitudinal length of individual calcium deposits were recorded. Cross-sectional images were analyzed every 1 mm for calcium arc and depth, and these quantitative parameters were used to define individual deposits as spotty, large, and superficial. There was no significant difference between ST-segment-elevation myocardial infarction mediated by plaque rupture and stable angina pectoris groups in the number of total (P=0.58), spotty (P=0.87), or large calcium deposits (P=0.27). Minimum calcium depth was similar between groups (P=0.27), as was the number of superficial deposits (P=0.35 using a 65-mu m depth threshold and P=0.84 using a 100-mu m depth threshold). Conclusions The number and pattern of culprit plaque calcifications did not differ between patients presenting with ST-segment-elevation myocardial infarction mediated by plaque rupture versus stable angina pectoris. The optical coherence tomographic assessment of coronary calcification may not be a useful marker of local plaque vulnerability as previously suspected. Registration Information URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538. C1 [Ong, Daniel S.; Lee, Jay S.; Soeda, Tsunenari; Minami, Yoshiyasu; Wang, Zhao; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Higuma, Takumi; Yokoyama, Hiroaki; Yokota, Takashi; Okumura, Ken] Hirosaki Univ, Grad Sch Med, Dept Cardiol, Hirosaki, Aomori, Japan. [Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea. RP Jang, IK (reprint author), Div Cardiol, Massachusetts Gen Hosp GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@mgh.harvard.edu RI Wang, Zhao/E-3515-2015 OI Wang, Zhao/0000-0002-3628-5699 FU St. Jude Medical FX Dr Jang received a research grant and honorarium from St. Jude Medical, and his research was also supported by Michael Park and Kathryn Park and by Allan Gray and Gillian Gray. The other authors report no conflicts. NR 33 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2016 VL 9 IS 1 AR e003929 DI 10.1161/CIRCIMAGING.115.003929 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DB6FE UT WOS:000368608500001 ER PT J AU Parikh, SA Drachman, DE AF Parikh, Sahil A. Drachman, Douglas E. TI Will Bivalirudin Have an Impact in Peripheral Vascular Interventions? SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE Editorials; bivalirudin; hemorrhage; percutaneous coronary intervention; peripheral arterial disease ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; HEPARIN; REVASCULARIZATION; TRIAL C1 [Parikh, Sahil A.] Univ Hosp Case Med Ctr, Harrington Heart & Vasc Inst, Div Cardiovasc Med, Dept Med, Cleveland, OH USA. [Parikh, Sahil A.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Drachman, Douglas E.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Drachman, Douglas E.] Harvard Univ, Sch Med, Boston, MA USA. RP Parikh, SA (reprint author), Univ Hosp Case Med Ctr, Harrington Heart & Vasc Inst, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM sahil.parikh@uhhospitals.org NR 15 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD JAN PY 2016 VL 9 IS 1 AR e003424 DI 10.1161/CIRCINTERVENTIONS.115.003424 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB6GV UT WOS:000368613500001 PM 26747851 ER PT J AU Sihag, S Haas, MS Kim, KM Guerrero, JL Beaudoin, J Alicot, EM Schuerpf, F Gottschall, JD Puro, RJ Madsen, JC Sachs, DH Newman, W Carroll, MC Allan, JS AF Sihag, Smita Haas, Michael S. Kim, Karen M. Guerrero, J. Luis Beaudoin, Jonathan Alicot, Elisabeth M. Schuerpf, Franziska Gottschall, James D. Puro, Robyn J. Madsen, Joren C. Sachs, David H. Newman, Walter Carroll, Michael C. Allan, James S. TI Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE immunology; inflammation; left ventricular function; myocardial infarction; troponin T ID PERCUTANEOUS CORONARY INTERVENTION; ISCHEMIA-REPERFUSION INJURY; MYOSIN HEAVY-CHAIN; DETERMINING EJECTION FRACTION; HORIZONS-AMI TRIAL; ISCHEMIA/REPERFUSION INJURY; SKELETAL-MUSCLE; ACCURATE METHOD; HEART-FAILURE; CELL AB Background Acute coronary syndrome is the leading cause of mortality worldwide. However, treatment of acute coronary occlusion inevitably results in ischemia-reperfusion injury. Circulating natural IgM has been shown to play a significant role in mouse models of ischemia-reperfusion injury. A highly conserved self-antigen, nonmuscle myosin heavy chain II, has been identified as a target of pathogenic IgM. We hypothesized that a monoclonal antibody (m21G6) directed against nonmuscle myosin heavy chain II may inhibit IgM binding and reduce injury in a preclinical model of myocardial infarction. Thus, our objective was to evaluate the efficacy of intravenous m21G6 treatment in limiting infarct expansion, troponin release, and left ventricular dysfunction in a swine myocardial infarction model. Methods and Results Massachusetts General Hospital miniature swine underwent occlusion of the midleft anterior descending coronary artery for 60 minutes, followed by 1 hour, 5-day, or 21-day reperfusion. Specificity and localization of m21G6 to injured myocardium were confirmed using fluorescently labeled m21G6. Treatment with m21G6 before reperfusion resulted in a 49% reduction in infarct size (P<0.005) and a 61% reduction in troponin-T levels (P<0.05) in comparison with saline controls at 5-day reperfusion. Furthermore, m21G6-treated animals recovered 85.4% of their baseline left ventricular function as measured by 2-dimensional transthoracic echocardiography in contrast to 67.1% in controls at 21-day reperfusion (P<0.05). Conclusions Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial ischemia-reperfusion injury. C1 [Sihag, Smita; Gottschall, James D.; Madsen, Joren C.; Sachs, David H.; Allan, James S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. [Guerrero, J. Luis; Beaudoin, Jonathan; Allan, James S.] Massachusetts Gen Hosp, Cardiac Surg Res Lab, Boston, MA 02114 USA. [Haas, Michael S.; Alicot, Elisabeth M.; Schuerpf, Franziska; Puro, Robyn J.; Newman, Walter] DecImmune Therapeut, Cambridge, MA USA. [Carroll, Michael C.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kim, Karen M.] Hosp Univ Penn, Div Cardiovasc Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. RP Haas, MS (reprint author), Decimmune Therapeut, 200 Technol Sq,Suite 402, Cambridge, MA 02139 USA. EM mhaas@decimmune.com FU National Institutes of Health (NIH) [HL084821, P01HL018646, CO6RR020135-01]; DecImmune Therapeutics, Inc. FX This work was partly funded by grants from the National Institutes of Health (NIH; HL084821 for E.M. Alicot) as well as support from DecImmune Therapeutics, Inc. Additional NIH funding included P01HL018646 (Drs Allan and Madsen) as well as CO6RR020135-01 for construction of the facility used for the production and maintenance of miniature swine. NR 38 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD JAN PY 2016 VL 9 IS 1 AR e002547 DI 10.1161/CIRCINTERVENTIONS.115.002547 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB6GF UT WOS:000368611700001 PM 26671971 ER PT J AU Huffman, JC Beale, EE Celano, CM Beach, SR Belcher, AM Moore, SV Suarez, L Motiwala, SR Gandhi, PU Gaggin, HK Januzzi, JL AF Huffman, Jeff C. Beale, Eleanor E. Celano, Christopher M. Beach, Scott R. Belcher, Arianna M. Moore, Shannon V. Suarez, Laura Motiwala, Shweta R. Gandhi, Parul U. Gaggin, Hanna K. Januzzi, James L. TI Effects of Optimism and Gratitude on Physical Activity, Biomarkers, and Readmissions After an Acute Coronary Syndrome The Gratitude Research in Acute Coronary Events Study SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute coronary syndrome; comorbidity; confidence intervals; exercise; myocardial infarction; optimism ID RANDOMIZED CONTROLLED-TRIAL; LIFE ORIENTATION TEST; HEART-DISEASE; DISPOSITIONAL OPTIMISM; MYOCARDIAL-INFARCTION; DEPRESSION SCALE; HOSPITAL ANXIETY; UNSTABLE ANGINA; HEALTH; MORTALITY AB Background Positive psychological constructs, such as optimism, are associated with beneficial health outcomes. However, no study has separately examined the effects of multiple positive psychological constructs on behavioral, biological, and clinical outcomes after an acute coronary syndrome (ACS). Accordingly, we aimed to investigate associations of baseline optimism and gratitude with subsequent physical activity, prognostic biomarkers, and cardiac rehospitalizations in post-ACS patients. Methods and Results Participants were enrolled during admission for ACS and underwent assessments at baseline (2 weeks post-ACS) and follow-up (6 months later). Associations between baseline positive psychological constructs and subsequent physical activity/biomarkers were analyzed using multivariable linear regression. Associations between baseline positive constructs and 6-month rehospitalizations were assessed via multivariable Cox regression. Overall, 164 participants enrolled and completed the baseline 2-week assessments. Baseline optimism was significantly associated with greater physical activity at 6 months (n=153; =102.5; 95% confidence interval, 13.6-191.5; P=0.024), controlling for baseline activity and sociodemographic, medical, and negative psychological covariates. Baseline optimism was also associated with lower rates of cardiac readmissions at 6 months (n=164), controlling for age, sex, and medical comorbidity (hazard ratio, 0.92; 95% confidence interval, [0.86-0.98]; P=0.006). There were no significant relationships between optimism and biomarkers. Gratitude was minimally associated with post-ACS outcomes. Conclusions Post-ACS optimism, but not gratitude, was prospectively and independently associated with superior physical activity and fewer cardiac readmissions. Whether interventions that target optimism can successfully increase optimism or improve cardiovascular outcomes in post-ACS patients is not yet known, but can be tested in future studies. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01709669. C1 [Huffman, Jeff C.; Celano, Christopher M.; Beach, Scott R.; Suarez, Laura; Motiwala, Shweta R.; Gandhi, Parul U.; Gaggin, Hanna K.; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Huffman, Jeff C.; Beale, Eleanor E.; Celano, Christopher M.; Beach, Scott R.; Moore, Shannon V.; Suarez, Laura] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Belcher, Arianna M.; Gandhi, Parul U.; Gaggin, Hanna K.; Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Motiwala, Shweta R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, Boston, MA 02215 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. EM jhuffman@partners.org FU Expanding the Science and Practice of Gratitude Project by UC Berkeley's Greater Good Science Center; UC Davis; John Templeton Foundation [15627]; National Institutes of Health [R01HL113272]; 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) [8UL1TR000170-05]; Harvard University, affiliated academic health care centers FX This research project was supported by the Expanding the Science and Practice of Gratitude Project run by UC Berkeley's Greater Good Science Center in partnership with UC Davis with funding from the John Templeton Foundation (grant 15627) to Dr Huffman. Time for analysis and article preparation was also funded by National Institutes of Health under grant R01HL113272 to Dr Huffman. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Harvard Catalyst Program and the Singulex Corporation provided support for analysis of selected biomarkers. This work was also conducted with support from 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 8UL1TR000170-05) and financial contributions from Harvard University and its affiliated academic health care centers. Measurement of NT-proBNP and IL-6 was performed by Singulex, Inc. NR 50 TC 9 Z9 9 U1 5 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2016 VL 9 IS 1 BP 55 EP 63 DI 10.1161/CIRCOUTCOMES.115.002184 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB6FZ UT WOS:000368611000009 PM 26646818 ER PT J AU Rose, AJ Allen, AL Minichello, T AF Rose, Adam J. Allen, Arthur L. Minichello, Tracy TI A Call to Reduce the Use of Bridging Anticoagulation SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE anticoagulants; evidence-based medicine; heparin; low-molecular weight; humans; perioperative care; practice guideline; warfarin ID VENOUS THROMBOEMBOLISM; WARFARIN INTERRUPTION; ATRIAL-FIBRILLATION; BLOOD-COAGULATION; WITHDRAWAL; REGISTRY; ABRUPT AB Because of the recent publication of several important studies, there has been a major change in how we think about perioperative management of anticoagulation. Because of these changes, existing consensus guidelines are suddenly out of date and can no longer be used as is, particularly the 2012 American College of Chest Physicians Antithrombotic Guidelines, version 9. We estimate that well over 90% of patients receiving warfarin therapy should not receive bridging anticoagulation during periprocedural interruptions of therapy, except under unusual circumstances and with appropriate justification. Accumulating evidence also suggests that bridging is not indicated among patients receiving direct-acting oral anticoagulant therapy. The large number of patients potentially affected represents an important safety concern and requires an immediate change in practice. C1 [Rose, Adam J.] Bedford VA Med Ctr, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Bldg 70, Bedford, MA USA. [Rose, Adam J.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02215 USA. [Allen, Arthur L.] VA Salt Lake City Healthcare Syst, Dept Pharm, Salt Lake City, UT USA. [Minichello, Tracy] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Minichello, Tracy] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. RP Rose, AJ (reprint author), Bedford VA Med Ctr, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Bldg 70, Bedford, MA USA. EM adamrose@bu.edu NR 13 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2016 VL 9 IS 1 BP 64 EP 67 DI 10.1161/CIRCOUTCOMES.115.002430 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB6FZ UT WOS:000368611000010 PM 26715651 ER PT J AU Garimella, PS Katz, R Patel, KV Kritchevsky, SB Parikh, CR Ix, JH Fried, LF Newman, AB Shlipak, MG Harris, TB Sarnak, MJ AF Garimella, Pranav S. Katz, Ronit Patel, Kushang V. Kritchevsky, Stephen B. Parikh, Chirag R. Ix, Joachim H. Fried, Linda F. Newman, Anne B. Shlipak, Michael G. Harris, Tamara B. Sarnak, Mark J. CA Hlth ABC Study TI Association of Serum Erythropoietin With Cardiovascular Events, Kidney Function Decline, and Mortality The Health Aging and Body Composition Study SO CIRCULATION-HEART FAILURE LA English DT Article DE cardiovascular outcomes; chronic kidney disease; death; erythropoietin; heart failure ID CONGESTIVE-HEART-FAILURE; EPOETIN-ALPHA; ENDOGENOUS ERYTHROPOIETIN; DARBEPOETIN-ALPHA; OLDER-ADULTS; CYSTATIN-C; INFLAMMATORY MARKERS; DISEASE; ANEMIA; RISK AB Background Studies suggest that in patients with heart failure (HF), high serum erythropoietin is associated with risk of recurrent HF and mortality. Trials of erythropoietin-stimulating agents in persons with kidney disease have also suggested an increased incidence of adverse clinical events. No large studies of which we are aware have evaluated the association of endogenous erythropoietin levels with clinical outcomes in the community-living older adults. Methods and Results Erythropoietin concentration was measured in 2488 participants aged 70-79 years in the Health, Aging and Body Composition Study. Associations of erythropoietin with incident HF, coronary heart disease, stroke, mortality, and 30% decline in estimated glomerular filtration rate were examined using Cox proportional hazards and logistic regression over 10.7 years of follow-up. Mean (SD) age was 75 (3) years and median (quartile 1, quartile 3) erythropoietin was 12.3 (9.0, 17.2) mIU/mL. There were 503 incident HF events, and each doubling of serum erythropoietin was associated with a 25% increased risk of incident HF 1.25 (95% confidence interval 1.13, 1.48) after adjusting for demographics, prevalent cardiovascular disease, cardiovascular disease risk factors, kidney function, and serum hemoglobin. There was no interaction of serum erythropoietin with chronic kidney disease or anemia (P>0.50). There were 330 incident coronary heart disease events, 161 strokes, 1112 deaths, and 698 outcomes of 30% decline in estimated glomerular filtration rate. Serum erythropoietin was not significantly associated with these outcomes. Conclusions Higher levels of endogenous erythropoietin are associated with incident HF in older adults. Studies need to elucidate the mechanisms through which endogenous erythropoietin levels associate with specific outcomes. C1 [Garimella, Pranav S.; Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. [Katz, Ronit] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Parikh, Chirag R.] Yale Univ, Sch Med, Dept Med, Nephrol Sect, New Haven, CT 06510 USA. [Ix, Joachim H.] Univ Calif San Diego, Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol & Prevent Med, San Diego, CA 92103 USA. [Fried, Linda F.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15260 USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol Biostat & Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. RP Sarnak, MJ (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA. EM msarnak@tuftsmedicalcenter.org RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU Intramural Research Program of the National Institutes of Health (NIH); National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, 5R01AG027002]; NINR [R01-NR012459]; American Heart Association [14EIA18560026]; National Center on Minority Health and Health Disparities, NIH [MD-07-080] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH) and the National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR012459. Drs Shlipak, Sarnak, Ix, and Katz were supported by NIA grant 5R01AG027002, Dr Ix by an American Heart Association Award #14EIA18560026, and Dr Patel was supported by National Center on Minority Health and Health Disparities, NIH grant MD-07-080. The study sponsors had no role in study design; collection, analysis, and interpretation of the data; writing the report; and the decision to submit the report for publication. NR 44 TC 3 Z9 3 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2016 VL 9 IS 1 AR e002124 DI 10.1161/CIRCHEARTFAILURE.115.002124 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB6HN UT WOS:000368615500001 PM 26721912 ER PT J AU Valero-Munoz, M Li, SP Wilson, RM Hulsmans, M Aprahamian, T Fuster, JJ Nahrendorf, M Scherer, PE Sam, F AF Valero-Munoz, Maria Li, Shanpeng Wilson, Richard M. Hulsmans, Maarten Aprahamian, Tamar Fuster, Jose J. Nahrendorf, Matthias Scherer, Philipp E. Sam, Flora TI Heart Failure With Preserved Ejection Fraction Induces Beiging in Adipose Tissue SO CIRCULATION-HEART FAILURE LA English DT Article DE brown adipose tissue; diastolic heart failure; natriuretic peptides; white adipose tissue ID BROWN FAT; DISEASE PATHOGENESIS; NATRIURETIC PEPTIDES; HUMAN ADIPOCYTES; OBESITY; WHITE; THERMOGENESIS; METABOLISM; HUMANS; PATHOPHYSIOLOGY AB Background Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there are no evidence-based therapies for HFpEF. Clinical studies suggest a relationship between obesity-associated dysfunctional adipose tissue (AT) and HFpEF. However, an apparent obesity paradox exists in some HF populations with a higher body mass index. We sought to determine whether HFpEF exerted effects on AT and investigated the involved mechanisms. Methods and Results Mice underwent d-aldosterone infusion, uninephrectomy, and were given 1% saline for 4 weeks. HFpEF mice developed hypertension, left ventricular hypertrophy, and diastolic dysfunction and had higher myocardial natriuretic peptide expression. Although body weights were similar in HFpEF and sham-operated mice, white AT was significantly smaller in HFpEF than in sham (epididymal AT, 7.59 versus 10.67 mg/g; inguinal AT, 6.34 versus 8.38 mg/g). These changes were associated with smaller adipocyte size and increased beiging markers (ucp-1, cidea, and eva) in white AT. Similar findings were seen in HFpEF induced by transverse aortic constriction. Increased activation of natriuretic peptide signaling was seen in white AT of HFpEF mice. The ratio of the signaling receptor, natriuretic peptide receptor type A, to the clearance receptor, nprc, was increased as was p38 mitogen-activated protein kinase activation. However, HFpEF mice failed to regulate body temperature during cold temperature exposure. In HFpEF, despite a larger brown AT mass (5.96 versus 4.50 mg/g), brown AT showed reduced activity with decreased uncoupling protein 1 (ucp-1), cell death-inducing DFFA-like effector a (cidea), and epithelial V-like antigen (eva) expression and decreased expression of lipolytic enzymes (hormone-sensitive lipase, lipoprotein lipase, and fatty acid binding protein 4) versus sham. Conclusions These findings show that HFpEF is associated with beiging in white AT and with dysfunctional brown AT. C1 [Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M.; Aprahamian, Tamar; Fuster, Jose J.; Sam, Flora] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. [Hulsmans, Maarten; Nahrendorf, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Scherer, Philipp E.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Touchstone Diabet Ctr, Dallas, TX 75390 USA. [Scherer, Philipp E.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Touchstone Diabet Ctr, Dallas, TX 75390 USA. [Sam, Flora] Boston Univ, Sch Med, Cardiovasc Sect, Boston, MA 02215 USA. [Aprahamian, Tamar; Sam, Flora] Boston Univ, Sch Med, Evans Dept Internal Med, Boston, MA 02215 USA. RP Sam, F (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiovasc Med Sect, 700 Albany St,W507, Boston, MA 02118 USA. EM flora.sam@bmc.org RI Fuster, Jose/A-2117-2017; OI Fuster, Jose/0000-0002-5970-629X; Sam, Flora/0000-0001-8442-9362 FU National Institutes of Health [HL117153] FX This work was supported by the National Institutes of Health (HL117153) to Dr Sam. NR 48 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2016 VL 9 IS 1 AR e002724 DI 10.1161/CIRCHEARTFAILURE.115.002724 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB6KX UT WOS:000368625000001 PM 26721917 ER PT J AU McCollister, K Yang, X Mckay, JR AF McCollister, Kathryn Yang, Xuan McKay, James R. TI Cost-effectiveness analysis of a continuing care intervention for cocaine-dependent adults SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Continuing care; Cost-effectiveness analysis; Substance use disorders; Economic evaluation ID SUBSTANCE USE DISORDERS; ALCOHOL DEPENDENCE; RANDOMIZED-TRIAL; 24-MONTH OUTCOMES; MANAGEMENT; FRAMEWORK; BENEFITS; ABUSERS; DISEASE AB Introduction: The study conducts a cost-effectiveness analysis (CEA) of a continuing care Telephone Monitoring and Counseling (TMC) intervention for adults diagnosed with cocaine dependence. Participants were randomly assigned to a control condition of intensive outpatient treatment only (treatment-as usual, or TAU; N = 108), or to one of two treatment conditions featuring TMC (N=106) and TMC plus incentives (TMC-plus; N = 107). Follow-up assessments were conducted over a 2-year period. Methods: Intervention and client costs were collected with the program and client versions of the Drug Abuse Treatment Cost Analysis Program (DATCAP). Effectiveness was measured as the number of days abstinent during follow-up. Secondary analyses consider alternative measures of effectiveness and the reduced societal costs of physical and mental health problems and criminal justice involvement. Results: From the societal perspective, TMC dominates both TAU and TMC-plus as a cost-effective and cost saving intervention. Results varied by substance-using status, however, with the subgroup of participants in TMC-plus that were using drugs at intake and early in treatment having the greatest number of days of abstinence and generating similar savings during follow-up than the TMC subgroup using drugs at intake. Conclusions: Telephone monitoring and counseling appears to be a cost-effective and potentially cost saving strategy for reducing substance use among chronic substance users. Providing client incentives added to total intervention costs but did not improve overall effectiveness. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [McCollister, Kathryn; Yang, Xuan] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Clin Res Bldg,Off 1026,1120 NW 14th St, Miami, FL 33136 USA. [McKay, James R.] Univ Penn, Philadelphia, PA 19104 USA. [McKay, James R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP McCollister, K (reprint author), Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Clin Res Bldg,Off 1026,1120 NW 14th St, Miami, FL 33136 USA. EM kmccolli@miami.edu FU National Institute on Drug Abuse (NIDA) [R01 DA020623, R01 DA031785] FX Financial assistance for this study was provided by the National Institute on Drug Abuse (NIDA; grant numbers R01 DA020623 & R01 DA031785). The funding sources had no involvement in the study design, in the collection, analysis and interpretation of the data, in the writing of the report, or in the decision to submit the article for publication. NR 28 TC 1 Z9 1 U1 1 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 JAN 1 PY 2016 VL 158 BP 38 EP 44 DI 10.1016/j.drugalcdep.2015.10.032 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DB5PN UT WOS:000368566200005 PM 26621551 ER PT J AU Tan, ASL Lee, CJ Bigman, CA AF Tan, Andy S. L. Lee, Chul-joo Bigman, Cabral A. TI Comparison of beliefs about e-cigarettes' harms and benefits among never users and ever users of e-cigarettes SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Electronic cigarette; Beliefs; Harms; Benefits; United States; Public opinion ID NICOTINE DELIVERY-SYSTEMS; ELECTRONIC CIGARETTES; TOBACCO PRODUCTS; YOUNG-ADULTS; SMOKING; PERCEPTIONS; PREVALENCE; INTERNET; AWARENESS; REASONS AB Introduction: E-cigarette use is rapidly increasing, especially among youth and young adults. We need to learn what factors are associated with uptake in e-cigarettes. One important set of predictors is beliefs about e-cigarettes' potential harms and benefits. Methods: Online survey data were collected in July, 2014 from 527 U.S. adults from a nationally representative online panel (KnowledgePanel) who reported being aware of e-cigarettes. Participants were asked to rate 7 statements related to e-cigarettes harms or benefits (e.g., breathing vapors from other people's e-cigarettes is harmful to my health; vaping or using e-cigarettes can help people quit smoking regular cigarettes completely). Responses were categorized into agree, disagree, or no opinion. We compared the proportions of agreement between respondents who ever used e-cigarettes and those who had never used. Multinomial logistic regression was used to predict agree or no opinion versus disagree (base outcome) for each belief. Relative risk ratios (RRRs) are reported. The analyses were completed in December, 2014 and were weighted to match the general U.S. adult population. Results: Agreement across the 7 beliefs ranged from 33% (vaping can help people quit smoking) to 56% (e-cigarettes make smoking look more acceptable to youth). Ever use of e-cigarettes was associated with lower relative risk of agreeing with statements about potential harms and higher relative risk of agreeing with statements about benefits (versus disagreeing) compared with never users. Discussion: These findings provide timely data on beliefs about e-cigarettes between e-cigarette users and non-users to inform potential message topics for health campaign interventions. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Tan, Andy S. L.] Dana Farber Canc Inst, Div Populat Sci, Ctr Community Based Res, Boston, MA 02115 USA. [Tan, Andy S. L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Lee, Chul-joo] Seoul Natl Univ, Dept Commun, Seoul, South Korea. [Bigman, Cabral A.] Univ Illinois, Dept Commun, Urbana, IL USA. [Tan, Andy S. L.] Dana Farber Canc Inst, 450 Brookline Ave,LW 662, Boston, MA 02215 USA. RP Tan, ASL (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW 662, Boston, MA 02215 USA. EM andy_tan@dfci.harvard.edu FU Invitation Program for Distinguished Scholars at Seoul National University; Institute of Communication Research at Seoul National University; CPRC program of MSIP/IITP [IITP-2015-H8201-15-1004] FX Preparation of this article was supported by the Invitation Program for Distinguished Scholars at Seoul National University, by the Institute of Communication Research at Seoul National University, and by the CPRC program of MSIP/IITP (IITP-2015-H8201-15-1004) to Chul-joo Lee. The study sponsors had no role in the study design, collection, analysis, and interpretation of data, writing the report, and the decision to submit the report for publication. NR 45 TC 5 Z9 5 U1 8 U2 28 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 JAN 1 PY 2016 VL 158 BP 67 EP 75 DI 10.1016/j.drugalcdep.2015.11.003 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DB5PN UT WOS:000368566200009 PM 26621550 ER PT J AU Chavez, LJ Liu, CF Tefft, N Hebert, PL Clark, BJ Rubinsky, AD Lapham, GT Bradley, KA AF Chavez, Laura J. Liu, Chuan-Fen Tefft, Nathan Hebert, Paul L. Clark, Brendan J. Rubinsky, Anna D. Lapham, Gwen T. Bradley, Katharine A. TI Unhealthy alcohol use in older adults: Association with readmissions and emergency department use in the 30 days after hospital discharge SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol screening; Quality; Unhealthy alcohol use; Emergency department; Readmissions; Post-discharge care ID CARE TRANSITIONS INTERVENTION; VETERANS-AFFAIRS; SCREENING SCORES; USE DISORDERS; AUDIT-C; MEDICARE BENEFICIARIES; HEALTH-CARE; RISK; METAANALYSIS; CONSUMPTION AB Background: Unhealthy alcohol use could impair recovery of older patients after medical or surgical hospitalizations. However, no prior research has evaluated whether older patients who screen positive for unhealthy alcohol use are at increased risk of readmissions or emergency department (ED) visits within 30 days after discharge. This study examined the association between AUDIT-C alcohol screening results and 30-day readmissions or ED visits. Methods: Veterans Affairs (VA) patients age 65 years or older, were eligible if they were hospitalized for a medical or surgical condition (2/1/2009-10/1/2011) and had an AUDIT-C score documented in their VA electronic medical record in the year before they were hospitalized. VA and Medicare data identified VA or non-VA index hospitalizations, readmissions, and ED visits. Primary analyses adjusted for demographics, comorbid conditions, and past-year health care utilization. Results: Among 579,330 hospitalized patients, 13.7% were readmitted and 12.0% visited an ED within 30 days of discharge. In primary analyses, high-risk drinking (n = 7,167) and nondrinking (n = 357,086) were associated with increased probability of readmission (13.8%, 95% CI 13.0-14.6%; and 14.2%, 95% CI 14.1-14.3%, respectively), relative to low-risk drinking (12.9%; 95% CI 12.7-13.0%). Only nondrinkers had increased risk for ED visits. Conclusions: Alcohol screening results indicating high-risk drinking that were available in medical records were modestly associated with risk for 30-day readmissions and were not associated with risk for ED visits. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Chavez, Laura J.; Liu, Chuan-Fen; Hebert, Paul L.; Rubinsky, Anna D.; Lapham, Gwen T.; Bradley, Katharine A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Ctr Innovat Vet Ctr & Value Driven Care, Hlth Serv Res & Dev, 1660 S Columbian Way, Seattle, WA 98108 USA. [Rubinsky, Anna D.; Bradley, Katharine A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, 1660 S Columbian Way, Seattle, WA 98108 USA. [Chavez, Laura J.; Liu, Chuan-Fen; Hebert, Paul L.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, 1959 NE Pacific St,Box 357660, Seattle, WA 98195 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, 1959 NE Pacific St, Seattle, WA 98195 USA. [Tefft, Nathan] Bates Coll, 2 Andrews Rd, Lewiston, ME 04240 USA. [Clark, Brendan J.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, 12700 E 19th Ave, Aurora, CO 80045 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. RP Chavez, LJ (reprint author), Univ Washington, Dept Hlth Serv, 1959 NE Pacific St,Box 357660, Seattle, WA 98195 USA. EM ljchavez@uw.edu; chuan-fen.liu@va.gov; ntefft@bates.edu; paul.hebert2@va.gov; brendan.clark@ucdenver.edu; anna.rubinsky@va.gov; lapham.g@ghc.org; bradley.k@ghc.org FU Agency for Healthcare Research and Quality (AHRQ) [NIH 1R36HS022800-01]; Center of Excellence for Substance Abuse Treatment and Education (CESATE) at VA Puget Sound; NIAAA R21 [5R21AA020894-02]; NIH [K23 AA 021814] FX Ms. Chavez's work on this study was supported by an Agency for Healthcare Research and Quality (AHRQ) Dissertation Grant (NIH 1R36HS022800-01). Dr. Bradley's and Ms. Rubinsky's time on this study was supported by the Center of Excellence for Substance Abuse Treatment and Education (CESATE) at VA Puget Sound. Dr. Bradley's NIAAA R21 (5R21AA020894-02) supported the collection of the data used in this study. Dr. Clark is supported by NIH grant K23 AA 021814. NR 55 TC 2 Z9 2 U1 2 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 JAN 1 PY 2016 VL 158 BP 94 EP 101 DI 10.1016/j.drugalcdep.2015.11.008 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DB5PN UT WOS:000368566200012 PM 26644137 ER PT J AU Briseno, MR Phukan, RD Leonard, DA Herzog, TL Cho, CH Schwab, JH Wood, KB Bono, CM Cha, TD AF Briseno, Michael R. Phukan, Rishabh D. Leonard, Dana A. Herzog, Tyler L. Cho, Charles H. Schwab, Joseph H. Wood, Kirkham B. Bono, Christopher M. Cha, Thomas D. TI The influence of adjacent level disc disease on discectomy outcomes SO EUROPEAN SPINE JOURNAL LA English DT Article DE Adjacent level disease; Lumbar spine; Discectomy; Quality of life; Outcomes ID LOW-BACK-PAIN; LONG-TERM OUTCOMES; LUMBAR SPINE; HERNIATION; SCIATICA; TRIAL; DEGENERATION; MORPHOLOGY; FRAGMENT; FUSION AB The state of adjacent level discs and its impact on surgical outcomes following single-level lumbar discectomy have not been previously investigated. The purpose of the present study was to determine if a significant relationship exists between the degree of preoperative adjacent level disc degeneration and post-operative clinical outcomes following lumbar discectomy. This study retrospectively used preoperative magnetic resonance imaging (MRI) and prospectively collected data from a randomized clinical trial at two tertiary-care academic hospitals. Patients who underwent a primary, single-level lumbar discectomy were included. Exclusion criteria included prior lumbar surgery. Outcome measures were the Modified Oswestry Disability Index (ODI) score and Visual Analog Scale (VAS) scores for back and leg pain. These were recorded at baseline and at 3 months, 1, and 2 years postoperatively. An independent reviewer graded adjacent level disc degeneration on all preoperative MRIs using the Pfirrmann grading scale. These data were then analyzed for correlation with each outcome measure. Forty-seven patients were included in the study. No statistically significant correlations were found when comparing preoperative 3-month or 1-year postoperative scores or change from baseline of any outcome measure between Pfirrmann grades. Only about half the patients had 2-year follow-up, but at that time point a statistically significant difference in back VAS scores was observed between Pfirrmann groups. No other significant differences were observed at that point. The degree of preoperative adjacent level degeneration does not significantly affect functional or pain relief outcomes following lumbar discectomy up to 1 year after surgery. C1 [Briseno, Michael R.; Phukan, Rishabh D.; Herzog, Tyler L.; Schwab, Joseph H.; Wood, Kirkham B.; Cha, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Briseno, Michael R.; Leonard, Dana A.; Cho, Charles H.; Bono, Christopher M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Spine Surg, 75 Francis St, Boston, MA 02115 USA. RP Leonard, DA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Spine Surg, 75 Francis St, Boston, MA 02115 USA. EM dleonard7@partners.org OI Leonard, Dana Angell/0000-0002-6828-3794 FU North American Spine Society; Gordon and Betty MooreFoundation; OREF; AOSpine; K2M; JAAOS; NIH; Depuy FX Thomas D. Cha consults for Bio2 and GE Healthcare, gives expert testimony for the Gordon and BettyMoore Foundation, and has grants from the North American Spine Society and the Gordon and Betty MooreFoundation. His institution receives fellowship support from OREF, AOSpine, and K2M. Christopher M. Bono consults for United Health Care, gives expert testimony for Crico, receives royalties from Wolters Kluwer, and receives a stipend from JAAOS for being a deputy editor. Kirkham B. Wood gives expert testimony for Morrison Mahoney and has TranSi stock. His institution receives grants from NIH and fellowship support from OREF, K2M, Depuy, and AOSpine. Joseph H. Schwab consults for Stryker and Depuy Synthes Spine. For the remaining authors, no disclosures were reported. NR 20 TC 2 Z9 2 U1 6 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 EI 1432-0932 J9 EUR SPINE J JI Eur. Spine J. PD JAN PY 2016 VL 25 IS 1 BP 230 EP 234 DI 10.1007/s00586-015-4200-y PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DB6FI UT WOS:000368608900028 PM 26363560 ER PT S AU Khaleghi, M Guignard, J Furlong, C Rosowski, JJ AF Khaleghi, Morteza Guignard, Jeremie Furlong, Cosme Rosowski, John J. BE Sciammarella, C Considine, J Gloeckner, P TI Full-Field Three-Dimensional Characterization of Non-repetitive Motions by Single-Shot Multiplexed Digital Holography SO EXPERIMENTAL AND APPLIED MECHANICS, VOL 4 SE Conference Proceedings of the Society for Experimental Mechanics Series LA English DT Proceedings Paper CT Annual Conference and Exposition of Society-for-Experimental-Mechanics on Experimental and Applied Mechanics CY JUN 08-11, 2015 CL Costa Mesa, CA SP Soc Experimental Mech DE 3D displacement measurements; Digital holography; High-speed measurements; Image registration; Multiplexed holography AB Typically, in 3D displacement measurements, the sample is repeatedly loaded at least three times and the displacement fields are obtained from multiple sensitivity vectors. However, for studying transient and non-repetitive phenomena, including, but not limited to, displacement fields of temporally-varying biological tissues, repeating the experiment is not an option. Therefore, to measure 3D displacements in such applications, all the measurements have to be done concomitantly. In this paper, single-frame, multiplexed holography is used for simultaneous quantification of 3D displacement fields. In our approach, the hologram of an object of interest is recorded in an off-axis configuration, with three simultaneous incoherently-superimposed pairs of reference and object beams. Three different spatial carrier frequencies are realized by small differences in the angle of illumination of each reference wave with respect to the CCD sensor. Therefore, the reconstructed image corresponding to each illumination direction is reconstructed at a particular position on the image plane. Because of the differences in the position of each reference beam and wavelength of each pair of beams, the reconstruction distance and magnification of each sensitivity vector are different. Therefore, we developed and implemented registration algorithms to accurately translate individual views into a single global coordinate system. Representative results highlighting the 3D measuring capabilities of our holographic system are presented. C1 [Khaleghi, Morteza; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron CHSLT, Worcester, MA 01609 USA. [Guignard, Jeremie; Furlong, Cosme; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Guignard, Jeremie; Furlong, Cosme; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Khaleghi, M (reprint author), Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron CHSLT, Worcester, MA 01609 USA. EM khaleghi29@gmail.com NR 12 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2191-5644 BN 978-3-319-22449-7; 978-3-319-22448-0 J9 C PROC SOC EXP MECH PY 2016 BP 11 EP 18 DI 10.1007/978-3-319-22449-7_2 PG 8 WC Mechanics SC Mechanics GA BE1UI UT WOS:000368587400002 ER PT J AU Hettmer, S Lin, MM Tchessalova, D Tortorici, SJ Castiglioni, A Desai, T Mao, J McMahon, AP Wagers, AJ AF Hettmer, Simone Lin, Michael M. Tchessalova, Daria Tortorici, Sara J. Castiglioni, Alessandra Desai, Tushar Mao, Junhao McMahon, Andrew P. Wagers, Amy J. TI Hedgehog-driven myogenic tumors recapitulate skeletal muscle cellular heterogeneity SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Skeletal muscle; Differentiation; Hedgehog signaling; Intratumoral cellular heterogeneity ID SATELLITE CELLS; SONIC HEDGEHOG; EMBRYONAL RHABDOMYOSARCOMA; MOUSE MODEL; STEM-CELLS; DIFFERENTIATION; REGENERATION; PROGENITORS; PATHWAY; MYOD AB Hedgehog (Hh) pathway activation in R26-SmoM2;CAGGS-CreER mice, which carry a tamoxifen-inducible activated Smoothened allele (SmoM2), results in numerous microscopic tumor foci in mouse skeletal muscle. These tumors exhibit a highly differentiated myogenic phenotype and resemble human fetal rhabdomyomas. This study sought to apply previously established strategies to isolate lineally distinct populations of normal mouse myofiber-associated cells in order to examine cellular heterogeneity in SmoM2 tumors. We demonstrate that established SmoM2 tumors are composed of cells expressing myogenic, adipocytic and hematopoietic lineage markers and differentiation capacity. SmoM2 tumors thus recapitulate the phenotypic and functional hetereogeneity observed in normal mouse skeletal muscle. SmoM2 tumors also contain an expanded population of PAX7+ and MyoD+ satellite-like cells with extremely low clonogenic activity. Selective activation of Hh signaling in freshly isolated muscle satellite cells enhanced terminal myogenic differentiation without stimulating proliferation. Our findings support the conclusion that SmoM2 tumors represent an aberrant skeletal muscle state and demonstrate that, similar to normal muscle, myogenic tumors contain functionally distinct cell subsets, including cells lacking myogenic differentiation potential. (C) 2015 Elsevier Inc. All rights reserved. C1 [Hettmer, Simone; Lin, Michael M.; Tchessalova, Daria; Tortorici, Sara J.; Castiglioni, Alessandra; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hettmer, Simone; Lin, Michael M.; Tchessalova, Daria; Tortorici, Sara J.; Castiglioni, Alessandra; Wagers, Amy J.] Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. [Hettmer, Simone] Univ Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, Univ Med Ctr Freiburg, Freiburg, Germany. [Desai, Tushar] Stanford Univ, Sch Med, Dept Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Mao, Junhao] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA 01605 USA. [McMahon, Andrew P.] Univ So Calif, Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90089 USA. RP Hettmer, S (reprint author), Zentrum Kinder & Jugendmed, Mathildenstr 1, D-79106 Freiburg, Germany. EM simone.hettmer@uniklinik-freiburg.de OI Lin, Michael/0000-0001-8739-4329 FU NIH [DK036836]; Burroughs-Wellcome Fund; Harvard Stem Cell Institute, from Hope Street Kids; P.A.L.S. Bermuda/St. Baldrick's, ALSF and Bear Necessities; NINDS [NS033642] FX We thank G. Buruzula, J. LaVecchio, and A. Wakabayashi at Joslin's DRC Flow Cytometry Core for excellent flow cytometry support, A. Pinkhasov and T. Genest at Joslin's DRC Histology Core for help with tumor sectioning, and C.L. Unitt and T. Bowman at the DF/HCC Histopathology Core for help with immunohistochemistry. This work was funded in part by grants from the NIH (DK036836), the Burroughs-Wellcome Fund and the Harvard Stem Cell Institute (to AJW), from Hope Street Kids, P.A.L.S. Bermuda/St. Baldrick's, ALSF and Bear Necessities (to SH) and from NINDS (NS033642; to APM). The authors declare no competing interests. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies. NR 37 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 1 PY 2016 VL 340 IS 1 BP 43 EP 52 DI 10.1016/j.yexcr.2015.10.008 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DB5RG UT WOS:000368570700005 PM 26460176 ER PT S AU Sharaf, R Mempel, TR Murooka, TT AF Sharaf, Radwa Mempel, Thorsten R. Murooka, Thomas T. BE Prasad, VR Kalpana, GV TI Visualizing the Behavior of HIV-Infected T Cells In Vivo Using Multiphoton Intravital Microscopy SO HIV PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Multiphoton intravital microscopy; In vivo imaging; Popliteal lymph node; Lymphocyte motility; HIV-1; Humanized mice; Fluorescent protein; Mean track velocity ID HUMANIZED BLT MICE; TRANSMISSION; MIGRATION; VIRUS AB The introduction of multiphoton microscopy has dramatically broadened the scope of intravital imaging studies and has allowed researchers to validate and refine basic mechanistic concepts in many areas of biology within the context of physiologically relevant tissue microenvironments. This has also led to new insights into the behavior of immune cells at steady state, and how their behaviors are altered during an immune response. At the same time, advances in the humanized mouse model have allowed for in vivo studies of strictly human pathogens, such as HIV-1. Here, we describe in detail an intravital microscopy approach to visualize the dynamic behavior of HIV-infected T cells within the lymph nodes of live, anesthetized humanized mice. C1 [Sharaf, Radwa; Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol,Med Sch, Boston, MA USA. [Murooka, Thomas T.] Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. [Murooka, Thomas T.] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. RP Sharaf, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol,Med Sch, Boston, MA USA. NR 20 TC 1 Z9 1 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3046-3; 978-1-4939-3045-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1354 BP 189 EP 201 DI 10.1007/978-1-4939-3046-3_13 D2 10.1007/978-1-4939-3046-3 PG 13 WC Immunology; Virology SC Immunology; Virology GA BE1XH UT WOS:000368688500014 PM 26714713 ER PT S AU Thomas, T Seay, K Zheng, JH Zhang, C Ochsenbauer, C Kappes, JC Goldstein, H AF Thomas, Tynisha Seay, Kieran Zheng, Jian Hua Zhang, Cong Ochsenbauer, Christina Kappes, John C. Goldstein, Harris BE Prasad, VR Kalpana, GV TI High-Throughput Humanized Mouse Models for Evaluation of HIV-1 Therapeutics and Pathogenesis SO HIV PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE HIV-1; Mouse model; Antiretroviral treatment ID IMMUNODEFICIENCY-VIRUS TYPE-1; RAG2(-/-)GAMMA(-/-)(C) MICE; CYCLIN T1; INFECTION; REPLICATION; CELLS; TAT AB Mice cannot be used as a model to evaluate HIV-1 therapeutics because they do not become infected by HIV-1 due to structural differences between several human and mouse proteins required for HIV-1 replication. This has limited their use for in vivo assessment of anti-HIV-1 therapeutics and the mechanism by which cofactors, such as illicit drug use accelerate HIV-1 replication and disease course in substance abusers. Here, we describe the development and application of two in vivo humanized mouse models that are highly sensitive and useful models for the in vivo evaluation of candidate anti-HIV therapeutics. The first model, hu-spl-PBMC-NSG mice, uses NOD-SCID IL2r gamma(-/-) (NSG) mice intrasplenically injected with human peripheral blood mononuclear cells (PBMC) which develop productive splenic HIV-1 infection after intrasplenic inoculation with a replication-competent HIV-1 expressing Renilla reniformis luciferase (HIVLucR) and enables investigators to use bioluminescence to visualize and quantitate the temporal effects of therapeutics on HIV-1 infection. The second model, hCD4/R5/cT1 mice, consists of transgenic mice carrying human CD4, CCR5 and cyclin T1 genes, which enables murine CD4-expressing cells to support HIV-1 entry, Tat-mediated LTR transcription and consequently develop productive infection. The hCD4/R5/cT1 mice develop disseminated infection of tissues including the spleen, small intestine, lymph nodes and lungs after intravenous injection with HIV-1-LucR. Because these mice can be infected with HIV-LucR expressing transmitted/founder and clade A/E and C Envs, these mouse models can also be used to evaluate the in vivo efficacy of broadly neutralizing antibodies and antibodies induced by candidate HIV-1 vaccines. Furthermore, because hCD4/R5/cT1 mice can be infected by vaginal inoculation with replication-competent HIV-1 expressing NanoLuc (HIV-nLucR)-, this mouse model can be used to evaluate the mechanisms by which substance abuse and other factors enhance mucosal transmission of HIV-1. C1 [Thomas, Tynisha; Seay, Kieran; Zheng, Jian Hua; Zhang, Cong; Goldstein, Harris] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Ochsenbauer, Christina; Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. [Goldstein, Harris] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. RP Thomas, T (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. OI Ochsenbauer, Christina/0000-0003-1166-5879 FU NIAID NIH HHS [P30 AI027767]; NIDA NIH HHS [R01 DA033788, R01 DA036171] NR 25 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3046-3; 978-1-4939-3045-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1354 BP 221 EP 235 DI 10.1007/978-1-4939-3046-3_15 D2 10.1007/978-1-4939-3046-3 PG 15 WC Immunology; Virology SC Immunology; Virology GA BE1XH UT WOS:000368688500016 PM 26714715 ER PT J AU Dusser, D Wise, RA Dahl, R Anzueto, A Carter, K Fowler, A Calverley, PM AF Dusser, Daniel Wise, Robert A. Dahl, Ronald Anzueto, Antonio Carter, Kerstine Fowler, Andy Calverley, Peter M. TI Differences in outcomes between GOLD groups in patients with COPD in the TIOSPIR (R) trial SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE TIOSPIR (R); GOLD; cardiovascular comorbidity; mortality; respiratory death; cardiovascular death ID OBSTRUCTIVE PULMONARY-DISEASE; ECLIPSE COHORT; CLASSIFICATION; EXACERBATION; DYSPNEA; DEATH AB Background: The aim of this study was to evaluate whether Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification could predict mortality risk factors and whether baseline treatment intensity would relate to mortality within each group, using data from TIOSPIR (R), the largest randomized clinical trial in COPD performed to date. Methods: A total of 17,135 patients from TIOSPIR (R) were pooled and grouped by GOLD grading (A-D) according to baseline Medical Research Council breathlessness score, exacerbation history, and spirometry. All-cause mortality and adjudicated cardiovascular (CV) and respiratory mortality were assessed. Results: Of the 16,326 patients classified, 1,248 died on treatment. Group B patients received proportionally more CV treatment at baseline. CV mortality risk, but not all-cause mortality risk, was significantly higher in Group B than Group C patients (CV mortality - hazard ratio [HR] = 1.74, P = 0.004; all-cause mortality - HR = 1.18, P = 0.11). Group D patients had a higher incidence of all-cause mortality than Group B patients (10.9% vs 6.6%). Similar trends were observed regardless of respiratory or CV medication at baseline. In contrast, respiratory deaths increased consistently from Groups A-D (0.3%, 0.8%, 1.6%, and 4.2% of patients, respectively). Conclusion: The data obtained from the TIOSPIR (R) trial, supporting earlier studies, suggest that proportionally more CV medication and CV deaths occur in GOLD Group B COPD patients, although deaths attributed to respiratory causes are more prevalent in Groups C and D. C1 [Dusser, Daniel] Univ Paris 05, AP HP, Hop Cochin, Sorbonne Paris Cite,Serv Pneumol, 27 Rue Faubourg St Jacques, F-75679 Paris 14, France. [Wise, Robert A.] Johns Hopkins Univ, Sch Med, Asthma & Allergy Ctr, Baltimore, MD USA. [Dahl, Ronald] Odense Univ Hosp, Allergy Ctr, DK-5000 Odense C, Denmark. [Anzueto, Antonio] Univ Texas San Antonio, Pulm Crit Care, San Antonio, TX USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Carter, Kerstine] Boehringer Ingelheim Pharmaceut Inc, 90 E Ridge POB 368, Ridgefield, CT 06877 USA. [Fowler, Andy] Boehringer Ingelheim Pharma Ltd, Bracknell, Berks, England. [Calverley, Peter M.] Univ Liverpool, Inst Ageing & Chron Dis, Liverpool L69 3BX, Merseyside, England. RP Dusser, D (reprint author), Univ Paris 05, AP HP, Hop Cochin, Sorbonne Paris Cite,Serv Pneumol, 27 Rue Faubourg St Jacques, F-75679 Paris 14, France. EM daniel.dusser@aphp.fr FU Boehringer Ingelheim; Pfizer; Novartis; Chiesi; Nycomed; Dey Pharma; GlaxoSmithKline; Pearl Therapeutics; Forest Laboratories; Bristol-Myers Squibb; Janssen; Mylan; Sunovion; Pulmonx; Spiration; Roche; Grifols; AstraZeneca; Takeda FX Daniel Dusser reports receiving consulting fees, lecture fees, and payment for the development of educational activities from Boehringer Ingelheim, Pfizer, Novartis, Chiesi, Nycomed, and Dey Pharma. Robert Wise reports receiving consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Mylan, Novartis, Pfizer, Sunovion, Pulmonx, Spiration, Roche, Grifols, and AstraZeneca, and grant support from Boehringer Ingelheim, GlaxoSmithKline, Pearl Therapeutics, and Forest Laboratories. Ronald Dahl reports receiving consulting fees, lecture fees, and grant support from Boehringer Ingelheim and Novartis. Antonio Anzueto reports receiving consulting fees, lecture fees, and travel support from AstraZeneca, Boehringer Ingelheim, Forest Laboratories, GlaxoSmithKline, and Novartis, and grant support from GlaxoSmithKline. Kerstine Carter and Andy Fowler report being employees of Boehringer Ingelheim. Peter Calverley reports receiving consulting fees, lecture fees, and travel support from Novartis, GlaxoSmithKline, Boehringer Ingelheim, and Takeda. The authors report no other conflicts of interest in this work. NR 15 TC 0 Z9 0 U1 0 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2005 J9 INT J CHRONIC OBSTR JI Int. J. Chronic Obstr. Pulm. Dis. PY 2016 VL 11 BP 133 EP 145 DI 10.2147/COPD.S97924 PG 13 WC Respiratory System SC Respiratory System GA DB3KP UT WOS:000368410400002 PM 26855568 ER PT J AU Sedaghat, AR Matsui, EC Baxi, SN Bollinger, ME Miller, R Perzanowski, M Phipatanakul, W AF Sedaghat, Ahmad R. Matsui, Elizabeth C. Baxi, Sachin N. Bollinger, Mary E. Miller, Rachel Perzanowski, Matthew Phipatanakul, Wanda TI Mouse Sensitivity is an Independent Risk Factor for Rhinitis in Children with Asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Mouse; Allergy; Rhinitis; Asthma; Pediatric; IgE; Risk factor ID INNER-CITY ADOLESCENTS; SCHOOL-AGED CHILDREN; ALLERGIC RHINITIS; CHRONIC RHINOSINUSITIS; EXPOSURE; MORBIDITY; SENSITIZATION; ASSOCIATIONS; PREVALENCE; EMERGENCY AB BACKGROUND: Although mouse and cockroach allergy is known to be important in urban children with asthma, the independent association of mouse and cockroach sensitization with rhinitis in these children is unknown. OBJECTIVE: To determine the association of mouse and cockroach sensitization with rhinitis in urban children with asthma. METHODS: As part of the Mouse Allergen and Asthma Intervention Trial, 499 urban children (5-17 years) with persistent asthma underwent spirometry, skin prick testing to 14 common environmental allergens, and serology for mouse-specific IgE. In 269 subjects, cockroach-specific IgE serology was also obtained. Patient/parent-reported rhinitis in the last 2 weeks and the last 1 year was the primary outcome measure. Mouse/cockroach exposure was measured by reported frequency of sightings. Mouse allergen-settled bedroom dust samples were also measured in mouse-sensitized children. RESULTS: Rhinitis was reported in 49.9% and 70.2% of the participants within the last 2 weeks and the last 1 year, respectively. Serum mouse IgE level of 0.35 IU/mL or more was associated with rhinitis in the past 2 weeks (adjusted odds ratio, 2.15; 95% CI, 1.02-4.54; P = .04) and the past 1 year (adjusted odds ratio, 2.40; 95% CI, 1.12-5.1; P = .02) after controlling for age, race, sex, the presence of any smokers at home, primary caregiver education level, number of allergen sensitivities, cockroach IgE level of 0.35 IU/mL or more, and study site (Boston or Baltimore). Measures of home mouse exposure were not associated with rhinitis, regardless of mouse sensitivity. Cockroach sensitivity was not associated with rhinitis regardless of sensitization to other allergens. CONCLUSIONS: In urban children with asthma, increased mouse IgE, but not cockroach IgE, in the sera (mouse IgE >= 0.35 IU/mL) may be associated independently with rhinitis. (C) 2015 American Academy of Allergy, Asthma & Immunology C1 [Sedaghat, Ahmad R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Sedaghat, Ahmad R.] Boston Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. [Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Baxi, Sachin N.; Phipatanakul, Wanda] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Bollinger, Mary E.] Univ Maryland, Sch Med, Dept Pediat, Div Pulmonol & Allergy, Baltimore, MD 21201 USA. [Miller, Rachel] Columbia Univ, Med Ctr, Div Pulm, Allergy,Crit Care Med, New York, NY USA. [Miller, Rachel; Perzanowski, Matthew] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA. RP Phipatanakul, W (reprint author), Boston Childrens Hosp, Div Immunol, 300 Longwood Ave,Fegan 6, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu FU National Institutes of Health [K24 AI 106822, R01 AI 073964, U01 Al 110397, U01 Al 083238] FX This study was supported by the National Institutes of Health (grant nos. K24 AI 106822, R01 AI 073964, U01 Al 110397, and U01 Al 083238). NR 36 TC 3 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN-FEB PY 2016 VL 4 IS 1 BP 82 EP + DI 10.1016/j.jaip.2015.09.006 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA DB7AT UT WOS:000368667500012 PM 26441149 ER PT J AU Saff, RR Camargo, CA Clark, S Rudders, SA Long, ADA Banerji, A AF Saff, Rebecca R. Camargo, Carlos A., Jr. Clark, Sunday Rudders, Susan A. Long, Aidan A. Banerji, Aleena TI Utility of ICD-9-CM Codes for Identification of Allergic Drug Reactions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes; Adverse drug reactions; Drug allergy; Drug hypersensitivity; Epidemiology; Emergency department ID EMERGENCY-DEPARTMENT VISITS; NATIONAL SURVEILLANCE; CLAIMS DATA; ANAPHYLAXIS; CHILDREN; EVENTS; EPIDEMIOLOGY; ADOLESCENTS; PNEUMONIA; DATABASES AB BACKGROUND: The epidemiology of allergic drug reactions is poorly understood due, in large part, to difficulty in identifying true cases in population data sets. Use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes is a potentially valuable approach that requires formal evaluation. OBJECTIVE: To better understand the utility of ICD-9-CM codes for identification of allergic drug reactions, including the validation of specific codes by chart review. METHODS: We reviewed randomly sampled medical records of patients treated in the emergency department (ED) between January 1, 2001, and December 31, 2006, with ICD-9-CM codes for drug allergy and E codes (E930-949) for adverse drug reactions. RESULTS: During the 6-year period, 11,130 charts were identified by ICD-9-CM and E codes and 1,634 were reviewed. Allergic drug reactions were found in 444 (27%) of the reviewed ED visits. The codes that identified the highest percentage of true allergic drug reactions were dermatitis due to drug (693.0; 87%), adverse reaction to drug (995.2; 52%), and anaphylaxis (995.0; 38%). Patients with both an ICD-9-CM code and an E code had a high likelihood of having an allergic drug reaction (76%). Most allergic drug reactions were attributed to antibiotics (42%), intravenous contrast (7%), and nonsteroidal anti-inflammatory drugs (6%). The estimated frequency of allergic drug reactions increased from 0.49% of ED visits in 2001 to 0.94% in 2012. CONCLUSIONS: Specific ICD-9-CM and E codes can be used in combination to identify allergic drug reactions. Further study of these codes in the inpatient and outpatient settings is necessary to better understand the utility of diagnosis codes for improving epidemiologic research on drug allergy. (C) 2015 American Academy of Allergy, Asthma & Immunology C1 [Saff, Rebecca R.; Camargo, Carlos A., Jr.; Long, Aidan A.; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Saff, Rebecca R.; Camargo, Carlos A., Jr.; Long, Aidan A.; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Rudders, Susan A.] Brown Univ, Rhode Isl Hosp, Dept Pediat, Div Asthma & Allergy,Alpert Sch Med, Providence, RI 02903 USA. RP Saff, RR (reprint author), Dept Med, Div Rheumatol Allergy & Immunol, 55 Fruit St,COX 201, Boston, MA 02114 USA. EM rsaff@partners.org FU Mylan; Sanofi Aventis; UpToDate FX C. A. Camargo has received consultancy fees from Mylan and Sanofi Aventis. A. A. Long has received payment for developing educational presentations from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. NR 25 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN-FEB PY 2016 VL 4 IS 1 BP 114 EP + DI 10.1016/j.jaip.2015.07.013 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA DB7AT UT WOS:000368667500016 PM 26372539 ER PT J AU Goto, T Tsugawa, Y Camargo, CA Hasegawa, K AF Goto, Tadahiro Tsugawa, Yusuke Camargo, Carlos A., Jr. Hasegawa, Kohei TI Sex differences in the risk of hospitalization among patients presenting to US emergency departments with asthma exacerbation, 2010-2012 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Letter ID FREQUENT UTILIZATION; ADULTS C1 [Goto, Tadahiro; Camargo, Carlos A., Jr.; Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Tsugawa, Yusuke] Harvard Univ, Harvard Interfac Initiat Hlth Policy, Boston, MA 02115 USA. RP Goto, T (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM tag695@mail.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN-FEB PY 2016 VL 4 IS 1 BP 149 EP + DI 10.1016/j.jaip.2015.11.023 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA DB7AT UT WOS:000368667500022 PM 26772929 ER PT J AU Blumenthal, KG Ziegler, JB AF Blumenthal, Kimberly G. Ziegler, John B. TI Hypersensitivity Reactions, Dietary Supplements, and the Importance of the Case Report SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Editorial Material ID STEVENS-JOHNSON SYNDROME; ADVERSE DRUG-REACTIONS; TOXIC EPIDERMAL NECROLYSIS; SYSTEMIC SYMPTOMS; DRESS SYNDROME; SAFETY; EOSINOPHILIA; ALLERGY C1 [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Blumenthal, Kimberly G.] Massachusetts Gen Profess Org, Massachusetts Gen Hosp, Edward P Lawrence Ctr Qual & Safety, Boston, MA USA. [Blumenthal, Kimberly G.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ziegler, John B.] Sydney Childrens Hosp, Dept Immunol & Infect Dis, Randwick, NSW 2031, Australia. [Ziegler, John B.] Univ New S Wales, Sch Womens & Childrens Hlth, Sydney, NSW 2052, Australia. RP Blumenthal, KG (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Cox 201 Allergy Associates, Boston, MA 02114 USA. EM kblumenthal1@partners.org FU NHLBI NIH HHS [T32 HL116275] NR 21 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN-FEB PY 2016 VL 4 IS 1 BP 177 EP 178 DI 10.1016/j.jaip.2015.08.001 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA DB7AT UT WOS:000368667500034 PM 26772930 ER PT J AU Luk, FS Kim, RY Li, K Ching, D Wong, DK Joshi, SK Imhof, I Honbo, N Hoover, H Zhu, BQ Lovett, DH Karliner, JS Raffai, RL AF Luk, Fu Sang Kim, Roy Y. Li, Kang Ching, Daniel Wong, David K. Joshi, Sunil K. Imhof, Isabella Honbo, Norman Hoover, Holly Zhu, Bo-Qing Lovett, David H. Karliner, Joel S. Raffai, Robert L. TI Immunosuppression With FTY720 Reverses Cardiac Dysfunction in Hypomorphic ApoE Mice Deficient in SR-BI Expression That Survive Myocardial Infarction Caused by Coronary Atherosclerosis SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE FTY720; S1P; ApoE; coronary atherosclerosis; heart failure; cardioprotection; immunosuppression ID MATRIX METALLOPROTEINASE-2 EXPRESSION; ISCHEMIA-REPERFUSION INJURY; NFAT NUCLEAR FACTOR; SPHINGOSINE-1-PHOSPHATE ANALOG; SPHINGOSINE 1-PHOSPHATE; GENE REPAIR; IN-VIVO; HEART; CELL; PROMOTES AB Aims:We recently reported that immunosuppression with FTY720 improves cardiac function and extends longevity in Hypomorphic ApoE mice deficient in scavenger receptor Type-BI expression, also known as the HypoE/SR-BI-/- mouse model of diet-induced coronary atherosclerosis and myocardial infarction (MI). In this study, we tested the impact of FTY720 on cardiac dysfunction in HypoE/SR-BI-/- mice that survive MI and subsequently develop chronic heart failure.Methods/Results:HypoE/SR-BI-/- mice were bred to Mx1-Cre transgenic mice, and offspring were fed a high-fat diet (HFD) for 3.5 weeks to provoke hyperlipidemia, coronary atherosclerosis, and recurrent MIs. In contrast to our previous study, hyperlipidemia was rapidly reversed by inducible Cre-mediated gene repair of the HypoE allele and switching mice to a normal chow diet. Mice that survived the period of HFD were subsequently given oral FTY720 in drinking water or not, and left ventricular (LV) function was monitored using serial echocardiography for up to 15 weeks. In untreated mice, LV performance progressively deteriorated. Although FTY720 treatment did not initially prevent a decline of heart function among mice 6 weeks after Cre-mediated gene repair, it almost completely restored normal LV function in these mice by 15 weeks. Reversal of heart failure did not result from reduced atherosclerosis as the burden of aortic and coronary atherosclerosis actually increased to similar levels in both groups of mice. Rather, FTY720 caused systemic immunosuppression as assessed by reduced numbers of circulating T and B lymphocytes. In contrast, FTY720 did not enhance the loss of T cells or macrophages that accumulated in the heart during the HFD feeding period, but it did enhance the loss of B cells soon after plasma lipid lowering. Moreover, FTY720 potently reduced the expression of matrix metalloproteinase-2 and genes involved in innate immunity-associated inflammation in the heart.Conclusions:Our data demonstrate that immunosuppression with FTY720 prevents postinfarction myocardial remodeling and chronic heart failure. C1 [Luk, Fu Sang; Kim, Roy Y.; Li, Kang; Ching, Daniel; Wong, David K.; Raffai, Robert L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Surg, San Francisco, CA 94121 USA. [Joshi, Sunil K.; Imhof, Isabella; Honbo, Norman; Hoover, Holly; Zhu, Bo-Qing; Lovett, David H.; Karliner, Joel S.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. RP Raffai, RL (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Surg, 4150 Clement St, San Francisco, CA 94121 USA. EM robert.raffai@ucsf.edu FU National Institutes of Health [HL089871, HL090606]; Department of Veterans Affairs [5I01BX000532] FX This work was supported by Grants from the National Institutes of Health HL089871 (RLR) and HL090606 (JSK) which were administered by the Northern California Institute for Research and Education, and a Merit Review grant from the Department of Veterans Affairs 5I01BX000532 to RLR, and with resources of the Veterans Affairs Medical Center, San Francisco, California. NR 42 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0160-2446 EI 1533-4023 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD JAN PY 2016 VL 67 IS 1 BP 47 EP 56 DI 10.1097/FJC.0000000000000312 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA DB4SW UT WOS:000368504500006 PM 26322923 ER PT J AU Huang, T Wang, ZH Wei, LN Kindy, M Zheng, YF Xi, TF Gao, BZ AF Huang, Ting Wang, Zhonghai Wei, Lina Kindy, Mark Zheng, Yufeng Xi, Tingfei Gao, Bruce Z. TI Microelectrode Array-evaluation of Neurotoxic Effects of Magnesium as an Implantable Biomaterial SO JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY LA English DT Article DE Magnesium; Microelectrode array; Neuroelectrophysiology; Neuron viability; Neuronal network ID NEURONAL APOPTOSIS; IN-VITRO; ALLOYS; CORROSION; CULTURE; ASSAYS; CELLS; TERM; PH AB Magnesium (Mg)-based biomaterials have shown great potential in clinical applications. However, the cytotoxic effects of excessive Mg2+ and the corrosion products from Mg-based biomaterials, particularly their effects on neurons, have been little studied. Although viability tests are most commonly used, a functional evaluation is critically needed. Here, both methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays were used to test the effect of Mg2+ and Mg-extract solution on neuronal viability. Microelectrode arrays (MEAs), which provide long-term, real-time recording of extracellular electro-physiological signals of in vitro neuronal networks, were used to test for toxic effects. The minimum effective concentrations (ECmin) of Mg2+ from the MTT and LDH assays were 3 mmol/L and 100 mmol/L, respectively, while the ECmin obtained from the MEA assay was 0.1 mmol/L. MEA data revealed significant loss of neuronal network activity when the culture was exposed to 25% Mg-extract solution, a concentration that did not affect neuronal viability. For evaluating the biocompatibility of Mg-based biomaterials with neurons, MEA electrophysiological testing is a more precise method than basic cell-viability testing. Copyright (C) 2015, The editorial office of Journal of Materials Science & Technology. Published by Elsevier Limited. All rights reserved. C1 [Huang, Ting; Wei, Lina; Zheng, Yufeng; Xi, Tingfei] Peking Univ, Acad Adv Interdisciplinary Studies, Ctr Biomed Mat & Tissue Engn, Beijing 100871, Peoples R China. [Wang, Zhonghai; Kindy, Mark; Gao, Bruce Z.] Clemson Univ, Dept Bioengn, Clemson, SC 29634 USA. [Kindy, Mark] Med Univ S Carolina, Dept Neurosci & Regenerat Med, Charleston, SC 29466 USA. [Kindy, Mark] Med Univ S Carolina, Dept Cell Biol, Charleston, SC 29466 USA. [Kindy, Mark] Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. [Zheng, Yufeng] Peking Univ, Coll Engn, Dept Mat Sci & Engn, Beijing 100871, Peoples R China. [Xi, Tingfei] Peking Univ, Shenzhen Inst, Shenzhen Key Lab Human Tissue Regenerat & Repair, Shenzhen 518057, Peoples R China. RP Xi, TF (reprint author), Peking Univ, Acad Adv Interdisciplinary Studies, Ctr Biomed Mat & Tissue Engn, Beijing 100871, Peoples R China.; Gao, BZ (reprint author), Clemson Univ, Dept Bioengn, Clemson, SC 29634 USA. EM xitingfei@pku.edu.cn; zgao@clemson.edu RI Zheng, Yufeng/A-4146-2010 OI Zheng, Yufeng/0000-0002-7402-9979 FU National Basic Research Program of China (973 Program) [2012CB619102]; National Natural Science Foundation of China [31070847, 31370956]; National Science and Technology Support Program [2012BAI18B01]; Strategic New Industry Development Special Foundation of Shenzhen, China [JCYJ20130402172114948]; Guangdong Provincial Department of Science and Technology, China [2011B050400011]; NIH NIGMS COBRE [NIH P20GM103444] FX This work was supported by the National Basic Research Program of China (973 Program, No. 2012CB619102); the National Natural Science Foundation of China (Nos. 31070847 and 31370956); the National Science and Technology Support Program (No. 2012BAI18B01); the Strategic New Industry Development Special Foundation of Shenzhen, China (No. JCYJ20130402172114948); the Guangdong Provincial Department of Science and Technology, China (No. 2011B050400011); and NIH NIGMS COBRE (No. NIH P20GM103444). NR 18 TC 1 Z9 1 U1 4 U2 8 PU JOURNAL MATER SCI TECHNOL PI SHENYANG PA 72 WENHUA RD, SHENYANG 110015, PEOPLES R CHINA SN 1005-0302 J9 J MATER SCI TECHNOL JI J. Mater. Sci. Technol. PD JAN PY 2016 VL 32 IS 1 BP 89 EP 96 DI 10.1016/j.jmst.2015.08.009 PG 8 WC Materials Science, Multidisciplinary; Metallurgy & Metallurgical Engineering SC Materials Science; Metallurgy & Metallurgical Engineering GA DB5NI UT WOS:000368560500013 PM 27110081 ER PT J AU Alexander, SI Madsen, JC AF Alexander, Stephen I. Madsen, Joren C. TI Organ Transplant Tolerance for Children; in Sight for Some SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID MAINTENANCE IMMUNOSUPPRESSION; KIDNEY-TRANSPLANTATION; RECIPIENTS; LIFE C1 [Alexander, Stephen I.] Univ Sydney, Ctr Kidney Res, Sydney, NSW 2006, Australia. [Alexander, Stephen I.] Childrens Hosp Westmead, Dept Nephrol, Westmead, NSW 2145, Australia. [Madsen, Joren C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. [Madsen, Joren C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci,Dept Surg, Boston, MA USA. RP Alexander, SI (reprint author), Childrens Hosp Westmead, Dept Nephrol, Westmead, NSW 2145, Australia. EM stephen.alexander@health.nsw.gov.au NR 12 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 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2016 VL 168 BP 232 EP 235 DI 10.1016/j.jpeds.2015.10.042 PG 4 WC Pediatrics SC Pediatrics GA DB5ZK UT WOS:000368592500047 PM 26581495 ER PT J AU Sabharwal, S AF Sabharwal, Sunil TI Making the right connections with telehealth SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Editorial Material ID DISEASE MANAGEMENT C1 [Sabharwal, Sunil] VA Boston Hlth Care Syst, Spinal Cord Injury Serv, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Hlth Care Syst, Spinal Cord Injury Serv, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2016 VL 39 IS 1 BP 13 EP 14 DI 10.1080/10790268.2015.1116727 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DB5AW UT WOS:000368526300001 PM 26796046 ER PT J AU Gray, DA Foo, D AF Gray, Damon A. Foo, Dominic TI Reversible myoclonus, asterixis, and tremor associated with high dose trimethoprim-sulfamethoxazole: a case report SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Trimethoprim-sulfamethoxazole combination; Myoclonus; Dyskinesias; Tremor; Spinal cord injuries; Pneumocystis jirovecii; Pneumonia; Pneumocystis; Physical and rehabilitation medicine; Etiracetam ID PATIENT; INFECTION AB Case Diagnosis: Reversible myoclonus, tremor, and asterixis induced by high dose trimethoprim-sulfamethoxazole. Case Description: The patient was a 66-year-old male with T9 AIS(1) C quadriplegia secondary to spinal cord compression by a tumor due to large B cell lymphoma. Subsequent to tumor resection and chemotherapy, the patient was discovered to have Pneumocystis jiroveci pneumonia (PJP). Once started on high dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy (15.6 mg/kg/day of trimethoprim) for the treatment of PJP, he displayed bilateral upper extremity myoclonic jerks at rest, asterixis, and postural tremor. Symptoms resolved once TMP-SMX therapy was discontinued. Discussion: Myoclonus, asterixis, and tremor have been linked to high dose TMP-SMX therapy as a toxic side effect. Our patient's symptoms did improve with levetiracetam therapy, but did not fully resolve until TMP-SMX was discontinued. Conclusions: This is thought to be the first reported case of reversible myoclonus, tremor, and asterixis induced by high dose TMP-SMX in the spinal cord injury population. Early recognition of TMP-SMX induced complications were of key importance as they negatively impacted the rehabilitation process. We also recommend consideration of symptomatic treatment with levetiracetam for the duration of required TMP-SMX therapy as it appeared to mitigate the severity of our patient's movement disorders. C1 [Gray, Damon A.] Tufts Med Ctr, Dept Phys Med & Rehabil, Boston, MA 02111 USA. [Foo, Dominic] VA Boston Healthcare Syst, Spinal Cord Injury Unit, West Roxbury, MA USA. [Gray, Damon A.] Tufts Med Ctr, 800 Washington St, Boston, MA 02111 USA. RP Gray, DA (reprint author), Tufts Med Ctr, 800 Washington St, Boston, MA 02111 USA. EM dgray1@tuftsmedicalcenter.org NR 3 TC 0 Z9 0 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2016 VL 39 IS 1 BP 115 EP 117 DI 10.1179/2045772315Y.0000000018 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA DB5AW UT WOS:000368526300016 PM 26111222 ER PT J AU Kaatz, A Dattalo, M Regner, C Filut, A Carnes, M AF Kaatz, Anna Dattalo, Melissa Regner, Caitlin Filut, Amarette Carnes, Molly TI Patterns of Feedback on the Bridge to Independence: A Qualitative Thematic Analysis of NIH Mentored Career Development Award Application Critiques SO JOURNAL OF WOMENS HEALTH LA English DT Article ID GENDER-DIFFERENCES; MEDICAL-FACULTY; SEX-DIFFERENCES; WOMENS HEALTH; DEVELOPMENT AWARDEES; ONE INSTITUTION; JOB APPLICANTS; FEMALE; DISCRIMINATION; RECOMMENDATION AB Background: NIH Mentored Career Development (K) Awards bridge investigators from mentored to independent research. A smaller proportion of women than men succeed in this transition. The aim of this qualitative study was to analyze reviewers' narrative critiques of K award applications and explore thematic content of feedback provided to male and female applicants. Method: We collected 88 critiques, 34 from 9 unfunded and 54 from 18 funded applications, from 70% (n=26) of investigators at the University of Wisconsin-Madison with K awards funded between 2005 and 2009 on the first submission or after revision. We qualitatively analyzed text in the 5 critique sections: candidate, career development plan, research plan, mentors, and environment and institutional commitment. We explored thematic content within these sections for male and female applicants and for applicants who had received a subsequent independent research award by 2014. Results: Themes revealed consistent areas of criticism for unfunded applications and praise for funded applications. Subtle variations in thematic content appeared for male and female applicants: For male applicants criticism was often followed by advice but for female applicants it was followed by questions about ability; praise recurrently characterized male but not female applicants' research as highly significant with optimism for future independence. Female K awardees that obtained subsequent independent awards stood out as having track records described as outstanding. Conclusion: This exploratory study suggests that K award reviewer feedback, particularly for female applicants, should be investigated as a potential contributor to research persistence and success in crossing the bridge to independence. C1 [Kaatz, Anna; Filut, Amarette] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Regner, Caitlin] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53715 USA. [Dattalo, Melissa] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Coll Engn, Dept Ind & Syst Engn, Madison, WI 53715 USA. RP Kaatz, A (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM akaatz@wisc.edu FU NIH [R25GM083252, R01GM111002]; Department of Medicine; Shapiro Research Scholars Program in the School of Medicine and Public Health at the University of Wisconsin-Madison; Shaprio Summer Research Program at the UW-Madison School; Medicine and Public Health FX The authors wish to thank Kristin Cox and Katherine Muratore at University of Wisconsin's Center for Women's Health Research who aided in formatting and de-identifying critiques. Dr. Carnes' and Dr. Kaatz's work on increasing scientific workforce diversity is funded by NIH grants R01GM111002 and R25GM083252, the Department of Medicine, and the Shapiro Research Scholars Program in the School of Medicine and Public Health at the University of Wisconsin-Madison. Ms. Regner received funding to participate in this research from the Shaprio Summer Research Program at the UW-Madison School or Medicine and Public Health. The funders played no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. This study was approved by the University of Wisconsin-Madison institutional review board. NR 57 TC 0 Z9 0 U1 3 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD JAN 1 PY 2016 VL 25 IS 1 BP 78 EP 90 DI 10.1089/jwh.2015.5254 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA DB4YX UT WOS:000368520700013 PM 26418619 ER PT J AU Banks, WA Abrass, CK Hansen, KM AF Banks, William A. Abrass, Christine K. Hansen, Kim M. TI Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Cytokines; Obesity; Leptin; Amyloid precursor protein ID COLONY-STIMULATING FACTOR; ALZHEIMERS-DISEASE; CALORIC RESTRICTION; COGNITIVE IMPAIRMENT; OBESITY; INFLAMMATION; LEPTIN; INSULIN; DIET; INJECTIONS AB Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights. By comparing groups and using path analysis, we found divergent influences of chronological aging versus body weight, our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue compartments. C1 [Banks, William A.; Hansen, Kim M.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Abrass, Christine K.] Dept Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Care Med, Seattle, WA USA. RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Rm 810A,Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU Veterans Affairs Merit Reviews; AG [RO-1029839] FX The authors were supported by Veterans Affairs Merit Reviews (W.A.B.; C.K.A.) and AG RO-1029839 (W.A.B.). NR 34 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2016 VL 71 IS 1 BP 21 EP 29 DI 10.1093/gerona/glu100 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DB2UZ UT WOS:000368366900003 PM 25128822 ER PT J AU David, V Martin, A Isakova, T Spaulding, C Qi, LX Ramirez, V Zumbrennen-Bullough, KB Sun, CC Lin, HY Babitt, JL Wolf, M AF David, Valentin Martin, Aline Isakova, Tamara Spaulding, Christina Qi, Lixin Ramirez, Veronica Zumbrennen-Bullough, Kimberly B. Sun, Chia Chi Lin, Herbert Y. Babitt, Jodie L. Wolf, Myles TI Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production SO KIDNEY INTERNATIONAL LA English DT Article DE anemia; bone; FGF23; hypoxia; inflammation; mineral metabolism ID CHRONIC KIDNEY-DISEASE; FAMILIAL TUMORAL CALCINOSIS; PARATHYROID-HORMONE; MINERAL METABOLISM; MOUSE MODEL; VITAMIN-D; SYNOVIAL FIBROBLASTS; FGF23 ELEVATION; BONE LOSS; ANEMIA AB Circulating levels of fibroblast growth factor 23 (FGF23) are elevated in patients with chronic kidney disease (CKD), but the mechanisms are poorly understood. Here we tested whether inflammation and iron deficiency regulate FGF23. In wild-type mice, acute inflammation induced by single injections of heat-killed Brucella abortus or interleukin-1 beta (IL-1 beta) decreased serum iron within 6 h, and was accompanied by significant increases in osseous Fgf23 mRNA expression and serum levels of C-terminal FGF23, but no changes in intact FGF23. Chronic inflammation induced by repeated bacteria or IL-1 beta injections decreased serum iron, increased osseous Fgf23 mRNA, and serum C-terminal FGF23, but modestly increased biologically active, intact FGF23 serum levels. Chronic iron deficiency mimicked chronic inflammation. Increased osseous FGF23 cleavage rather than a prolonged half-life of C-terminal FGF23 fragments accounted for the elevated C-terminal FGF23 but near-normal intact FGF23 levels in inflammation. IL-1 beta injection increased Fgf23 mRNA and C-terminal FGF23 levels similarly in wildtype and Col4a3(ko) mice with CKD but markedly increased intact FGF23 levels only in the CKD mice. Inflammation increased Fgf23 transcription by activating Hif1 alpha signaling. Thus, inflammation and iron deficiency stimulate FGF23 production. Simultaneous upregulation of FGF23 cleavage in osteocytes maintains near-normal levels of biologically active, intact circulating FGF23, whereas downregulated or impaired FGF23 cleavage may contribute to elevated intact serum FGF23 in CKD. C1 [David, Valentin; Martin, Aline; Isakova, Tamara; Spaulding, Christina; Qi, Lixin; Ramirez, Veronica; Wolf, Myles] Northwestern Univ, Feinberg Sch Med, Inst Publ Hlth & Med, Div Nephrol & Hypertens,Dept Med, Chicago, IL 60611 USA. [David, Valentin; Martin, Aline; Isakova, Tamara; Spaulding, Christina; Qi, Lixin; Ramirez, Veronica; Wolf, Myles] Northwestern Univ, Feinberg Sch Med, Inst Publ Hlth & Med, Ctr Translat Metab & Hlth, Chicago, IL 60611 USA. [Zumbrennen-Bullough, Kimberly B.; Sun, Chia Chi; Lin, Herbert Y.; Babitt, Jodie L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nephrol Div,Program Membrane Biol, Boston, MA USA. [Zumbrennen-Bullough, Kimberly B.; Sun, Chia Chi; Lin, Herbert Y.; Babitt, Jodie L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. RP David, V (reprint author), Northwestern Univ, Feinberg Sch Med, Inst Publ Hlth & Med, Div Nephrol & Hypertens,Dept Med, 320 East Super St,Searle Bldg,Suite 10-517, Chicago, IL 60611 USA. EM valentin.david@northwestern.edu FU National Institutes of Health [R01DK102815, R01DK076116, K24DK093723, R01DK087727]; Howard Goodman Fellowship Award from the Massachusetts General Hospital FX This study was supported by Grants R01DK102815 to VD, R01DK076116 and K24DK093723 to MW and R01DK087727 to JLB from the National Institutes of Health and by a Howard Goodman Fellowship Award from the Massachusetts General Hospital to JLB. NR 60 TC 16 Z9 16 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2016 VL 89 IS 1 BP 135 EP 146 DI 10.1038/ki.2015.290 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA DB2EO UT WOS:000368321300022 PM 26535997 ER PT J AU Pavkov, ME Weil, EJ Fufaa, GD Nelson, RG Lemley, KV Knowler, WC Niewczas, MA Krolewski, AS AF Pavkov, Meda E. Weil, E. Jennifer Fufaa, Gudeta D. Nelson, Robert G. Lemley, Kevin V. Knowler, William C. Niewczas, Monika A. Krolewski, Andrzej S. TI Tumor necrosis factor receptors 1 and 2 are associated with early glomerular lesions in type 2 diabetes SO KIDNEY INTERNATIONAL LA English DT Article DE diabetic nephropathy; endothelium; kidney biopsy ID STRUCTURAL-FUNCTIONAL RELATIONSHIPS; TNF-ALPHA SYSTEM; ENDOTHELIAL-CELL; KIDNEY-DISEASE; RENAL-FUNCTION; NEPHROPATHY; MELLITUS; ALBUMINURIA; PROTEINURIA; PROGRESSION AB Elevated serum tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2) concentrations are strongly associated with increased risk of end-stage renal disease in type 2 diabetes. However, little is known about the early glomerular structural lesions that develop in patients when these markers are elevated. Here, we examined the relationships between TNFRs and glomerular structure in 83 American Indians with type 2 diabetes. Serum TNFRs and glomerular filtration rate (GFR, iothalamate) were measured during a research exam performed within a median of 0.9 months from a percutaneous kidney biopsy. Associations of TNFRs with glomerular structural variables were quantified by Spearman's correlations and by multivariable linear regression after adjustment for age, gender, diabetes duration, hemoglobin A1c, body mass index, and mean arterial pressure. The baseline mean age was 46 years, median GFR 130 ml/min, median albumin/creatinine ratio 26 mg/g, median TNFR1 1500 pg/ml, and median TNFR2 3284 pg/ml. After multivariable adjustment, TNFR1 and TNFR2 significantly correlated inversely with the percentage of endothelial cell fenestration and the total filtration surface per glomerulus. There were significant positive correlations with mesangial fractional volume, glomerular basement membrane width, podocyte foot process width, and percentage of global glomerular sclerosis. Thus, TNFRs may be involved in the pathogenesis of early glomerular lesions in diabetic nephropathy. C1 [Pavkov, Meda E.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Weil, E. Jennifer; Fufaa, Gudeta D.; Nelson, Robert G.; Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. [Lemley, Kevin V.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90033 USA. [Niewczas, Monika A.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Niewczas, Monika A.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Nelson, RG (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, 1550 East Indian Sch Rd, Phoenix, AZ 85014 USA. EM rnelson@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases; American Diabetes Association (Clinical Science Award) [1-08-CR-42]; National Institutes of Health: DRC [P30DK036836, DK41526, DK67638] FX This study was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, by the American Diabetes Association (Clinical Science Award 1-08-CR-42), and by grants from the National Institutes of Health: DRC P30DK036836 to MAN; DK41526 and DK67638 to ASK. Parts of this study were presented in abstract form at the American Society of Nephrology annual meeting and scientific exposition in Philadelphia, Pennsylvania, 13-16 November 2014. NR 35 TC 3 Z9 3 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2016 VL 89 IS 1 BP 226 EP 234 DI 10.1038/ki.2015.278 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA DB2EO UT WOS:000368321300032 PM 26398493 ER PT J AU Oaklander, AL AF Oaklander, Anne Louise TI Immunotherapy Prospects for Painful Small-fiber Sensory Neuropathies and Ganglionopathies SO NEUROTHERAPEUTICS LA English DT Review DE Ganglionitis; Complex regional pain syndrome; Polyneuropathy; C-fiber; Neuropathic pain; Small-fiber neuropathy ID REFLEX SYMPATHETIC DYSTROPHY; SYNDROME TYPE-I; PRIMARY SJOGREN SYNDROME; PERIPHERAL NERVOUS-SYSTEM; INTRAVENOUS IMMUNOGLOBULIN; CELIAC-DISEASE; SKIN BIOPSY; NEUROGENIC INFLAMMATION; CLINICAL-FEATURES; RANDOMIZED-TRIAL AB The best-known peripheral neuropathies are those affecting the large, myelinated motor and sensory fibers. These have well-established immunological causes and therapies. Far less is known about the somatic and autonomic "small fibers"; the unmyelinated C-fibers, thinly myelinated A-deltas, and postganglionic sympathetics. The small fibers sense pain and itch, innervate internal organs and tissues, and modulate the inflammatory and immune responses. Symptoms of small-fiber neuropathy include chronic pain and itch, sensory impairment, edema, and skin color, temperature, and sweating changes. Small-fiber polyneuropathy (SFPN) also causes cardiovascular, gastrointestinal, and urological symptoms, the neurologic origin of which often remains unrecognized. Routine electrodiagnostic study does not detect SFPN, so skin biopsies immunolabeled to reveal axons are recommended for diagnostic confirmation. Preliminary evidence suggests that dysimmunity causes some cases of small-fiber neuropathy. Several autoimmune diseases, including Sjogren and celiac, are associated with painful small-fiber ganglionopathy and distal axonopathy, and some patients with "idiopathic" SFPN have evidence of organ-specific dysimmunity, including serological markers. Dysimmune SFPN first came into focus in children and teenagers as they lack other risk factors, for example diabetes or toxic exposures. In them, the rudimentary evidence suggests humoral rather than cellular mechanisms and complement consumption. Preliminary evidence supports efficacy of corticosteroids and immunoglobulins in carefully selected children and adult patients. This paper reviews the evidence of immune causality and the limited data regarding immunotherapy for small-fiber-predominant ganglionitis, regional neuropathy (complex regional pain syndrome), and distal SFPN. These demonstrate the need to develop case definitions and outcome metrics to improve diagnosis, enable prospective trials, and dissect the mechanisms of small-fiber neuropathy. C1 [Oaklander, Anne Louise] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Dept Pathol Neuropathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA.; Oaklander, AL (reprint author), Harvard Univ, Sch Med, Dept Pathol Neuropathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM aloaklander@mgh.harvard.edu FU National Institutes of Health [K24NS059892, R01NS093653] FX This work was supported, in part, by the National Institutes of Health (K24NS059892, R01NS093653). I acknowledge the mentorship of the late John W. Griffin MD with gratitude. NR 96 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2016 VL 13 IS 1 BP 108 EP 117 DI 10.1007/s13311-015-0395-1 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DB5SU UT WOS:000368574700010 PM 26526686 ER PT J AU Reyes, RC Cittolin-Santos, GF Kim, JE Won, SJ Brennan-Minnella, AM Katz, M Glass, GA Swanson, RA AF Reyes, Reno C. Cittolin-Santos, Giordano Fabricio Kim, Ji-Eun Won, Seok Joon Brennan-Minnella, Angela M. Katz, Maya Glass, Graham A. Swanson, Raymond A. TI Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid SO NEUROTHERAPEUTICS LA English DT Article DE Cysteine; Parkinson's disease; oxidative stress; human; cerebrospinal fluid; target engagement ID PARKINSONS-DISEASE; OXIDATIVE STRESS; NITRIC-OXIDE; ACETYLCYSTEINE; METABOLISM; DEPLETION; BRAIN; SUPEROXIDE; NEURODEGENERATION; DEFICIENCY AB N-acetyl cysteine (NAC) supports the synthesis of glutathione (GSH), an essential substrate for fast, enzymatically catalyzed oxidant scavenging and protein repair processes. NAC is entering clinical trials for adrenoleukodystrophy, Parkinson's disease, schizophrenia, and other disorders in which oxidative stress may contribute to disease progression. However, these trials are hampered by uncertainty about the dose of NAC required to achieve biological effects in human brain. Here we describe an approach to this issue in which mice are used to establish the levels of NAC in cerebrospinal fluid (CSF) required to affect brain neurons. NAC dosing in humans can then be calibrated to achieve these NAC levels in human CSF. The mice were treated with NAC over a range of doses, followed by assessments of neuronal GSH levels and neuronal antioxidant capacity in ex vivo brain slices. Neuronal GSH levels and antioxidant capacity were augmented at NAC doses that produced peak CSF NAC concentrations of >= 50 nM. Oral NAC administration to humans produced CSF concentrations of up to 10 mu M, thus demonstrating that oral NAC administration can surpass the levels required for biological activity in brain. Variations of this approach may similarly facilitate and rationalize drug dosing for other agents targeting central nervous system disorders. C1 [Reyes, Reno C.; Cittolin-Santos, Giordano Fabricio; Kim, Ji-Eun; Won, Seok Joon; Brennan-Minnella, Angela M.; Katz, Maya; Glass, Graham A.; Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol Serv, 4150 Clement St, San Francisco, CA 94121 USA. [Reyes, Reno C.; Cittolin-Santos, Giordano Fabricio; Kim, Ji-Eun; Won, Seok Joon; Brennan-Minnella, Angela M.; Katz, Maya; Glass, Graham A.; Swanson, Raymond A.] Univ Calif San Francisco, Med Ctr, Dept Neurol, San Francisco, CA 94143 USA. [Cittolin-Santos, Giordano Fabricio] Univ Fed Rio Grande do Sul, Programa Pos Grad Ciencias Biol Bioquim, Porto Alegre, RS, Brazil. [Cittolin-Santos, Giordano Fabricio] CNPq, Sci Borders, Brasilia, DF, Brazil. RP Swanson, RA (reprint author), San Francisco VA Med Ctr, Neurol Serv, 4150 Clement St, San Francisco, CA 94121 USA.; Swanson, RA (reprint author), Univ Calif San Francisco, Med Ctr, Dept Neurol, San Francisco, CA 94143 USA. EM raymond.swanson@ucsf.edu FU Michael J. Fox Foundation; San Luis Obispo County Community Foundation; Singing Field Foundation; Department of Veterans Affairs FX We thank Drs. Caroline Tanner (University of California San Francisco) and Dean Jones (Emory University) for many helpful discussions. This study was supported by the Michael J. Fox Foundation, the San Luis Obispo County Community Foundation, the Singing Field Foundation, and the Department of Veterans Affairs. NR 39 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2016 VL 13 IS 1 BP 217 EP 225 DI 10.1007/s13311-015-0404-4 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DB5SU UT WOS:000368574700019 PM 26572666 ER PT J AU Reyes, RC Cittolin-Santos, GF Kim, JE Won, SJ Brennan-Minnella, AM Katz, M Glass, GA Swanson, RA AF Reyes, Reno C. Cittolin-Santos, Giordano Fabricio Kim, Ji-Eun Won, Seok Joon Brennan-Minnella, Angela M. Katz, Maya Glass, Graham A. Swanson, Raymond A. TI Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid (vol 13, pg 217, 2016) SO NEUROTHERAPEUTICS LA English DT Correction C1 [Reyes, Reno C.; Cittolin-Santos, Giordano Fabricio; Kim, Ji-Eun; Won, Seok Joon; Brennan-Minnella, Angela M.; Katz, Maya; Glass, Graham A.; Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol Serv, 4150 Clement St, San Francisco, CA 94121 USA. [Reyes, Reno C.; Cittolin-Santos, Giordano Fabricio; Kim, Ji-Eun; Won, Seok Joon; Brennan-Minnella, Angela M.; Katz, Maya; Glass, Graham A.; Swanson, Raymond A.] Univ Calif San Francisco, Med Ctr, Dept Neurol, San Francisco, CA 94143 USA. [Cittolin-Santos, Giordano Fabricio] Univ Fed Rio Grande do Sul, Programa Pos Grad Ciencias Biol Bioquim, Porto Alegre, RS, Brazil. [Cittolin-Santos, Giordano Fabricio] CNPq, Sci Without Borders, Brasilia, DF, Brazil. RP Swanson, RA (reprint author), San Francisco VA Med Ctr, Neurol Serv, 4150 Clement St, San Francisco, CA 94121 USA.; Swanson, RA (reprint author), Univ Calif San Francisco, Med Ctr, Dept Neurol, San Francisco, CA 94143 USA. EM raymond.swanson@ucsf.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2016 VL 13 IS 1 BP 239 EP 239 DI 10.1007/s13311-015-0413-3 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DB5SU UT WOS:000368574700023 PM 26659493 ER PT J AU Lee, JM AF Lee, Jong-Min TI Genetic Modifiers of Huntington Disease SO NEUROTHERAPEUTICS LA English DT Meeting Abstract C1 [Lee, Jong-Min] 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 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2016 VL 13 IS 1 BP 241 EP 241 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DB5SU UT WOS:000368574700027 ER PT J AU Wheelock, V Tempkin, T Duffy, S Martin, A Mooney, L Scher, L Farias, S Swadell, D DeCarli, C Brunberg, J Li, CS Yarborough, M Dayananthan, A Stout, J Hersch, S Aylward, E Fink, KD Annett, J Nolta, J AF Wheelock, V. Tempkin, T. Duffy, S. Martin, A. Mooney, L. Scher, L. Farias, S. Swadell, D. DeCarli, C. Brunberg, J. Li, C. -S Yarborough, M. Dayananthan, A. Stout, J. Hersch, S. Aylward, E. Fink, K. D. Annett, J. Nolta, J. TI PRE-CELL: Preparing for a Future Planned Phase 1 Trial of Genetically Modified Stem Cells Over-expressing Brain-derived Neurotrophic Factor in Patients with Huntington Disease. SO NEUROTHERAPEUTICS LA English DT Meeting Abstract C1 [Wheelock, V.; Tempkin, T.; Duffy, S.; Martin, A.; Mooney, L.; Farias, S.; Swadell, D.; DeCarli, C.; Dayananthan, A.] Univ Calif Davis, Sch Med, Dept Neurol, Sacramento, CA USA. [Wheelock, V.; Tempkin, T.; Duffy, S.; Martin, A.; Mooney, L.; Farias, S.; Swadell, D.; DeCarli, C.; Dayananthan, A.] Univ Calif Davis, Sch Med, HDSA Ctr Excellence, Sacramento, CA USA. [Scher, L.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA USA. [Brunberg, J.] Univ Calif Davis, Sch Med, Dept Radiol, Sacramento, CA USA. [Li, C. -S] Univ Calif Davis, Sch Med, Dept Biostat, Davis, CA USA. [Yarborough, M.] Univ Calif Davis, Sch Med, Bioeth Program, Sacramento, CA USA. [Stout, J.] Monash Univ, Dept Psychol, Clayton, Vic 3800, Australia. [Hersch, S.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Aylward, E.] Seattle Childrens Hosp, Dept Radiol, Seattle, WA USA. [Fink, K. D.; Annett, J.; Nolta, J.] Univ Calif Davis, Sch Med, UC Davis Inst Regenerat Cures, Sacramento, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2016 VL 13 IS 1 MA 2 BP 244 EP 244 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DB5SU UT WOS:000368574700032 ER PT J AU Moscovitch-Lopatin, M DiFiglia, M Kegel-Gleason, K Ritch, JJ Rosenthal, SJ Sapp, E Wheelock, V Duffy, A Chopra, V Rosas, HD Hersch, SM AF Moscovitch-Lopatin, M. DiFiglia, M. Kegel-Gleason, K. Ritch, J. J. Rosenthal, S. J. Sapp, E. Wheelock, V. Duffy, A. Chopra, V. Rosas, H. D. Hersch, S. M. TI A Novel Translational Bioassay for Conformers of Mutant Huntingtin. SO NEUROTHERAPEUTICS LA English DT Meeting Abstract C1 [Moscovitch-Lopatin, M.; DiFiglia, M.; Kegel-Gleason, K.; Ritch, J. J.; Rosenthal, S. J.; Sapp, E.; Chopra, V.; Rosas, H. D.; Hersch, S. M.] Massachusetts Gen Hosp, Dept Neurol, MassGeneral Inst Neurodegenerat, Charlestown, MA USA. [Moscovitch-Lopatin, M.; DiFiglia, M.; Kegel-Gleason, K.; Ritch, J. J.; Rosenthal, S. J.; Sapp, E.; Chopra, V.; Rosas, H. D.; Hersch, S. M.] Harvard Univ, Sch Med, Charlestown, MA USA. [Wheelock, V.; Duffy, A.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2016 VL 13 IS 1 MA 27 BP 254 EP 254 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DB5SU UT WOS:000368574700053 ER PT J AU Stagner, AM Jakobiec, FA AF Stagner, Anna M. Jakobiec, Frederick A. TI Peripheral Nerve Sheath Tumors of the Eyelid Dermis: A Clinicopathologic and Immunohistochemical Analysis SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SOLITARY CIRCUMSCRIBED NEUROMA; PALISADED ENCAPSULATED NEUROMAS; SCHWANNOMA; SKIN; NEUROFIBROMATOSIS; CELLS AB Purpose: To determine the incidences, clinical features, and detailed histopathologic and immunohistochemical findings of 10 peripheral nerve tumors (isolated neurofibromas, solitary circumscribed neuromas [SCNs], and schwannomas) localized to the eyelid dermis. Methods: In this retrospective clinicopathologic study, clinical records and paraffin sections subjected to hematoxylin and eosin, Masson trichrome, periodic acid-Schiff, reticulin, and Alcian blue staining were critically reviewed from each case. Additional paraffin sections were immunoreacted for S100, neurofilament, CD34, epithelial membrane antigen (EMA), glucose transporter-1 (glut-1), and calretinin. Results: Ten patients with a median age of 57 years had solitary, small, flesh-colored papules, 70% at the eyelid margin. Microscopically, they were diagnosed either as a SCN or an isolated neurofibroma. SCN was diffusely S100-positive (and sometimes diffusely calretinin-positive) with myriad neurofilaments. Fascicles of cells were separated by CD34-positive septa, and the lesions were surrounded by a glut-1/EMA-positive capsule. Neurofibromas were calretinin-negative and had a moderate number of S100-positive cells, with widely scattered neurofilaments, many CD34-postive intermixed cells, and no capsule. No schwannomas were diagnosed. Conclusions: Peripheral nerve tumors of the eyelid have a distinct clinical presentation at the eyelid margin. Careful histopathologic and immunohistochemical studies can reliably separate the entities in the categories of isolated neurofibroma, SCN, and schwannoma when the last occurs. These distinctions can have important systemic implications. C1 [Stagner, Anna M.; Jakobiec, Frederick A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, Boston, MA USA. [Stagner, Anna M.; Jakobiec, Frederick A.] Harvard Univ, Sch Med, Dept Ophthalmol, 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 35 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2016 VL 32 IS 1 BP 40 EP 45 DI 10.1097/IOP.0000000000000424 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DB4SS UT WOS:000368504100008 PM 25794028 ER PT J AU Jakobiec, FA Stagner, AM Sassoon, J Goldstein, S Mihm, MC AF Jakobiec, Frederick A. Stagner, Anna M. Sassoon, Jodi Goldstein, Scott Mihm, Martin C. TI A Hyalinized Trichilemmoma of the Eyelid in a Teenager SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID DESMOPLASTIC TRICHILEMMOMA; COWDENS-SYNDROME AB A 16-year-old African American male, the youngest patient to date, presented with a well-circumscribed upper eyelid lesion. On excision, the dermal nodule was contiguous with the epidermis, displayed trichohyalin-like bodies in an expanded outer root sheath, and was composed chiefly of small cellular clusters separated by a prominent network of periodic acid Schiff -positive hyaline bands of basement membrane material. The tumor cells were positive for high molecular weight cytokeratins (CK) 5/6, CK14, and CK34E12 and were negative for CK7, carcinoembryonic antigen and epithelial membrane antigen. Negative S100, glial fibrillary acidic protein, and smooth muscle actin immunoreactions ruled out a myoepithelial lesion. The Ki-67 proliferation index was <10%. The diagnosis was a hyalinized trichilemmoma, contrasting with the more common lobular type. As an isolated lesion, trichilemmoma does not portend Cowden syndrome. C1 [Jakobiec, Frederick A.; Stagner, Anna M.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jakobiec, Frederick A.; Stagner, Anna M.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Sassoon, Jodi] CBLPath Inc, Dept Ophthalm Pathol, New York, NY USA. [Goldstein, Scott] Thomas Jefferson Univ, Wills Eye Hosp, Oculoplast & Orbital Serv, Philadelphia, PA 19107 USA. [Mihm, Martin C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Suite 328 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2016 VL 32 IS 1 BP E9 EP E12 DI 10.1097/IOP.0000000000000389 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DB4SU UT WOS:000368504300005 PM 26020717 ER PT J AU Jakobiec, FA Roh, M Stagner, AM Yoon, MK AF Jakobiec, Frederick A. Roh, Miin Stagner, Anna M. Yoon, Michael K. TI Choristomatous Respiratory Cyst Restricted to the Upper Eyelid SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ORBIT; EPITHELIUM AB A 79-year-old man underwent excision of an upper eyelid mass that had been enlarging for 3 months. Histopathologic evaluation demonstrated a cyst lined by pseudostratified columnar epithelium with myriad goblet cells and cilia, and immunostaining revealed cytokeratins indicative of a respiratory origin. This rare condition, the first described exclusively in an eyelid, arises either from a congenital embryologic respiratory epithelial ectopia or the displacement of mature sinus mucosa following trauma or chronic sinus disease. The current case lacked any signs or symptoms of sinus disease or a history of trauma. C1 [Jakobiec, Frederick A.; Roh, Miin; Stagner, Anna M.; Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Jakobiec, Frederick A.; Stagner, Anna M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, Boston, MA USA. [Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Plast Surg, 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 13 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2016 VL 32 IS 1 BP E15 EP E18 DI 10.1097/IOP.0000000000000373 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DB4SU UT WOS:000368504300007 PM 25675165 ER PT J AU Keller, AC Knaub, LA McClatchey, PM Connon, CA Bouchard, R Miller, MW Geary, KE Walker, LA Klemm, DJ Reusch, JEB AF Keller, Amy C. Knaub, Leslie A. McClatchey, P. Mason Connon, Chelsea A. Bouchard, Ron Miller, Matthew W. Geary, Kate E. Walker, Lori A. Klemm, Dwight J. Reusch, Jane E. B. TI Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID NITRIC-OXIDE SYNTHASE; OXYGEN SPECIES PRODUCTION; REACTIVE OXYGEN; ENDOTHELIAL DYSFUNCTION; OXIDATIVE STRESS; INSULIN-RESISTANCE; SKELETAL-MUSCLE; BIOGENESIS; DYNAMICS; HEART AB Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p < 0.05). Mitochondrial superoxide increased with high glucose in Wistar SMCs (p < 0.05) with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets. C1 [Keller, Amy C.; Knaub, Leslie A.; McClatchey, P. Mason; Connon, Chelsea A.; Miller, Matthew W.; Geary, Kate E.; Reusch, Jane E. B.] Univ Colorado, Div Endocrinol, Anschutz Med Campus, Aurora, CO 80045 USA. [Keller, Amy C.; Knaub, Leslie A.; McClatchey, P. Mason; Connon, Chelsea A.; Bouchard, Ron; Miller, Matthew W.; Geary, Kate E.; Reusch, Jane E. B.] Denver VA Med Ctr, Dept Med, Denver, CO 80220 USA. [McClatchey, P. Mason] Univ Colorado, Dept Bioengn, Aurora, CO 80045 USA. [Walker, Lori A.] Univ Colorado, Dept Cardiol, Aurora, CO 80045 USA. [Klemm, Dwight J.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Reusch, Jane E. B.] Univ Colorado, Sch Med, Ctr Womens Hlth Res, Aurora, CO 80045 USA. RP Reusch, JEB (reprint author), Univ Colorado, Div Endocrinol, Anschutz Med Campus, Aurora, CO 80045 USA.; Reusch, JEB (reprint author), Denver VA Med Ctr, Dept Med, Denver, CO 80220 USA.; Reusch, JEB (reprint author), Univ Colorado, Sch Med, Ctr Womens Hlth Res, Aurora, CO 80045 USA. EM jane.reusch@ucdenver.edu FU VA Merit, Denver Research Institute [NIH-5T32HL007171, NIH-5P01HL014985, CCTSI-UL1RR025780]; Center for Women's Health Research; Department of Bioengineering; National Cancer Institute Cancer Center Support Grant [P30CA046934] FX The authors wish to acknowledge Dr. Pete Watson, University of Colorado Anschutz Medical Campus, for his intellectual contributions to this work, Dr. Rebecca Scalzo, University of Colorado Anschutz Medical Campus, for critical input on the paper, and Ms. Molly McCullough for her initial mitochondrial imaging analyses. Sources of funding for this study were provided by VA Merit, Denver Research Institute, NIH-5T32HL007171 (Amy C. Keller), NIH-5P01HL014985 (Amy C. Keller), CCTSI-UL1RR025780 (Jane E. B. Reusch), the Center for Women's Health Research (Jane E. B. Reusch), and the Department of Bioengineering (P. Mason McClatchey). Flow Cytometry is supported through a National Cancer Institute Cancer Center Support Grant (P30CA046934). NR 58 TC 1 Z9 1 U1 1 U2 2 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2016 AR 8524267 DI 10.1155/2016/8524267 PG 15 WC Cell Biology SC Cell Biology GA DB9SN UT WOS:000368857300001 ER PT J AU Simis, M Doruk, D Imamura, M Anghinah, R Morales-Quezada, L Fregni, F Battistella, LR AF Simis, Marcel Doruk, Deniz Imamura, Marta Anghinah, Renato Morales-Quezada, Leon Fregni, Felipe Battistella, Linamara Rizzo TI Neurophysiologic predictors of motor function in stroke SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Stroke; cerebrovascular disease; cortical excitability; plasticity; transcranial magnetic stimulation (TMS); quantitative electroencephalography (qEEG); motor recovery ID TRANSCRANIAL MAGNETIC STIMULATION; ISCHEMIC-STROKE; QUANTITATIVE EEG; UNAFFECTED HEMISPHERE; CORTEX DISINHIBITION; EVOKED-POTENTIALS; FOLLOW-UP; RECOVERY; REHABILITATION; REORGANIZATION AB Purpose: Understanding the neural mechanisms of stroke recovery is of paramount importance for neurorehabilitation. Methods: For this purpose, we analyzed several TMS and EEG variables and their association with motor recovery. Thirty-five subjects with chronic stroke were recruited. The neurophysiological examination included assessments by transcranial magnetic stimulation (TMS), intra-and inter-hemispheric EEG coherence in different frequency bands (e.g.alpha(8-13 Hz)) as determined by quantitative electroencephalography (qEEG). Motor function was measured by Fugl-Meyer (FM). Multiple univariate and multivariate linear regression analyses were performed to identify the predictors for FM. Results: Multivariate analyses, showed a significant interaction effect of motor threshold (MT) in the lesioned hemisphere and beta coherence in the unlesioned hemisphere. This interaction suggests that higher beta activity in the unlesioned hemisphere strengthens the negative association between MT and FM scores. Conclusions: Our results suggest that MT in the lesioned hemisphere is the strongest predictors of motor recovery after stroke. Moreover, cortical activity in the unlesioned hemisphere measured by qEEG provides additional information, specifying the association between MT and FM scores. Therefore, complementary application of EEG and TMS can help constitute a better model of the lesioned and the unlesioned hemispheres that supports the importance of bihemispheric activity in recovery. C1 [Simis, Marcel; Imamura, Marta; Anghinah, Renato; Fregni, Felipe; Battistella, Linamara Rizzo] Univ Sao Paulo, Sch Med, Gen Hosp, Phys & Rehabil Med Inst, BR-04116030 Sao Paulo, SP, Brazil. [Simis, Marcel; Doruk, Deniz; Morales-Quezada, Leon; Fregni, Felipe] Spaulding Rehabil Hosp, Neuromodulat Ctr, 79-96 13th St, Charlestown, MA 02129 USA. [Simis, Marcel; Doruk, Deniz; Morales-Quezada, Leon; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Simis, Marcel] Univ Sao Paulo, Sch Med, Clin Hosp, Inst Phys Med & Rehabil, St Domingo de Soto 100, BR-04116030 Sao Paulo, SP, Brazil. RP Fregni, F (reprint author), Spaulding Rehabil Hosp, Neuromodulat Ctr, 79-96 13th St, Charlestown, MA 02129 USA.; Simis, M (reprint author), Univ Sao Paulo, Sch Med, Clin Hosp, Inst Phys Med & Rehabil, St Domingo de Soto 100, BR-04116030 Sao Paulo, SP, Brazil. EM marcel.simis@hc.fm.usp.br; fregni.felipe@mgh.harvard.edu FU FAPESP Center for Neuromathematics (S.Paulo Research Foundation) [2013/ 07699-0]; NIH [5 R21 HD079048-02] FX This article was produced as part of the activities of FAPESP Center for Neuromathematics (grant #2013/ 07699-0, S.Paulo Research Foundation). The authors gratefully acknowledge NIH support (Support to Dr. Fregni - NIH grant 5 R21 HD079048-02). Authors are grateful to Artur Aquino dos Santos, Jessica Natuline Ianof, Denise Matheus, Mariana Vita Milazzotto, Gracinda Rodrigues Tsukimoto, Vivian Daniella Vicente, Denise Rodrigues Tsukimoto and Thais Tavares Terranova for assistance with data collection and study monitoring. NR 42 TC 0 Z9 0 U1 6 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 EI 1878-3627 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2016 VL 34 IS 1 BP 45 EP 54 DI 10.3233/RNN-150550 PG 10 WC Neurosciences SC Neurosciences & Neurology GA DB6NW UT WOS:000368632700004 ER PT J AU Dale, CL Brown, EG Fisher, M Herman, AB Dowling, AF Hinkley, LB Subramaniam, K Nagarajan, SS Vinogradov, S AF Dale, Corby L. Brown, Ethan G. Fisher, Melissa Herman, Alexander B. Dowling, Anne F. Hinkley, Leighton B. Subramaniam, Karuna Nagarajan, Srikantan S. Vinogradov, Sophia TI Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article ID REMEDIATION THERAPY; MAGNETIC-FIELDS; HUMAN-BRAIN; MEMORY; LOCALIZATION; PERFORMANCE; COMPONENT; DYNAMICS; DEFICITS; SPEECH AB Schizophrenia is characterized by dysfunction in basic auditory processing, as well as higher-order operations of verbal learning and executive functions. We investigated whether targeted cognitive training of auditory processing improves neural responses to speech stimuli, and how these changes relate to higher-order cognitive functions. Patients with schizophrenia performed an auditory syllable identification task during magnetoencephalography before and after 50 hours of either targeted cognitive training or a computer games control. Healthy comparison subjects were assessed at baseline and after a 10 week no-contact interval. Prior to training, patients N = 34) showed reduced M100 response in primary auditory cortex relative to healthy participants N = 13). At reassessment, only the targeted cognitive training patient group N = 18) exhibited increased M100 responses. Additionally, this group showed increased induced high gamma band activity within left dorsolateral prefrontal cortex immediately after stimulus presentation, and later in bilateral temporal cortices. Training-related changes in neural activity correlated with changes in executive function scores but not verbal learning and memory. These data suggest that computerized cognitive training that targets auditory and verbal learning operations enhances both sensory responses in auditory cortex as well as engagement of prefrontal regions, as indexed during an auditory processing task with low demands on working memory. This neural circuit enhancement is in turn associated with better executive function but not verbal memory. C1 [Dale, Corby L.; Herman, Alexander B.; Dowling, Anne F.; Hinkley, Leighton B.; Nagarajan, Srikantan S.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Dale, Corby L.; Fisher, Melissa; Subramaniam, Karuna; Vinogradov, Sophia] San Francisco VA Med Ctr, NCIRE, San Francisco, CA USA. [Brown, Ethan G.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Fisher, Melissa; Subramaniam, Karuna; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Herman, Alexander B.; Nagarajan, Srikantan S.] Univ Calif Berkeley, UC San Francisco Grad Program Bioengn, San Francisco, CA USA. RP Dale, CL (reprint author), Biomagnet Imaging Lab, Box 0628,513 Parnassus Ave,S362, San Francisco, CA 94143 USA. EM corby.dale@ucsf.edu FU National Institutes of Health [R01DC004855, R01DC010145, R21NS076171, R01MH068725]; Howard Hughes Medical Institute Research Fellowship program; San Francisco Department of Veterans' Affairs Medical Center FX National Institutes of Health (R01DC004855, R01DC010145, R21NS076171, R01MH068725); Howard Hughes Medical Institute Research Fellowship program (to E.G.B.); San Francisco Department of Veterans' Affairs Medical Center. The cognitive training software used in this study was supplied to the senior author free of charge by Posit Science Corporation. NR 41 TC 6 Z9 6 U1 5 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2016 VL 42 IS 1 BP 220 EP 228 DI 10.1093/schbul/sbv087 PG 9 WC Psychiatry SC Psychiatry GA DB6ML UT WOS:000368629000025 PM 26152668 ER PT J AU Daly, MC Patel, MS Bhatia, NN Bederman, SS AF Daly, Michael C. Patel, Madhukar S. Bhatia, Nitin N. Bederman, S. Samuel TI The Influence of Insurance Status on the Surgical Treatment of Acute Spinal Fractures SO SPINE LA English DT Article DE health disparities; health resource utilization; health services research; hierarchical logistic regression; insurance; National Trauma Data Bank; propensity score; spinal cord injury; spine fracture; spine surgery; trauma ID TRAUMA DATA-BANK; INJURY SEVERITY SCORE; CORD-INJURY; RACIAL DISPARITIES; UNINSURED ADULTS; UNITED-STATES; RISK-FACTORS; MORTALITY; CARE; CLASSIFICATION AB Study Design.A retrospective, propensity score, multivariate analysis of the National Trauma Data Bank (NTDB) between 2008 and2011.Objective.The aim of this study was to determine the relationship between insurance status and rates of surgery for acute spinal fractures with and without spinal cord injury (SCI).Summary of Background Data.The decision for surgery in patients with spinal fractures is often based on fracture pattern and stability, associated SCI, and the presence of ligamentous and other associated injuries. It is poorly understood how nonclinical factors, such as insurance status, influence the decision for surgical intervention in patients sustaining spinal trauma.Methods.Using NTDB admission years 2008 to 2011, we included patients 18 to 64 years old who sustained a fracture of the cervical or thoracolumbar spine. Patients were excluded if they sustained polytrauma (Injury Severity Score 27) or a major injury (Abbreviated Injury Scale severity 3) to the head, thorax, or abdomen. Our main outcome measure was surgical versus nonsurgical treatment for spinal injury; our main predictor was insurance status. Hierarchical multivariate regression analysis and propensity scores were used to determine the relationship between insurance status and surgical treatment, controlling for other factors. We calculated adjusted odds ratios (ORs) for rates of surgery.Results.Our propensity score multivariate analysis demonstrated significantly higher rates of surgery in patients with SCI (OR=11.76, P<0.001), insurance (OR=1.27, P<0.001), white (OR=1.21, P=0.018) versus black race, blunt trauma (OR=5.63, P<0.001), shock (OR=1.62, P<0.001), higher Glasgow Coma Scale (GCS) score (OR=1.02, P=0.002), transfer from lower acuity hospital (OR=1.51, P<0.001), and treatment at teaching hospitals (OR=1.49, P<0.001). Multivariable subgroup analysis of SCI patients similarly revealed higher surgical rates for insured patients (OR=1.46, P<0.001) than those without insurance.Conclusion.Patients with traumatic spine fractures were more likely to receive surgery if they were insured, regardless of the presence of SCI.Level of Evidence: 3 C1 [Daly, Michael C.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Combined Orthopaed Residency Program, Boston, MA 02114 USA. [Patel, Madhukar S.] Massachusetts Gen Hosp, Gen Surg Residency Training Program, Dept Gen Surg, Boston, MA USA. [Bhatia, Nitin N.; Bederman, S. Samuel] Univ Calif Irvine, Irvine Med Ctr, Dept Orthopaed Surg, Orange, CA 92668 USA. [Bederman, S. Samuel] Texas Back Inst, Scoliosis & Spine Tumor Ctr, Plano, TX 75093 USA. RP Bederman, SS (reprint author), Texas Back Inst, Scoliosis & Spine Tumor Ctr, 6020 W Parker Rd,Suite 200A, Plano, TX 75093 USA. EM sbederman@texasback.com NR 39 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JAN PY 2016 VL 41 IS 1 BP E37 EP E45 DI 10.1097/BRS.0000000000001177 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DB4UR UT WOS:000368509600012 PM 26555838 ER PT J AU Raugi, GJ Nelson, W Miethke, M Boyd, M Markham, C Dougall, B Bratten, D Comer, T AF Raugi, Gregory J. Nelson, William Miethke, Marion Boyd, Marvin Markham, Craig Dougall, Brittany Bratten, Dustin Comer, Tara TI Teledermatology Implementation in a VHA Secondary Treatment Facility Improves Access to Face-to-Face Care SO TELEMEDICINE AND E-HEALTH LA English DT Article DE dermatology; teledermatology; telehealth; telemedicine ID FORWARD TELEDERMATOLOGY; DERMATOLOGY AB Background:Teledermatology is a mainstream modality for delivering care in the Veterans Health Administration, especially in rural areas where access to traditional dermatology care is constrained. Previous investigations of the effect of teledermatology on improving patient access have focused largely on the metrics of visits avoided. However, the effect of teledermatology on improving patient access to face-to-face dermatology has not been well documented. The purpose of this study was to assess the impact of the implementation of store-and-forward teledermatology on access to face-to-face dermatology at the Mann-Grandstaff Spokane Veterans Administration (VA) Medical Center in Spokane, WA.Materials and Methods:Completed requests for dermatology and teledermatology consultation originating from the Spokane main facility from January 1, 2012 through June 30, 2013 were obtained from the Corporate Data Warehouse by SQL query. The numbers of consult requests and wait times for care for overall dermatology, face-to-face dermatology, and teledermatology were compared across the baseline, transition, and intervention periods.Results:Within 6 months of implementation, the total number of requests for dermatology services increased by 40%. Access to face-to-face dermatology care improved, with a decrease in the duration of the interval between consultation request and consultation completion from a mean of 64.2 days to 20.3 days; overall access to dermatology (teledermatology and face-to-face dermatology) care improved with a decrease in the duration of the same from a mean of 61.2 days to 10.3 days.Conclusions:Implementation of a teledermatology program at the Mann-Grandstaff Spokane VA Medical Center improved access to face-to-face dermatology care. C1 [Raugi, Gregory J.; Markham, Craig; Dougall, Brittany; Bratten, Dustin; Comer, Tara] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Raugi, Gregory J.] Univ Washington, Dept Med, Div Dermatol, Seattle, WA 98115 USA. [Nelson, William; Miethke, Marion; Boyd, Marvin] Spokane VA Med Ctr, Spokane, WA 99205 USA. RP Raugi, GJ (reprint author), Fed Off Bldg 909 1st Ave,Suite 630, Seattle, WA 98104 USA. EM gregory.raugi@va.gov NR 11 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JAN 1 PY 2016 VL 22 IS 1 BP 12 EP 17 DI 10.1089/tmj.2015.0036 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DB3YE UT WOS:000368448900003 PM 26393782 ER PT J AU Perkins, RB Handal-Orefice, R Hanchate, AD Lin, MY Paasche-Orlow, MK AF Perkins, Rebecca B. Handal-Orefice, Roxane Hanchate, Amresh D. Lin, Mengyun Paasche-Orlow, Michael K. TI Risk of Undetected Cancer at the Time of Laparoscopic Supracervical Hysterectomy and Laparoscopic Myomectomy: Implications for the Use of Power Morcellation SO WOMENS HEALTH ISSUES LA English DT Article ID INSUFFLATED ISOLATION BAG; ENDOMETRIAL STROMAL SARCOMA; UTERINE LEIOMYOSARCOMA; TUMOR MORCELLATION; CASE SERIES; SURGERY; OUTCOMES; IMPACT; WOMEN; PATHOLOGY AB Background: Power morcellation during gynecological procedures may cause seeding of undiagnosed cancers. We used a national database to determine the prevalence of malignant and premalignant conditions that were present but undetected at the time of laparoscopic supracervical hysterectomy and laparoscopic myomectomy, surgeries in which morcellation is commonly used. Methods: Data from 2007 to 2012 were obtained from MarketScan, an administrative database of diagnostic and treatment data for 55.7 million commercially insured women in the United States. Because power morcellation is not captured with billing codes, we limited our analysis to women undergoing procedures that typically use morcellation and that are contraindicated in the case of suspected malignancy to describe the rates at which undetected cancers occur, thus potentially putting patients at risk for seeding of malignant tissue. We defined the rate of preoperative endometrial biopsy and postoperative cancers and hyperplasia by manually reviewing inpatient and outpatient International Classification of Disease, 9th edition, and Current Procedural Terminology codes for all suspected cases. Results: In all, 17,903 women underwent laparoscopic supracervical hysterectomy and 1,603 underwent laparoscopic myomectomy. The rate of uterine cancer among women undergoing hysterectomy was 2.96 per 1000 and increased with age from 0 per 1,000 at age younger than 35 to 9.07 per 1,000 at ages 55 to 64 (p < .05 for age >= 45 compared with < 45). Preoperative endometrial biopsy was documented in 47% of women subsequently diagnosed with uterine cancer. The overall rate of malignant and premalignant gynecological conditions was 5.14 per 1,000 for laparoscopic supracervical hysterectomy and 1.87 per 1,000 for laparoscopic myomectomy. Conclusion: Approximately 1 in 350 women undergoing laparoscopic supracervical hysterectomy had an undiagnosed uterine cancer, with higher risks among older women. Approximately one-half of women had endometrial biopsies documented before hysterectomy. Safer alternatives, such as contained morcellation, should be evaluated to reduce the risk of complications after morcellation procedures. Copyright (C) 2016 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Perkins, Rebecca B.; Handal-Orefice, Roxane; Hanchate, Amresh D.; Lin, Mengyun; Paasche-Orlow, Michael K.] Boston Univ, Med Ctr, Sch Med, Boston, MA 02118 USA. [Hanchate, Amresh D.] VA Boston Healthcare Syst, Boston, MA USA. RP Perkins, RB (reprint author), 85 E Concord St,6th Floor, Boston, MA 02118 USA. EM rbperkin@bu.edu FU American Cancer Society Mentored Research Scholar Grant [MRSG-09-151-01] FX This study was funded by American Cancer Society Mentored Research Scholar Grant (MRSG-09-151-01). NR 41 TC 4 Z9 4 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2016 VL 26 IS 1 BP 21 EP 26 DI 10.1016/j.whi.2015.09.008 PG 6 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA DB1IS UT WOS:000368262500006 PM 26701205 ER PT J AU Kwon, I Bharmal, N Choi, S Araiza, D Moore, MR Trejo, L Sarkisian, CA AF Kwon, Ivy Bharmal, Nazleen Choi, Sarah Araiza, Daniel Moore, Mignon R. Trejo, Laura Sarkisian, Catherine A. TI Older Ethnic Minority Women's Perceptions of Stroke Prevention and Walking SO WOMENS HEALTH ISSUES LA English DT Article ID AMERICAN-HEART-ASSOCIATION; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; GENDER-DIFFERENCES; SEX-DIFFERENCES; RISK-FACTORS; HEALTH; EPIDEMIOLOGY; BARRIERS; BELIEFS AB Objective: To inform the development of a tailored behavioral stroke risk reduction intervention for ethnic minority seniors, we sought to explore gender differences in perceptions of stroke prevention and physical activity (walking). Methods: In collaboration with community-based organizations, we conducted 12 mixed-gender focus groups of African American, Latino, Chinese, and Korean seniors aged 60 years and older with a history of hypertension (89 women and 42 men). Transcripts were coded and recurring topics compared by gender. Results: Women expressed beliefs that differed from men in 4 topic areas: 1) stroke-related interest, 2) barriers to walking, 3) facilitators to walking, and 4) health behavior change attitudes. Compared with men, women were more interested in their role in response to a stroke and post-stroke care. Women described walking as an acceptable form of exercise, but cited neighborhood safety and pain as walking barriers. Fear of nursing home placement and weight loss were identified as walking facilitators. Women were more prone than men to express active/control attitudes toward health behavior change. Conclusions: Older ethnic minority women, a high-risk population for stroke, may be more receptive to behavioral interventions that address the gender-specific themes identified by this study. Published by Elsevier Inc. C1 [Kwon, Ivy; Araiza, Daniel; Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Bharmal, Nazleen] RAND Corp, Hlth Unit, Arlington, VA USA. [Choi, Sarah] Univ Calif Irvine, Coll Hlth Sci, Dept Nursing Sci, Irvine, CA USA. [Moore, Mignon R.] Univ Calif Los Angeles, Dept Sociol, Los Angeles, CA 90095 USA. [Trejo, Laura] City Los Angeles Dept Aging, Los Angeles, CA USA. [Sarkisian, Catherine A.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. RP Sarkisian, CA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, 10945 Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM csarkisian@mednet.ucla.edu OI Kwon, Ivy/0000-0003-4160-6546 FU National Institute of Neurological Disorders and Stroke [1U54NS081764]; National Institutes of Health Office of Research on Women's Health [1U54NS081764-03S1]; National Institute on Aging [1K24AG047899-01]; National Institute on Aging UCLA Older Americans Independence Center [P30AG028747]; National Institute on Aging Resource Centers for Minority Aging Research IV/Center for Health Improvement of Minority Elderly III [2P30AG021684] FX This work was supported by the National Institute of Neurological Disorders and Stroke [1U54NS081764]; National Institutes of Health Office of Research on Women's Health [1U54NS081764-03S1]; and the National Institute on Aging [1K24AG047899-01]. Additional sources of support for this project include the National Institute on Aging UCLA Older Americans Independence Center [P30AG028747] and National Institute on Aging Resource Centers for Minority Aging Research IV/Center for Health Improvement of Minority Elderly III [2P30AG021684]. No competing financial interests exist. NR 41 TC 0 Z9 0 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2016 VL 26 IS 1 BP 80 EP 86 DI 10.1016/j.whi.2015.08.003 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA DB1IS UT WOS:000368262500017 PM 26411494 ER PT J AU Kroll-Desrosiers, AR Crawford, SL Simas, TAM Rosen, AK Mattocks, KM AF Kroll-Desrosiers, Aimee R. Crawford, Sybil L. Simas, Tiffany A. Moore Rosen, Amy K. Mattocks, Kristin M. TI Improving Pregnancy Outcomes through Maternity Care Coordination: A Systematic Review SO WOMENS HEALTH ISSUES LA English DT Article ID LOW-BIRTH-WEIGHT; HUMAN-IMMUNODEFICIENCY-VIRUS; PRENATAL CASE-MANAGEMENT; PROGRAM; WOMEN; COLLABORATION; SERVICES; DELIVERY; DOSAGE; RATES AB Background: Care during pregnancy is multifaceted and often goes beyond traditional prenatal care from an obstetrical care provider. Coordinating care between multiple providers can be challenging, but is beneficial for providers and patients. Care coordination is associated with decreased costs, greater patient satisfaction, and a reduction in medical errors. To our knowledge, no previous review has examined maternity care coordination (MCC) programs and their association with pregnancy outcomes. Methods: Using a search algorithm comprised of relevant MCC terminology, studies were identified through a systematic search of PubMed, Scopus, ClinicalTrials.gov, and Google Scholar. Studies meeting eligibility criteria (e.g., defining the care coordination components and examining at least one quantitative outcome) were fully abstracted and quality rated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Main Findings: Thirty-three observational studies of MCC were included in this review. Quality scores ranged from 27% to 100%. Most studies included strategies with a team approach to decision making and/or individual case management. Social service referrals to outside organizations were also common. Twenty-seven studies reported infant birth weight as a main outcome; 12 found a significant improvement in birth weights among care coordination participants. Conclusions: Roughly one-third of the included studies reported improved birth weights among care coordination participants. However, it remains unknown what effect care coordination strategies have on patient and provider satisfaction in the prenatal care setting, two aspects of maternity care that may advance the quality and utilization of prenatal health services. Published by Elsevier Inc. C1 [Kroll-Desrosiers, Aimee R.; Mattocks, Kristin M.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01605 USA. [Crawford, Sybil L.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Simas, Tiffany A. Moore] Univ Massachusetts, Sch Med, UMass Mem Hlth Care, Dept Obstet & Gynecol, Worcester, MA 01605 USA. [Simas, Tiffany A. Moore] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01605 USA. [Rosen, Amy K.] Boston Univ, Sch Med, Boston VA Healthcare Syst, Dept Surg,CHOIR, Boston, MA 02118 USA. [Mattocks, Kristin M.] VA Cent Western Massachusetts, Res & Dev, Leeds, MA USA. RP Kroll-Desrosiers, AR (reprint author), Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, 368 Plantat St, Worcester, MA 01605 USA. EM aimee.kroll@umassmed.edu NR 52 TC 3 Z9 3 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2016 VL 26 IS 1 BP 87 EP 99 DI 10.1016/j.whi.2015.10.003 PG 13 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA DB1IS UT WOS:000368262500018 PM 26586143 ER PT J AU Kang, YJ Bi, WL Dubuc, AM Martineau, L Ligon, AH Berkowitz, AL Aizer, AA Lee, EQ Ligon, KL Ramkissoon, SH Dunn, IF AF Kang, Yun Jee Bi, Wenya Linda Dubuc, Adrian M. Martineau, Louine Ligon, Azra H. Berkowitz, Aaron L. Aizer, Ayal A. Lee, Eudocia Q. Ligon, Keith L. Ramkissoon, Shakti H. Dunn, Ian F. TI Integrated Genomic Characterization of a Pineal Parenchymal Tumor of Intermediate Differentiation SO WORLD NEUROSURGERY LA English DT Article DE Clinical management; Genomics; Pineal parenchymal tumor; Pineal tumor ID CENTRAL-NERVOUS-SYSTEM; GERM-CELL TUMORS; CONTEMPORARY MANAGEMENT; CYTOLOGIC PLEOMORPHISM; HISTOLOGICAL FEATURES; TUBEROUS SCLEROSIS; ADULT PATIENTS; GENE TSC1; CANCER; PINEOCYTOMA AB BACKGROUND: Pineal parenchymal tumors of intermediate differentiation (PPTIDs) are rare lesions. The differential diagnosis and management strategy for PPTIDs can be challenging because of the variable prognostic and pathologic characteristics of these tumors. METHODS: A 24-year-old man presented with progressive headaches, gait abnormalities, and abulia. Magnetic resonance imaging revealed a large T1-hypointense, T2-isointense, contrast-enhancing, partially cystic mass of the pineal and tectal region. Near-total resection was achieved in a 2-stage operation followed by focal and craniospinal irradiation and adjuvant chemotherapy. RESULTS: Immunohistochemical analysis including use of pineal lineage marker confirmed a diagnosis of PPTID. Targeted exome sequencing showed mutations in TSC1(L388P) and IKZF3(F206C), whereas high-resolution array cytogenetics revealed losses in chromosomes 2, 3, 4, 8, 10, 11, 17, and 20, leading to single-copy loss of PTEN and TP53. CONCLUSIONS: Pineal parenchymal tumors reflect a broad spectrum of malignancy potential and prognoses, which mandate better understanding of the disease mechanism for rational therapeutic strategies. We present a case of PPTID and report several mutations and chromosomal abnormalities previously unrecognized in this tumor subtype. Review of the literature highlights a need for surgical resection followed by adjuvant chemoradiation. Further investigation of these novel variants may improve understanding of the pathogenesis underlying pineal parenchymal tumors. C1 [Kang, Yun Jee; Ligon, Keith L.; Ramkissoon, Shakti H.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Lee, Eudocia Q.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Bi, Wenya Linda; Dunn, Ian F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Dubuc, Adrian M.; Ligon, Azra H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cytogenet,Dept Pathol, Boston, MA 02115 USA. [Berkowitz, Aaron L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Aizer, Ayal A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Ligon, Keith L.; Ramkissoon, Shakti H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Neuropathol,Dept Pathol, Boston, MA 02115 USA. [Martineau, Louine] Hop Univ Mirebalais, Mirebalais, Haiti. RP Dunn, IF (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. EM idunn@partners.org FU NINDS NIH HHS [K08 NS087118] NR 66 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD JAN PY 2016 VL 85 BP 96 EP 105 DI 10.1016/j.wneu.2015.07.032 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DB0WW UT WOS:000368229700020 PM 26226092 ER PT J AU Wu, WW Bi, WL Kang, YJ Ramkissoon, SH Prasad, S Shih, HA Reardon, DA Dunn, IF AF Wu, Winona W. Bi, Wenya Linda Kang, Yun Jee Ramkissoon, Shakti H. Prasad, Sashank Shih, Helen A. Reardon, David A. Dunn, Ian F. TI Adult Atypical Teratoid/Rhabdoid Tumors SO WORLD NEUROSURGERY LA English DT Article DE Atypical teratoid/rhabdoid tumor; Brain tumor; Clinical management; Genomics; Pineal tumor; Rhabdoid tumor ID MALIGNANT RHABDOID TUMOR; CENTRAL-NERVOUS-SYSTEM; ACTIN CYTOSKELETON ORGANIZATION; OF-THE-LITERATURE; A-CASE-REPORT; PLEOMORPHIC XANTHOASTROCYTOMA; YOUNG-ADULT; BRAIN; GLIOBLASTOMA; GLIOMA AB BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant neoplasms that rarely occur in adults. Due to the complex histology of AT/RTs, the differential diagnosis of these tumors is quite challenging and increasingly relies on demonstration of characteristic SMARCB1/INI1 inactivation in tumor cells. CASE DESCRIPTION: A 51-year-old man presented with diplopia, lethargy, and memory deficit owing to Parinaud syndrome and hydrocephalus. Magnetic resonance imaging revealed a T2-hyperintense and homogeneously enhancing tectal mass that extended to the pineal region. Initial biopsy suggested a World Health Organization grade II myxopapillary astrocytoma. However, subsequent definitive resection revealed an AT/RT, with loss of SMARCB1/INI1 observed through immunohistochemical staining as well as array cytogenetic analysis. Molecular profiling revealed additional mutations in RHPN2(L385I), MDM4(D396G), FLT3(V194M), and NPRL3(D53N). CONCLUSIONS: Pathologic diagnoses in the modern era increasingly integrate molecular data for confirmation as well as prognostication. We present a rare case of a tectal AT/RT in an adult patient and report several novel mutations previously unrecognized in this tumor subtype, in addition to canonical SMARCB1/INI1 loss. Further investigation of these novel variants may improve understanding of the pathogenesis underlying AT/RTs. C1 [Wu, Winona W.; Bi, Wenya Linda; Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Kang, Yun Jee; Ramkissoon, Shakti H.] Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA. [Prasad, Sashank] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Reardon, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Dunn, IF (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. EM idunn@partners.org FU NINDS NIH HHS [K08 NS087118] NR 62 TC 2 Z9 2 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD JAN PY 2016 VL 85 BP 197 EP 204 DI 10.1016/j.wneu.2015.08.076 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DB0WW UT WOS:000368229700033 PM 26344637 ER PT J AU Wilkinson, H AF Wilkinson, Harold TI Long Follow-Up of Radiosurgery for Brainstem Cavernoma SO WORLD NEUROSURGERY LA English DT Article DE Cavernous angioma; Late complications; Radiosurgery ID MALFORMATIONS AB BACKGROUND: There is a relative paucity of long-term follow-up of treatment of brainstem cavernous angiomas. This has led to uncertainty and a lack of consensus regarding optimum therapy, especially radiosurgery. METHODS: Report of a single case with a 24-year follow-up. RESULTS: This patient was minimally symptomatic before her radiosurgery procedure. She developed an acute complication, from which she incompletely recovered. Two decades later she has become more symptomatic, with new deficits, and magnetic resonance imagings disclose progressive brainstem atrophy. CONCLUSIONS: Long-term follow-up of patients treated with radiosurgery is important. C1 [Wilkinson, Harold] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Wilkinson, H (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM HrldAWlknsn@Verizon.net NR 4 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 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD JAN PY 2016 VL 85 AR UNSP 366.e5 DI 10.1016/j.wneu.2015.09.006 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DB0WW UT WOS:000368229700061 PM 26370289 ER PT J AU Bianchi, MT Goparaju, B Moro, M AF Bianchi, M. T. Goparaju, B. Moro, M. TI Sleep apnea in patients reporting insomnia or restless legs symptoms SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE ambulatory care; diagnosis; insomnia; polysomnography; restless legs; sleep disorders ID COMORBID INSOMNIA; BREATHING DISORDERS; NOCTURNAL OXIMETRY; HYPOPNEA SYNDROME; MEDICAL-CENTER; POLYSOMNOGRAPHY; ASSOCIATION; DIAGNOSIS; PREVALENCE; CHALLENGES AB Objective - Insomnia and restless legs syndrome (RLS) are defined by self-reported symptoms, and polysomnography (PSG) is not routinely indicated. Occult obstructive sleep apnea (OSA), common even in asymptomatic adults, may complicate management of patients presenting with insomnia or restless legs. To this end, we investigated objective sleep apnea metrics in a large retrospective cohort according to self-reported symptom profiles. Methods - We compared sleep apnea findings in patients referred to our center according to self-reported symptoms associated with insomnia, sleep apnea, and restless legs. The cohort included over 1900 adults who underwent diagnostic (n = 1418) or split-night (n = 504) PSGs and completed a symptom and medical history questionnaire. Results - More than 30% of patients who did not endorse any OSA symptoms, but did endorse insomnia or restless legs symptoms, were found to have OSA based on apnea-hypopnea index (AHI) > 5 during overnight laboratory testing. Regression models of the full cohort showed that the risk of OSA was related, as expected, to older age, male sex, elevated body mass index, and presence of OSA symptoms. The presence of insomnia symptoms did not alter the risk of OSA. The presence of restless legs symptoms showed a small odds ratio for lowered OSA risk. Conclusions - Objective evidence of OSA occurs similarly in those with insomnia or restless legs symptoms, even among those without self-reported OSA symptoms. Providers should be aware of the potential for occult OSA in populations with insomnia and restless legs, which may complicate their management in addition to presenting an independent medical risk itself. C1 [Bianchi, M. T.; Goparaju, B.; Moro, M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bianchi, M. T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang Neurol 7, 55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Milton Family Foundation; Center for Integration of Medicine and Innovative Technology; MGH-MIT Strategic Initiative's Grand Challenge; Servier FX MTB receives funding from the Department of Neurology, Massachusetts General Hospital, the Milton Family Foundation, the Center for Integration of Medicine and Innovative Technology, and MGH-MIT Strategic Initiative's Grand Challenge. MTB has a patent pending on a home sleep monitoring device, serves on the advisory board of Foramis, has provided expert testimony for sleep-related lawsuits, and has received travel funding from Servier. BG has no conflicts. MM has no conflicts. NR 40 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-6314 EI 1600-0404 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD JAN PY 2016 VL 133 IS 1 BP 61 EP 67 DI 10.1111/ane.12439 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DA9PH UT WOS:000368141300008 PM 25974333 ER PT J AU Goldstone, RN Austen, WG AF Goldstone, Robert N. Austen, William G., Jr. TI Commentary on: Human Adipose Tissue-Derived Stromal/Stem Cells Promote Migration and Early Metastasis of Head and Neck Cancer Xenografts SO AESTHETIC SURGERY JOURNAL LA English DT Editorial Material ID MESENCHYMAL STEM-CELLS; REGENERATIVE THERAPY; IN-VIVO; GROWTH C1 [Goldstone, Robert N.; Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Goldstone, Robert N.; Austen, William G., Jr.] Massachusetts Gen Hosp, Div Burn Surg, Boston, MA 02114 USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM wausten@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1090-820X EI 1527-330X J9 AESTHET SURG J JI Aesthet. Surg. J. PD JAN PY 2016 VL 36 IS 1 BP 105 EP 106 DI 10.1093/asj/sjv103 PG 2 WC Surgery SC Surgery GA DB2QY UT WOS:000368355300027 PM 26082093 ER PT J AU Powis, KM Smeaton, L Hughes, MD Tumbare, EA Souda, S Jao, J Wirth, KE Makhema, J Lockman, S Fawzi, W Essex, M Shapiro, RL AF Powis, Kathleen M. Smeaton, Laura Hughes, Michael D. Tumbare, Esther A. Souda, Sajini Jao, Jennifer Wirth, Kathleen E. Makhema, Joseph Lockman, Shahin Fawzi, Wafaie Essex, Max Shapiro, Roger L. TI In-utero triple antiretroviral exposure associated with decreased growth among HIV-exposed uninfected infants in Botswana SO AIDS LA English DT Article DE growth; HIV-exposed uninfected infants; in-utero triple antiretrovirals ID MIDDLE-INCOME COUNTRIES; SINGLE-DOSE NEVIRAPINE; CHILD UNDERNUTRITION; ANTIBACTERIAL ACTIVITY; ZIDOVUDINE; TRANSMISSION; MORTALITY; PROPHYLAXIS; PREGNANCY; THERAPY AB Objective:To assess associations between in-utero triple antiretrovirals (cART) versus zidovudine (ZDV) monotherapy exposure and growth among HIV-uninfected children of HIV-infected women in Botswana.Design:Secondary retrospective data analysis from two randomized intervention trials of mother-to-child HIV transmission prevention.Methods:The Mashi and Mma Bana studies enrolled HIV-infected pregnant women, following their children through 24 months of age. This analysis includes singleton, full-term, HIV-exposed uninfected children. Mothers received cART or ZDV at least 2 weeks predelivery, and breastfed up to 6 months. Weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) z-scores were derived. Mean z-scores were compared by exposure group at 24 months (t-test, linear regression).Results:Of 819 children, 303 were ZDV- and 516 cART-exposed in utero. Maternal median enrolment CD4(+) was higher among ZDV versus cART-treated mothers (393 versus 324cells/l; P<0.0001). Median duration of antepartum antiretroviral use was shorter among ZDV-treated women (5.7 versus 12.0 weeks; P<0.0001). Median months breastfed were similar (5.9 and 6.0; P=0.43). At 24 months, mean LAZ and WAZ were significantly lower among cART-exposed children (LAZ -1.01 versus -0.74; P=0.003) (WAZ -0.53 versus -0.30; P=0.002) in unadjusted analyses. Adjusting for maternal CD4(+), viral load, enrolment site and maternal anthropometric measures, cART-exposed children had significantly lower LAZ and WAZ at 24 months (P=0.0004 for both).Conclusion:At 24 months, in-utero cART-exposed children had significantly lower LAZ and WAZ. Poor growth impacts childhood and adult mortality. These findings raise concerns for potential lasting health impacts among HIV-exposed uninfected children with in-utero cART exposure. C1 [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Powis, Kathleen M.; Lockman, Shahin; Essex, Max; Shapiro, Roger L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Powis, Kathleen M.; Makhema, Joseph; Lockman, Shahin; Essex, Max; Shapiro, Roger L.] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Smeaton, Laura; Hughes, Michael D.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tumbare, Esther A.] Elizabeth Glaser Pediat AIDS Fdn, Harare, Zimbabwe. [Souda, Sajini] Univ Botswana, Fac Med, Gaborone, Botswana. [Jao, Jennifer] Icahn Sch Med Mt Sinai, Dept Obstet Gynecol & Reprod Sci, Div Infect Dis, New York, NY 10029 USA. [Jao, Jennifer] Icahn Sch Med Mt Sinai, Dept Obstet Gynecol & Reprod Sci, Div Gen Med, New York, NY 10029 USA. [Wirth, Kathleen E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lockman, Shahin] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Fawzi, Wafaie] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Fawzi, Wafaie] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fawzi, Wafaie] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Dept Infect Dis, Boston, MA 02215 USA. RP Powis, KM (reprint author), 125 Nashua St,Off 8426, Boston, MA 02114 USA. EM kpowis@mgh.harvard.edu FU Boehringer Ingelheim; Pfizer; Tibotec; Medicines Development; National Institute of Child Health and Human Development [1K23HD070774-01A1, 1K23HD070760-01A1]; National Institutes of Health, National Institute of Child Health and Human Development [R01 HD37793]; National Institute of Allergy and Infectious Diseases [U01-AI066454]; Brigham and Women's Global Women's Health Fellowship; Fogarty AITRP [D43 TW000004] FX M.H. has served as a paid Data Safety and Monitoring Board member for Boehringer Ingelheim, Pfizer, Tibotec and Medicines Development. L.S. served as a paid Data Monitoring Committee member for Pfizer.; K.M.P. received salary support from the National Institute of Child Health and Human Development (1K23HD070774-01A1). J.J. received salary support from the National Institute of Child Health and Human Development (1K23HD070760-01A1). The Mashi study was supported by a grant from the National Institutes of Health, National Institute of Child Health and Human Development (R01 HD37793). The Mma Bana study was supported by a grant from the National Institute of Allergy and Infectious Diseases (U01-AI066454). Funding support from Brigham and Women's Global Women's Health Fellowship supported K.P.'s salary during the Mma Bana study. The Fogarty AITRP grant (D43 TW000004) provided funding for A.O. and S.M. Mma Bana study drugs were provided by Abbott Pharmaceuticals, GlaxoSmithKline, and the government of Botswana. NR 21 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN PY 2016 VL 30 IS 2 BP 211 EP 220 DI 10.1097/QAD.0000000000000895 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DA7VL UT WOS:000368012800002 PM 26684818 ER PT J AU Gupta, V Rodrigues, R Nguyen, D Sauk, J Khalili, H Yajnik, V Ananthakrishnan, AN AF Gupta, V. Rodrigues, R. Nguyen, D. Sauk, J. Khalili, H. Yajnik, V. Ananthakrishnan, A. N. TI Adjuvant use of antibiotics with corticosteroids in inflammatory bowel disease exacerbations requiring hospitalisation: a retrospective cohort study and meta-analysis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SEVERE ULCERATIVE-COLITIS; CROHNS-DISEASE; UNITED-STATES; BIOLOGICAL THERAPY; CONTROLLED-TRIAL; ADJUNCT; RATES; TIME; GASTROENTEROLOGY; METRONIDAZOLE AB Background Patients hospitalised with an exacerbation of inflammatory bowel disease (IBD) often receive antibiotics in addition to intravenous steroids. However, their efficacy in this setting is unclear. Aim To ascertain if the addition of antibiotics to intravenous steroids modifies short and long-term clinical outcomes. Methods Our study included IBD patients hospitalised between 2009 and 2014 who received intravenous (IV) steroids with or without adjuvant antibiotics. Outcomes of interest included length of stay (LOS), need for medical and surgical rescue therapy during the hospitalisation, and at 90 and 365 days. A meta-analysis of previously published randomised trials was additionally performed. Results A total of 354 patients were included [145 ulcerative colitis (UC); 209 Crohn's disease (CD)]. In CD, combination of IV steroids and antibiotics did not change need for in-hospital medical rescue therapy, surgery or hospitalisations at 1 year but was associated with greater LOS (6.1 vs. 4.6 days, P = 0.02). In UC, patients receiving antibiotics were less likely to require in-hospital medical rescue therapy [odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.93] but experienced no statistically significant differences in LOS, in-hospital surgery, re-hospitalisations or surgery by 1 year. A meta-analysis of three relevant randomised trials demonstrated no difference in clinical improvement with antibiotics over placebo (OR: 1.08, 95% CI: 0.50-2.32). Conclusions The addition of antibiotics to intravenous steroids for treatment of IBD exacerbations was associated with a reduced need for in-hospital medical rescue therapy in ulcerative colitis without significant long-term benefit, and did not affect short-or long-term outcomes in Crohn's disease. C1 [Gupta, V.; Nguyen, D.; Sauk, J.; Khalili, H.; Yajnik, V.; Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rodrigues, R.] North Shore Community Hlth Ctr, Salem, MA USA. [Nguyen, D.; Sauk, J.; Khalili, H.; Yajnik, V.; Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Nguyen, D.; Sauk, J.; Khalili, H.; Yajnik, V.; Ananthakrishnan, A. N.] Harvard Univ, Sch Med, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 165 Cambridge St, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU National Institutes of Health [K23 DK097142]; American Gastroenterological Association (AGA); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; National Institutes of Health (NIH) [P30 DK043351] FX Ananthakrishnan was supported in part by a grant from the National Institutes of Health (K23 DK097142). Khalili was supported by a career development award from the American Gastroenterological Association (AGA) and by National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). This study was also supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. NR 30 TC 0 Z9 0 U1 0 U2 3 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 JAN PY 2016 VL 43 IS 1 BP 52 EP 60 DI 10.1111/apt.13454 PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA DB0HB UT WOS:000368188100005 PM 26541937 ER PT J AU Lee, MS Eum, KD Rodrigues, EG Magari, SR Fang, SC Modest, GA Christiani, DC AF Lee, Mi-Sun Eum, Ki-Do Rodrigues, Ema G. Magari, Shannon R. Fang, Shona C. Modest, Geoffrey A. Christiani, David C. TI Effects of Personal Exposure to Ambient Fine Particulate Matter on Acute Change in Nocturnal Heart Rate Variability in Subjects Without Overt Heart Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID AIR-POLLUTION; CARDIOVASCULAR-DISEASE; TIME-COURSE; INDIVIDUALS; ASSOCIATION; PARTICLES; STATEMENT; RESPONSES; PM2.5; RISK AB The immediate effect within minutes to hours of personal exposure to ambient fine particulate matter (PM2.5) on cardiac autonomic function is limited, particularly at night. Our study aimed to assess the lagged association between personal exposure to PM2.5 and nocturnal heart rate variability. Repeated measures panel study among 21 community adults recruited from a local health clinic during the period of March 1, 2004, to August 31, 2004, in Boston, Massachusetts, in the United States. Ambulatory electrocardiogram and continuous monitoring of personal exposure to PM2.5 and were measured for up to 2 consecutive days. We calculated 5-minute time-specific average PM2.5 exposure for each participant. Mixed-effects models were fit for 5-minute SD of normal-to-normal intervals (SDNN) and 5-minute heart rate in relation to 5minute PM2.5 exposure lagged in 5-minute intervals up to 4 hours. We found an 8.4% decrease in nocturnal SDNN (95% confidence interval [CI] - 11.3% to - 5.5%) and a 1.9% increase in nighttime heart rate (95% CI 1.1% to 2.7%) for an interquairtile range increase in PM2.5 (13.6 mu g/m(3)), after adjusting for confounders. Significant decreases in nocturnal SDNN associated with PM2.5 exposure occurred within 2.5 hours. The largest decrease in nocturnal SDNN of - 12.8% (95% CI -16.4 to - 9.1%) that was associated with PM2.5 exposure was found with a lag of 25 minutes. Rapid changes in nocturnal heart rate variability associated with personal PM2.5 exposure occurred within the previous 2.5 hours, with the largest effects at 25 minutes, suggesting immediate cardiac autonomic effects of fine particulate exposure. (c) 2016 Elsevier Inc. All rights reserved. C1 [Lee, Mi-Sun; Eum, Ki-Do; Rodrigues, Ema G.; Magari, Shannon R.; Fang, Shona C.; Christiani, David C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth Environm & Occupat Med, Boston, MA 02115 USA. [Lee, Mi-Sun; Eum, Ki-Do; Rodrigues, Ema G.; Magari, Shannon R.; Fang, Shona C.; Christiani, David C.] Harvard Univ, TH Chan Sch Publ Hlth, Program Epidemiol, Boston, MA 02115 USA. [Magari, Shannon R.] Colden Corp, New York, NY 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.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth Environm & Occupat Med, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU US. Environmental Protection Agency (EPA), Washington, DC [RD-83083801]; National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC [ES000002] FX This study was supported by the Science to Achieve Results (STAR) grant (#RD-83083801) from the US. Environmental Protection Agency (EPA), Washington, DC, and grant (ES000002) from National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC. NR 27 TC 4 Z9 4 U1 3 U2 10 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 JAN 1 PY 2016 VL 117 IS 1 BP 151 EP 156 DI 10.1016/j.amjcard.2015.10.015 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA8IS UT WOS:000368048900024 PM 26552502 ER PT J AU Fernandez, AC Amoyal, NR Paiva, AL Prochaska, JO AF Fernandez, Anne C. Amoyal, Nicole R. Paiva, Andrea L. Prochaska, James O. TI Motivation for HPV Vaccination Among Young Adult Men: Validation of TTM Decisional Balance and Self-Efficacy Constructs SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Human Papillomavirus; Transtheoretical Model; Decisional Balance; Self-Efficacy; Vaccine; Stage of Change; Prevention Research ID HUMAN-PAPILLOMAVIRUS INFECTION; POPULATION-BASED REAPPRAISAL; ANAL-CANAL CANCER; INTEGRATIVE MODEL; SCALE DEVELOPMENT; HEALTH-PROMOTION; UNITED-STATES; INTERVENTION; SMOKING; WOMEN AB Purpose. In the United States, 36% of human papillomavirus (HPV)-related cancers occur among men. HPV vaccination can substantially reduce the risk of HPV infection; however, the vast majority of men are unvaccinated. This study developed and validated transtheoretical model-based measures for HPV vaccination in young adult men. Design. Cross-sectional measurement development. Setting. Online survey of young adult men. Subjects. Three hundred twenty-nine mostly college-attending men, ages 18 to 26 Measures. Stage of change, decisional balance (pros/cons), and self-efficacy. Analysis. The sample was randomly split into halves for exploratory principal components analysis (PCA), followed by confirmatory factor analyses (CFA) to test measurement models. Multivariate analyses examined relationships between scales. Results. For decisional balance, PCA revealed two uncorrelated five-item factors (pros alpha = .78; cons alpha = .83). For the self-efficacy scale, PCA revealed a single-factor solution (alpha = .83). CFA confirmed that the two-factor uncorrelated model for decisional balance and a single-factor model for self-efficacy. Follow-up analyses of variance supported the theoretically predicted relationships between stage of change, pros, and self-efficacy. Conclusion. This study resulted in reliable and valid measures of pros and self-efficacy for HPV vaccination that can be used in future clinical research. C1 [Fernandez, Anne C.] Brown Univ, Dept Publ Hlth, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Amoyal, Nicole R.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Prochaska, James O.] Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. RP Fernandez, AC (reprint author), Brown Univ, Dept Publ Hlth, Ctr Alcohol & Addict Studies, Box G-S121-5, Providence, RI 02912 USA. EM anne_fernandez@brown.edu FU National Institute of Alcohol Abuse and Alcoholism at the National Institute of Health [T32 AA0007459] FX This research was supported in part by grant number T32 AA0007459 from the National Institute of Alcohol Abuse and Alcoholism at the National Institute of Health. NR 66 TC 1 Z9 1 U1 2 U2 9 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 EI 2168-6602 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JAN-FEB PY 2016 VL 30 IS 3 BP 163 EP 171 DI 10.4278/ajhp.131108-QUAN-570 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DA8JC UT WOS:000368049900005 PM 25806567 ER PT J AU Van Cott, EM Khor, B Zehnder, JL AF Van Cott, Elizabeth M. Khor, Bernard Zehnder, James L. TI Factor V Leiden SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACTIVATED PROTEIN-C; DEEP-VEIN THROMBOSIS; POOR ANTICOAGULANT RESPONSE; COAGULATION-FACTOR-V; HONG-KONG CHINESE; VENOUS THROMBOSIS; FUNCTIONAL-CHARACTERIZATION; MYOCARDIAL-INFARCTION; LABORATORY EVALUATION; RESISTANCE ASSAY AB Factor V Leiden (FVLeiden) is a common hereditary thrombophilia that causes activated protein C (APC) resistance. This review describes many of the most fascinating features of FVLeiden, including background features, mechanisms of hypercoagulability, the founder mutation concept, the "FVLeiden paradox," synergistic interaction with other thrombotic risk factors, the intertwined relationship between FVLeiden and APC resistance testing, and other, uncommon mutations implicated in causing APC resistance. In addition, there are several conditions where laboratory tests for APC resistance and FVLeiden are or can be discrepant, including lupus anticoagulants, anticoagulants such as direct thrombin inhibitors (dabigatran, argatroban, and bivalirudin) and rivaroxaban, as well as pseudohomozygous, pseudo-wildtype, liver transplant, and bone marrow transplant patients. The laboratory test error rate for FVLeiden is also presented.(c) 2015 Wiley Periodicals, Inc. C1 [Van Cott, Elizabeth M.; Khor, Bernard] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zehnder, James L.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. RP Van Cott, EM (reprint author), GRJ235 Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM evancott@mgh.harvard.edu NR 56 TC 2 Z9 2 U1 1 U2 10 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 JAN PY 2016 VL 91 IS 1 SI SI BP 46 EP 49 DI 10.1002/ajh.24222 PG 4 WC Hematology SC Hematology GA DA6PH UT WOS:000367926900008 PM 26492443 ER PT J AU Kekre, N Ho, VT AF Kekre, Natasha Ho, Vincent T. TI Allogeneic hematopoietic stem cell transplantation for myelofibrosis and chronic myelomonocytic leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID PROGNOSTIC SCORING SYSTEM; INTERNATIONAL WORKING GROUP; CORD BLOOD TRANSPLANTATION; ADVANCED POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; MARROW-TRANSPLANTATION; MYELOID METAPLASIA; SOCIETE FRANCAISE; EUROPEAN GROUP; THERAPIE CELLULAIRE AB The efficacy of hematopoietic stem cell transplantation (HSCT) is not well established in Philadelphia chromosome negative myeloproliferative neoplasms (Ph- MPNs). Without randomized prospective trials comparing HSCT to non-HSCT options or comparing HSCT regimens, physicians must rely on prognostic scoring systems and clinical experience when making decisions about who and when to transplant patients with Ph- MPNs. These patients are vulnerable to hepatic toxicity and graft failure after HSCT because of their increased likelihood of portal hypertension, massive splenomegaly, and extensive bone marrow fibrosis related to their disease. In this review, we aim to outline the indications and modalities of HSCT as they pertain to the Ph- MPNs and CMML based on the currently available evidence. We will further highlight the challenges of HSCT in these diseases, including but not limited to the incorporation of JAK inhibitors into HSCT for myelofibrosis. (c) 2015 Wiley Periodicals, Inc. C1 [Kekre, Natasha; Ho, Vincent T.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. RP Ho, VT (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM Vincent_ho@dfci.harvard.edu NR 66 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2016 VL 91 IS 1 SI SI BP 123 EP 130 DI 10.1002/ajh.24215 PG 8 WC Hematology SC Hematology GA DA6PH UT WOS:000367926900017 PM 26453238 ER PT J AU Blosnich, JR Nasuti, LJ Mays, VM Cochran, SD AF Blosnich, John R. Nasuti, Laura J. Mays, Vickie M. Cochran, Susan D. TI Suicidality and Sexual Orientation: Characteristics of Symptom Severity, Disclosure, and Timing Across the Life Course SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article DE mental disorders; gay; lesbian; bisexual; sexual minority; suicide ID NATIONAL COMORBIDITY SURVEY; WORLD-HEALTH-ORGANIZATION; MENTAL-HEALTH; RISK-FACTORS; PSYCHOLOGICAL DISTRESS; REPRESENTATIVE SAMPLE; BISEXUAL POPULATIONS; GENERAL-POPULATION; UNITED-STATES; SUBSTANCE USE AB This investigation explored suicide-related characteristics and help-seeking behavior by sexual orientation. Population-based data are from the California Quality of Life Surveys, which included 1,478 sexual minority (lesbian, gay, bisexual, and homosexually experienced individuals) and 3,465 heterosexual individuals. Bisexual women had a nearly six-fold increased risk of lifetime suicide attempts than heterosexual women (RR = 5.88, 95%CI: 3.89-8.90), and homosexually experienced men had almost 7 times higher risk of lifetime suicide attempts than heterosexual men (RR = 6.93, 95%CI: 3.65-13.15). Sexual minority men and women were more likely than heterosexual men and women to have disclosed suicide attempts to a medical professional (RR = 1.48 and RR = 1.44, respectively). Among persons who ever attempted suicide, sexual minority women had a younger age of index attempt than heterosexual women (15.9 vs. 19.6 years of age, respectively). Healthcare professionals should be aware of suicidal risk heterogeneity among sexual minority individuals, including vulnerable points of risk and evidenced-based treatments. C1 [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15260 USA. [Nasuti, Laura J.; Cochran, Susan D.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Mays, Vickie M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. [Mays, Vickie M.; Cochran, Susan D.] Univ Calif Los Angeles, Ctr Bridging Res Innovat Training & Educ Minor Hl, Los Angeles, CA 90024 USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151-CU,Bldg 30, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov FU NIDA NIH HHS [R01 DA020826, R01 DA015539]; NIMHD NIH HHS [P60 MD000508]; VA [VA999999] NR 62 TC 0 Z9 0 U1 3 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0002-9432 EI 1939-0025 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD JAN PY 2016 VL 86 IS 1 BP 69 EP 78 DI 10.1037/ort0000112 PG 10 WC Psychiatry; Social Work SC Psychiatry; Social Work GA DA9HQ UT WOS:000368120000007 PM 26752446 ER PT J AU Austin, LA Osseiran, S Evans, CL AF Austin, Lauren A. Osseiran, Sam Evans, Conor L. TI Raman technologies in cancer diagnostics SO ANALYST LA English DT Review ID BASAL-CELL CARCINOMA; IN-VIVO DIAGNOSIS; BACKGROUND SUBTRACTION ALGORITHM; INVASIVE DUCTAL CARCINOMA; BREAST-CANCER; SCATTERING MICROSCOPY; LABEL-FREE; SILVER ELECTRODE; BRAIN-TISSUE; SPECTROSCOPIC CHARACTERIZATION AB Despite significant effort, cancer still remains a leading cause of death worldwide. In order to reduce its burden, the development and improvement of noninvasive strategies for early detection and diagnosis of cancer are urgently needed. Raman spectroscopy, an optical technique that relies on inelastic light scattering arising from molecular vibrations, is one such strategy, as it can noninvasively probe cancerous markers using only endogenous contrast. In this review, spontaneous, coherent and surface enhanced Raman spectroscopies and imaging, as well as the fundamental principles governing the successful use of these techniques, are discussed. Methods for spectral data analysis are also highlighted. Utilization of the discussed Raman techniques for the detection and diagnosis of cancer in vitro, ex vivo and in vivo is described. The review concludes with a discussion of the future directions of Raman technologies, with particular emphasis on their clinical translation. C1 [Austin, Lauren A.; Osseiran, Sam; Evans, Conor L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Charlestown, MA 02129 USA. [Osseiran, Sam] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Evans, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 149 13th St, Charlestown, MA 02129 USA. EM Evans.Conor@mgh.harvard.edu FU Ludwig Center at Harvard Award FX The authors would like to thank the financial support of the 2015 Ludwig Center at Harvard Award. The authors would also like to thank Dr Hequn (Tracy) Wang for her helpful suggestions and edits. NR 193 TC 10 Z9 10 U1 18 U2 72 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 EI 1364-5528 J9 ANALYST JI Analyst PY 2016 VL 141 IS 2 BP 476 EP 503 DI 10.1039/c5an01786f PG 28 WC Chemistry, Analytical SC Chemistry GA DB0GB UT WOS:000368185500011 PM 26539569 ER PT J AU Gonorazky, H Liang, MG Cummings, B Lek, M Micallef, J Hawkins, C Basran, R Cohn, R Wilson, MD MacArthur, D Marshall, CR Ray, PN Dowling, JJ AF Gonorazky, Hernan Liang, Minggao Cummings, Beryl Lek, Monkol Micallef, Johann Hawkins, Cynthia Basran, Raveen Cohn, Ronald Wilson, Michael D. MacArthur, Daniel Marshall, Christian R. Ray, Peter N. Dowling, James J. TI RNAseq analysis for the diagnosis of muscular dystrophy SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article ID DISEASES; EXOME; GENE; SITE AB The precise genetic cause remains elusive in nearly 50% of patients with presumed neurogenetic disease, representing a significant barrier for clinical care. This is despite significant advances in clinical genetic diagnostics, including the application of whole-exome sequencing and next-generation sequencing-based gene panels. In this study, we identify a deep intronic mutation in the DMD gene in a patient with muscular dystrophy using both conventional and RNAseq-based transcriptome analyses. The implications of our data are that noncoding mutations likely comprise an important source of unresolved genetic disease and that RNAseq is a powerful platform for detecting such mutations. C1 [Gonorazky, Hernan; Dowling, James J.] Hosp Sick Children, Div Neurol, Toronto, ON M5G A04, Canada. [Gonorazky, Hernan; Liang, Minggao; Micallef, Johann; Cohn, Ronald; Wilson, Michael D.; Ray, Peter N.; Dowling, James J.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G A04, Canada. [Gonorazky, Hernan; Cohn, Ronald; Dowling, James J.] Univ Toronto, Dept Paediat, Toronto, ON M5G AO4, Canada. [Liang, Minggao; Cohn, Ronald; Wilson, Michael D.; Ray, Peter N.; Dowling, James J.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G AO4, Canada. [Cummings, Beryl; Lek, Monkol; MacArthur, Daniel] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Cummings, Beryl; Lek, Monkol; MacArthur, Daniel] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Cummings, Beryl; Lek, Monkol; MacArthur, Daniel] MIT, Cambridge, MA 02139 USA. [Hawkins, Cynthia; Basran, Raveen; Marshall, Christian R.; Ray, Peter N.] Hosp Sick Children, Pediat Lab Med, Toronto, ON M5G A04, Canada. RP Dowling, JJ (reprint author), 686 Bay St, Toronto, ON M5G 0A4, Canada. EM james.dowling@sickkids.ca OI Wilson, Michael/0000-0002-4015-3066 NR 20 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD JAN PY 2016 VL 3 IS 1 BP 55 EP 60 DI 10.1002/acn3.267 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA8VE UT WOS:000368083700006 PM 26783550 ER PT J AU Milling, TJ Refaai, MA Goldstein, JN Schneider, A Omert, L Harman, A Lee, ML Sarode, R AF Milling, Truman J., Jr. Refaai, Majed A. Goldstein, Joshua N. Schneider, Astrid Omert, Laurel Harman, Amy Lee, Martin L. Sarode, Ravi TI Thromboembolic Events After Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate: Exploratory Analyses of Two Randomized, Plasma-Controlled Studies SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID WARFARIN; ANTICOAGULATION; GUIDELINES; SAFETY; THROMBOSIS AB Study objective: We evaluated thromboembolic events after vitamin K antagonist reversal in post hoc analyses of pooled data from 2 randomized trials comparing 4-factor prothrombin complex concentrate (4F-PCC) (Beriplex/Kcentra) with plasma. Methods: Unblinded investigators identified thromboembolic events, using standardized terms (such as "myocardial infarction," "deep vein thrombosis," "pulmonary embolism," and "ischemic stroke"). A blinded safety adjudication board reviewed serious thromboembolic events, as well as those referred by an independent unblinded data and safety monitoring board. We descriptively compared thromboembolic event and patient characteristics between treatment groups and included detailed patient-level outcome descriptions. We did not power the trials to assess safety. Results: We enrolled 388 patients (4F-PCC: n=191; plasma: n=197) in the trials. Thromboembolic events occurred in 14 of 191 patients (7.3%) in the 4F-PCC group and 14 of 197 (7.1%) in the plasma group (risk difference 0.2%; 95% confidence interval 5.5% to 6.0%). Investigators reported serious thromboembolic events in 16 patients (4F-PCC: n=8; plasma: n=8); the data and safety monitoring board referred 2 additional myocardial ischemia events (plasma group) to the safety adjudication board for review. The safety adjudication board judged serious thromboembolic events in 10 patients (4F-PCC: n=4; plasma: n=6) as possibly treatment related. There were 8 vascular thromboembolic events in the 4F-PCC group versus 4 in the plasma group, and 1 versus 6 cardiac events, respectively. Among patients with thromboembolic events, 3 deaths occurred in each treatment group. All-cause mortality for the pooled population was 13 per group. We observed no relationship between thromboembolic event occurrence and factor levels transiently above the upper limit of normal; there were no notable differences in median factor or proteins C and S levels up to 24 hours postinfusion start in patients with and without thromboembolic events. Conclusion: The incidence of thromboembolic events after vitamin K antagonist reversal with 4F-PCC or plasma was similar and independent of coagulation factor levels; small differences in the number of thromboembolic event subtypes were observed between treatment groups. C1 [Milling, Truman J., Jr.] Univ Med Ctr Brackenridge, Dell Childrens Med Ctr, Seton UT Southwestern Clin Res Inst Austin, Austin, TX 78701 USA. [Refaai, Majed A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schneider, Astrid] CSL Behring GmbH, Marburg, Germany. [Omert, Laurel; Harman, Amy] CSL Behring LLC, King Of Prussia, PA USA. [Lee, Martin L.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Sarode, Ravi] UT Southwestern Med Ctr, Dallas, TX USA. RP Milling, TJ (reprint author), Univ Med Ctr Brackenridge, Dell Childrens Med Ctr, Seton UT Southwestern Clin Res Inst Austin, Austin, TX 78701 USA. EM tmilling@seton.org RI Goldstein, Joshua/H-8953-2016 FU CSL Behring FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The studies were sponsored by CSL Behring. Preparation and review of the article, as well as the decision to submit the article for publication, were performed by a publication steering committee that included academic medical experts and representatives of the sponsor. Medical writing assistance was funded by the sponsor. Drs. Milling and Refaai have received consulting fees and serve on the speakers' bureau for CSL Behring. Dr. Goldstein has received consulting fees and research funding from CSL Behring. Drs. Schneider and Omert and Ms. Harman are employees of CSL Behring. Dr. Lee has received consulting fees from CSL Behring. Dr. Sarode has received consulting fees and honoraria from CSL Behring. NR 20 TC 18 Z9 18 U1 2 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 2016 VL 67 IS 1 BP 96 EP 105 DI 10.1016/j.annemergmed.2015.04.036 PG 10 WC Emergency Medicine SC Emergency Medicine GA DA8HS UT WOS:000368046300021 PM 26094105 ER PT J AU Weingart, SD Trueger, S Wong, N Singh, N Rudolph, SS AF Weingart, Scott D. Trueger, Seth Wong, Nelson Singh, Neil Rudolph, Soren S. TI Delayed Sequence Intubation: Danger in Delaying Definitive Airway? Reply SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter ID PREOXYGENATION C1 [Weingart, Scott D.] Stony Brook Med, Div Emergency Crit Care, Stony Brook, NY 11794 USA. [Trueger, Seth] Univ Chicago, Sect Emergency Med, Chicago, IL 60637 USA. [Wong, Nelson] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Singh, Neil] Montefiore Hosp, Dept Emergency Med, New York, NY USA. [Rudolph, Soren S.] Rigshosp, Dept Anesthesia, DK-2100 Copenhagen, Denmark. RP Weingart, SD (reprint author), Stony Brook Med, Div Emergency Crit Care, Stony Brook, NY 11794 USA. NR 6 TC 1 Z9 1 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 2016 VL 67 IS 1 BP 144 EP 145 DI 10.1016/j.annemergmed.2015.08.013 PG 2 WC Emergency Medicine SC Emergency Medicine GA DA8HS UT WOS:000368046300035 PM 26707527 ER PT J AU Raggi, D Miceli, R Sonpavde, G Giannatempo, P Mariani, L Galsky, MD Bellmunt, J Necchi, A AF Raggi, D. Miceli, R. Sonpavde, G. Giannatempo, P. Mariani, L. Galsky, M. D. Bellmunt, J. Necchi, A. TI Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis SO ANNALS OF ONCOLOGY LA English DT Review DE urothelial carcinoma; chemotherapy; salvage therapy; single-agent chemotherapy; combination chemotherapy ID TRANSITIONAL-CELL CARCINOMA; PHASE-II TRIAL; COOPERATIVE-ONCOLOGY-GROUP; CISPLATIN-BASED CHEMOTHERAPY; PLATINUM-CONTAINING REGIMEN; BLADDER-CANCER; WEEKLY PACLITAXEL; PRETREATED PATIENTS; ORAL CYCLOPHOSPHAMIDE; GEMCITABINE AB The efficacy and safety of a combination of chemotherapeutic agent compared with single-agent chemotherapy in the second-line setting of advanced urothelial carcinoma (UC) are unclear. We aimed to study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced UC. Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after platinum-based chemotherapy. Random-effects models were used to pool trial-level data according to treatment arm, including median progression-free survival (PFS), overall survival (OS), objective response rate (ORR) probability, and grade 3-4 toxicity. Univariable and multivariable analyses, including sensitivity analyses, were carried out, adjusting for the percent of patients with ECOG performance status >= 1 and hepatic metastases. Forty-six arms of trials including 1910 patients were selected: 22 arms with single agent (n = 1202) and 24 arms with doublets (n = 708). The pooled ORR with single agents was 14.2% [95% confidence interval (CI) 11.1-17.9] versus 31.9% [95% CI 27.3-36.9] with doublet chemotherapy. Pooled median PFS was 2.69 and 4.05 months, respectively. The pooled median OS was 6.98 and 8.50 months, respectively. Multivariably, the odds ratio for ORR and the pooled median difference of PFS were statistically significant (P < 0.001 and P = 0.002) whereas the median difference in OS was not (P = 0.284). When including single-agent vinflunine or taxanes only, differences were significant only for ORR (P < 0.001) favoring doublet chemotherapy. No statistically significant differences in grade 3-4 toxicity were seen between the two groups. Despite significant improvements in ORR and PFS, doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC. Prospective trials are necessary to elucidate the role of combination chemotherapy, with or without targeted agents, in the salvage setting. Currently, improvements in this field should be pursued considering single-agent chemotherapy as the foundation for new more active combinations. C1 [Raggi, D.; Miceli, R.; Giannatempo, P.; Mariani, L.; Necchi, A.] Fdn IRCCS Ist Nazl Tumori, I-20133 Milan, Italy. [Sonpavde, G.] UAB, Ctr Comprehens Canc, Birmingham, AL USA. [Galsky, M. D.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Bellmunt, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellmunt, J.] Harvard Univ, Sch Med, Boston, MA USA. RP Necchi, A (reprint author), Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via G Venezian 1, I-20133 Milan, Italy. EM andrea.necchi@istitutotumori.mi.it RI Miceli, Rosalba/C-1215-2017; Mariani, Luigi/C-2580-2017; OI Miceli, Rosalba/0000-0003-0954-375X; Mariani, Luigi/0000-0001-6208-4084; Necchi, Andrea/0000-0002-3007-2756 NR 59 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2016 VL 27 IS 1 BP 49 EP 61 DI 10.1093/annonc/mdv509 PG 13 WC Oncology SC Oncology GA DB2QR UT WOS:000368354600006 PM 26487582 ER PT J AU Li, BT Drilon, A Johnson, ML Hsu, M Sima, CS McGinn, C Sugita, H Kris, MG Azzoli, CG AF Li, B. T. Drilon, A. Johnson, M. L. Hsu, M. Sima, C. S. McGinn, C. Sugita, H. Kris, M. G. Azzoli, C. G. TI A prospective study of total plasma cell-free DNA as a predictive biomarker for response to systemic therapy in patients with advanced non-small-cell lung cancers SO ANNALS OF ONCOLOGY LA English DT Article DE plasma cell-free DNA; non-small-cell lung cancer; chemotherapy; biomarker ID CIRCULATING TUMOR DNA; NONINVASIVE DETECTION; NECROTIC CELLS; QUANTIFICATION; CHEMOTHERAPY; GEFITINIB; ADENOCARCINOMA; GENERATION; MUTATIONS; ORIGIN AB While previous studies have reported on the prognostic value of total plasma cell-free deoxyribonucleic acid (cfDNA) in lung cancers, few have prospectively evaluated its predictive value for systemic therapy response. We conducted a prospective study to evaluate the association between changes in total cfDNA and radiologic response to systemic therapy in patients with stage IIIB/IV non-small-cell lung cancers (NSCLCs). Paired blood collections for cfDNA and computed tomography (CT) assessments by RECIST v1.0 were performed at baseline and 6-12 weeks after therapy initiation. Total cfDNA levels were measured in plasma using quantitative real-time polymerase chain reaction. Associations between changes in cfDNA and radiologic response, progression-free survival (PFS), and overall survival (OS) were measured using Kruskal-Wallis and Kaplan-Meier estimates. A total of 103 patients completed paired cfDNA and CT response assessments. Systemic therapy administered included cytotoxic chemotherapy in 57% (59/103), molecularly targeted therapy in 17% (17/103), and combination therapy in 26% (27/103). Median change in cfDNA from baseline to response assessment did not significantly differ by radiologic response categories of progression of disease, stable disease and partial response (P = 0.10). However, using radiologic response as continuous variable, there was a weak positive correlation between change in radiologic response and change in cfDNA (Spearman's correlation coefficient 0.21, P = 0.03). Baseline cfDNA levels were not associated with PFS [hazard ratio (HR) = 1.06, 95% confidence interval (CI) 0.93-1.20, P = 0.41] or OS (HR = 1.04, 95% CI 0.93-1.17, P = 0.51), neither were changes in cfDNA. In this large prospective study, changes in total cfDNA over time did not significantly predict radiologic response from systemic therapy in patients with advanced NSCLC. Pretreatment levels of total cfDNA were not prognostic of survival. Total cfDNA level is not a highly specific predictive biomarker and future investigations in cfDNA should focus on tumor-specific genomic alterations using expanded capabilities of next-generation sequencing. C1 [Li, B. T.; Drilon, A.; Johnson, M. L.; McGinn, C.; Kris, M. G.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, Thorac Oncol Serv, New York, NY 10065 USA. [Li, B. T.; Drilon, A.; Johnson, M. L.; McGinn, C.; Kris, M. G.] Weill Cornell Med Coll, New York, NY USA. [Li, B. T.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Hsu, M.; Sima, C. S.] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10065 USA. [Sugita, H.] Univ So Calif, Keck Sch Med, Dept Biochem, Los Angeles, CA 90033 USA. [Azzoli, C. G.] Massachusetts Gen Hosp, Ctr Canc, Thorac Oncol Program, Boston, MA USA. RP Kris, MG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, Thorac Oncol Serv, 300 East 66th St,12th Floor, New York, NY 10065 USA. EM krism@mskcc.org OI Li, Bob/0000-0001-6661-8733 FU NCI NIH HHS [P30 CA008748, R01-CA092315-02] NR 32 TC 8 Z9 8 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2016 VL 27 IS 1 BP 154 EP 159 DI 10.1093/annonc/mdv498 PG 6 WC Oncology SC Oncology GA DB2QR UT WOS:000368354600018 PM 26487589 ER PT J AU Cooper, Z Koritsanszky, LA Cauley, CE Frydman, JL Bernacki, RE Mosenthal, AC Gawande, AA Block, SD AF Cooper, Zara Koritsanszky, Luca A. Cauley, Christy E. Frydman, Julia L. Bernacki, Rachelle E. Mosenthal, Anne C. Gawande, Atul A. Block, Susan D. TI Recommendations for Best Communication Practices to Facilitate Goal-concordant Care for Seriously Ill Older Patients With Emergency Surgical Conditions SO ANNALS OF SURGERY LA English DT Article DE acute emergencies; older adults; palliative care; serious illness; surgeon-patient communication ID SHARED DECISION-MAKING; HIGH-RISK PATIENTS; QUALITY-OF-LIFE; INTENSIVE-CARE; TREATMENT PREFERENCES; ELDERLY-PATIENTS; FAMILY-MEMBERS; UNIT PATIENTS; BUY-IN; END AB Objective:To address the need for improved communication practices to facilitate goal-concordant care in seriously ill, older patients with surgical emergencies.Summary Background Data:Improved communication is increasingly recognized as a central element in providing goal-concordant care and reducing health care utilization and costs among seriously ill older patients. Given high rates of surgery in the last weeks of life, high risk of poor outcomes after emergency operations in these patients, and barriers to quality communication in the acute setting, we sought to create a framework to support surgeons in communicating with seriously ill, older patients with surgical emergencies.Methods:An interdisciplinary panel of 23 national leaders was convened for a 1-day conference at Harvard Medical School to provide input on concept, content, format, and usability of a communication framework. A prototype framework was created.Results:Participants supported the concept of a structured approach to communication in these scenarios, and delineated 9 key elements of a framework: (1) formulating prognosis, (2) creating a personal connection, (3) disclosing information regarding the acute problem in the context of the underlying illness, (4) establishing a shared understanding of the patient's condition, (5) allowing silence and dealing with emotion, (6) describing surgical and palliative treatment options, (7) eliciting patient's goals and priorities, (8) making a treatment recommendation, and (9) affirming ongoing support for the patient and family.Conclusions:Communication with seriously ill patients in the acute setting is difficult. The proposed communication framework may assist surgeons in delivering goal-concordant care for high-risk patients. C1 [Cooper, Zara; Koritsanszky, Luca A.; Cauley, Christy E.; Bernacki, Rachelle E.; Gawande, Atul A.; Block, Susan D.] Ariadne Labs, Boston, MA USA. [Cooper, Zara; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Cooper, Zara] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Cauley, Christy E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Frydman, Julia L.] Harvard Univ, Sch Med, Boston, MA USA. [Bernacki, Rachelle E.; Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Mosenthal, Anne C.] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ USA. [Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Block, Susan D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Cooper, Z (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM zcooper@partners.org FU Joint Center for Health System Innovation, Brigham and Women's Hospital FX Sources of support: Joint Center for Health System Innovation, Brigham and Women's Hospital. NR 43 TC 8 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2016 VL 263 IS 1 BP 1 EP 6 DI 10.1097/SLA.0000000000001491 PG 6 WC Surgery SC Surgery GA DA7SN UT WOS:000368004500002 PM 26649587 ER PT J AU Lawson, EH Louie, R Zingmond, DS Sacks, GD Brook, RH Hall, BL Ko, CY AF Lawson, Elise H. Louie, Rachel Zingmond, David S. Sacks, Greg D. Brook, Robert H. Hall, Bruce Lee Ko, Clifford Y. TI Using Both Clinical Registry and Administrative Claims Data to Measure Risk-adjusted Surgical Outcomes SO ANNALS OF SURGERY LA English DT Article DE ACS-NSQIP; administrative claims; clinical registry; quality measure; surgery ID QUALITY IMPROVEMENT PROGRAM; POSTOPERATIVE ADVERSE EVENTS; AMERICAN-COLLEGE; VALIDITY; CARE AB Objective:To examine the validity of hybrid quality measures that use both clinical registry and administrative claims data, capitalizing on the strengths of each data source.Background:Previous studies demonstrate substantial disagreement between clinical registry and administrative claims data on the occurrence of postoperative complications. Clinical data have greater validity than claims data for quality measurement but can be burdensome for hospitals to collect.Methods:American College of Surgeons National Surgical Quality Improvement Program records were linked to Medicare inpatient claims (2005-2008). National Quality Forum-endorsed risk-adjusted measures of 30-day postoperative complications or death assessed hospital quality for patients undergoing colectomy, lower extremity bypass, or all surgical procedures. Measures use hierarchical multivariable logistic regression to identify statistical outliers. Measures were applied using clinical data, claims data, or a hybrid of both data sources. Kappa statistics assessed agreement on determinations of hospital quality.Results:A total of 111,984 patients participated from 206 hospitals. Agreement on hospital quality between clinical and claims data was poor. Hybrid models using claims data to risk-adjust complications identified by clinical data had moderate agreement with all clinical data models, whereas hybrid models using clinical data to risk-adjust complications identified by claims data had routinely poor agreement with all clinical data models.Conclusions:Assessments of hospital quality differ substantially when using clinical registry versus administrative claims data. A hybrid approach using claims data for risk adjustment and clinical data for complications may be a valid alternative with lower data collection burden. For quality measures focused on postoperative complications to be meaningful, such policies should require, at a minimum, collection of clinical outcomes data. C1 [Lawson, Elise H.; Sacks, Greg D.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Lawson, Elise H.; Hall, Bruce Lee; Ko, Clifford Y.] Amer Coll Surgeons, Div Res & Optimal Patient Care, Chicago, IL USA. [Lawson, Elise H.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Louie, Rachel; Zingmond, David S.; Brook, Robert H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Brook, Robert H.] RAND Corp, Santa Monica, CA USA. [Brook, Robert H.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Hall, Bruce Lee] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Hall, Bruce Lee] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Hall, Bruce Lee] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce Lee] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Hall, Bruce Lee] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Hall, Bruce Lee] BJC Healthcare, St Louis, MO USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave 72-215 CHS, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu FU VA Health Services Research and Development program [RWJ 65-020]; American College of Surgeons (ACS) through the Robert Wood Johnson Foundation Clinical Scholars Program; Centers for Medicare & Medicaid Services FX E.H.L.'s time was supported by the VA Health Services Research and Development program (RWJ 65-020) and the American College of Surgeons (ACS) through the Robert Wood Johnson Foundation Clinical Scholars Program. R.L., D.S.Z., and B.L.H. are consultants for the ACS, and C.Y.K. is staff at the ACS. Supported by a contract from the Centers for Medicare & Medicaid Services. The remaining authors declare no conflicts of interest. NR 17 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2016 VL 263 IS 1 BP 50 EP 57 DI 10.1097/SLA.0000000000001031 PG 8 WC Surgery SC Surgery GA DA7SN UT WOS:000368004500011 PM 25405553 ER PT J AU Adsay, V Mino-Kenudson, M Furukawa, T Basturk, O Zamboni, G Marchegiani, G Bassi, C Salvia, R Malleo, G Paiella, S Wolfgang, CL Matthaei, H Offerhaus, GJ Adham, M Bruno, MJ Reid, MD Krasinskas, A Kloppel, G Ohike, N Tajiri, T Jang, KT Roa, JC Allen, P Fernandez-del Castillo, C Jang, JY Klimstra, DS Hruban, RH AF Adsay, Volkan Mino-Kenudson, Mari Furukawa, Toru Basturk, Olca Zamboni, Giuseppe Marchegiani, Giovanni Bassi, Claudio Salvia, Roberto Malleo, Giuseppe Paiella, Salvatore Wolfgang, Christopher L. Matthaei, Hanno Offerhaus, G. Johan Adham, Mustapha Bruno, Marco J. Reid, Michelle D. Krasinskas, Alyssa Kloeppel, Guenter Ohike, Nobuyuki Tajiri, Takuma Jang, Kee-Taek Roa, Juan Carlos Allen, Peter Fernandez-del Castillo, Carlos Jang, Jin-Young Klimstra, David S. Hruban, Ralph H. CA Verona Consensus Meeting TI Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract Recommendations of Verona Consensus Meeting SO ANNALS OF SURGERY LA English DT Article DE intraductal; IPMN; mucinous; neoplasm; pancreas; papillary ID FINE-NEEDLE-ASPIRATION; MULTIFOCAL/MULTICENTRIC BREAST-CARCINOMA; IMPORTANT PROGNOSTIC-FACTOR; INVASIVE DUCTAL CARCINOMA; LYMPH-NODE METASTASIS; LONG-TERM SURVIVAL; CLINICOPATHOLOGICAL FEATURES; CYSTIC NEOPLASMS; MARGIN STATUS; EXTRAPANCREATIC MALIGNANCIES AB Background:There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs).Design:An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations.Results:(1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term minimally invasive should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; 0.5, >0.5-1, >1cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of indeterminate/(suspicious) for invasion is acceptable for rare cases. (6) The term malignant IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic).Conclusions:These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms. C1 [Adsay, Volkan; Reid, Michelle D.; Krasinskas, Alyssa] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Furukawa, Toru] Tokyo Womens Med Univ, Dept Pathol, Tokyo, Japan. [Basturk, Olca; Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Zamboni, Giuseppe] Univ Verona, Dept Pathol, I-37100 Verona, Italy. [Marchegiani, Giovanni] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bassi, Claudio; Salvia, Roberto; Malleo, Giuseppe; Paiella, Salvatore] Univ Verona, Dept Surg, I-37100 Verona, Italy. [Wolfgang, Christopher L.] Johns Hopkins Univ, Sch Med, Dept Surg, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Matthaei, Hanno] Univ Bonn, Dept Surg, Bonn, Germany. [Offerhaus, G. Johan] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands. [Adham, Mustapha] Hop Edouard Herriot, Dept Surg, HCL, Lyon, France. [Bruno, Marco J.] Erasmus Univ, Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands. [Kloeppel, Guenter] Tech Univ Munich, Dept Pathol, D-80290 Munich, Germany. [Ohike, Nobuyuki] Showa Univ, Fujigaoka Hosp, Dept Pathol, Yokohama, Kanagawa 227, Japan. [Tajiri, Takuma] Tokai Univ, Dept Pathol, Hachioji Hosp, Tokyo 151, Japan. [Jang, Kee-Taek] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea. [Roa, Juan Carlos] Pontificia Univ Catolica Chile, Dept Pathol, Santiago, Chile. [Allen, Peter] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Jang, Jin-Young] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea. [Hruban, Ralph H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. RP Adsay, V (reprint author), Emory Univ, Anat Pathol, 1364 Clifton Rd NE,Room H-180B, Atlanta, GA 30322 USA. EM volkan.adsay@emory.edu RI Adham, Mustapha/A-1270-2017 FU Department of Health [PB-PG-0407-13363]; NCI NIH HHS [P30 CA008748, P50 CA062924] NR 226 TC 17 Z9 17 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2016 VL 263 IS 1 BP 162 EP 177 DI 10.1097/SLA.0000000000001173 PG 16 WC Surgery SC Surgery GA DA7SN UT WOS:000368004500027 PM 25775066 ER PT J AU D'Agostino, RS Jacobs, JP Badhwar, V Paone, G Rankin, JS Han, JM McDonald, D Shahian, DM AF D'Agostino, Richard S. Jacobs, Jeffrey P. Badhwar, Vinay Paone, Gaetano Rankin, J. Scott Han, Jane M. McDonald, Donna Shahian, David M. TI The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2016 Update on Outcomes and Quality SO ANNALS OF THORACIC SURGERY LA English DT Article ID MEASUREMENT TASK-FORCE; BYPASS-GRAFTING SURGERY; NATIONAL DATABASE; COMPOSITE MEASURE; MORTALITY; FAILURE; RESCUE; IMPROVEMENT; COMMITTEE; MEDICARE AB The Society of Thoracic Surgeons Adult Cardiac Database is one of the longest-standing, largest, and most highly regarded clinical data registries in health care. It serves as the foundation for all quality measurement and improvement activities of The Society of Thoracic Surgeons. This report summarizes current aggregate national outcomes in adult cardiac surgery and reviews database-related activities in the areas of quality measurement and performance improvement. (C) 2016 by The Society of Thoracic Surgeons C1 [D'Agostino, Richard S.] Lahey Hosp & Med Ctr, Dept Thorac & Cardiovasc Surg, Burlington, MA 01805 USA. Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. Johns Hopkins All Childrens Heart Inst, St Petersburg, FL USA. All Childrens Hosp, Tampa, FL USA. Florida Hosp Children, Orlando, FL USA. Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA. Henry Ford Hosp, Div Cardiac Surg, Detroit, MI 48202 USA. Cardiothorac Surg Associates, Nashville, TN USA. Soc Thorac Surg, Chicago, IL USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP D'Agostino, RS (reprint author), Lahey Hosp & Med Ctr, Dept Thorac & Cardiovasc Surg, 41 Mall Rd, Burlington, MA 01805 USA. EM richard.s.d'agostino@lahey.org NR 27 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2016 VL 101 IS 1 BP 24 EP 32 DI 10.1016/j.athoracsur.2015.11.032 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DB0FP UT WOS:000368184300014 PM 26616408 ER PT J AU Jacobs, JP Shahian, DM He, X O'Brien, SM Badhwar, V Cleveland, JC Furnary, AP Magee, MJ Kurlansky, PA Rankin, JS Welke, KF Filardo, G Dokholyan, RS Peterson, ED Brennan, JM Han, JM McDonald, D Schmitz, D Edwards, FH Prager, RL Grover, FL AF Jacobs, Jeffrey P. Shahian, David M. He, Xia O'Brien, Sean M. Badhwar, Vinay Cleveland, Joseph C., Jr. Furnary, Anthony P. Magee, Mitchell J. Kurlansky, Paul A. Rankin, J. Scott Welke, Karl F. Filardo, Giovanni Dokholyan, Rachel S. Peterson, Eric D. Brennan, J. Matthew Han, Jane M. McDonald, Donna Schmitz, DeLaine Edwards, Fred H. Prager, Richard L. Grover, Frederick L. TI Penetration, Completeness, and Representativeness of The Society of Thoracic Surgeons Adult Cardiac Surgery Database SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-28, 2015 CL San Diego, CA SP Soc Thorac Surg ID MEASUREMENT TASK-FORCE; SOCIAL-SECURITY DATA; SUCCESSFUL LINKING; COMPOSITE SCORE; SURVIVAL; EXAMINE AB Background. The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) has been successfully linked to the Centers for Medicare and Medicaid (CMS) Medicare database, thereby facilitating comparative effectiveness research and providing information about long-term follow-up and cost. The present study uses this link to determine contemporary completeness, penetration, and representativeness of the STS ACSD. Methods. Using variables common to both STS and CMS databases, STS operations were linked to CMS data for all CMS coronary artery bypass graft (CABG) surgery hospitalizations discharged between 2000 and 2012, inclusive. For each CMS CABG hospitalization, it was determined whether a matching STS record existed. Results. Center-level penetration (number of CMS sites with at least one matched STS participant divided by the total number of CMS CABG sites) increased from 45% in 2000 to 90% in 2012. In 2012, 973 of 1,081 CMS CABG sites (90%) were linked to an STS site. Patient-level penetration (number of CMS CABG hospitalizations done at STS sites divided by the total number of CMS CABG hospitalizations) increased from 51% in 2000 to 94% in 2012. In 2012, 71,634 of 76,072 CMS CABG hospitalizations (94%) occurred at an STS site. Completeness of case inclusion at STS sites (number of CMS CABG cases at STS sites linked to STS records divided by the total number of CMS CABG cases at STS sites) increased from 88% in 2000 to 98% in 2012. In 2012, 69,213 of 70,932 CMS CABG hospitalizations at STS sites (98%) were linked to an STS record. Conclusions. Linkage of STS and CMS databases demonstrates high and increasing penetration and completeness of the STS database. Linking STS and CMS data facilitates studying long-term outcomes and costs of cardiothoracic surgery. (C) 2016 by The Society of Thoracic Surgeons C1 [Jacobs, Jeffrey P.] Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. [Jacobs, Jeffrey P.] John Hopkins All Childrens Heart Inst, Div Cardiovasc Surg, Dept Surg, St Petersburg, FL 33701 USA. [Jacobs, Jeffrey P.] All Childrens Hosp, Tampa, FL USA. [Jacobs, Jeffrey P.] Florida Hosp Children, Orlando, FL USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [He, Xia; O'Brien, Sean M.; Dokholyan, Rachel S.; Peterson, Eric D.; Brennan, J. Matthew] Duke Univ, DCRI, Durham, NC USA. [Badhwar, Vinay] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Cleveland, Joseph C., Jr.; Grover, Frederick L.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Furnary, Anthony P.] Starr Wood Cardiac Grp, Portland, OR USA. [Magee, Mitchell J.] Baylor Univ, Med Ctr, Med City Dallas Hosp, Dallas, TX USA. [Kurlansky, Paul A.] Columbia Univ, New York, NY USA. [Rankin, J. Scott] Vanderbilt Univ, Nashville, TN 37235 USA. [Welke, Karl F.] Univ Illinois, Coll Med, Childrens Hosp Illinois, Sect Congenital Cardiovasc Surg, Peoria, IL 61656 USA. [Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. [Han, Jane M.; McDonald, Donna; Schmitz, DeLaine] Soc Thorac Surg, Chicago, IL USA. [Edwards, Fred H.] Univ Florida, Coll Med, Jacksonville, FL USA. [Prager, Richard L.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Jacobs, JP (reprint author), John Hopkins All Childrens Heart Inst, Div Cardiovasc Surg, 601 Fifth St S, St Petersburg, FL 33701 USA. EM jeffjacobs@msn.com NR 15 TC 8 Z9 8 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2016 VL 101 IS 1 BP 33 EP 41 DI 10.1016/j.athoracsur.2015.08.055 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DB0FP UT WOS:000368184300015 PM 26542437 ER PT J AU Feins, EN Yeh, DD Bhatt, AB Stefanescu, A Youniss, MA Ghoshhajra, BB Inglessis-Azuaje, I Liberthson, RR MacGillivray, TE AF Feins, Eric N. Yeh, Doreen DeFaria Bhatt, Ami B. Stefanescu, Ada Youniss, Mohamed A. Ghoshhajra, Brian B. Inglessis-Azuaje, Ignacio Liberthson, Richard R. MacGillivray, Thomas E. TI Anomalous Aortic Origin of a Coronary Artery: Surgical Repair With Anatomic- and Function-Based Follow-Up SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-28, 2015 CL San Diego, CA SP Soc Thorac Surg ID SUDDEN CARDIAC DEATH; OPPOSITE SINUS; YOUNG-ADULTS; VALSALVA; DIAGNOSIS AB Background. Anomalous aortic origin of the coronary artery (AAOCA) with an interarterial (IAC) course is an uncommon congenital anomaly. Surgical indications and repair techniques have evolved. We have managed 259 adult patients with AAOCA over 40 years. Our management strategy includes anatomic-and function-based surveillance to select surgical candidates. We reviewed our surgical cohort and analyzed anatomic and functional outcomes. Methods. We queried our heart center databases to obtain the names of all patients with AAOCA managed at our institution between 1974 and 2014. We performed a retrospective chart review. Results. Two hundred fifty-nine patients were managed for AAOCA. Sixty-one underwent surgical intervention. Twenty-six with associated coronary atherosclerosis were excluded. Thirty-one who underwent surgical repair were analyzed. Mean age was 42.5 +/- 2.7 years. Twenty-four patients (77.4%) had right AAOCA. Six (19.4%) had left AAOCA. One (3.2%) had bilateral coronary anomalies. Repair techniques included 21 unroofing procedures (67.7%), 6 translocations (19.4%), and 4 coronary artery bypass grafting (CABG) procedures (12.9%). Mean follow-up was 3.8 +/- 0.8 years. Thirteen patients underwent follow-up anatomic testing with computed tomography. Twelve of these patients had widely patent coronary arteries, and 1 patient had mild coronary artery stenosis. Seventeen patients underwent functional testing. Fifteen of these patients had no evidence of ischemia. One patient had reversible ischemia after CABG, and 1 had subclinical ischemia after unroofing. There was 1 late mortality from endocarditis. Conclusions. Our multidisciplinary program uses a treatment algorithm to select patients with AAOCA for surgical intervention. Only a small subset requires an operation, and we favor unroofing and translocation techniques. With this paradigm, outcomes are excellent, as validated with anatomic- and function-based testing. (C) 2016 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP MacGillivray, TE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Cox 650, Boston, MA 02114 USA. EM tmacgillivray@partners.org OI Stefanescu Schmidt, Ada/0000-0002-5692-2616 NR 25 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2016 VL 101 IS 1 BP 169 EP 176 DI 10.1016/j.athoracsur.2015.07.003 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DB0FP UT WOS:000368184300033 PM 26428691 ER PT J AU Robich, MP Flagg, A Lapar, DJ Odell, DD Stein, W Aftab, M Berfield, KS Eilers, AL Groth, SS Lazar, JF Shah, AA Smith, DA Stephens, EH Stock, CT DeNino, WF Tchantchaleishvili, V Soltesz, EG AF Robich, Michael P. Flagg, Andrew LaPar, Damien J. Odell, David D. Stein, William Aftab, Muhammad Berfield, Kathleen S. Eilers, Amanda L. Groth, Shawn S. Lazar, John F. Shah, Asad A. Smith, Danielle A. Stephens, Elizabeth H. Stock, Cameron T. DeNino, Walter F. Tchantchaleishvili, Vakhtang Soltesz, Edward G. TI Understanding Why Residents May Inaccurately Log Their Role in Operations: A Look at the 2013 In-Training Examination Survey SO ANNALS OF THORACIC SURGERY LA English DT Article ID CARDIOTHORACIC RESIDENTS; FUTURE; EDUCATION AB Background. With increased time and quality pressures, it may be more difficult for residents in cardiothoracic surgery residency programs to get independent operative experience. That may lead residents to inaccurately report their role as "surgeon" to meet American Board of Thoracic Surgery (ABTS) case requirements. Methods. The 2013 In-Training Examination surveyed 312 cardiothoracic surgery residents and was used to contrast residents in traditional 2-year and 3-year cardiothoracic surgery residencies (traditional, n = 216) with those in 6-year integrated or 3+4-year programs (integrated, n = 96). Results. Traditional program residents reported a higher percentage of cases that met the ABTS criteria of surgeon than did integrated program residents (p = 0.05) but were less likely to meet requirements if all cases were logged accurately (p = 0.03). The majority of residents in each program believed that their case log accurately reflected their experience as "surgeon." Residents who tended to log cases incorrectly had lower self-reported 2012 In-Training Examination percentiles, were less likely to meet case requirements if logged properly, and felt less prepared for board examinations and eventual practice compared with residents who logged cases correctly (all p < 0.001). Residents who believed they would not meet case requirements if logged correctly cited limited surgical opportunities, poor case diversity, and a compromised training environment but not the 80-hour work week, excessive simulation, or disproportionate number of complex cases as causes. Conclusions. Overall cardiothoracic surgery residents appear to be satisfied with their training. There were specific subsets of trainees in both traditional and Integrated programs that are misrepresenting their role on cases because they otherwise may not meet the requirements. (C) 2016 by The Society of Thoracic Surgeons C1 Cleveland Clin, Dept Thorac & Cardiovasc Surg, Inst Heart & Vasc, Cleveland, OH 44195 USA. Univ Virginia, Charlottesville, VA USA. Univ Pittsburgh, Pittsburgh, PA USA. Emory Univ, Atlanta, GA 30322 USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas San Antonio, San Antonio, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Pinnacle Hlth CardioVasc Inst, Wormleysburg, PA USA. Duke Univ, Med Ctr, Durham, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Columbia Univ, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Soltesz, EG (reprint author), Cleveland Clin, Dept Thorac & Cardiovasc Surg, 9500 Euclid Ave,Desk J4-1, Cleveland, OH 44195 USA. EM soltese@ccf.org NR 13 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2016 VL 101 IS 1 BP 323 EP 328 DI 10.1016/j.athoracsur.2015.07.047 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DB0FP UT WOS:000368184300055 PM 26453419 ER PT J AU Peterson, AL McGuire, JF Wilhelm, S Piacentini, J Woods, DW Walkup, JT Hatch, JP Villarreal, R Scahill, L AF Peterson, Alan L. McGuire, Joseph F. Wilhelm, Sabine Piacentini, John Woods, Douglas W. Walkup, John T. Hatch, John P. Villarreal, Robert Scahill, Lawrence TI An Empirical Examination of Symptom Substitution Associated With Behavior Therapy for burette's Disorder SO BEHAVIOR THERAPY LA English DT Article DE Tourette's disorder; chronic tic disorder; behavior therapy; symptom substitution; comprehensive behavioral intervention for tics ID RANDOMIZED CONTROLLED-TRIAL; SYNDROME IMPACT SURVEY; CHRONIC TIC DISORDERS; TOURETTE-SYNDROME; HABIT REVERSAL; FUNCTIONAL IMPAIRMENT; INTERVIEW SCHEDULE; PARENT VERSIONS; BULIMIA-NERVOSA; SEVERITY-SCALE AB Over the past six decades, behavior therapy has been a major contributor to the development of evidence-based psychotherapy treatments. However, a long-standing concern with behavior therapy among many nonbehavioral clinicians has been the potential risk for symptom substitution. Few studies have been conducted to evaluate symptom substitution in response to behavioral treatments, largely due to measurement and definitional challenges associated with treated psychiatric symptoms. Given the overt motor and vocal tics associated with Tourette's disorder, it presents an excellent opportunity to empirically evaluate the potential risk for symptom substitution associated with behavior therapy. The present study examined the possible presence of symptom substitution using four methods: (a) the onset of new tic symptoms, (b) the occurrence of adverse events, (c) change in tic medications, and (d) worsening of co-occurring psychiatric symptoms. Two hundred twenty-eight participants with Tourette's disorder or persistent motor or vocal tic disorders were randomly assigned to receive behavioral therapy or supportive therapy for tics. Both therapies consisted of eight sessions over 10 weeks. Results indicated that participants treated with behavior therapy were not more likely to have an onset of new tic symptoms, experience adverse events, increase tic medications, or have an exacerbation in co-occurring psychiatric symptoms relative to participants treated with supportive therapy. Further analysis suggested that the emergence of new tics was attributed with the normal waxing and waning nature of Tourette's disorder. Findings provide empirical support to counter the long-standing concern of symptom substitution in response to behavior therapy for individuals with Tourette's disorder. C1 [Peterson, Alan L.; Hatch, John P.; Villarreal, Robert] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Peterson, Alan L.] South Texas Vet Hlth Care Syst, Houston, TX USA. [Peterson, Alan L.] Univ Texas San Antonio, San Antonio, TX USA. [McGuire, Joseph F.; Piacentini, John] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA 90024 USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Woods, Douglas W.] Texas A&M Univ, College Stn, TX 77843 USA. [Walkup, John T.] Weill Cornell Med Coll, New York, NY USA. [Scahill, Lawrence] Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Peterson, AL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7550 IH 10 West,Suite 1325, San Antonio, TX 78229 USA. EM petersona3@uthscsa.edu FU National Institute of Mental Health (NIMH) [R01MH070802, R01MH069874, RO1MH069875, 5R01MH069877] FX This research was supported by National Institute of Mental Health (NIMH) Grants R01MH070802 (Dr. Piacentini), R01MH069874 (Dr. Scahill), RO1MH069875 (Dr. Peterson), and 5R01MH069877 (Dr. Wilhelm) from the NIMH with subcontracts to Drs. Walkup and Woods. The funding agency played no role in the study design; collection, analysis, or interpretation of data; the writing of this article; or the decision to submit the article for publication. NR 56 TC 0 Z9 1 U1 4 U2 6 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 JAN PY 2016 VL 47 IS 1 BP 29 EP 41 PG 13 WC Psychology, Clinical SC Psychology GA DB2CF UT WOS:000368315200003 PM 26763495 ER PT J AU Dedert, EA Resick, PA McFall, ME Dennis, PA Olsen, M Beckham, JC AF Dedert, Eric A. Resick, Patricia A. McFall, Miles E. Dennis, Paul A. Olsen, Maren Beckham, Jean C. TI Pilot Cases of Combined Cognitive Processing Therapy and Smoking Cessation for Smokers With Posttraumatic Stress Disorder SO BEHAVIOR THERAPY LA English DT Article DE tobacco use cessation; posttraumatic stress disorder; cognitive therapy; comorbidity; psychotherapy ID CIGARETTE-SMOKING; CONTROLLED-TRIAL; BECK DEPRESSION; CLINICAL-TRIAL; VETERANS; PTSD; INVENTORY; SURVIVORS; SYMPTOMS; OUTCOMES AB Posttraumatic stress disorder (PTSD) and smoking are often comorbid, and both problems are in need of improved access to evidence-based treatment. The combined approach could address two high-priority problems and increase patient access to both treatments, but research is needed to determine whether this is feasible and has promise for addressing both PTSD and smoking. We collected data from 15 test cases that received a treatment combining two evidence-based treatments: cognitive processing therapy cognitive version (CPT-C) for PTSD and integrated care for smoking cessation (ICSC). We explored two combined treatment protocols including a brief (six-session) CPT-C with five follow-up in-person sessions focused on smoking cessation (n = 9) and a full 12-session CPT-C protocol with ICSC (n = 6). The combined interventions were feasible and acceptable to patients with PTSD making a quit attempt. Initial positive benefits of the combined treatments were observed. The six-session dose of CPT-C and smoking cessation resulted in 6-month bioverified smoking abstinence in two of nine participants, with clinically meaningful PTSD symptom reduction in three of nine participants. In the second cohort (full CPT-C and smoking treatment), both smoking and PTSD symptoms were improved, with three of six participants abstinent from smoking and four of six participants reporting clinically meaningful reduction in PTSD symptoms. Results suggested that individuals with PTSD who smoke are willing to engage in concurrent treatment of these problems and that combined treatment is feasible. C1 [Dedert, Eric A.; Dennis, Paul A.; Beckham, Jean C.] Durham Vet Affairs Med Ctr, 508 Fulton St,Bldg 16,2nd Floor, Durham, NC 27705 USA. [Dedert, Eric A.; Beckham, Jean C.] Vet Affairs Midatlantic Reg Mental Illness Res Ed, Durham, NC USA. [Dedert, Eric A.; Resick, Patricia A.; Dennis, Paul A.; Beckham, Jean C.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [McFall, Miles E.] VA Puget Sound Hlth Care Syst, Seattle Div, New York, NY USA. [McFall, Miles E.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Olsen, Maren] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Olsen, Maren] Duke Univ, Sch Med, Durham, NC 27706 USA. RP Dedert, EA (reprint author), Durham Vet Affairs Med Ctr, 508 Fulton St,Bldg 16,2nd Floor, Durham, NC 27705 USA. EM eric.dedert@duke.edu FU CSRAMP;D Research AMP; Development Service of the VA Office of Research and Development [1IK2CX000718] FX The authors thank all of the veterans who volunteered to participate in this study. The views expressed in this paper are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the U.S. government. The project described was supported by Award Number 1IK2CX000718 to Dr. Dedert from the CSR&D Research & Development Service of the VA Office of Research and Development. NR 39 TC 0 Z9 0 U1 4 U2 7 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 JAN PY 2016 VL 47 IS 1 BP 54 EP 65 PG 12 WC Psychology, Clinical SC Psychology GA DB2CF UT WOS:000368315200005 PM 26763497 ER PT J AU Wisco, BE Baker, AS Sloan, DM AF Wisco, Blair E. Baker, Aaron S. Sloan, Denise M. TI Mechanisms of Change in Written Exposure Treatment of Posttraumatic Stress Disorder SO BEHAVIOR THERAPY LA English DT Article DE exposure; emotional processing theory; PTSD; psychophysiology; written exposure treatment ID PROLONGED EXPOSURE; HEART-RATE; VIETNAM VETERANS; FEAR ACTIVATION; CLINICAL-TRIAL; PTSD; THERAPY; IMAGERY; HABITUATION; RETURN AB Although the effectiveness of exposure therapy for PTSD is recognized, treatment mechanisms are not well understood. Emotional processing theory (EPT) posits that fear reduction within and between sessions creates new learning, but evidence is limited by self-report assessments and inclusion of treatment components other than exposure. We examined trajectories of physiological arousal and their relation to PTSD treatment outcome in a randomized controlled trial of written exposure treatment, a protocol focused on exposure to trauma memories. Hierarchical linear modeling was used to model reduction in Clinician Administered PTSD Scale score as a predictor of initial activation and within- and between-session change in physiological arousal. Treatment gains were significantly associated with initial physiological activation, but not with within- or between-session changes in physiological arousal. Treatment gains were associated with larger between-session reductions in self-reported arousal. These findings highlight the importance of multimethod arousal assessment and add to a growing literature suggesting refinements of EPT. C1 [Wisco, Blair E.; Baker, Aaron S.; Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Wisco, Blair E.; Baker, Aaron S.; Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Wisco, Blair E.] Univ N Carolina, Greensboro, NC 27412 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@va.gov FU National Institute of Mental Health [T32MH019836, R34MH077658] FX This study was supported by National Institute of Mental Health grants (T32MH019836 awarded to Terence M. Keane for which Aaron Baker and Blair Wisco were supported; R34MH077658 awarded to Denise M. Sloan). NR 41 TC 2 Z9 2 U1 5 U2 10 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 JAN PY 2016 VL 47 IS 1 BP 66 EP 74 PG 9 WC Psychology, Clinical SC Psychology GA DB2CF UT WOS:000368315200006 PM 26763498 ER PT J AU Eidelman, P Talbot, L Ivers, H Belanger, L Morin, CM Harvey, AG AF Eidelman, Polina Talbot, Lisa Ivers, Hans Belanger, Lynda Morin, Charles M. Harvey, Allison G. TI Change in Dysfunctional Beliefs About Sleep in Behavior Therapy, Cognitive Therapy, and Cognitive-Behavioral Therapy for Insomnia SO BEHAVIOR THERAPY LA English DT Article DE insomnia; beliefs; sleep; cognitive-behavioral therapy; behavioral experiments ID RANDOMIZED CONTROLLED-TRIAL; SOCIAL-ADJUSTMENT SCALE; PERSISTENT INSOMNIA; COMPONENT ANALYSIS; ANXIETY DISORDER; SEVERITY INDEX; OLDER-ADULTS; ATTITUDES; EFFICACY; WORK AB As part of a larger randomized controlled trial, 188 participants were randomized to behavior therapy (BT), cognitive therapy (CT), or cognitive-behavioral therapy (CBT) for insomnia. The aims of this study were threefold: (a) to determine whether change in dysfunctional beliefs about sleep was related to change in sleep, insomnia symptoms, and impairment following treatment; (b) to determine whether BT, CT, and CBT differ in their effects on dysfunctional beliefs; and (c) to determine whether the treatments differ in their effects on particular kinds of dysfunctional beliefs. Beliefs, sleep, insomnia symptoms, and sleep-related psychosocial impairment were assessed at pretreatment, posttreatment, and 6- and 12-month follow-up. Greater change in dysfunctional beliefs occurring over the course of BT, CT, or CBT was associated with greater improvement in insomnia symptoms and impairment at posttreatment and both follow-ups. All groups experienced a significant decrease in dysfunctional beliefs during treatment, which were sustained through 6- and 12-month follow-up. Compared with the BT group, a greater proportion of participants in the CT and/or CBT groups endorsed dysfunctional beliefs below a level considered clinically significant at posttreatment and 12-month follow-up. The results demonstrate the importance of targeting dysfunctional beliefs in insomnia treatment, suggest that beliefs may be significantly modified with BT alone, and indicate that cognitive interventions may be particularly powerful in enhancing belief change. C1 [Eidelman, Polina] Cognit Behav Therapy & Sci Ctr, Oakland, CA USA. [Talbot, Lisa] San Francisco VA Med Ctr, San Francisco, CA USA. [Ivers, Hans; Belanger, Lynda; Morin, Charles M.] Univ Laval, Quebec City, PQ G1K 7P4, Canada. [Harvey, Allison G.] Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Harvey, AG (reprint author), Univ Calif Berkeley, Dept Psychol, 2205 Tolman Hall 1650, Berkeley, CA 94720 USA. EM aharvey@berkeley.edu FU National Institute of Mental Health [RO1MH079188] FX This project was supported by National Institute of Mental Health Grant RO1MH079188 (C.M.M., A.G.H.); clinical trial NCT 00869934. NR 51 TC 1 Z9 1 U1 5 U2 18 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 JAN PY 2016 VL 47 IS 1 BP 102 EP 115 PG 14 WC Psychology, Clinical SC Psychology GA DB2CF UT WOS:000368315200009 PM 26763501 ER PT J AU Harris, AC Young, R Devine, S Hogan, WJ Ayuk, F Bunworasate, U Chanswangphuwana, C Efebera, YA Holler, E Litzow, M Ordemann, R Qayed, M Renteria, AS Reshef, R Wolfl, M Chen, YB Goldstein, S Jagasia, M Locatelli, F Mielke, S Porter, D Schechter, T Shekhovtsova, Z Ferrara, JLM Levine, JE AF Harris, Andrew C. Young, Rachel Devine, Steven Hogan, William J. Ayuk, Francis Bunworasate, Udomsak Chanswangphuwana, Chantiya Efebera, Yvonne A. Holler, Ernst Litzow, Mark Ordemann, Rainer Qayed, Muna Renteria, Anne S. Reshef, Ran Woelfl, Matthias Chen, Yi-Bin Goldstein, Steven Jagasia, Madan Locatelli, Franco Mielke, Stephan Porter, David Schechter, Tal Shekhovtsova, Zhanna Ferrara, James L. M. Levine, John E. TI International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Bone marrow transplant; BMT; Graft-versus-host disease; Guidance; Guidelines; GVHD; staging; standardization ID HEMATOPOIETIC-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; SURVIVAL; THERAPY; MORTALITY; DIAGNOSIS; CENTERS; SCORE AB Acute graft-versus-host disease (GVHD) remains a leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. The clinical staging of GVHD varies greatly between transplant centers and is frequently not agreed on by independent reviewers. The lack of standardized approaches to handle common sources of discrepancy in GVHD grading likely contributes to why promising GVHD treatments reported from single centers have failed to show benefit in randomized multicenter clinical trials. We developed guidelines through international expert consensus opinion to standardize the diagnosis and clinical staging of GVHD for use in a large international GVHD research consortium. During the first year of use, the guidance followed discussion of complex clinical phenotypes by experienced transplant physicians and data managers. These guidelines increase the uniformity of GVHD symptom capture, which may improve the reproducibility of GVHD clinical trials after further prospective validation. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Harris, Andrew C.; Young, Rachel; Goldstein, Steven; Levine, John E.] Univ Michigan, Blood & Marrow Transplantat Program, Ann Arbor, MI 48109 USA. [Harris, Andrew C.] Univ Utah, Blood & Marrow Transplantat Program, Salt Lake City, UT USA. [Young, Rachel; Renteria, Anne S.; Ferrara, James L. M.] Mt Sinai Hosp, Icahn Sch Med, Blood & Marrow Transplantat Program, New York, NY 10029 USA. [Devine, Steven; Efebera, Yvonne A.] Ohio State Univ, Blood & Marrow Transplantat Program, Columbus, OH 43210 USA. [Hogan, William J.; Litzow, Mark] Mayo Clin, Blood & Marrow Transplantat Program, Rochester, MN USA. [Ayuk, Francis] Univ Med Ctr, Dept Stem Cell Transplantat, Hamburg, Germany. [Bunworasate, Udomsak; Chanswangphuwana, Chantiya] Chulalongkorn Univ, Blood & Marrow Transplantat program, Bangkok 5, Thailand. [Holler, Ernst] Univ Regensburg, Blood & Marrow Transplantat Program, D-93053 Regensburg, Germany. [Ordemann, Rainer] Univ Hosp TU Dresden, Blood & Marrow Transplantat Program, Dresden, Germany. [Qayed, Muna] Emory Univ, Aflac Canc & Blood Disorders Ctr, Pediat Blood & Marrow Transplantat Program, Atlanta, GA 30322 USA. [Qayed, Muna] Childrens Hlthcare Atlanta, Atlanta, GA USA. [Reshef, Ran] Columbia Univ Med Ctr, Blood & Marrow Transplantat Program, New York, NY USA. [Woelfl, Matthias] Univ Wurzburg, Childrens Hosp, Pediat Blood & Marrow Transplantat Program, D-97070 Wurzburg, Germany. [Chen, Yi-Bin] Massachusetts Gen Hosp, Bone Marrow Transplantat Program, Boston, MA 02114 USA. [Jagasia, Madan] Vanderbilt Univ Sch Med, Div Hematol Oncol, Nashville, TN USA. [Locatelli, Franco] Osped Pediat Bambino Gesu, Pediat Blood & Marrow Transplantat Program, Rome, Italy. [Mielke, Stephan] Univ Wurzburg, Blood & Marrow Transplantat Program, D-97070 Wurzburg, Germany. [Porter, David] Univ Penn, Blood & Marrow Transplantat Program, Philadelphia, PA 19104 USA. [Schechter, Tal] Hosp Sick Children, Pediat Blood & Marrow Transplantat Program, Toronto, ON M5G 1X8, Canada. [Shekhovtsova, Zhanna] Fed Clin Res Ctr Childrens Hematol Oncol & Immuno, Moscow, Russia. RP Levine, JE (reprint author), Blood & Marrow Transplantat Program, 1 Gustave L Levy Pl Box 1410, New York, NY 10029 USA. EM john.levine@mssm.edu RI Efebera, Yvonne/E-3012-2011; OI Harris, Andrew/0000-0002-4538-8817 FU National Institutes of Health [CA039542] FX Supported by National Institutes of Health grant CA039542. NR 27 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2016 VL 22 IS 1 BP 4 EP 10 DI 10.1016/j.bbmt.2015.09.001 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DB0SW UT WOS:000368218800003 PM 26386318 ER PT J AU Perales, MA Sauter, CS Armand, P AF Perales, Miguel-Angel Sauter, Craig S. Armand, Philippe TI Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE lmmunotherapy; Autologous stem cell transplantation; Checkpoint inhibitors; Lymphoma; Myeloma; Adoptive cell therapy ID CHIMERIC ANTIGEN RECEPTOR; ENGINEERED T-CELLS; IMMUNE CHECKPOINT BLOCKADE; NATURAL-KILLER-CELLS; HIGH-DOSE THERAPY; MULTIPLE-MYELOMA; HODGKIN-LYMPHOMA; HEMATOLOGIC MALIGNANCIES; MARROW TRANSPLANTATION; CYTOTOXIC THERAPY AB Autologous stem cell transplantation (ASCT) is indicated in a number of hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Relapse, however, remains 1 of the main causes of post-ASCT failure, and several strategies are being investigated to decrease the risk of relapse of progression. Recent advances in the treatment of hematological malignancies have included adoptive transfer of genetically modified T cells that express chimeric antigen receptors or T cell receptors, as well the use of checkpoint inhibitors. Early clinical results in nontransplantation patients have been very promising. This review will focus on the use of gene-modified T cells and checkpoint inhibitors in stem cell transplantation. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Perales, Miguel-Angel; Sauter, Craig S.] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, New York, NY 10065 USA. [Perales, Miguel-Angel; Sauter, Craig S.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Perales, MA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, 1275 York Ave,Box 298, New York, NY 10065 USA. EM peralesm@mskcc.org FU National Institutes of Health/National Cancer Institute Cancer Center Support Grant [P30 CA008748] FX This research was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748 (M.A.P. and C.S.) NR 83 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2016 VL 22 IS 1 BP 17 EP 22 DI 10.1016/j.bbmt.2015.10.014 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DB0SW UT WOS:000368218800005 PM 26485445 ER PT J AU El-Jawahri, A Li, SL Ballen, KK Cutler, C Dey, BR Driscoll, J Hunnewell, C Ho, VT McAfee, SL Poliquin, C Saylor, M Soiffer, RJ Spitzer, TR Alyea, E Chen, YB AF El-Jawahri, Areej Li, Shuli Ballen, Karen K. Cutler, Corey Dey, Bimalangshu R. Driscoll, Jessica Hunnewell, Chrisa Ho, Vincent T. McAfee, Steven L. Poliquin, Cathleen Saylor, Meredith Soiffer, Robert J. Spitzer, Thomas R. Alyea, Edwin Chen, Yi-Bin TI Phase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Busulfan/clofarabine; Allogeneic transplant; Acute leukemia ID ACUTE MYELOGENOUS LEUKEMIA; MARROW-TRANSPLANTATION; COMPLETE REMISSION; RISK-ASSESSMENT; DOSE INTENSITY; EUROPEAN-GROUP; PATIENTS OLDER; WORKING PARTY; CLOFARABINE; BUSULFAN AB Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML] n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [Cl], 1.0 to 17.4) and 24% (95% Cl, 11 to 39), respectively. The 2-year relapse rate was 26% (95% Cl, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% Cl, 32 to 65) and OS was 56% (95% Cl, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [El-Jawahri, Areej; Ballen, Karen K.; Dey, Bimalangshu R.; Driscoll, Jessica; Hunnewell, Chrisa; McAfee, Steven L.; Poliquin, Cathleen; Saylor, Meredith; Spitzer, Thomas R.; Chen, Yi-Bin] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Li, Shuli] Dana Farber Canc Inst, Div Computat Biol & Biostat, Boston, MA 02115 USA. [Cutler, Corey; Ho, Vincent T.; Soiffer, Robert J.; Alyea, Edwin] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bone Marrow Transplant Unit, Yawkey 9E-9052,55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org FU Otsuka Pharmaceuticals, Inc. FX This research was supported by a grant from Otsuka Pharmaceuticals, Inc. NR 33 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2016 VL 22 IS 1 BP 80 EP 85 DI 10.1016/j.bbmt.2015.08.001 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DB0SW UT WOS:000368218800013 PM 26260679 ER PT J AU Ullrich, CK Rodday, AM Bingen, K Kupst, MJ Patel, SK Syrjala, KL Harris, LL Recklitis, CJ Schwartz, L Davies, S Guinan, EC Chang, G Wolfe, J Parsons, SK AF Ullrich, Christina K. Rodday, Angie Mae Bingen, Kristin Kupst, Mary Jo Patel, Sunita K. Syrjala, Karen L. Harris, Lynnette L. Recklitis, Christopher J. Schwartz, Lisa Davies, Stella Guinan, Eva C. Chang, Grace Wolfe, Joanne Parsons, Susan K. TI Parent Outlook: How Parents View the Road Ahead as They Embark on Hematopoietic Stem Cell Transplantation for Their Child SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Health-related quality of life; Hematopoietic stem cell transplantation; Pediatrics; Supportive care ID QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVORS; PSYCHOLOGICAL DISTRESS; INFORMED-CONSENT; ACUTE-LEUKEMIA; PEDIATRIC SCT; UNITED-STATES; CANCER; STRESS AB Pediatric hematopoietic stem cell transplantation (HSCT) offers cure for high-risk malignancies and other conditions, but carries a risk of complications. Parental outlook regarding their child's transplantation course and future health has been largely unexplored. This report presents the Parent Outlook Scale, describes its properties, and examines the outlook of parents embarking on their child's transplantation course and the associated variables. Parents of children scheduled to undergo HSCT (n = 363) at 8 US transplantation centers completed the Parent Outlook Scale, comprising 4 items assessing frequency of the parent's thoughts about the potential difficulty of the child's transplantation (Transplant Difficult subscale) and worsened health (Health Worse subscale). Item responses were rated on a 5-point Likert scale (ranging from "none" to "all of the time") and, along with scale/subscale scores, transformed to 100-point scales, with higher scores connoting greater thought frequency. Psychometrics were explored. Multivariable models identified personal and clinical characteristics associated with scale and subscale scores. The Parent Outlook Scale (alpha = 0.75) and subscales were found to have sound psychometric properties. Factor loading supported the single scale with 2 subscales representing distinct aspects of overall outlook. Mean scores (Parent Outlook, 52.5 +/- 21.7; Transplant Difficult, 64.4 +/- 25.6; Health Worse, 40.7 +/- 25.7) revealed variability within and across scale/subscales. Significantly different mean subscale scores (P < .001) indicated more frequent Transplant Difficult thoughts than Health Worse thoughts. Clinical factors (solid tumor diagnosis and unrelated donor transplant) and a parent factor (worse emotional functioning) were associated with higher scale and subscale scores. Our findings show that the outlook of parents embarking on their child's HSCT course is varied and not solely a product of clinical factors readily apparent to clinicians. Referring and transplantation clinicians should create opportunities to explore with parents their perspectives and concerns before and during the course of HSCT. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Ullrich, Christina K.; Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Ullrich, Christina K.; Recklitis, Christopher J.; Guinan, Eva C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Ullrich, Christina K.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. [Ullrich, Christina K.; Recklitis, Christopher J.; Guinan, Eva C.; Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Rodday, Angie Mae; Parsons, Susan K.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Rodday, Angie Mae; Parsons, Susan K.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Bingen, Kristin; Kupst, Mary Jo] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Dept Populat Sci, Med Ctr, Duarte, CA USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Dept Support Care Med, Med Ctr, Duarte, CA USA. [Syrjala, Karen L.] Fred Hutchinson Canc Res Ctr, Biobehav Sci Dept, Seattle, WA 98104 USA. [Harris, Lynnette L.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Schwartz, Lisa] Univ Penn, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Schwartz, Lisa] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Davies, Stella] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplant & Immune Deficiency, Cincinnati, OH 45229 USA. [Chang, Grace] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Parsons, Susan K.] Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. RP Ullrich, CK (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM christina_ullrich@dfci.harvard.edu FU National Cancer Institute [5R01 CA119196]; American Cancer Society [5RSGPB-02-186]; National Heart, Lung, and Blood Institute [1K23HL107452-01] FX Supported by National Cancer Institute grant no. 5R01 CA119196 (S.K.P., PI), American Cancer Society grant no. 5RSGPB-02-186 (S.K.P., PI), and National Heart, Lung, and Blood Institute grant no. 1K23HL107452-01 (C.K.U., PI). NR 62 TC 0 Z9 0 U1 2 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 JAN PY 2016 VL 22 IS 1 BP 104 EP 111 DI 10.1016/j.bbmt.2015.08.040 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DB0SW UT WOS:000368218800016 PM 26348891 ER PT J AU Harrold, I Carbonneau, S Moore, BM Nguyen, G Anderson, NM Saini, AS Kanki, JP Jette, CA Feng, H AF Harrold, Itrat Carbonneau, Seth Moore, Bethany M. Nguyen, Gina Anderson, Nicole M. Saini, Amandeep S. Kanki, John P. Jette, Cicely A. Feng, Hui TI Efficient transgenesis mediated by pigmentation rescue in zebrafish SO BIOTECHNIQUES LA English DT Article DE zebrafish; transgenesis; pigmentation rescue ID GERM-LINE TRANSMISSION; I-SCEI; TRANSPOSITION; MEGANUCLEASE; EXPRESSION; ELEMENT; FISH; COINJECTION; INTEGRATION; LEUKEMIA AB The zebrafish represents a revolutionary tool in large-scale genetic and small-molecule screens for gene and drug discovery. Transgenic zebrafish are often utilized in these screens. Many transgenic fish lines are maintained in the heterozygous state due to the lethality associated with homozygosity; thus, their progeny must be sorted to ensure a population expressing the transgene of interest for use in screens. Sorting transgenic embryos under a fluorescence microscope is very labor-intensive and demands fine-tuned motor skills. Here we report an efficient transgenic method of utilizing pigmentation rescue of nacre mutant fish for accurate naked-eye identification of both mosaic founders and stable transgenic zebrafish. This was accomplished by co-injecting two constructs with the I-SceI meganuclease enzyme into pigmentless nacre embryos: I-SceI-mitfa: mitfa-I-SceI to rescue the pigmentation and I-SceI-zpromoter: gene-of- interest-I-SceI to express the gene of interest under a zebrafish promoter (zpromoter). Pigmentation rescue reliably predicted transgene integration. Compared with other transgenic techniques, our approach significantly increases the overall percentage of founders and facilitates accurate naked-eye identification of stable transgenic fish, greatly reducing laborious fluorescence microscope sorting and PCR genotyping. Thus, this approach is ideal for generating transgenic fish for large-scale screens. C1 [Harrold, Itrat; Moore, Bethany M.; Nguyen, Gina; Anderson, Nicole M.; Saini, Amandeep S.; Feng, Hui] Boston Univ, Sch Med, Sect Hematol & Med Oncol, Dept Pharmacol,Canc Res Ctr, Boston, MA 02118 USA. [Carbonneau, Seth; Kanki, John P.; Jette, Cicely A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Feng, H (reprint author), Boston Univ, Sch Med, Sect Hematol & Med Oncol, Dept Pharmacol,Canc Res Ctr, 72 East Concord St,K-712A, Boston, MA 02118 USA. EM huifeng@bu.edu FU National Institutes of Health (NIH) [R00CA134743, 1K01DK074555, 5T32HL007501-30] FX This work was supported by grants from the National Institutes of Health (NIH): R00CA134743 (H.F.) and 1K01DK074555 (C.A.J.). I.H. acknowledges support from the NIH: 5T32HL007501-30. We thank Jennifer Kilgore, Alejandro Gutierrez, and Ruta Grebliunaite for help with the Tg(rag2:MYC-ER) fish, Julia Etchin and Nicholas Nagykery for help with gamma-irradiation of the fish, Derek Walsh and John Lyon for fish husbandry, and members of the Feng lab for proofreading and helpful suggestions. This paper is subject to the NIH Public Access Policy. NR 29 TC 1 Z9 1 U1 7 U2 12 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 EI 1940-9818 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2016 VL 60 IS 1 BP 13 EP 20 DI 10.2144/000114368 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA8MG UT WOS:000368058400001 PM 26757807 ER PT J AU Chhatbar, PY Ramakrishnan, V Kautz, S George, MS Adams, RJ Feng, WW AF Chhatbar, Pratik Y. Ramakrishnan, Viswanathan Kautz, Steven George, Mark S. Adams, Robert J. Feng, Wuwei TI Transcranial Direct Current Stimulation Post-Stroke Upper Extremity Motor Recovery Studies Exhibit a Dose-Response Relationship SO BRAIN STIMULATION LA English DT Article DE Stroke; Transcranial direct current stimulation; tDCS; Motor recovery; Dose-response relationship; Meta-analysis; Meta-regression; Hedge's g ID INTERHEMISPHERIC INHIBITION; SUBACUTE STROKE; TDCS; METAANALYSIS; THERAPY; CORTEX; BRAIN; EXCITABILITY; MODULATION; PHASE AB Background and purpose: Transcranial direct current stimulation (tDCS) has shown mixed results in poststroke motor recovery, possibly because of tDCS dose differences. The purpose of this meta-analysis was to explore whether the outcome has a dose-response relationship with various dose-related parameters. Methods: The literature was searched for double-blind, randomized, sham-controlled clinical trials investigating the role of tDCS (= 5 sessions) in post-stroke motor recovery as measured by the Fugl-Meyer Upper Extremity (FM-UE) scale. Improvements in FM-UE scores were compared between active and sham groups by calculating standardized mean differences (Hedge's g) to derive a summary effect size. Inversevariance- weighted linear meta-regression across individual studies was performed between various tDCS parameters and Hedge's g to test for dose-response relationships. Results: Eight studies with total of 213 stroke subjects were included. Summary Hedge's g was statistically significant in favor of the active group (Hedge's g = 0.61, p = 0.02) suggesting moderate effect. Specifically, studies that used bihemispheric tDCS montage (Hedge's g = 1.30, p = 0.08) or that recruited chronic stroke patients (Hedge's g = 1.23, p = 0.02) showed large improvements in the active group. A positive dose-response relationship was found with current density (p = 0.017) and charge density (p = 0.004), but not with current amplitude. Moreover, a negative dose-response relationship was found with electrode size (p < 0.001, smaller electrodes were more effective). Conclusions: Our meta-analysis and meta-regression results suggest superior motor recovery in the active group when compared to the sham group and dose-response relationships relating to electrode size, charge density and current density. These results need to be confirmed in future dedicated studies. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chhatbar, Pratik Y.; Adams, Robert J.; Feng, Wuwei] Med Univ S Carolina, Coll Med, Dept Neurol, Charleston, SC 29425 USA. [Ramakrishnan, Viswanathan] Med Univ S Carolina, Coll Med, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Kautz, Steven; Feng, Wuwei] Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Kautz, Steven; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [George, Mark S.] Med Univ S Carolina, Coll Med, Brain Stimulat Lab, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Feng, WW (reprint author), Med Univ S Carolina, Coll Med, Dept Neurol, Charleston, SC 29425 USA. EM feng@musc.edu FU National Institute of General Medical Sciences of the National Institutes of Health [P20GM109040]; American Heart Association [14SDG1829003]; Rehabilitation Research and Development Service of the VA FX All of authors are supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM109040. Dr. Feng is also supported by American Heart Association (14SDG1829003). Dr. Kautz is also funded by the Rehabilitation Research and Development Service of the VA. NR 46 TC 12 Z9 12 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD JAN-FEB PY 2016 VL 9 IS 1 BP 16 EP 26 DI 10.1016/j.brs.2015.09.002 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA8XF UT WOS:000368089500003 PM 26433609 ER PT J AU Cano, M Cardoner, N Urretavizcaya, M Martinez-Zalacain, I Goldberg, X Via, E Contreras-Rodriguez, O Camprodon, J de Arriba-Arnau, A Hernandez-Ribas, R Pujol, J Soriano-Mas, C Menchon, JM AF Cano, Marta Cardoner, Narcis Urretavizcaya, Mikel Martinez-Zalacain, Ignacio Goldberg, Ximena Via, Esther Contreras-Rodriguez, Oren Camprodon, Joan de Arriba-Arnau, Aida Hernandez-Ribas, Rosa Pujol, Jesus Soriano-Mas, Carles Menchon, Jose M. TI Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study SO BRAIN STIMULATION LA English DT Article DE Electroconvulsive therapy; Treatment-resistant depression; Intralimbic modulation; Limbic-prefrontal modulation; Treatment early biomarkers ID FUNCTIONAL CONNECTIVITY; EMOTION PERCEPTION; RIGHT-HEMISPHERE; DISORDERS; RECOMMENDATIONS; NEUROBIOLOGY; EFFICACY; AMYGDALA; OUTCOMES; CORTEX AB Background: Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. Objective: To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. Methods: Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. Results: An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. Conclusions: Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cano, Marta; Cardoner, Narcis; Urretavizcaya, Mikel; Martinez-Zalacain, Ignacio; Goldberg, Ximena; Via, Esther; Contreras-Rodriguez, Oren; de Arriba-Arnau, Aida; Hernandez-Ribas, Rosa; Soriano-Mas, Carles; Menchon, Jose M.] Bellvitge Univ Hosp IDIBELL, Dept Psychiat, Barcelona, Spain. [Cano, Marta; Cardoner, Narcis; Urretavizcaya, Mikel; Via, Esther; Hernandez-Ribas, Rosa; Menchon, Jose M.] Univ Barcelona, Sch Med, Dept Clin Sci, Barcelona, Spain. [Cardoner, Narcis; Urretavizcaya, Mikel; Goldberg, Ximena; Contreras-Rodriguez, Oren; Hernandez-Ribas, Rosa; Pujol, Jesus; Soriano-Mas, Carles; Menchon, Jose M.] CIBERSAM, Carlos III Hlth Inst, Barcelona, Spain. [Cardoner, Narcis] Univ Autonoma Barcelona, Dept Mental Hlth, E-08193 Barcelona, Spain. [Camprodon, Joan] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pujol, Jesus] Hosp del Mar, MRI Res Unit, Barcelona, Spain. [Soriano-Mas, Carles] Univ Autonoma Barcelona, Dept Psychobiol & Methodol Hlth Sci, E-08193 Barcelona, Spain. RP Cardoner, N (reprint author), Bellvitge Univ Hosp IDIBELL, Dept Psychiat, Barcelona, Spain. EM ncardoner@tauli.cat; csoriano@idibell.cat OI Goldberg, Ximena/0000-0001-9681-5826; VIA, ESTHER/0000-0002-2331-3232; Cardoner, Narcis/0000-0001-9633-0888 FU Carlos III Health Institute [PS09/01961, PI13/01958, CIBER-CB06/03/0034, CD13/00282, CD14/00246, CP10/00604]; FEDER funds, "A way to build Europe"; Agency of University and Research Funding Management of the Catalan Government (AGAUR) [2014SGR1672]; Spanish Ministry for Education, Culture and Sport [FPU13/02141] FX This study was supported in part by the Carlos III Health Institute (PS09/01961, PI13/01958 and CIBER-CB06/03/0034), FEDER funds, "A way to build Europe", and by the Agency of University and Research Funding Management of the Catalan Government (AGAUR; 2014SGR1672). M.C. is supported by a grant from the Spanish Ministry for Education, Culture and Sport (FPU13/02141). X.G. and O.C.-R. are supported by Sara Borrell postdoctoral fellowships from the Carlos III Health Institute (CD13/00282 and CD14/00246). C.S.-M. is funded by a Miguel Servet contract from the Carlos III Health Institute (CP10/00604). NR 37 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD JAN-FEB PY 2016 VL 9 IS 1 BP 65 EP 71 DI 10.1016/j.brs.2015.08.016 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA8XF UT WOS:000368089500009 PM 26440406 ER PT J AU Chen, CF Lin, YT Chen, WS Fregni, F AF Chen, Chiun-Fan Lin, Yin-Tsong Chen, Wen-Shiang Fregni, Felipe TI Contribution of Corticospinal Modulation and Total Electrical Energy for Peripheral-Nerve-Stimulation-Induced Neuroplasticity as Indexed by Additional Muscular Force SO BRAIN STIMULATION LA English DT Article DE Electrical stimulation; Peripheral nerve stimulation; Intensity; Frequency; Neuroplasticity ID HUMAN MOTOR CORTEX; FREQUENCY NEUROMUSCULAR STIMULATION; SKELETAL-MUSCLE; SPINAL-CORD; QUADRICEPS FEMORIS; HUMAN MOTONEURONS; CONTRACTIONS; EXCITABILITY; UNITS; POTENTIALS AB Background: Protocols to induce motor related neuroplasticity are usually directed to central neural structures such as the motor cortex or the spinal cord. Objective: Herein, we aimed to evaluate the effects of peripheral nerve stimulation using a current intensity (stimulation intensity) approach to understand the contribution of the corticospinal system and total energy to electrically-induced neuroplasticity. Methods: Electrical stimulation trains of lower intensity, interlaced with 2-s bursts of higher intensity, were applied to anesthetized rabbits. Nerve blocks were applied to the proximal side of the stimulation site with identical stimulation trains in a different session to block the contribution of corticospinal volleys during intensity-modulated electrical stimulation. Results: Additional force corresponding to additional recruitment of motoneurons was observed when a 2-s burst of high intensity was present (burst/constant: 24.7 +/- 3.6%/2.09 +/- 4.8%; p <.001). Additional force was absent in sessions when the neural pathway to the spinal cord was blocked (unblocked/ blocked: 29.3 +/- 3.8%/-2.49 +/- 4.8%; p <.001). Conclusions: The results suggest that induced neuroplasticity indexed by the additional force is dependent on the total energy applied and connectivity to central structures. These results give additional evidence for the contribution of two factors for induced neuroplasticity: (i) modulation by corticospinal structures and (ii) total energy of stimulation. Further protocols should explore simultaneous peripheral and central stimulation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chen, Chiun-Fan; Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Neuromodulat Ctr,Spaulding Rehabil Hosp, Boston, MA USA. [Chen, Chiun-Fan; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chen, Chiun-Fan] Natl Taiwan Univ, Hlth Sci & Wellness Ctr, Taipei 10764, Taiwan. [Lin, Yin-Tsong] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 10764, Taiwan. [Chen, Wen-Shiang] Natl Taiwan Univ Hosp, Dept Phys Med & Rehabil, Taipei, Taiwan. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Neuromodulat Ctr,Spaulding Rehabil Hosp, Boston, MA USA. EM Fregni.Felipe@mgh.harvard.edu OI Chen, Wen-Shiang/0000-0003-1488-5164 FU National Science Council Taiwan [103-2917-I-564-059] FX This study was supported in part by a grant from National Science Council Taiwan (103-2917-I-564-059) to C.F. Chen. NR 47 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD JAN-FEB PY 2016 VL 9 IS 1 BP 133 EP 140 DI 10.1016/j.brs.2015.09.012 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA8XF UT WOS:000368089500017 PM 26586043 ER PT J AU Crall, C Morley, KW Rabinowits, G Schmidt, B Broyles, AD Huang, JT AF Crall, C. Morley, K. W. Rabinowits, G. Schmidt, B. Broyles, A. Dioun Huang, J. T. TI Merkel cell carcinoma in a patient with GATA2 deficiency: a novel association with primary immunodeficiency SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article AB A 55-year-old woman with GATA2 deficiency and neurofibromatosis 1 was diagnosed with Merkel cell carcinoma (MCC). This polyomavirus-associated cutaneous malignancy has previously been associated with immunosuppression and acquired immunodeficiencies such as HIV/AIDS. However, MCC has not been previously reported in the setting of underlying primary or inherited immunodeficiency. C1 [Crall, C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Morley, K. W.] Harvard Combined Dermatol Program, Boston, MA 02115 USA. [Rabinowits, G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rabinowits, G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schmidt, B.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Broyles, A. Dioun] Boston Childrens Hosp, Div Allergy Immunol, Boston, MA 02115 USA. [Huang, J. T.] Boston Childrens Hosp, Dermatol Program, Boston, MA 02115 USA. RP Huang, JT (reprint author), Boston Childrens Hosp, Dermatol Program, 300 Longwood Ave, Boston, MA 02115 USA. EM Jennifer.Huang@childrens.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2016 VL 174 IS 1 BP 169 EP 171 DI 10.1111/bjd.14062 PG 3 WC Dermatology SC Dermatology GA DB4JW UT WOS:000368480300026 PM 26252413 ER PT J AU Mahal, BA Aizer, AA Efstathiou, JA Nguyen, PL AF Mahal, Brandon A. Aizer, Ayal A. Efstathiou, Jason A. Nguyen, Paul L. TI Association of very low prostate-specific antigen levels with increased cancer-specific death in men with high-grade prostate cancer SO CANCER LA English DT Article DE aggressive disease; cancer outcome; Gleason score; prostatic neoplasm; prostate-specific antigen ID RADICAL PROSTATECTOMY; GLEASON SCORE AB BACKGROUNDThe objective of this study was to determine whether a very low presenting prostate-specific antigen (PSA) level was associated with greater prostate cancer-specific mortality (PCSM) among men with a Gleason score (GS) of 8 to 10. METHODSThe Surveillance, Epidemiology, and End Results program was used to identify 328,904 men diagnosed with clinicalT1 (cT1)-4N0M0 prostate cancer between 2004 and 2010. A multivariate Fine-Gray competing risks regression analysis was used to determine PCSM as a function of the PSA level (2.5, 2.6-4, 4.1-10, 10.1-20, 20.1-40, or>40ng/mL) and GS (8-10 vs7). RESULTSThe median follow-up was 38 months. Among men with GS 8-10 disease, with a PSA level of 4.1 to 10ng/mL as the referent, the adjusted hazard ratio for PCSM for men was 2.15 with a PSA level2.5ng/mL (95% confidence interval [CI], 1.65-2.79; P<.001), 1.60 with a PSA level of 2.6 to 4ng/mL (95% CI, 1.22-2.10; P=.001), 1.60 with a PSA level of 10.1 to 20ng/mL (95% CI, 1.41-1.82; P<.001), 2.08 with a PSA level of 20.1 to 40ng/mL (95% CI, 1.81-2.38; P<.001), and 3.23 with a PSA level>40ng/mL (95% CI, 2.85-3.65; P<.001). This suggested a U-shaped distribution. There was a significant interaction between the PSA level and GS (P-interaction<.001) such that only a PSA level2.5ng/mL significantly predicted poorer PCSM among patients with GS 8-10 disease. CONCLUSIONSAmong patients with high-grade disease, patients with PSA levels2.5ng/mL or PSA levels of 2.6 to 4ng/mL appear to have a higher risk for cancer-specific death in comparison with patients with PSA levels of 10.1 to 20ng/mL, and this supports the notion that low PSA levels in GS 8-10 disease may be a sign of aggressive and very poorly differentiated or anaplastic low PSA-producing tumors. Patients with low-PSA, GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents for very high-risk prostate cancers. Cancer 2016;122:78-83. (c) 2015 American Cancer Society. C1 [Mahal, Brandon A.] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. [Aizer, Ayal A.; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Aizer, Ayal A.; Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@lroc.harvard.edu FU 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, Hugh Simons (in honor of Frank and Anne Simons), and a grant from an anonymous family foundation. NR 18 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2016 VL 122 IS 1 BP 78 EP 83 DI 10.1002/cncr.29691 PG 6 WC Oncology SC Oncology GA DA7LF UT WOS:000367984900012 PM 26371600 ER PT J AU Li, DK Chung, RT AF Li, Darrick K. Chung, Raymond T. TI Reply to Antiviral Therapy and Hepatocellular Carcinogenesis SO CANCER LA English DT Letter ID IMPACT C1 [Li, Darrick K.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Ctr Liver, Boston, MA 02114 USA. RP Li, DK (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU NIDDK NIH HHS [K24 DK078772] NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2016 VL 122 IS 1 BP 158 EP 158 DI 10.1002/cncr.29694 PG 1 WC Oncology SC Oncology GA DA7LF UT WOS:000367984900023 PM 26384130 ER PT J AU Stopsack, KH Ziehr, DR Rider, JR Giovannucci, EL AF Stopsack, Konrad H. Ziehr, David R. Rider, Jennifer R. Giovannucci, Edward L. TI Metformin and prostate cancer mortality: a meta-analysis SO CANCER CAUSES & CONTROL LA English DT Article DE Prostate cancer; Diabetes mellitus; Metformin; Mortality; Biochemical recurrence; Meta-analysis ID RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; CLINICAL-OUTCOMES; DIABETIC-PATIENTS; ALL-CAUSE; RISK; ASSOCIATION; TIME; DEATH; MEN AB Purpose Observational studies report conflicting results on the association between metformin exposure and prostate cancer outcomes. This meta-analysis summarizes studies reporting overall survival, prostate cancer-specific mortality, and biochemical recurrence. Methods PubMed and Embase were systematically reviewed to identify studies investigating the association between metformin use and clinical endpoints among men with prostate cancer while taking confounding by diabetes diagnosis into account. Pooled risk estimates (hazard ratios, HRs) and 95 % confidence intervals (CIs) were calculated using random-effects models. Sensitivity analyses for quality components and factors for heterogeneity were conducted. Results Of 549 articles identified, nine retrospective cohort studies representing 9,186 patients were included. There was significant heterogeneity between studies, and studies differed in quality. Metformin use was associated with improved overall survival in studies with clear risk window definition (HR 0.88, 95 % CI 0.86-0.90, p < 0.001) and in studies with potential immortal time bias (HR 0.52, 95 % CI 0.41-0.65, p < 0.001). No significant association with prostate cancer-specific mortality was detected (HR 0.76, 95 % CI 0.44-1.31, p = 0.33). Metformin use was associated with a decreased risk of biochemical recurrence (HR 0.79, 95 % CI 0.63-1.00, p = 0.047). Conclusions This meta-analysis suggests a benefit of metformin in men with diabetes and prostate cancer. However, further carefully designed studies are needed to confirm findings and to assess potential generalization to non-diabetic, non-white, and less aggressively treated men with prostate cancer. C1 [Stopsack, Konrad H.; Rider, Jennifer R.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ziehr, David R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ziehr, David R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rider, Jennifer R.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Rider, Jennifer R.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Stopsack, KH (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM stopsack@post.harvard.edu NR 40 TC 8 Z9 8 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2016 VL 27 IS 1 BP 105 EP 113 DI 10.1007/s10552-015-0687-0 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DA9TD UT WOS:000368151600010 PM 26537119 ER PT J AU Zhang, J Wu, GX Dai, HB AF Zhang, Jin Wu, Gongxiong Dai, Haibin TI The matricellular protein CCN1 regulates TNF-alpha induced vascular endothelial cell apoptosis SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE apoptosis; CCN1; P53; TNF-alpha; vascular endothelial cells ID IMMEDIATE-EARLY GENE; NEOINTIMAL HYPERPLASIA; FACTOR CYR61; EXPRESSION; GROWTH; PROLIFERATION; ANGIOGENESIS; ADHESION; RECEPTOR; INJURY AB Due to the epidemic obesity and associated diabetes, the incidence of atherosclerosis is increasing worldwide. Atherosclerosis is a chronic inflammatory disease characterized by the hardening and narrowing of arteries with plaques that consist of inflammatory cells, dead endothelial cells, lipids, and often hyper proliferated vascular smooth muscle cells. During the development of atherosclerosis, vascular endothelial cell (EC) apoptosis induced by the adipokine tumor necrosis factor alpha (TNF-alpha) is an early event in the plaque formation. However, TNF-alpha alone is not sufficient to induce apoptosis of endothelial cells. Recent studies suggested that the matricellular protein CCN family member 1 (CCN1) involves in endothelial cell dysfunction besides its well-known angiogenic function during tissue repair by promoting vascular smooth muscle cells proliferation and migration. Herein, we explored the possibility and mechanism of CCN1 in TNF-a induced endothelial cells apoptosis. Both mRNA and protein levels of CCN1 are found up-regulated in endothelial cells after TNF-a treatment. In addition, overexpression of CCN1 promoted endothelial cell apoptosis in the presence of TNF-alpha. Furthermore, CCN1 directly up-regulated the expression of TNF-a-target genes, and this up-regulation required the activation of P53 and NF-kappa B both in vivo and in vitro. Taken together, CNN1 regulates TNF-alpha induced endothelial cells apoptosis that may underlie poor response to TNF-alpha therapy and hence may be a better therapeutic target for preventing vascular dysfunction in obesity. C1 [Zhang, Jin] Lanzhou Univ, Hosp 1, Ctr Heart, Lanzhou 730000, Peoples R China. [Wu, Gongxiong] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Dai, Haibin] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China. RP Dai, HB (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China. EM wugongxiong@gmail.com; haibindai@zju.edu.cn FU Health Bureau of Zhejiang Province [2014KYB104, 2014RCA008]; Zhejiang Province Traditional Chinese Medicine Foundation of China [2014ZB067, 2012ZB091, 2011ZZ009]; Education Bureau of Zhejiang Province [Y201328670] FX This project was supported by the grants from the Foundation from the Health Bureau of Zhejiang Province (2014KYB104, 2014RCA008), the Zhejiang Province Traditional Chinese Medicine Foundation of China (2014ZB067, 2012ZB091, 2011ZZ009), and the Foundation from Education Bureau of Zhejiang Province (Y201328670). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 0 Z9 1 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-6995 EI 1095-8355 J9 CELL BIOL INT JI Cell Biol. Int. PD JAN PY 2016 VL 40 IS 1 BP 1 EP 6 DI 10.1002/cbin.10469 PG 6 WC Cell Biology SC Cell Biology GA DA8RA UT WOS:000368072600001 PM 25820828 ER PT J AU Schwarz, DS Blower, MD AF Schwarz, Dianne S. Blower, Michael D. TI The endoplasmic reticulum: structure, function and response to cellular signaling SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Interphase; Mitosis; Unfolded protein response; Organization; Fertilization; Phosphorylation ID UNFOLDED PROTEIN RESPONSE; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CALCIUM-DEPENDENT RIBONUCLEASE; SYNTHESIZING SECRETORY PROTEIN; NUCLEAR-ENVELOPE FORMATION; TO-TUBULE TRANSFORMATION; MEMBRANE-BOUND RIBOSOMES; XENOPUS EGG EXTRACTS; ER NETWORK FORMATION; SEA-URCHIN EGG AB The endoplasmic reticulum (ER) is a large, dynamic structure that serves many roles in the cell including calcium storage, protein synthesis and lipid metabolism. The diverse functions of the ER are performed by distinct domains; consisting of tubules, sheets and the nuclear envelope. Several proteins that contribute to the overall architecture and dynamics of the ER have been identified, but many questions remain as to how the ER changes shape in response to cellular cues, cell type, cell cycle state and during development of the organism. Here we discuss what is known about the dynamics of the ER, what questions remain, and how coordinated responses add to the layers of regulation in this dynamic organelle. C1 [Schwarz, Dianne S.; Blower, Michael D.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Schwarz, Dianne S.; Blower, Michael D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Blower, MD (reprint author), New England Biolabs Inc, Ipswich, MA 01938 USA. EM blower@molbio.mgh.harvard.edu NR 164 TC 4 Z9 4 U1 5 U2 17 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JAN PY 2016 VL 73 IS 1 BP 79 EP 94 DI 10.1007/s00018-015-2052-6 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DA6LU UT WOS:000367917100005 PM 26433683 ER PT J AU Dunn, EC Busso, DS Raffeld, MR Smoller, JW Nelson, CA Doyle, AE Luk, G AF Dunn, Erin C. Busso, Daniel S. Raffeld, Miriam R. Smoller, Jordan W. Nelson, Charles A. Doyle, Alysa E. Luk, Gigi TI Does developmental timing of exposure to child maltreatment predict memory performance in adulthood? Results from a large, population-based sample SO CHILD ABUSE & NEGLECT LA English DT Article DE Epidemiology; Memory; Cognition; Sensitive periods; Etiology; Maltreatment ID SPATIAL WORKING-MEMORY; SEXUAL-ABUSE; COGNITIVE FUNCTION; BRAIN-DEVELOPMENT; PSYCHIATRIC-DISORDERS; SENSITIVE PERIODS; NATIONAL SAMPLE; SHORT-TERM; LONG-TERM; STRESS AB Although maltreatment is a known risk factor for multiple adverse outcomes across the lifespan, its effects on cognitive development, especially memory, are poorly understood. Using data from a large, nationally representative sample of young adults (Add Health), we examined the effects of physical and sexual abuse on working and short-term memory in adulthood. We examined the association between exposure to maltreatment as well as its timing of first onset after adjusting for covariates. Of our sample, 16.50% of respondents were exposed to physical abuse and 4.36% to sexual abuse by age 17. An analysis comparing unexposed respondents to those exposed to physical or sexual abuse did not yield any significant differences in adult memory performance. However, two developmental time periods emerged as important for shaping memory following exposure to sexual abuse, but in opposite ways. Relative to non-exposed respondents, those exposed to sexual abuse during early childhood (ages 3-5), had better number recall and those first exposed during adolescence (ages 14-17) had worse number recall. However, other variables, including socioeconomic status, played a larger role (than maltreatment) on working and short-term memory. We conclude that a simple examination of "exposed" versus "unexposed" respondents may obscure potentially important within-group differences that are revealed by examining the effects of age at onset to maltreatment. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Dunn, Erin C.; Raffeld, Miriam R.; Smoller, Jordan W.; Doyle, Alysa E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dunn, Erin C.; Smoller, Jordan W.; Doyle, Alysa E.] Harvard Univ, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. [Dunn, Erin C.; Smoller, Jordan W.; Doyle, Alysa E.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Boston, MA USA. [Busso, Daniel S.; Nelson, Charles A.; Luk, Gigi] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. [Smoller, Jordan W.; Nelson, Charles A.] Boston Childrens Hosp, Boston, MA USA. [Nelson, Charles A.] Harvard Univ, Ctr Dev Child, Cambridge, MA 02138 USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St,Simches Res Bldg 6th Floor, Boston, MA 02114 USA. FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [P01-HD31921]; National Institute of Mental Health (NIMH) [K01 MH102403, K24 MH094614]; Harvard University Center on the Developing Child FX This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website (http://www.cpc.unc.edu/addhealth). No direct support was received from grant P01-HD31921 for this analysis. Visit Add Health at: https://www.cpc.unc.edu/projects/addhealth. Research reported in this publication was supported, in part, by the Harvard University Center on the Developing Child (Drs. Smoller, Dunn, Nelson, and Luk) and the National Institute of Mental Health (NIMH) under award number (K01 MH102403 Dunn and K24 MH094614 Smoller). NR 66 TC 1 Z9 1 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 EI 1873-7757 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD JAN PY 2016 VL 51 BP 181 EP 191 DI 10.1016/j.chiabu.2015.10.014 PG 11 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA DB0PW UT WOS:000368211000018 PM 26585216 ER PT J AU Torres-Cornejo, A BenMarzouk-Hidalgo, OJ Viciana, P Sanchez, B Lopez-Ruz, MA Lopez-Cortes, LF Gutierrez-Valencia, A AF Torres-Cornejo, A. BenMarzouk-Hidalgo, O. J. Viciana, P. Sanchez, B. Lopez-Ruz, M. A. Lopez-Cortes, L. F. Gutierrez-Valencia, A. TI Protease inhibitor monotherapy is effective in controlling human immunodeficiency virus 1 shedding in the male genital tract SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE Human immunodeficiency virus 1 infection; human immunodeficiency virus 1 treatment; male genital tract; protease inhibitor monotherapy; triple therapy ID REVERSE-TRANSCRIPTASE INHIBITORS; ANTIRETROVIRAL THERAPY; VIRAL LOAD; HIV-1-INFECTED MEN; BLOOD-PLASMA; HIV-1 RNA; SEMEN; LOPINAVIR/RITONAVIR; RITONAVIR; TYPE-1 AB Cross-sectional study comparing seminal human immunodeficiency virus type 1 (HIV-1) shedding in patients receiving boosted protease inhibitor monotherapy (mtPI/rtv) (n = 66) versus triple therapy (TT) (n = 61). Seminal HIV-1 shedding rates in patients with undetectable plasma HIV-RNA were 16.0% on mtPI/rtv compared with 28.6% on TT (p 0.173). Aviraemic status and time on viral suppression were independently associated with lack of seminal HIV-1 shedding. During TT, non PI/rtv-based regimens were associated with a better control of HIV infection in semen despite similar time on viral suppression. The use of mtPI/rtv in well-controlled patients is not associated with increased seminal HIV excretion compared with TT. (C)2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 [Torres-Cornejo, A.; BenMarzouk-Hidalgo, O. J.; Viciana, P.; Lopez-Cortes, L. F.; Gutierrez-Valencia, A.] Univ Seville, Inst Biomed Sevilla, Enfermedades Infecciosas Microbiol & Med Prevent, Hosp Univ Virgen Rocio,CSIC, Seville, Spain. [Sanchez, B.] Univ Seville, Inst Biomed Sevilla, Serv Inmunol, Hosp Univ Virgen Rocio,CSIC, Seville, Spain. [Lopez-Ruz, M. A.] Hosp Univ Virgen Nieves, Inst Invest Biosanitaria Granada, Enfermedades Infecciosas, Granada, Spain. RP Torres-Cornejo, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Dept, Boston, MA 02138 USA. EM ATORRES-CORNEJO@mgh.harvard.edu; lflopez@us.es FU Direccion Gerencia del Servicio Andaluz de Salud, Consejeria de Salud, Junta de Andalucia [exp PI-0168-2012] FX This project was supported by a grant from the Direccion Gerencia del Servicio Andaluz de Salud, Consejeria de Salud, Junta de Andalucia (exp PI-0168-2012). NR 18 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1198-743X EI 1469-0691 J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD JAN PY 2016 VL 22 IS 1 DI 10.1016/j.cmi.2015.09.028 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA DA7ZT UT WOS:000368024800032 ER PT J AU Bozic, KJ Ong, K Kurtz, S Lau, E Vail, TP Rubash, H Berry, D AF Bozic, Kevin J. Ong, Kevin Kurtz, Steven Lau, Edmund Vail, Thomas P. Rubash, Harry Berry, Daniel TI Short-term Risk of Revision THA in the Medicare Population Has Not Improved With Time SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; ACETABULAR COMPONENT; REPLACEMENT; OSTEOLYSIS; POLYETHYLENE; OUTCOMES; FAILURE; WEAR AB Introduction Advances in surgical technique, implant design, and clinical care pathways have resulted in higher expectations for improved clinical outcomes after primary THA; however, despite these advances, it is unclear whether the risk of revision THA actually has decreased with time. Understanding trends in short- and mid-term risks of revision will be helpful in directing clinical, research, and policy efforts to improve THA outcomes. Question/purposes We therefore asked (1) whether there have been changes in overall short- and mid-term risks of revision THA among patients in the Medicare population who underwent primary THA between 1998 and 2010; and (2) whether there are different demographic factors associated with short-and mid-term risks of revision THA. Methods Using the Medicare 5% national sample database, patients who underwent primary THA between 1998 and 2010 followed by subsequent revision through 2011 were identified by ICD-9-CM procedure codes 81.51 and 81.53/80.05/00.70-00.73, respectively. This dataset included a random sample of Medicare beneficiaries based on their social security number. Only patients with minimum 1-year followup after primary THA were included in our analysis. A total of 64,260 patients who underwent primary THA were identified from the 1998 to 2010 Medicare 5% dataset. Eighty-eight percent of the patients had 1-year followup providing a final study cohort of 56,700 patients. The risk of revision was evaluated at 1, 3, 5, and 7 years. Multivariate Cox regression was used to evaluate temporal trends in revision risk using two methods to account for time effects with periods 1998 to 2002, 2003 to 2007, and 2008 to 2010 for the index year of primary THA, and individual year of index of primary THA as independent variables. The analysis adjusted for patient age, sex, race, census region, Charlson score, and socioeconomic status. Results The 7-year crude risk of revision THA declined from 7.10% in 1998 to 2002 to 6.09% in 2008 to 2010, representing a 14.4% overall reduction in adjusted risk of revision (p = 0.0058; 95% CI, 4.4%-23%). Similarly, the 5-year crude risk of revision THA declined from 5.96% in 1998 to 2002 to 5.11% in 2008 to 2010, representing a 14.2% overall reduction in adjusted risk of revision (p = 0.0069; 95% CI, 4.1%-23%). However, the adjusted risk of revision THA at 3 years was not different from 1998 to 2002 (4.70%) and 2008 to 2010 (4.03%; p = 0.1176). Similarly, the adjusted risk of revision at 1 year did not differ from 1998 to 2002 (2.83%) and 2008 to 2010 (2.42%; p = 0.3386). Patients with more comorbidities had a greater adjusted risk of revision (p<0.001) at all times: 94% (95% CI, 58%-138%) and 56% (95% CI, 33%-84%) at 1 year and 7 years, respectively, for Charlson score of 5+ vs 0). Conclusions Although the mid-term (5 and 7 years) risk of revision THA has decreased during the past 14 years among Medicare beneficiaries who underwent primary THA, the short-term risk has not. These findings suggest that greater clinical, research, and policy emphasis is needed to identify potentially avoidable causes of early failure after primary THA in patients in the Medicare population, and multistakeholder solutions are needed to optimize short-term outcomes. Level of Evidence Level III, therapeutic study. C1 [Bozic, Kevin J.] Univ Texas Austin, Dell Med Sch, Dept Surg & Preoperat Care, Austin, TX 78712 USA. [Ong, Kevin; Kurtz, Steven] Exponent Inc, Philadelphia, PA USA. [Lau, Edmund] Exponent Inc, Menlo Pk, CA USA. [Kurtz, Steven; Berry, Daniel] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. [Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. [Rubash, Harry] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bozic, KJ (reprint author), Univ Texas Austin, Dell Med Sch, Dept Surg & Preoperat Care, 1912 Speedway,Suite 564,Sanchez Bldg, Austin, TX 78712 USA. EM kevin.bozic@austin.utexas.edu FU DePuy; Stryker/MAKO; Ceramtec; Lippincott; Williams; Wilkins; Flexion Therapeutics; Pacira FX One of the authors certifies that he (TPV), or a member of his or her immediate family, has received or may receive payments or benefits, during the study period-royalty for certain and hip and knee products, DePuy, USD 100,001 to USD 1,000,000. One of the authors certifies that he (DB), or a member of his or her immediate family, has received or may receive payments or benefits, during the study period-royalty for certain hip and knee implants, DePuy, USD 100,001 to USD 1,000,000. One of the authors certifies that he (HR), or a member of his or her immediate family, has received or may receive payments or benefits, during the study period USD 10,000 to USD 100,000 from Stryker/MAKO for Institutional Royalties, less than USD 10,000 from Ceramtec for consulting, less than USD 10,000 from Lippincott, Williams, & Wilkins for royalties, less than USD 10,000 from Flexion Therapeutics for consulting, less than USD 10,000 from Pacira for consulting. One of the authors certifies that he (KJB), or a member of his or her immediate family, has received or may receive payments or benefits, during the study period less than USD 10,000 from Institute for Healthcare Improvement for consulting, less than USD 10,000 from Harvard Business School for consulting, USD 10,000 to 100,000 from Centers for Medicare and Medicaid Services for consulting. NR 34 TC 1 Z9 1 U1 3 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 JAN PY 2016 VL 474 IS 1 BP 156 EP 163 DI 10.1007/s11999-015-4520-6 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DA7YX UT WOS:000368022600030 PM 26400249 ER PT J AU Madanat, R Hussey, DK Donahue, GS Potter, HG Wallace, R Bragdon, C Muratoglu, O Malchau, H AF Madanat, Rami Hussey, Daniel K. Donahue, Gabrielle S. Potter, Hollis G. Wallace, Robert Bragdon, Charles Muratoglu, Orhun Malchau, Henrik TI Early Lessons From a Worldwide, Multicenter, Followup Study of the Recalled Articular Surface Replacement Hip System SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID IMAGING FINDINGS; MRI FINDINGS; METAL; ARTHROPLASTY; PSEUDOTUMORS; REVISION; OUTCOMES; IMPLANTS; SURGERY; COMMON AB Background Adverse local tissue reactions (ALTRs) around hip arthroplasties are an important reason for failure of metal-on-metal (MoM) hip implants. Little is known about capsular dehiscence patterns as ALTRs decompress from the hip into the surrounding tissue planes; these patterns may also influence the onset and severity of patient symptoms. Questions/ purposes Through a multicenter study approach, we asked: (1) Is ALTR location related to the surgical approach used for arthroplasty in patients who underwent hip arthroplasty (resurfacing or THA) with a single, recalled hip arthroplasty system? (2) Do ALTR severity and location affect patient-reported outcomes in these patients? (3) Is ALTR severity different between patients who received the resurfacing version of this component (Articular Surface Replacement [ASR]) and those who received the THA implant in this system (ASR XL)? Methods In a multicenter prospective study of patients who had undergone surgery with use of the ASR and ASR XL hip system (DePuy Orthopaedics, Warsaw, IN, USA), 288 patients (333 hips) from two centers had a metal artifact reduction sequence MRI of the hip performed at a mean time of 6 years postsurgery. Procedures included 166 hips (50%) with ASR resurfacing and 167 hips (50%) with ASR XL THA performed between 2004 and 2010. One hundred twenty-nine hips (39%) had been operated on using a direct lateral approach and 204 using a posterior approach (61%). The EQ-5D, Harris hip score, UCLA activity score, and visual analog scale pain score were obtained for each patient. ALTRs were classified using the Anderson ALTR grading system, and the location, synovial thickness, and diameter of the ATLRs were assessed. The relationship between ALTR location and surgical approach as well as for ALTR severity and patient-reported outcomes were evaluated, and logistic regression was used to identify predictors for moderate-to-severe ALTRs. Results Moderate or severe ALTRs were identified in 79 hips (24%); 41 of these hips had been operated on using the direct lateral approach and 38 using the posterior approach. In patients in whom the lateral approach was used, 83% had an anterior ALTR. Similarly, 71% of patients in the posterior approach group had posterior ALTRs. There were no differences in patient-reported outcome measures between patients with moderate-to-severe ALTRs and those with no ALTR findings on MRI (p>0.09). Use of ASR XL was an independent risk factor for moderate-to-severe ALTRs (odds ratio, 2.8; 95% confidence interval, 1.4-5.5 p = 0.004) and patients with ASR XL also had a thicker synovium (median ASR XL = 3.6 mm [1.2-10.6 mm], median ASR = 2.6 mm [1.2-10.7 mm], p<0.001) and larger maximal ALTR diameter (median ASR XL = 47.6 mm [14-109.70 mm], median ASR = 38.4 [17.21-18.0 mm], p = 0.02) than patients treated with ASR. Conclusions The location of ALTRs can be predicted based on the previous surgical approach to the hip. Patients with ASR XL are more likely to develop moderate-to-severe ALTRs compared with ASR patients. An extensive range of patient-reported outcome measures may not identify all patients with ALTRs further supporting the use of MRI as a screening measure for ALTRs. Level of Evidence Level II, therapeutic study. C1 [Madanat, Rami; Hussey, Daniel K.; Donahue, Gabrielle S.; Bragdon, Charles; Muratoglu, Orhun; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Potter, Hollis G.] Hosp Special Surg, Dept Radiol & Imaging, New York, NY 10021 USA. [Wallace, Robert] Sportsmed SA, Stepney, Australia. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1231, Boston, MA 02114 USA. EM hmalchau@partners.org FU Biomet (Warsaw, IN, USA),; Smith & Nephew (London, UK); Zimmer Inc (Warsaw, IN, USA); Mako Surgical Corp (Ft Lauderdale, FL, USA); Mako Surgical Corp; DePuy Synthes (Warsaw, IN, USA); GE Healthcare (Waukesha, WI, USA); Zimmer Inc.; Corin (Cirencester, UK); Iconacy (Warsaw, IN, USA); Renovis (Redlands, CA, USA); Conformis (Burlington, MA, USA); Aston Medical (Saint-Etienne, France); Meril Healthcare (Vapi, Gujarat, India); Arthex (Naples, FL, USA); Orthopaedic Technology Group (Boston, MA, USA); Zimmer Inc; Biomet; Cambridge Polymer Group (Boston, MA, USA); Corin; RSA Biomedical (Umea, Sweden) FX One of the authors (HM) has received research support funding from Biomet (Warsaw, IN, USA), Smith & Nephew (London, UK), Zimmer Inc (Warsaw, IN, USA), and Mako Surgical Corp (Ft Lauderdale, FL, USA). One author (OM) has received research support funding from Mako Surgical Corp. The institution of one or more of the authors (RM, DKH, GSD, CB, OM, HM) has received, during the study period, funding from DePuy Synthes (Warsaw, IN, USA).; The institution of one of the authors (HGP) has received, during the study period, funding from GE Healthcare (Waukesha, WI, USA). One of the authors (CB), or a member of his or her immediate family, has or may receive payments or benefits, during the study period, an amount of USD 10,000 to USD 100,000 from Zimmer Inc. One of the authors (OM), or a member of his or her immediate family, has or may receive payments or benefits, during the study period, an amount of less than USD 10,000 from Corin (Cirencester, UK), Iconacy (Warsaw, IN, USA), Renovis (Redlands, CA, USA), Conformis (Burlington, MA, USA), Aston Medical (Saint-Etienne, France), Meril Healthcare (Vapi, Gujarat, India), Arthex (Naples, FL, USA), Orthopaedic Technology Group (Boston, MA, USA); USD 10,000 to USD 100,000, from Mako Surgical Corp; USD 100,000 to USD 1,000,000 from Zimmer Inc; and more than USD 1,000,000 from Biomet and Cambridge Polymer Group (Boston, MA, USA). One of the authors (HM), or a member of his or her immediate family, has or may receive payments or benefits, during the study period, an amount of USD 10,000 to USD 100,000, from Zimmer Inc, Biomet, Corin, and RSA Biomedical (Umea, Sweden). NR 32 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2016 VL 474 IS 1 BP 166 EP 174 DI 10.1007/s11999-015-4456-x PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DA7YX UT WOS:000368022600032 PM 26310677 ER PT J AU Claessen, FMAP Braun, Y Peters, RM Dyer, G Doornberg, JN Ring, D AF Claessen, Femke M. A. P. Braun, Yvonne Peters, Rinne M. Dyer, George Doornberg, Job N. Ring, David TI Factors Associated With Reoperation After Fixation of Displaced Olecranon Fractures SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PLATE FIXATION; TENSION AB Background Surgery for fixation of olecranon fractures is associated with reoperation, mostly for implant removal. A study of a large cohort of patients treated by many different surgeons allows us to determine if specific techniques or implants are associated with a higher rate of reoperation. Questions/purposes After open reduction and internal fixation of isolated olecranon fractures, what factors are associated with (1) reoperation and (2) implant removal? Methods Three hundred ninety-two adult patients who had operative treatment of a displaced olecranon fracture not associated with other fractures, dislocation, or subluxation at two area hospitals between January 2002 and May 2014 were analyzed to determine factors associated with reoperation. One hundred thirty-eight (35%) patients had plate and screw fixation and 254 (65%) tension band wiring. Nearly 100% of patients with displaced olecranon fractures are currently treated operatively at our hospitals. All patients were followed for at least four months. Two hundred three of the 392 (52%) patients were followed for one year or more. Ninety-nine patients (25%) had a second operation, 92 (93%) at least in part for implant removal (12 for wire migration [3% of all fractures, 12% of reoperations]). We considered patient-related, fracture-related, and implant-related endpoints as possible factors associated with reoperation. With a total sample size of 99 reoperations, an alpha of 0.05, and an effect size of 0.3, we had 87% power. Results Reoperation was less common in men (36 [36%], women: 63 [64%]; adjusted odds ratio, 0.32; 95% confidence interval, 0.18-0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87; p < 0.001). Similarly, request for implant removal was less in men (33 [36%], women: 59 [64%], adjusted odds ratio, 0.31; 95% confidence interval, 0.18-0.56; p<0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87; p < 0.001). Conclusions Patients who have operative fixation of a fracture of the olecranon can be counseled that most patients keep their implants, that only 3% experience implant migration, and that technical factors such as the type or configuration of an implant seem less important than personal factors in determining who requests a second surgery for implant removal. Level of Evidence Level III, prognostic study. C1 [Claessen, Femke M. A. P.; Braun, Yvonne; Peters, Rinne M.; Ring, David] Massachusetts Gen Hosp, Hand Surg, Boston, MA 02114 USA. [Dyer, George] Brigham Womens Hosp, Dept Orthopaed Surg, Upper Extrem Div, Boston, MA USA. [Doornberg, Job N.] Univ Amsterdam, Orthopaed Residency Program PGY 6, Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands. [Ring, David] Harvard Univ, Yawkey Ctr, Orthopaed Surg, Sch Med, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Yawkey Ctr, Orthopaed Surg, Sch Med, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@mgh.harvard.edu FU Skeletal Dynamics (Miami, FL, USA); Wright Medical (Memphis, TN, USA); Biomet (Warsaw, IN, USA); Acumed (Hillsboro, OR, USA); IlluminOss Medical, Inc (East Providence, RI, USA) FX One of the authors (DR) received grants from Skeletal Dynamics (Miami, FL, USA) in the amount of USD 10,000 to USD 100,000, other from Wright Medical (Memphis, TN, USA) in the amount of less than USD 10,000, personal fees from Biomet (Warsaw, IN, USA) in the amount of less than USD 10,000, personal fees from Acumed (Hillsboro, OR, USA) in the amount of less than USD 10,000), other from IlluminOss Medical, Inc (East Providence, RI, USA; stock options only), personal fees as Deputy Editor for the Journal of Hand Surgery (less than USD 10,000), personal fees as Deputy Editor for Clinical Orthopaedics and Related Research (less than USD 10,000), personal fees from universities and hospitals (less than USD 10,000), and personal fees from lawyers (less than USD 10,000) outside the submitted work. NR 21 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2016 VL 474 IS 1 BP 193 EP 200 DI 10.1007/s11999-015-4488-2 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DA7YX UT WOS:000368022600036 PM 26250137 ER PT J AU Nguyen, HQ Bailey, A Coleman, KJ Desai, S Fan, VS Gould, MK Maddock, L Miller, K Towner, W Xiang, AH Moy, ML AF Nguyen, Huong Q. Bailey, Adrienne Coleman, Karen J. Desai, Smita Fan, Vincent S. Gould, Michael K. Maddock, Leah Miller, Kimberly Towner, William Xiang, Anny H. Moy, Marilyn L. TI Patient-centered physical activity coaching in COPD (Walk On!): A study protocol for a pragmatic randomized controlled trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE COPD; Physical activity; Hospitalizations; Death; Pragmatic design ID OBSTRUCTIVE PULMONARY-DISEASE; REHABILITATION; INTERVENTION; PROGRAM; EXACERBATIONS; READMISSION; VALIDATION; PREDICTOR; PEDOMETER; MORTALITY AB Background: Physical inactivity is significantly associated with more frequent hospitalizations and increased mortality in COPD even after adjusting for disease severity. While practice guidelines recommend regular physical activity for all patients with COPD, health systems are challenged in operationalizing an effective and sustainable approach to assist patients in being physically active. Methods: A pragmatic randomized controlled trial design was used to determine the effectiveness of a 12-month home and community-based physical activity coaching intervention (Walk On!) compared to standard care for 1650 patients at high risk for COPD exacerbations from a large integrated health care system. Eligible patients with a COPD-related hospitalization, emergency department visit, or observational stay in the previous 12 months were automatically identified from the electronic medical records (EMR) system and randomized to treatment arms. The Walk On! intervention included collaborative monitoring of step counts, semi-automated step goal recommendations, individualized reinforcement from a physical activity coach, and peer/family support. Results: The primary composite outcome included all-cause hospitalizations, emergency department visits, observational stays, and death in the 12 months following randomization. Secondary outcomes included COPD-related utilization, cardio-metabolic markers, physical activity, symptoms, and health-related quality of life. With the exception of patient reported outcomes, all utilization and clinical variables were automatically captured from the EMR. Conclusions: If successful, findings from this multi-stakeholder driven trial of a generalizable and scalable physical activity intervention, carefully designed with sufficient flexibility, intensity, and support for a large ethnically diverse sample could re-define the standard of care to effectively address physical inactivity in COPD. (C) 2015 Elsevier Inc. All rights reserved. C1 [Nguyen, Huong Q.; Coleman, Karen J.; Gould, Michael K.; Maddock, Leah; Miller, Kimberly; Towner, William; Xiang, Anny H.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Desai, Smita] Kaiser Permanente So Calif, San Diego, CA USA. [Fan, Vincent S.] Univ Washington, Seattle, WA 98195 USA. [Moy, Marilyn L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Pulm & Crit Care Sect, Cambridge, MA 02138 USA. RP Nguyen, HQ (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, 100 S Los Robles Ave,2nd Floor, Pasadena, CA 91101 USA. EM huong.q2.nguyen@kp.org OI Xiang, Anny/0000-0003-2786-1268 FU Patient-Centered Outcomes Research Institute (PCORI) [1403-14117] FX Funding in part by the Patient-Centered Outcomes Research Institute, PCORI 1403-14117, 2015-2018 to Dr. Nguyen. NR 66 TC 1 Z9 1 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2016 VL 46 BP 18 EP 29 DI 10.1016/j.cct.2015.10.010 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DB0NH UT WOS:000368204300005 PM 26597414 ER PT J AU Gewirtz, H AF Gewirtz, Henry TI Functional Versus Anatomic Imaging of CAD: Lessons Learned from Recent Clinical Trials SO CURRENT CARDIOLOGY REPORTS LA English DT Review DE Fractional flow reserve; Coronary stenosis; Coronary revascularization; CAD clinical outcomes trials; PET myocardial blood flow ID FRACTIONAL FLOW RESERVE; CORONARY-ARTERY-DISEASE; MYOCARDIAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; PHYSIOLOGICAL ASSESSMENT; VELOCITY RESERVE; MEDICAL THERAPY; SYNTAX SCORE; GUIDED PCI; PERFUSION AB Recent clinical trials directed at imaging of coronary artery disease (CAD) have demonstrated a paradigm shift away from endpoints related to detection of CAD in favor of those related to clinical outcomes. The objective of such trials has been to determine whether physiological metrics are superior to anatomical ones for guiding therapy and improving outcomes in patients with known or suspected CAD. The present review focuses on selected trials in this area in particular DEFER, FAME 1 and 2, a meta-analysis comparing FFR to anatomically guided treatment outcomes and COURAGE SPECT MPI sub study. The rationale for using physiological as opposed to anatomical endpoints to optimize patient management, in particular coronary revascularization decisions, is emphasized. The results of the FFR-based trials are concordant and indicate physiological metrics are superior to anatomical ones for guiding therapy and improving clinical outcomes in patients with known or suspected CAD. C1 [Gewirtz, Henry] Harvard Univ, Sch Med, Dept Med, Cardiac Unit,Cardiol Div,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Sch Med, Dept Med, Cardiac Unit,Cardiol Div,Massachusetts Gen Hosp, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM gewirtz.henry@mgh.harvard.edu NR 43 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD JAN PY 2016 VL 18 IS 1 DI 10.1007/s11886-015-0686-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA9QU UT WOS:000368145400004 ER PT J AU Berman, NC Sullivan, A Wilhelm, S Cohen, IG AF Berman, Noah Chase Sullivan, Alexandra Wilhelm, Sabine Cohen, I. Glenn TI Effect of a legal prime on clinician's assessment of suicide risk SO DEATH STUDIES LA English DT Article ID BEHAVIOR; METAANALYSIS; RULES AB The present study evaluates how liability influences mental health clinicians' assessment of suicide risk. In this online vignette-based experiment, clinicians (N=268) were either primed with a legal standard prior to a case vignette or presented the case vignette alone. Clinicians then rated the patient's likelihood of suicide and need for hospitalization. Results indicated that trainees provided significantly lower ratings of suicide risk following presentation of the legal standard, but this was not associated with hospitalization endorsement. Results have training and legal implications for improving the accuracy of suicide risk assessment in both trainees and licensed professionals. C1 [Berman, Noah Chase; Sullivan, Alexandra; Wilhelm, Sabine] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cohen, I. Glenn] Harvard Univ, Sch Law, Cambridge, MA 02138 USA. RP Berman, NC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM nberman@mgh.harvard.edu FU Mind Brain Behavior Interfaculty Initiative at Harvard University FX This study was supported by a foundational grant from the Mind Brain Behavior Interfaculty Initiative at Harvard University. Funding was awarded to Noah Chase Berman, Sabine Wilhelm, and I. Glenn Cohen. The authors have no conflict of interest directly relevant to this work. NR 25 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0748-1187 EI 1091-7683 J9 DEATH STUD JI Death Stud. PY 2016 VL 40 IS 1 BP 61 EP 67 DI 10.1080/07481187.2015.1068248 PG 7 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA DA8WI UT WOS:000368087000008 PM 26207570 ER PT J AU Giani, E Laffel, L AF Giani, Elisa Laffel, Lori TI Opportunities and Challenges of Telemedicine: Observations from the Wild West in Pediatric Type 1 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Editorial Material ID ADOLESCENTS; MANAGEMENT; CHILDREN; CARE C1 [Giani, Elisa; Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult, Boston, MA 02115 USA. [Giani, Elisa; Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet Sect, Boston, MA 02115 USA. [Giani, Elisa; Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Epidemiol Sect, Boston, MA 02115 USA. [Laffel, Lori] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Laffel, L (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK089349] NR 18 TC 2 Z9 2 U1 2 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JAN 1 PY 2016 VL 18 IS 1 BP 1 EP 3 DI 10.1089/dia.2015.0360 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DA7WB UT WOS:000368014600001 PM 26756102 ER PT J AU Zhang, HH Thoonen, R Yao, V Buys, ES Popovich, J Su, YR Wang, TJ Scherrer-Crosbie, M AF Zhang, Haihua Thoonen, Robrecht Yao, Vincent Buys, Emmanuel S. Popovich, John Su, Yan Ru Wang, Thomas J. Scherrer-Crosbie, Marielle TI Regulation of B-type natriuretic peptide synthesis by insulin in obesity in male mice SO EXPERIMENTAL PHYSIOLOGY LA English DT Article ID HIGH-FAT DIET; CONTRACTILE DYSFUNCTION; CARDIAC DYSFUNCTION; LIPID-ACCUMULATION; PRESSURE-OVERLOAD; HEART-FAILURE; RESISTANCE; EXPRESSION; GENE; HYPERINSULINEMIA AB Human studies suggest that insulin resistance and obesity are associated with a decrease in B-type natriuretic peptide (BNP) plasma concentrations. The objective of the study was to gain insights into the mechanisms involved in the association between insulin resistance and decreased BNP plasma concentrations. Mice fed a high-fat, high-fructose (HFHF) diet for 4 weeks developed mild obesity and systemic insulin resistance. Elevated plasma concentrations of insulin, glucose and triglycerides were noted. The HFHF diet was also associated with myocardial insulin resistance, characterized by an impaired response of the phosphoinositide 3-kinase-AKT (PI3K-AKT) pathway to insulin in the left ventricle. Myocardial BNP expression and protein were decreased in HFHF-fed mice compared with control animals. Exposure of cardiomyocytes to 100 nM insulin activated PI3K-AKT signalling (15 min) and induced a 1.9 +/- 0.3-fold increase in BNP gene expression (6 h). Prolonged exposure of cardiomyocytes to a high insulin concentration (100 nm) for 48 h induced insulin resistance, characterized by an impaired response of the PI3K-AKT signalling pathway and a decreased response of the BNP gene expression to insulin. The decreased response in BNP gene expression was reproduced by treating cardiomyocytes for 7 h with a PI3-kinase inhibitor (wortmannin). In conclusion, HFHF diet in vivo, prolonged exposure to an elevated concentration of insulin or inhibition of the PI3K-AKT pathway in vitro all decrease BNP mRNA levels; this decrease may in turn contribute to the decreased BNP peptide concentrations in plasma observed in insulin-resistant individuals. C1 [Zhang, Haihua; Thoonen, Robrecht; Yao, Vincent; Popovich, John; Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Cardiol Div,Dept Med, Boston, MA 02115 USA. [Buys, Emmanuel S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, Boston, MA 02115 USA. [Su, Yan Ru; Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 254,55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com FU Boston area diabetes and endocrinology research center (BADERC); National Institutes of Health [R21-DK092909, R01HL102780]; American Heart Association [10SDG2610313] FX This work was supported by a Boston area diabetes and endocrinology research center (BADERC) pilot and feasibility grant and National Institutes of Health grant R21-DK092909 (both to M.S.-C.), by National Institutes of Health grant R01HL102780 (to T.J.W.) and by a Scientist Development Grant 10SDG2610313 from the American Heart Association (to E.S.B.). NR 36 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0958-0670 EI 1469-445X J9 EXP PHYSIOL JI Exp. Physiol. PD JAN 1 PY 2016 VL 101 IS 1 BP 113 EP 123 DI 10.1113/EP085091 PG 11 WC Physiology SC Physiology GA DB1EX UT WOS:000368251900013 PM 26446173 ER PT J AU Cavallaro, NL Garry, J Shi, X Gerszten, RE Anderson, EJ Walford, GA AF Cavallaro, Nicole Landa Garry, Jamie Shi, Xu Gerszten, Robert E. Anderson, Ellen J. Walford, Geoffrey A. TI A pilot, short-term dietary manipulation of branched chain amino acids has modest influence on fasting levels of branched chain amino acids SO FOOD & NUTRITION RESEARCH LA English DT Article DE branched chain amino acids; dietary intervention; nutritional modulation; cross-over clinical trial; metabolism; insulin sensitivity ID INSULIN-RESISTANCE; FOREARM MUSCLE; PROTEIN MEAL; METABOLISM; LEUCINE; HUMANS; TURNOVER; EXERCISE; OBESITY; MEN AB Background: Elevated fasting levels of branched chain amino acids (BCAAs: valine, isoleucine, leucine) in venous blood are associated with a variety of metabolic impairments, including increased risk of type 2 diabetes (T2D). Fasting BCAA levels are influenced by non-dietary factors. However, it is unknown whether fasting BCAAs can be altered through manipulation of dietary intake alone. Objective: To test whether a specific dietary intervention, using differences in BCAA intake, alters fasting BCAA levels independent of other factors. Design: Five healthy male volunteers underwent 4 days of a low and 4 days of a high BCAA content dietary intervention (ClinicalTrials.gov [NCT02110602]). All food and supplements were provided. Fasting BCAAs were measured from venous blood samples by mass spectrometry at baseline and after each intervention. Results: Diets were isocaloric; contained equal percentages of calories from carbohydrate, fats, and protein; and differed from each other in BCAA content (1.5 +/- 0.1 vs. 14.0 +/- 0.6 g for valine; 4.5 +/- 0.9 g vs. 13.8 +/- 0.5 g for isoleucine; 2.1 +/- 0.2 g vs. 27.1 +/- 1.0 g for leucine; p < 0.0001 for all). Fasting valine was significantly lower (p = 0.02) and fasting isoleucine and leucine were numerically lower following the low BCAA content vs. the high BCAA content diet levels. The inter-individual response to the dietary interventions was variable and not explained by adherence. Conclusion: Short-term dietary manipulation of BCAA intake led to modest changes in fasting levels of BCAAs. The approach from our pilot study can be expanded to test the metabolic implications of dietary BCAA manipulation. C1 [Cavallaro, Nicole Landa; Walford, Geoffrey A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Garry, Jamie; Anderson, Ellen J.] Massachusetts Gen Hosp, Clin Res Ctr, Metab & Nutr Res, Boston, MA 02114 USA. [Garry, Jamie; Anderson, Ellen J.] Harvard Univ, Sch Med, Harvard Catalyst Clin Translat Sci Ctr, Boston, MA USA. [Shi, Xu; 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. [Gerszten, Robert E.; Walford, Geoffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Ellen J.; Walford, Geoffrey A.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Boston, MA 02114 USA. RP Walford, GA (reprint author), Ctr Human Genet Res, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM gwalford@partners.org FU Massachusetts General Hospital; NIH [R01DK081572]; Harvard Clinical and Translational Science Center; National Center for Advancing Translational Science; Massachusetts General Hospital CRC; [DK099249]; [8 UL1 TR000170-05] FX This work was supported by DK099249 (GAW) and the Massachusetts General Hospital Research Scholars Fund (to Dr. Jose C. Florez). This project was supported by Grant Number NIH R01DK081572 and by Grant Number 8 UL1 TR000170-05, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science. The authors gratefully acknowledge the help and support of the Massachusetts General Hospital CRC and Dr. Anand Vaidya, who was the designated safety officer for this project. MSUD Express was provided by Vitaflo for this research study without charge. NR 23 TC 0 Z9 0 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1654-6628 EI 1654-661X J9 FOOD NUTR RES JI Food Nutr. Res. PY 2016 VL 60 DI 10.3402/fnr.v60.28592 PG 9 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA DA8WY UT WOS:000368088800001 ER PT J AU Goodenberger, ML Thomas, BC Riegert-Johnson, D Boland, CR Plon, SE Clendenning, M Win, AK Senter, L Lipkin, SM Stadler, ZK Macrae, FA Lynch, HT Weitzel, JN de la Chapelle, A Syngal, S Lynch, P Parry, S Jenkins, MA Gallinger, S Holter, S Aronson, M Newcomb, PA Burnett, T Le Marchand, L Pichurin, P Hampel, H Terdiman, JP Lu, KH Thibodeau, S Lindor, NM AF Goodenberger, McKinsey L. Thomas, Brittany C. Riegert-Johnson, Douglas Boland, C. Richard Plon, Sharon E. Clendenning, Mark Win, Aung Ko Senter, Leigha Lipkin, Steven M. Stadler, Zsofia K. Macrae, Finlay A. Lynch, Henry T. Weitzel, Jeffrey N. de la Chapelle, Albert Syngal, Sapna Lynch, Patrick Parry, Susan Jenkins, Mark A. Gallinger, Steven Holter, Spring Aronson, Melyssa Newcomb, Polly A. Burnett, Terrilea Le Marchand, Loic Pichurin, Pavel Hampel, Heather Terdiman, Jonathan P. Lu, Karen H. Thibodeau, Stephen Lindor, Noralane M. TI PMS2 monoallelic mutation carriers: the known unknown SO GENETICS IN MEDICINE LA English DT Review DE Lynch screening; Lynch syndrome; mismatch repair; PMS2; PMS2 monoallelic ID NONPOLYPOSIS COLORECTAL-CANCER; DNA MISMATCH REPAIR; LYNCH-SYNDROME; COLON-CANCER; ENDOMETRIAL CANCER; GENE; HOMOLOG; RISKS; MSH6; FREQUENCY AB Germ-line mutations in MLH1, MSH2, MSH6, and PMS2 have been shown to cause Lynch syndrome. The penetrance of the cancer and tumor spectrum has been repeatedly studied, and multiple professional societies have proposed clinical management guidelines for affected individuals. Several studies have demonstrated a reduced penetrance for monoallelic carriers of PMS2 mutations compared with the other mismatch repair (MMR) genes, but clinical management guidelines have largely proposed the same screening recommendations for all MMR gene carriers. The authors considered whether enough evidence existed to propose new screening guidelines specific to PMS2 mutation carriers with regard to age at onset and frequency of colonic screening. Published reports of PMS2 germ-line mutations were combined with unpublished cases from the authors' research registries and clinical practices, and a discussion of potential modification of cancer screening guidelines was pursued. A total of 234 monoallelic PMS2 mutation carriers from 170 families were included. Approximately 8% of those with colorectal cancer (CRC) were diagnosed before age 30, and each of these tumors presented on the left side of the colon. As it is currently unknown what causes the early onset of CRC in some families with monoallelic PMS2 germline mutations, the authors recommend against reducing cancer surveillance guidelines in families found having monoallelic PMS2 mutations in spite of the reduced penetrance. C1 [Goodenberger, McKinsey L.; Thomas, Brittany C.; Thibodeau, Stephen] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Riegert-Johnson, Douglas] Mayo Clin, Dept Med Genet, Jacksonville, FL 32224 USA. [Boland, C. Richard] Baylor Univ, Med Ctr, Charles Sammons Canc Ctr, Dept Internal Med,Baylor Res Inst,Gastroenterol, Dallas, TX USA. [Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA. [Clendenning, Mark] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. [Win, Aung Ko; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Parkville, Vic 3052, Australia. [Senter, Leigha; de la Chapelle, Albert; Hampel, Heather] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Lipkin, Steven M.] Univ Calif Irvine, Genet Epidemiol Res Inst, Irvine, CA USA. [Stadler, Zsofia K.] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Macrae, Finlay A.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Lynch, Henry T.] Creighton Univ, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. [Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Div Clin Canc Genet, Duarte, CA USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Lynch, Patrick] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Parry, Susan] Auckland City Hosp, New Zealand Familial Gastrointestinal Canc Regist, Auckland, New Zealand. [Gallinger, Steven; Holter, Spring; Aronson, Melyssa] Mt Sinai Hosp, Familial Gastrointestinal Canc Registry, Zane Cohen Ctr Digest Dis, Toronto, ON M5G 1X5, Canada. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Burnett, Terrilea; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. [Pichurin, Pavel] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Terdiman, Jonathan P.] Univ Calif San Francisco, Sch Med, Div Gastroenterol, San Francisco, CA USA. [Lu, Karen H.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. RP Goodenberger, ML (reprint author), Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. EM goodenberger.mckinsey@mayo.edu RI Gallinger, Steven/E-4575-2013; Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Win, Aung Ko/0000-0002-2794-5261 FU National Cancer Institute [UM1 CA167551, RC4A153828]; Australasian Colorectal Cancer Family Registry [U01/U24 CA097735]; Stanford Consortium Colorectal Cancer Family Registry [U01/U24 CA074799]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01/U24 CA074800]; Ontario Registry for Studies of Familial Colorectal Cancer [U01/U24 CA074783]; Seattle Colorectal Cancer Family Registry [U01/U24 CA074794]; University of Hawaii Colorectal Cancer Family Registry [U01/U24 CA074806]; Ohio State University [R01CA67941, P30CA16058]; National Institutes of Health [CA72851-18] FX This work was supported by grant UM1 CA167551 from the National Cancer Institute and through cooperative agreements with the following Colon Cancer Family Registry (CCFR) centers: Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), Stanford Consortium Colorectal Cancer Family Registry (U01/U24 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794), and University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806). The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the CCFR. The City of Hope Clinical Cancer Genetics Community Research Network was supported in part by award RC4A153828 (primary investigator J.N.W.) from the National Cancer Institute, the Ohio State University (R01CA67941 and P30CA16058), and the National Institutes of Health (CA72851-18). NR 35 TC 2 Z9 2 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JAN PY 2016 VL 18 IS 1 BP 13 EP 19 DI 10.1038/gim.2015.27 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA DA9GG UT WOS:000368116400002 PM 25856668 ER PT J AU Lin, TY Wu, JS Lin, LL Ho, TC Lin, PY Chen, JJJ AF Lin, Tai-You Wu, Jin-Shang Lin, Linda L. Ho, Ting-Chuan Lin, Pei-Yi Chen, Jia-Jin J. TI Assessments of Muscle Oxygenation and Cortical Activity Using Functional Near-infrared Spectroscopy in Healthy Adults During Hybrid Activation SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Cortical activity; functional electrical stimulation; hybrid muscle activation; muscle oxygen demand ID NEUROMUSCULAR ELECTRICAL-STIMULATION; TISSUE OXYGENATION; PREMOTOR CORTEX; UPPER EXTREMITY; STROKE PATIENTS; WRIST EXTENSOR; MOTOR CORTEX; HUMAN BRAIN; VOLUNTARY; GAIT AB Hybrid activation (HA), patterned electrical stimulation (ES) superimposed on attempted voluntary movement in close synchrony, can augment muscle force output. It has been proposed for limb function restoration and neuromodulation. Limited studies have been performed to investigate the influences of HA on muscle oxygenation and brain cortical activity. The present study investigates muscle oxygenation and cortical activity during isometric knee extension tasks with voluntary contraction (VOL) only, ES only, and with HA at three stimulation intensities, namely 10 mA (HA-I), 30 mA (HA-II), and 50 mA (HA-III). A frequency-domain near-infrared spectroscopy system was employed to assess the muscle oxygenation in the vastus lateralis as well as the cortical activity from the bilateral sensorimotor cortices (SMCs), premotor cortices (PMCs), and supplementary motor areas (SMAs). Our results show that the increased ES contribution during HA significantly increased O2 demand in working muscle, implying that the intervention of ES accelerates the muscle metabolism during muscle contraction. For cortical activation, ES only had a similar cortical activation pattern to that during VOL but with lower activation in SMCs, PMCs, and SMAs. Augmented sensorimotor activation was observed during the HA-II condition. The enhanced level of cortical activation during HA was not only affected by the ES contribution within HA but also related to the functional specificity of cortical areas. Our results suggest that HA can effectively enhance the muscle oxygen demand as well as the activation of cortical regions, and that the ES contribution within HA is a key factor. C1 [Lin, Tai-You; Ho, Ting-Chuan; Chen, Jia-Jin J.] Natl Cheng Kung Univ, Dept Biomed Engn, Tainan 701, Taiwan. [Wu, Jin-Shang] Natl Cheng Kung Univ, Coll Med, Dept Family Med, Tainan 701, Taiwan. [Lin, Linda L.] Natl Cheng Kung Univ, Inst Phys Educ Hlth & Leisure Studies, Tainan 701, Taiwan. [Lin, Pei-Yi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Opt Div,Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Chen, Jia-Jin J.] Natl Cheng Kung Univ, Med Device Innovat Ctr, Tainan 701, Taiwan. RP Lin, TY (reprint author), Natl Cheng Kung Univ, Dept Biomed Engn, Tainan 701, Taiwan. EM terry.jasonbiolab@gmail.com; jins@mail.ncku.edu.tw; lin22@mail.ncku.edu.tw; kidorange@gmail.com; ivylin@nmr.mgh.harvard.edu; chenjj@mail.ncku.edu.tw FU National Science Council of Taiwan [NSC 101-2320-B-006-018-MY3] FX This work was supported in part by National Science Council of Taiwan under Grant NSC 101-2320-B-006-018-MY3. NR 53 TC 0 Z9 0 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD JAN PY 2016 VL 24 IS 1 BP 1 EP 9 DI 10.1109/TNSRE.2015.2429655 PG 9 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA DA6YD UT WOS:000367950800001 PM 25974942 ER PT J AU Schlosser, RJ Carroll, WW Soler, ZM Pasquini, WN Mulligan, JK AF Schlosser, Rodney J. Carroll, William W. Soler, Zachary M. Pasquini, Whitney N. Mulligan, Jennifer K. TI Reduced sinonasal levels of 1-hydroxylase are associated with worse quality of life in chronic rhinosinusitis with nasal polyps SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE vitamin D; sinusitis; 1-alpha-hydroxylase; nasal polyp; allergic fungal rhinosinusitis ID VITAMIN-D DEFICIENCY; ALLERGIC FUNGAL RHINOSINUSITIS; RANDOMIZED CLINICAL-TRIAL; 25-HYDROXYVITAMIN D; D SUPPLEMENTATION; D-METABOLISM; EXTRARENAL EXPRESSION; DENDRITIC CELLS; SINUS MUCOSA; ASTHMA AB BackgroundPatients with chronic rhinosinusitis with nasal polyps (CRSwNP) have deficiencies in circulating and sinonasal levels of the inactive form of vitamin D3, 25-hydroxycholecalciferol (25VD3). Moreover, CRSwNP patients have reduced epithelial cell-specific expression of 1-hydroxylase; the enzyme responsible for the conversion of 25VD3 to its metabolically active form, 1,25-dihydroxyvitamin D3 (1,25VD3). The objective of this work was to determine the impact of sinonasal 1-hydroxylase levels combined from all cellular sources on subjective disease severity and to identify variables influencing its expression. MethodsBlood and sinus tissue explants were collected at the time of surgery from control, chronic rhinosinusitis without nasal polyps (CRSsNP), CRSwNP, and allergic fungal rhinosinusitis (AFRS) patients. 1-Hydroxylase was measured by immunostaining with flow cytometric analysis. Subjective disease severity was measured by the 22-item Sino-Nasal Outcomes Test (SNOT-22). 1,25VD3 and 25VD3 were measured by enzyme-linked immunosorbent assay (ELISA). ResultsPatients with CRSwNP or AFRS have reduced 1-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Circulating 1,25VD3 levels were the same among all groups. No differences in sinonasal 1-hydroxylase or 1,25VD3 were found between CRSwNP and AFRS. Gender, age, race, atopy, and systemic 25VD3 had no impact on sinonasal 1-hydroxylase levels in any group. However, CRSwNP patients with asthma had higher 1-hydroxylase than those without asthma. Total 1-hydroxylase levels inversely correlated with SNOT-22 in CRSwNP, but not CRSsNP. ConclusionPatients with CRSwNP and AFRS both have reduced sinonasal 1-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Reductions in intracellular 1-hydroxylase combined from all sinonasal cell types were associated with more severe subjective disease severity in CRSwNP. C1 [Schlosser, Rodney J.; Carroll, William W.; Soler, Zachary M.; Pasquini, Whitney N.; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.; Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu FU Flight Attendant Medical Research Institute [113039, 092401]; Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award [CSRD 1I01CX000377-01A2] FX Funding sources for the study: Flight Attendant Medical Research Institute (113039 to R.J.S., 092401 to J.K.M.); Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award (CSRD 1I01CX000377-01A2 to R.J.S.). NR 51 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JAN PY 2016 VL 6 IS 1 BP 58 EP 65 DI 10.1002/alr.21576 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA DA7TU UT WOS:000368007900009 PM 26575398 ER PT J AU Charidimou, A AF Charidimou, Andreas TI Cerebral Amyloid Angiopathy-Related Inflammation Biomarkers: Where are we Now? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Editorial Material DE Alzheimer's disease; amyloid-related imaging abnormalities (ARIA); cerebral amyloid angiopathy; cerebral microbleeds; cerebrospinal fluid biomarker ID IMAGING ABNORMALITIES; ALZHEIMERS-DISEASE; SPECTRUM; TRIALS AB Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an aggressive disease subtype of CAA with characteristic clinical and radiological findings. CAA-ri is an important diagnosis to reach in clinical practice, as patients typically respond to prompt immunosuppressive treatment. A definitive diagnosis of CAA-ri still requires a brain biopsy, and hence developing non-invasive diagnostic criteria and biomarkers for this syndrome are key priorities in the field. CAA-ri has gained additional interest for its notable similarities to amyloid-related imaging abnormalities, a complication of immunotherapy treatments in Alzheimer's disease patients. In this commentary, the current state of biomarkers research for CAA-ri and recently suggested diagnostic criteria are put into context. C1 [Charidimou, Andreas] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr,Dept Neurol, Boston, MA 02114 USA. [Charidimou, Andreas] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Charidimou, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM andreas.charidimou.09@ucl.ac.uk NR 20 TC 0 Z9 0 U1 2 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 50 IS 1 BP 9 EP 11 DI 10.3233/JAD-151042 PG 3 WC Neurosciences SC Neurosciences & Neurology GA DA8VS UT WOS:000368085200002 PM 26756457 ER PT J AU Malishkevich, A Marshall, GA Schultz, AP Sperling, RA Aharon-Peretz, J Gozes, I AF Malishkevich, Anna Marshall, Gad A. Schultz, Aaron P. Sperling, Reisa A. Aharon-Peretz, Judith Gozes, Illana TI Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer's Disease Biomarkers SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Activity-dependent neuroprotective protein (ADNP); Alzheimer's disease; amyloid-beta; blood-borne biomarkers; cognitively normal; mild cognitive impairment; premorbid intelligence ID PITTSBURGH COMPOUND-B; CEREBROSPINAL-FLUID; AMYLOID DEPOSITION; TAU; NAP; DAVUNETIDE; BRAIN; SCHIZOPHRENIA; ASSOCIATION; COGNITION AB Biomarkers for Alzheimer's disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1) higher premorbid intelligence and greater serum ADNP, and 2) greater cortical amyloid and lower ADNP and ADNP2 mRNAs. Significant increases in ADNP mRNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD dementia. ADNP2 transcripts showed high correlation with ADNP transcripts, especially in AD dementia lymphocytes. ADNP plasma/serum and lymphocyte mRNA levels discriminated well between cognitively normal elderly, MCI, and AD dementia participants. Measuring ADNP blood-borne levels could bring us a step closer to effectively screening and tracking AD. C1 [Malishkevich, Anna; Gozes, Illana] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, Elton Lab Mol Neuroendocrinol,Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. [Malishkevich, Anna; Gozes, Illana] Tel Aviv Univ, Adams Super Ctr Brain Studies, IL-69978 Tel Aviv, Israel. [Marshall, Gad A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Marshall, Gad A.; Schultz, Aaron P.; Sperling, Reisa A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Aharon-Peretz, Judith] Rambam Med Ctr, Cognit Neurol Unit, Haifa, Israel. RP Gozes, I (reprint author), Tel Aviv Univ, Lily & Avraham Gildor Chair Invest Growth Factors, Dept Human Mol Genet & Biochem,Sackler Fac Med, Elton Lab Mol Neuroendocrinol,Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. EM igozes@post.tau.ac.il FU AMN Foundation; Israel Ministry of Science, Technology and Space; Israel Science Foundation; CFTAU Montreal Circle of Friends; Adams family; Adams Super Center for Brain Studies; Elton Laboratory for Molecular Neuroendocrinology; Lily and Avraham Gildor Chair for the Investigation of Growth Factors at Tel Aviv University; Harvard Aging Brain Study [P01 AGO36694, R01 AG037497]; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard NeuroDiscovery Center Biomarker Study (HBS) FX Professor Gozes laboratory is supported by the AMN Foundation, the Israel Ministry of Science, Technology and Space, Israel Science Foundation, CFTAU Montreal Circle of Friends and the Adams family, Adams Super Center for Brain Studies, the Elton Laboratory for Molecular Neuroendocrinology and the Lily and Avraham Gildor Chair for the Investigation of Growth Factors at Tel Aviv University. This study was further supported by the Harvard Aging Brain Study (P01 AGO36694, R01 AG037497), the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), the Harvard NeuroDiscovery Center Biomarker Study (HBS). NR 52 TC 4 Z9 4 U1 4 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 50 IS 1 BP 249 EP 260 DI 10.3233/JAD-150799 PG 12 WC Neurosciences SC Neurosciences & Neurology GA DA8VS UT WOS:000368085200023 PM 26639975 ER PT J AU Ren, LQ Ghani, MU Wu, D Zheng, B Chen, Y Yang, K Wu, XZ Liu, H AF Ren, Liqiang Ghani, Muhammad U. Wu, Di Zheng, Bin Chen, Yong Yang, Kai Wu, Xizeng Liu, Hong TI The impact of spectral filtration on image quality in micro-CT system SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE spectral filtration; image quality; microcomputed tomography (micro-CT); contrast-to-noise ratio (CNR); tissue characteristic ID COMPUTED-TOMOGRAPHY; PERFORMANCE EVALUATION; TUNGSTEN-ANODE; RESOLUTION; ASSURANCE; DETECTOR AB This paper aims to evaluate the impact of spectral filtration on image quality in a microcomputed tomography (micro-CT) system. A mouse phantom comprising 11rods for modeling lung, muscle, adipose, and bones was scanned with 17 s and 2min, respectively. The current (mu A) for each scan was adjusted to achieve identical entrance exposure to the phantom, providing a baseline for image quality evaluation. For each region of interest (ROI) within specific composition, CT number variations, noise levels, and contrast-to-noise ratios (CNRs) were evaluated from the reconstructed images. CT number variations and CNRs for bone with high density, muscle, and adipose were compared with theoretical predictions. The results show that the impact of spectral filtration on image quality indicators, such as CNR in a micro-CT system, is significantly associated with tissue characteristics. The findings may provide useful references for optimizing the scanning parameters of general micro-CT systems in future imaging applications. C1 [Ren, Liqiang; Ghani, Muhammad U.; Wu, Di; Zheng, Bin; Liu, Hong] Univ Oklahoma, Ctr Biomed Engn, Norman, OK 73019 USA. [Ren, Liqiang; Ghani, Muhammad U.; Wu, Di; Zheng, Bin; Liu, Hong] Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA. [Chen, Yong] Univ Oklahoma, Dept Radiat Oncol, Hlth Sci Ctr, Norman, OK 73019 USA. [Yang, Kai] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wu, Xizeng] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. RP Liu, H (reprint author), Univ Oklahoma, Ctr Biomed Engn, 101 David L Boren Blvd, Norman, OK 73019 USA. EM liu@ou.edu RI Ghani, Muhammad/P-5473-2016 FU National Institutes of Health (NIH) [RO1 CA193378]; University of Oklahoma Charles; Peggy Stephenson Cancer Center - Oklahoma Tobacco Settlement Endowment Trust; Charles and Jean Smith Chair endowment fund FX This research is supported in part by National Institutes of Health (NIH), RO1 CA193378, and supported in part by a grant from the University of Oklahoma Charles and Peggy Stephenson Cancer Center funded by the Oklahoma Tobacco Settlement Endowment Trust. The authors would like to acknowledge the support of Charles and Jean Smith Chair endowment fund, as well. NR 22 TC 0 Z9 0 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2016 VL 17 IS 1 BP 301 EP 315 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB2LW UT WOS:000368341200028 PM 28297492 ER PT J AU Horvitz-Lennon, M Braun, D Normand, SL AF Horvitz-Lennon, Marcela Braun, Danielle Normand, Sharon-Lise TI Challenges in the Use of Administrative Data for Heart Failure Services Research SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID PROPENSITY SCORES; VALIDATION DATA; CLAIMS C1 [Horvitz-Lennon, Marcela] RAND Corp, Boston, MA USA. [Horvitz-Lennon, Marcela] Cambridge Hlth Alliance, Dept Psychiat, Boston, MA USA. [Braun, Danielle; Normand, Sharon-Lise] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Braun, Danielle] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Normand, Sharon-Lise] Harvard Univ, Dept Hlth Care Policy, Sch Med, Boston, MA 02115 USA. RP Normand, SL (reprint author), Harvard Univ, Dept Hlth Care Policy, Sch Med, 180 Longwood Ave, Boston, MA 02115 USA. EM sharon@hcp.med.harvard.edu NR 13 TC 0 Z9 0 U1 2 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD JAN PY 2016 VL 22 IS 1 BP 61 EP 63 DI 10.1016/j.cardfail.2015.11.005 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA7EJ UT WOS:000367967100011 PM 26592981 ER PT J AU Gunda, S Reddy, M Nath, J Nagaraj, H Atoui, M Rasekh, A Ellis, CR Badhwar, N Lee, RJ di Biase, L Mansour, M Ruskin, JN Natale, A Earnest, M Lakkireddy, DR AF Gunda, Sampath Reddy, Madhu Nath, Jayant Nagaraj, Hosakote Atoui, Moustapha Rasekh, Abdi Ellis, Christopher R. Badhwar, Nitish Lee, Randall J. di Biase, Luigi Mansour, Moussa Ruskin, Jeremy N. Natale, Andrea Earnest, Matthew Lakkireddy, Dhanunjaya R. TI Impact of Periprocedural Colchicine on Postprocedural Management in Patients Undergoing a Left Atrial Appendage Ligation Using LARIAT SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; colchicine; LARIAT procedure; left atrial appendage; pericarditis; stroke ID PERICARDIAL-EFFUSION; RANDOMIZED-TRIAL; CARDIAC-SURGERY; DOUBLE-BLIND; POSTPERICARDIOTOMY-SYNDROME; LAA LIGATION; PREVENTION; MULTICENTER; EFFICACY; SAFETY AB Periprocedural Colchicine for Epicardial Access Procedures IntroductionLeft atrial appendage (LAA) can be effectively and safely excluded using a novel percutaneous LARIAT ligation system. However, due to pericardial catheter manipulation and LAA ligation and subsequent necrosis, postprocedural course is complicated by pericarditis. We intended to evaluate the preprocedural use of colchicine on the incidence of postprocedural pericardial complications. Methods and ResultsIn this multicenter observational study, we included all consecutive patients who underwent LARIAT procedure at the participating centers. Many patients received periprocedural colchicine at the discretion of the physician. We compared the postprocedural outcomes of patients who received prophylactic periprocedural colchicine (colchicine group) with those who did not receive colchicine (standard group). A total of 344 consecutive patients, 243 in the colchicine group and 101 in the standard group, were included. The mean age, median CHADS2VASc score, and HASBLED scores were 70 11 years, 3 +/- 1.7, and 3 +/- 1.1, respectively. There were no significant differences in major baseline characteristics between the two groups. Severe pericarditis was significantly lower in the colchicine group compared to the standard group (10 [4%] vs. 16 [16%] P<0.0001). The colchicine group, compared to the standard group, had lesser pericardial drain output (186 +/- 84 mL vs. 351 +/- 83, P<0.001), shorter pericardial drain duration (16 +/- 4 vs. 23 +/- 19 hours, P<0.04), and similar incidence of delayed pericardial effusion (4 [1.6%] to 3 [3%], P = 0.42) when compared to the standard group. ConclusionUse of colchicine periprocedurally was associated with significant reduction in postprocedural pericarditis and associated complications. C1 [Gunda, Sampath; Reddy, Madhu; Nath, Jayant; Atoui, Moustapha; Earnest, Matthew; Lakkireddy, Dhanunjaya R.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Nagaraj, Hosakote] Nebraska Heart Inst, Lincoln, NE USA. [Rasekh, Abdi] Texas Heart Inst, Houston, TX 77025 USA. [Ellis, Christopher R.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Badhwar, Nitish; Lee, Randall J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [di Biase, Luigi] Montefiore Hosp, St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA. [di Biase, Luigi] Montefiore Hosp, Albert Einstein Coll Med, Austin, TX USA. [Mansour, Moussa; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA. RP Lakkireddy, DR (reprint author), Univ Kansas Hosp, Mid Amer Cardiol, Kansas City, KS 66160 USA. EM dlakkireddy@kumc.edu OI Di Biase, Luigi/0000-0001-6508-4047 FU SentreHEART, Inc.; Biosense Webster Inc; St. Jude Medical FX L. Di Biase serves as a consultant/advisory board member of Biosense-Webster, St. Jude Medical, and Stereotaxis; he has received honoraria relevant to this topic from Biotronik, Medtronic, Boston Scientific, and EpiEP. A. Natale reports honoraria from Biosense Webster and serving as consultant/advisory board member of Janssen, Boston Scientific, Medtronic, and St. Jude Medical. R. Lee is a consultant for SentreHEART Inc, with equity in the company. D. Lakkireddy has received an unrestricted research grant from SentreHEART, Inc., Biosense Webster Inc, & St. Jude Medical; speakers honoraria from Boehringer Ingelheim, Biotronik, Janssen, Pfizer; Consultant to Biosense Webster and St. Jude Medical, advisory board to Sentreheart. C. Ellis reports honoraria from Atricure & SentreHeart and serving as consultant for them as well as advisory board member for Boston Scientific. M. Mansour reports serving as a consultant for SentreHeart. J. Ruskin reports serving as consultant/advisory board member for Advanced Medical Education, Biosense Webster, CardioInsight, Cardiome, Daiichi Sankyo, Gilead Sciences, InfoBionic, Laguna Medical, Medtronic, Pfizer, Portola. Other authors: No disclosures. NR 23 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JAN PY 2016 VL 27 IS 1 BP 60 EP 64 DI 10.1111/jce.12869 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA7WV UT WOS:000368017000008 PM 26515657 ER PT J AU Moussawi, K Lin, DJ Matiello, M Chew, S Morganstern, D Vaitkevicius, H AF Moussawi, Khaled Lin, David J. Matiello, Marcelo Chew, Sheena Morganstern, Daniel Vaitkevicius, Henrikas TI Brainstem and limbic encephalitis with paraneoplastic neuromyelitis optica SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Brainstem encephalitis; Breast cancer; Limbic encephalitis; Neuromyelitis optica; Neuromyelitis optica spectrum disorders; Paraneoplastic syndrome ID EXTENSIVE TRANSVERSE MYELITIS; AQUAPORIN-4; ANTIBODY; CANCER AB The spectrum of disorders associated with anti-neuromyelitis optica (NMO) antibody is being extended to include infrequent instances associated with cancer. We describe a patient with brainstem and limbic encephalitis from NMO-immunoglobulin G in serum and cerebrospinal fluid in the context of newly diagnosed breast cancer. The neurological features markedly improved with excision of her breast cancer and immune suppressive therapy. This case further broadens the NMO spectrum disorders (NMOSD) by an association between NMOSD and cancer and raises the question of coincidental occurrence and the appropriate circumstances to search for a tumor in certain instances of NMO. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Moussawi, Khaled; Lin, David J.; Matiello, Marcelo; Chew, Sheena; Vaitkevicius, Henrikas] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Moussawi, Khaled; Lin, David J.; Matiello, Marcelo; Chew, Sheena] Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. [Moussawi, Khaled; Lin, David J.; Matiello, Marcelo; Chew, Sheena; Morganstern, Daniel; Vaitkevicius, Henrikas] Harvard Univ, Sch Med, Boston, MA USA. [Morganstern, Daniel] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Moussawi, K (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM kmoussawi@partners.org OI Moussawi, Khaled/0000-0001-6378-0428 NR 12 TC 1 Z9 1 U1 1 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 JAN PY 2016 VL 23 BP 159 EP 161 DI 10.1016/j.jocn.2015.08.006 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DB0TR UT WOS:000368220900030 PM 26412254 ER PT J AU Brewster, ME Velez, BL Foster, A Esposito, J Robinson, MA AF Brewster, Melanie E. Velez, Brandon L. Foster, Aasha Esposito, Jessica Robinson, Matthew A. TI Minority Stress and the Moderating Role of Religious Coping Among Religious and Spiritual Sexual Minority Individuals SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article DE LGB; religiosity; spirituality; religious coping; minority stress ID LIFE EVENTS; INTERNALIZED HETEROSEXISM; PSYCHOLOGICAL DISTRESS; DEPRESSIVE SYMPTOMS; GAY MEN; IDENTITY; HEALTH; RACISM; ADULTS; POPULATIONS AB In prior research with primarily heterosexual religious and spiritual individuals, positive and negative forms of religious coping have been posited to moderate the links between minority stressors and psychological outcomes (Kim, Kendall, & Webb, 2015; Szymanski & Obiri, 2011). With a sample of 143 sexual minority people, the present study extended these hypotheses by examining the moderating roles of positive and negative religious coping in the link of 2 sexual minority-specific minority stress variables (heterosexist discrimination, internalized heterosexism) with psychological distress and well-being. In partial support of our hypotheses, we found that positive religious coping moderated the relation of internalized heterosexism and psychological well-being such that greater positive religious coping weakened the deleterious impact of internalized heterosexism on psychological well-being. Negative religious coping did not moderate any links. As the first test of the moderating roles of religious coping styles in the sexual minority stress-psychological distress link, the present study yields important findings for research and practice with religious and spiritual sexual minority individuals. C1 [Brewster, Melanie E.; Velez, Brandon L.; Foster, Aasha; Esposito, Jessica] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Robinson, Matthew A.] VA Boston Healthcare Syst, Boston, MA USA. RP Brewster, ME (reprint author), Columbia Univ, Teachers Coll, Dept Counseling & Clin Psychol, 525 W 120th St,Box 102, New York, NY 10027 USA. EM melanie.brewster@tc.columbia.edu NR 59 TC 0 Z9 0 U1 11 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 EI 1939-2168 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD JAN PY 2016 VL 63 IS 1 BP 119 EP 126 DI 10.1037/cou0000121 PG 8 WC Psychology, Educational; Psychology, Applied SC Psychology GA DA9HJ UT WOS:000368119300013 PM 26460976 ER PT J AU Wang, PY Fang, JC Gao, ZH Zhang, C Xie, SY AF Wang, Ping-Yu Fang, Jun-Chao Gao, Zong-Hua Zhang, Can Xie, Shu-Yang TI Higher intake of fruits, vegetables or their fiber reduces the risk of type 2 diabetes: A meta-analysis SO JOURNAL OF DIABETES INVESTIGATION LA English DT Article DE Meta-analysis; Nutrition intake; Type 2 diabetes ID MIDDLE-AGED WOMEN; DIETARY FIBER; GLYCEMIC INDEX; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; HEART-DISEASE; WHOLE-GRAIN; CONSUMPTION; HEALTH; PREVENTION AB Aims/Introduction: Some previous studies reported no significant association of consuming fruit or vegetables, or fruit and vegetables combined, with type 2 diabetes. Others reported that only a greater intake of green leafy vegetables reduced the risk of type 2 diabetes. To further investigate the relationship between them, we carried out a meta-analysis to estimate the independent effects of the intake of fruit, vegetables and fiber on the risk of type 2 diabetes. Materials and Methods: Searches of MEDLINE and EMBASE for reports of prospective cohort studies published from 1 January 1966 to 21 July 2014 were carried out, checking reference lists, hand-searching journals and contacting experts. Results: The primary analysis included a total of 23 (11 + 12) articles. The pooled maximum-adjusted relative risk of type 2 diabetes for the highest intake vs the lowest intake were 0.91 (95% confidence interval [CI] 0.87-0.96) for total fruits, 0.75 (95% CI 0.66-0.84) for blueberries, 0.87 (95% CI 0.81-0.93) for green leafy vegetables, 0.72 (95% CI 0.57-0.90) for yellow vegetables, 0.82 (95% CI 0.67-0.99) for cruciferous vegetables and 0.93 (95% CI 0.88-0.99) for fruit fiber in these high-quality studies in which scores were seven or greater, and 0.87 (95% CI 0.80-0.94) for vegetable fiber in studies with a follow-up period of 10 years or more. Conclusions: A higher intake of fruit, especially berries, and green leafy vegetables, yellow vegetables, cruciferous vegetables or their fiber is associated with a lower risk of type 2 diabetes. C1 [Wang, Ping-Yu; Fang, Jun-Chao; Gao, Zong-Hua; Xie, Shu-Yang] Binzhou Med Univ, Dept Biochem, Yantai, Shandong, Peoples R China. [Zhang, Can] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA USA. [Zhang, Can] Harvard Univ, Sch Med, Charlestown, MA USA. RP Xie, SY (reprint author), Binzhou Med Univ, Dept Biochem, Yantai, Shandong, Peoples R China. EM shuyangxie@aliyun.com FU National Natural Science Foundation [81200601, 31371321, 31440061] FX This study was supported by the National Natural Science Foundation (Nos. 81200601, 31371321, 31440061). NR 54 TC 2 Z9 2 U1 14 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2040-1116 EI 2040-1124 J9 J DIABETES INVEST JI J. Diabetes Investig. PD JAN PY 2016 VL 7 IS 1 BP 56 EP 69 DI 10.1111/jdi.12376 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB1VF UT WOS:000368296400009 PM 26816602 ER PT J AU Chew, BH Flannigan, R Kurtz, M Gershman, B Arsovska, O Paterson, RF Eisner, BH Lange, D AF Chew, Ben H. Flannigan, Ryan Kurtz, Michael Gershman, Boris Arsovska, Olga Paterson, Ryan F. Eisner, Brian H. Lange, Dirk TI A Single Dose of Intraoperative Antibiotics Is Sufficient to Prevent Urinary Tract Infection During Ureteroscopy SO JOURNAL OF ENDOUROLOGY LA English DT Article ID INFLAMMATORY RESPONSE SYNDROME; PERCUTANEOUS NEPHROLITHOTOMY; URETERAL STENTS; BIOFILM FORMATION; 2007 GUIDELINE; PROPHYLAXIS; COLONIZATION; FEVER; ENCRUSTATION; MANIPULATION AB Background: American Urology Association (AUA) Best Practice Guidelines for ureteroscopic stone treatment recommend antibiotic coverage for <24 hours following the procedure. The purpose of this study was to evaluate if the addition of postoperative antibiotics reduces urinary tract infections (UTIs) following ureteroscopic stone treatment beyond the recommended preoperative dose. Methods: A retrospective review was performed of consecutive patients at two institutions, University of British Columbia and Massachusetts General Hospital, Harvard. All patients received a single dose of antibiotics before ureteroscopic stone treatment. A subset of patients was also given postoperative antibiotics. The rate of UTI was compared in patients receiving only preoperative antibiotics (group 1) vs those who received pre- and postoperative antibiotics (group 2). Results: Eighty-one patients underwent ureteroscopy for renal calculi. Mean time to follow up was 4288 days. Eight (9.9%) patients in total (two from group 1 and six from group 2, p=0.1457) developed UTIs postoperatively. In group 1, both patients presented with pyelonephritis (n=2); those patients with infections in group 2 presented with urosepsis (n=2) and cystitis (n=2) and two patients had asymptomatic bacteriuria. Risk factors such as preoperative stenting, nephrostomy tubes, and foley catheters neither differed between groups nor did they predispose patients to postoperative infections. Conclusions: The postoperative UTI rate in this study (9.9%) is consistent with previous reports. Our data suggest that a single preoperative dose of antibiotics is sufficient, and additional postoperative antibiotics do not decrease infection rates after ureteroscopic stone treatment. Risk for selection bias is a potential limitation. C1 [Chew, Ben H.; Flannigan, Ryan; Arsovska, Olga; Paterson, Ryan F.; Lange, Dirk] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kurtz, Michael; Gershman, Boris; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Sch Med, Cambridge, MA 02138 USA. RP Chew, BH (reprint author), Univ British Columbia, Level 6-2775 Laurel St, Vancouver, BC V5Z 1M9, Canada. EM ben.chew@ubc.ca NR 28 TC 2 Z9 2 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 EI 1557-900X J9 J ENDOUROL JI J. Endourol. PD JAN 1 PY 2016 VL 30 IS 1 BP 63 EP 68 DI 10.1089/end.2015.0511 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DA7PK UT WOS:000367996100012 PM 26413885 ER PT J AU Oduyebo, T Hinchcliff, E Meserve, EE Seidman, MA Quade, BJ Rauh-Hain, JA George, S Nucci, MR del Carmen, MG Muto, MG AF Oduyebo, Titilope Hinchcliff, Emily Meserve, Emily E. Seidman, Michael A. Quade, Bradley J. Rauh-Hain, J. Alejandro George, Suzanne Nucci, Marisa R. del Carmen, Marcela G. Muto, Michael G. TI Risk Factors for Occult Uterine Sarcoma Among Women Undergoing Minimally Invasive Gynecologic Surgery SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Article DE Laparoscopy; Morcellation; Myoma; Sarcoma; Uterine leiomyosarcoma ID CLINICAL PRESENTATION; ABDOMINAL MYOMECTOMY; LEIOMYOSARCOMA; HYSTERECTOMY; LEIOMYOMAS; MANAGEMENT; MALIGNANCY; MYOMAS; MORCELLATION; DIAGNOSIS AB Study Objective: To determine factors that can identify a population at increased risk for uterine leiomyosarcoma. Design: Retrospective case-control study (Canadian Task Force classification II-2). Setting: University teaching hospitals. Patients: Seventy-two women who underwent minimally invasive gynecologic surgery for presumed leiomyoma. Patients diagnosed with leiomyosarcoma (cases) were matched with up to 4 controls on age, year of surgery, and surgeon specialty. Intervention: Cases were identified through the pathology database, and the diagnosis of leiomyosarcoma or leiomyoma was confirmed by gynecologic pathologists. The cumulative risk of leiomyosarcoma was calculated, and factors predictive of elevated risk for leiomyosarcoma were investigated using conditional logistic regression.. Measurements and Main Results: Fifteen patients with the diagnosis of inadvertently morcellated leiomyosarcoma were identified and matched with 57 controls. The cumulative risk of diagnosing uterine leiomyosarcoma on pathology after performing minimally invasive gynecologic surgery with morcellation was 0.19% (95% confidence interval [CI], 0.06%-0.56%). The presence of a hematocrit value <30% (adjusted odds ratio [aOR], 20; 95% CI, 1.08-100; p = .05) was independently associated with the diagnosis of uterine leiomyosarcoma on multivariate analysis. Increased myoma size (aOR, 9.73; 95% CI, 0.75-1.26; p = .08) and presence of a solitary myoma (aOR, 3.85; 95% CI, 0.65-25; p = .14) were associated with a greater risk of uterine leiomyosarcoma; however, the difference was not statistically significant. Conclusion: Anemia and myoma size >7 cm may be associated with occult leiomyosarcoma; however, these criteria are not sufficiently discriminatory to allow for preoperative identification of patients with uterine sarcoma. Future large multicenter studies are needed to further investigate these findings and the discovery of innovative ways to detect uterine leiomyosarcoma are urgently needed. Journal of Minimally Invasive Gynecology (C) 2016 AAGL. All rights reserved. C1 [Oduyebo, Titilope; Hinchcliff, Emily; Muto, Michael G.] Brigham & Womens Hosp, Dept Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Oduyebo, Titilope; Hinchcliff, Emily; Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Meserve, Emily E.; Seidman, Michael A.; Quade, Bradley J.; Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Oduyebo, Titilope; Hinchcliff, Emily; Meserve, Emily E.; Seidman, Michael A.; Quade, Bradley J.; Rauh-Hain, J. Alejandro; George, Suzanne; Nucci, Marisa R.; del Carmen, Marcela G.; Muto, Michael G.] Harvard Univ, Sch Med, Boston, MA USA. [George, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Muto, MG (reprint author), Brigham & Womens Hosp, Dept Gynecol Oncol, 75 Francis St,ASBI 3rd Floor, Boston, MA 02115 USA. EM mmuto@partners.org OI Seidman, Michael/0000-0002-9594-827X FU Brigham and Women's Hospital Obstetrics and Gynecology Department called Expanding Boundaries FX Dr. Muto was supported by an internal grant from the Brigham and Women's Hospital Obstetrics and Gynecology Department called Expanding Boundaries, which paid for data collection and analysis assistance. NR 34 TC 5 Z9 5 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 EI 1553-4669 J9 J MINIM INVAS GYN JI J. Mimim. Invasive Gynecol. PD JAN PY 2016 VL 23 IS 1 BP 34 EP 39 DI 10.1016/j.jmig.2015.07.017 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DB1XG UT WOS:000368301700007 PM 26253281 ER PT J AU Sabath, DE Bender, MA Sankaran, VG Vamos, E Kentsis, A Yi, HS Greisman, HA AF Sabath, Daniel E. Bender, Michael A. Sankaran, Vijay G. Vamos, Esther Kentsis, Alex Yi, Hye-Son Greisman, Harvey A. TI Characterization of Deletions of the HBA and HBB Loci by Array Comparative Genomic Hybridization SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID GLOBIN GENE-CLUSTER; DEPENDENT PROBE AMPLIFICATION; BETA-THALASSEMIA MUTATIONS; FETAL-HEMOGLOBIN; ALPHA-THALASSEMIA; MOLECULAR CHARACTERIZATION; HEREDITARY PERSISTENCE; PRENATAL-DIAGNOSIS; RAPID DETECTION; PCR AB Thalassemia is among the most common genetic diseases worldwide. alpha-Thalassemia is usually caused by deletion of one or more of the duplicated HBA genes on chromosome 16. In contrast, most beta-thalassemia results from point mutations that decrease or eliminate expression of the HBB gene on chromosome 11. Deletions within the HBB locus result in thalassemia or hereditary persistence of fetal Hb. Although routine diagnostic testing cannot distinguish thalassemia deletions from point mutations, deletional hereditary persistence of fetal Hb is notable for having an elevated HbF Level with a normal mean corpuscular volume. A small number of deletions accounts for most alpha-thalassemias; in contrast, there are no predominant HBB deletions causing beta-thalassemia. To facilitate the identification and characterization of deletions of the HBA and HBB globin loci, we performed array-based comparative genomic hybridization using a custom oligonucleotide microarray. We accurately mapped the breakpoints of known and previously uncharacterized HBB deletions defining previously uncharacterized deletion breakpoints by PCR amplification and sequencing. The array also successfully identified the common HBA deletions -(SEA) and -(FIL). In summary, comparative genomic hybridization can be used to characterize deletions of the HBA and HBB Loci, allowing high-resolution characterization of novel deletions that are not readily detected by PCR-based methods. C1 [Sabath, Daniel E.; Yi, Hye-Son; Greisman, Harvey A.] Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. [Bender, Michael A.] Univ Washington, Dept Pediat, Seattle, WA 98104 USA. [Bender, Michael A.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Sankaran, Vijay G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Sankaran, Vijay G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA USA. [Vamos, Esther] Univ Libre Bruxelles, Dept Pediat & Genet, Brussels, Belgium. [Kentsis, Alex] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Sabath, DE (reprint author), Univ Washington, Dept Lab Med, Harborview Med Ctr, Box 359743,3NJ-345-1,325 Ninth Ave, Seattle, WA 98104 USA. EM dsabath@uw.edu; hagreisman@gmail.com FU Department of Laboratory Medicine, University of Washington [DK44746] FX Supported by NM grant DK44746 (M.A.B.) and funds from the Department of Laboratory Medicine, University of Washington. NR 32 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2016 VL 18 IS 1 BP 92 EP 99 DI 10.1016/j.jmoldx.2015.07.011 PG 8 WC Pathology SC Pathology GA DB0PZ UT WOS:000368211300011 PM 26612711 ER PT J AU Lubitz, CC Parangi, S Holm, TM Bernasconi, MJ Schalck, AP Suh, H Economopoulos, KP Gunda, V Donovan, SE Sadow, PM Wirth, LJ Sullivan, RJ Panka, DJ AF Lubitz, Carrie C. Parangi, Sareh Holm, Tammy M. Bernasconi, M. Jordana Schalck, Aislyn P. Suh, Hyunsuk Economopoulos, Konstantinos P. Gunda, Viswanath Donovan, Samuel. E. Sadow, Peter M. Wirth, Lori J. Sullivan, Ryan J. Panka, David J. TI Detection of Circulating BRAF(V600E) in Patients with Papillary Thyroid Carcinoma SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID BRAF V600E MUTATION; NEEDLE-ASPIRATION BIOPSY; LYMPH-NODE METASTASIS; CANDIDATE DIAGNOSTIC MARKERS; COMBINED CLINICAL FACTORS; RISK STRATIFICATION; CANCER; MELANOMA; ASSOCIATION; DNA AB BRAF(V600E) is a common mutation in papillary thyroid carcinoma (PTC) correlated with aggressive features. Our objective was to assess the feasibility and accuracy of a novel RNA-based blood assay to identify individuals with a high-risk tumor mutation in patients with PTC. Patients with benign or malignant thyroid disorders were included between September 2013 and July 2014 before either thyroidectomy (n = 62) or treatment of recurrent or metastatic PTC (n = 8). RNA was isolated from peripheral blood lymphocytes and reverse transcribed and followed by two rounds of nested PCR amplification with a restriction digest specific for wild-type BRAF. BRAF(V600E) 5 levels were quantified with standardization curves. Circulating BRAF(V600E) levels were compared with BRAF mutation status from surgical pathologic DNA-based tissue assays. Testing characteristics and receiving-operator curve using tissue results as the gold standard were assessed. Matched blood and tissue assays for BRAF(V600E) were performed on 70 patients with PTC (stages I to IV, n = 48) or other (n = 22) thyroid tumors. Sixty-three percent of PTC patients tested positive for BRAF(V600E) with conventional tissue assays on surgical specimens. The correlation between the RNA-based blood assay and tissue BRAF status was 0.71. PTC patients harbor detectable BRAF(V600E) circulating tumor cells. This blood assay is feasible and has potential as a biomarker for prognosis, surveillance, clinical decision making, and assessment of treatment response to BRAF-targeted therapies. C1 [Lubitz, Carrie C.; Parangi, Sareh; Holm, Tammy M.; Bernasconi, M. Jordana; Suh, Hyunsuk; Economopoulos, Konstantinos P.; Gunda, Viswanath] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Schalck, Aislyn P.; Donovan, Samuel. E.; Wirth, Lori J.; Sullivan, Ryan J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lubitz, Carrie C.; Economopoulos, Konstantinos P.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Panka, David J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Lubitz, CC (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM clubitz@partners.org OI Economopoulos, Konstantinos/0000-0003-4856-0405 FU NIH National Cancer Institute Program in Cancer Outcomes Research Training grant [R25CA092203]; NIH National Cancer Institute [K07CA177900-01, R01CA149738-01A1]; Massachusetts General Hospital Department of Surgery; Massachusetts General Hospital American Cancer Society Institutional Research grant; Egan Memorial Melanoma Translational Research Fund; Conquer Cancer Foundation; Clinical Investigator Training Program, Harvard Medical School and Massachusetts Institute of Technology FX Supported by NIH National Cancer Institute Program in Cancer Outcomes Research Training grant R25CA092203 (C.C.L.); NIH National Cancer Institute grants K07CA177900-01 (C.C.L.) and R01CA149738-01A1 (S.P.); Massachusetts General Hospital Department of Surgery (C.C.L.); Massachusetts General Hospital American Cancer Society Institutional Research grant (C.C.L.); The Egan Memorial Melanoma Translational Research Fund (R.J.S.); the Conquer Cancer Foundation (R.J.S.); and the Clinical Investigator Training Program, Harvard Medical School and Massachusetts Institute of Technology (R.J.S.). NR 56 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2016 VL 18 IS 1 BP 100 EP 108 DI 10.1016/j.jmoldx.2015.08.003 PG 9 WC Pathology SC Pathology GA DB0PZ UT WOS:000368211300012 PM 26631873 ER PT J AU Dudley, JC Zheng, ZL McDonald, T McDonald, T Le, LP Dias-Santagata, D Borger, D Batten, J Vernovsky, K Sweeney, B Arpin, RN Brugge, WR Forcione, DG Pitman, MB Iafrate, AJ AF Dudley, Jonathan C. Zheng, Zongli McDonald, Thomas McDonald, Thomas Le, Long P. Dias-Santagata, Dora Borger, Darrell Batten, Julie Vernovsky, Kathy Sweeney, Brenda Arpin, Ronald N. Brugge, William R. Forcione, David G. Pitman, Martha B. Iafrate, A. John TI Next-Generation Sequencing and Fluorescence in Situ Hybridization Have Comparable Performance Characteristics in the Analysis of Pancreaticobiliary Brushings for Malignancy SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID PRIMARY SCLEROSING CHOLANGITIS; BILE-DUCT STRICTURES; BILIARY STRICTURES; MUTATIONS; CYTOLOGY; CANCER; GUIDELINES; MANAGEMENT; NEOPLASIA; DIAGNOSIS AB Cytological evaluation of pancreatic or biliary duct brushings is a specific, but insensitive, test for malignancy. We compared adjunctive molecular testing with next-generation sequencing (NGS) relative to fluorescence in situ hybridization (FISH) for detection of high-risk neoplasia or malignancy. Bile duct brushings from 81 specimens were subjected to cytological analysis, FISH using the UroVysion probe set, and targeted NGS. Specimens were placed into negative/atypical (negative) or suspicious/positive (positive) categories depending on cytology and negative or positive categories on the basis of FISH and NGS results. Performance characteristics for each diagnostic modality were calculated on the basis of clinicopathologic follow-up and compared in a receiver operating characteristic analysis. There were 33 high-risk neoplasia/malignant strictures (41%) and 48 benign (59 A)). NGS revealed driver mutations in 24 cases (30%), including KRAS (21 of 24 cases), TP53 (14 of 24 cases), SMAD4 (6 of 24 cases), and CDKN2A (4 of 24 cases). Cytology had a sensitivity of 67% (95% CI, 48%-82%) and a specificity of 98% (95% CI, 89%-100%). When added to cytology, NGS increased the sensitivity to 85% (95% CI, 68%-95%), Leading to a significant increase in the area under the curve in a receiver operating characteristic analysis (P = 0.03). FISH increased the sensitivity to 76% (95% CI, 58%-89%), without significantly increasing the area under the curve. These results suggest that ancillary NGS testing offers advantages over FISH, although studies with larger cohorts are needed to verify these findings. C1 [Dudley, Jonathan C.; Zheng, Zongli; McDonald, Thomas; McDonald, Thomas; Le, Long P.; Dias-Santagata, Dora; Borger, Darrell; Batten, Julie; Vernovsky, Kathy; Sweeney, Brenda; Arpin, Ronald N.; Pitman, Martha B.; Iafrate, A. John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Brugge, William R.; Forcione, David G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Brugge, William R.; Forcione, David G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gastroenterol, Boston, MA USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org; aiafrate@partners.org FU Massachusetts General Hospital Pathology Departmental Funds FX Supported by Massachusetts General Hospital Pathology Departmental Funds. NR 28 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 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2016 VL 18 IS 1 BP 124 EP 130 DI 10.1016/j.jmoldx.2015.08.002 PG 7 WC Pathology SC Pathology GA DB0PZ UT WOS:000368211300014 PM 26596524 ER PT J AU Wu, LM Ramirez, SH Andrews, AM Leung, W Itoh, K Wu, J Arai, K Lo, EH Lok, J AF Wu, Limin Ramirez, Servio H. Andrews, Allison M. Leung, Wendy Itoh, Kanako Wu, Jiang Arai, Ken Lo, Eng H. Lok, Josephine TI Neuregulin1-decreases interleukin-1-induced RhoA activation, myosin light chain phosphorylation, and endothelial hyperpermeability SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE endothelial; IL-1; myosin light chain; neuregulin-1; permeability; RhoA ID BLOOD-BRAIN-BARRIER; PRIMARY CULTURES; GTPASE ACTIVITY; CELLS; PERMEABILITY; DYSFUNCTION; DISRUPTION; PROMOTES; INTEGRITY; PATHOLOGY AB Neuregulin-1 ( NRG1) is an endogenous growth factor with multiple functions in the embryonic and postnatal brain. The NRG1 gene is large and complex, transcribing more than twenty transmembrane proteins and generating a large number of isoforms in tissue and cell type-specific patterns. Within the brain, NRG1 functions have been studied most extensively in neurons and glia, as well as in the peripheral vasculature. Recently, NRG1 signaling has been found to be important in the function of brain microvascular endothelial cells, decreasing IL1 beta- induced increases in endothelial permeability. In the current experiments, we have investigated the pathways through which the NRG1- beta isoform acts on IL- 1 beta- induced endothelial permeability. Our data show that NRG1- beta increases barrier function, measured by transendothelial electrical resistance, and decreases IL- 1 beta- induced hyperpermeability, measured by dextran- 40 extravasation through a monolayer of brain microvascular endothelial cells plated on transwells. An investigation of key signaling proteins suggests that the effect of NRG1- beta on endothelial permeability is mediated through RhoA activation and myosin light chain phosphorylation, events which affect filamentous actin morphology. In addition, AG825, an inhibitor of the erbB2- associated tyrosine kinase, reduces the effect of NRG1- beta on IL- 1 beta- induced RhoA activation and myosin light chain phosphorylation. These data add to the evidence that NRG1- beta signaling affects changes in the brain microvasculature in the setting of neuroinflammation. J. Neurochem. ( 2016) 136, 250- 257. C1 [Wu, Limin; Leung, Wendy; Itoh, Kanako; Arai, Ken; Lo, Eng H.; Lok, Josephine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. [Wu, Limin; Wu, Jiang] Jilin Univ, Bethune Hosp 1, Dept Neurol, Changchun 130023, Jilin, Peoples R China. [Ramirez, Servio H.; Andrews, Allison M.] Temple Univ, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19122 USA. [Ramirez, Servio H.] Temple Univ, Sch Med, Shriners Hosp Pediat Res Ctr, Philadelphia, PA 19122 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lok, Josephine] Harvard Univ, Sch Med, Dept Pediat, Pediat Crit Care Med,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lok, J (reprint author), Massachusetts Gen Hosp, Pediat Crit Care Med, 175 Cambridge St,5th Floor, Boston, MA 02115 USA. EM jlok1@mgh.harvard.edu FU Shriners Hospitals for Children [85110-PHI-14]; China Scholarship Council [201206170107]; [R37NS037074]; [R01NS076694]; [P01NS055104]; [K08NS057339]; [R01NS091573]; [R01NS086570] FX This work was supported by the following grants: R37NS037074 (EHL), R01NS076694 (EHL), P01NS055104 (EHL), K08NS057339 (JL), R01NS091573 (JL), R01NS086570 (SHR), The Shriners Hospitals for Children: 85110-PHI-14 (SHR), China Scholarship Council: #201206170107 (LW). Statistical support was provided by The Harvard Catalyst. The authors declare no conflict of interests. NR 42 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2016 VL 136 IS 2 BP 250 EP 257 DI 10.1111/jnc.13374 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DA7AK UT WOS:000367956800005 PM 26438054 ER PT J AU del Re, EC Gao, Y Eckbo, R Petryshen, TL Blokland, GAM Seidman, LJ Konishi, J Goldstein, JM McCarley, RW Shenton, ME Bouix, S AF del Re, Elisabetta C. Gao, Yi Eckbo, Ryan Petryshen, Tracey L. Blokland, Gabriella A. M. Seidman, Larry J. Konishi, Jun Goldstein, Jill M. McCarley, Robert W. Shenton, Martha E. Bouix, Sylvain TI A New MRI Masking Technique Based on Multi-Atlas Brain Segmentation in Controls and Schizophrenia: A Rapid and Viable Alternative to Manual Masking SO JOURNAL OF NEUROIMAGING LA English DT Article DE Schizophrenia; MABS; Dice coefficient; FreeSurfer; BET; Brainwash ID HUMAN CEREBRAL-CORTEX; IMAGE REGISTRATION; EXTRACTION; ALGORITHM; FUSION; SYSTEM; MODEL; TRUTH; HEAD; FSL AB Brain masking of MRI images separates brain from surrounding tissue and its accuracy is important for further imaging analyses. We implemented a new brain masking technique based on multi-atlas brain segmentation (MABS) and compared MABS to masks generated using FreeSurfer (FS; version 5.3), Brain Extraction Tool (BET), and Brainwash, using manually defined masks (MM) as the gold standard. We further determined the effect of different masking techniques on cortical and subcortical volumes generated by FreeSurfer. METHODSImages were acquired on a 3-Tesla MR Echospeed system General Electric scanner on five control and five schizophrenia subjects matched on age, sex, and IQ. Automated masks were generated from MABS, FS, BET, and Brainwash, and compared to MM using these metrics: a) volume difference from MM; b) Dice coefficients; and c) intraclass correlation coefficients. RESULTSMean volume difference between MM and MABS masks was significantly less than the difference between MM and FS or BET masks. Dice coefficient between MM and MABS was significantly higher than Dice coefficients between MM and FS, BET, or Brainwash. For subcortical and left cortical regions, MABS volumes were closer to MM volumes than were BET or FS volumes. For right cortical regions, MABS volumes were closer to MM volumes than were BET volumes. CONCLUSIONSBrain masks generated using FreeSurfer, BET, and Brainwash are rapidly obtained, but are less accurate than manually defined masks. Masks generated using MABS, in contrast, resemble more closely the gold standard of manual masking, thereby offering a rapid and viable alternative. C1 [del Re, Elisabetta C.; Konishi, Jun; McCarley, Robert W.; Shenton, Martha E.] VA Boston Healthcare Syst, Brockton, MA USA. [del Re, Elisabetta C.; Gao, Yi; Eckbo, Ryan; Petryshen, Tracey L.; Blokland, Gabriella A. M.; Seidman, Larry J.; Konishi, Jun; Goldstein, Jill M.; McCarley, Robert W.; Shenton, Martha E.; Bouix, Sylvain] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Radiol, Boston, MA 02115 USA. RP Bouix, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. EM sylvain@bwh.harvard.edu OI Blokland, Gabriella/0000-0003-0566-444X FU NIMH NIH HHS [R01 MH092380] NR 43 TC 1 Z9 1 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1051-2284 EI 1552-6569 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN-FEB PY 2016 VL 26 IS 1 BP 28 EP 36 DI 10.1111/jon.12313 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DA7VI UT WOS:000368012400003 PM 26585545 ER PT J AU Langer, R Vacanti, J AF Langer, Robert Vacanti, Joseph TI Advances in tissue engineering SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE tissue engineering; regenerative medicine; biodegradable materials ID SPINAL-CORD-INJURY; PLURIPOTENT STEM-CELLS; SMOOTH-MUSCLE; TRANSPLANTATION; BIOMATERIALS; GROWTH AB Nearly 30 years ago, we reported on a concept now known as Tissue Engineering. Here, we report on some of the advances in this now thriving area of research. In particular, significant advances in tissue engineering of skin, liver, spinal cord, blood vessels, and other areas are discussed. (C) 2016 Elsevier Inc. All rights reserved. C1 [Langer, Robert] MIT, Cambridge, MA 02139 USA. [Vacanti, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Langer, R (reprint author), MIT, 500 Main St,Room 76-661, Cambridge, MA 02139 USA. EM rlanger@mit.edu; jvacanti@partners.org FU NHLBI NIH HHS [R01 HL060435]; NIDCR NIH HHS [R01 DE013023] NR 26 TC 9 Z9 10 U1 11 U2 43 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2016 VL 51 IS 1 BP 8 EP 12 DI 10.1016/j.jpedsurg.2015.10.022 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA DA3KW UT WOS:000367696600002 PM 26711689 ER PT J AU Greenberg, JL Shaw, AM Reuman, L Schwartz, R Wilhelm, S AF Greenberg, Jennifer L. Shaw, Ashley M. Reuman, Lillian Schwartz, Rachel Wilhelm, Sabine TI Clinical features of olfactory reference syndrome: An internet-based study SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Jikoshu-kyofu; Malodour; Obsessive-compulsive spectrum disorders; Olfactory reference syndrome; Taijin kyofusho; Somatoform disorders ID BODY DYSMORPHIC DISORDER; OBSESSIVE-COMPULSIVE DISORDER; ANXIETY STRESS SCALES; PSYCHOMETRIC PROPERTIES; DEPRESSION; HALLUCINATIONS; PHENOMENOLOGY; RELIABILITY; IMPAIRMENT; COMPUTER AB Objective: Preoccupation with perceived bodily odor has been described in neuropsychiatric disorders for more than a century; however, empirical research on olfactory reference syndrome (ORS) is scarce. This study investigated the phenomenology of ORS in a broadly ascertained, diverse sample. Method: Data were obtained from 253 subjects in an internet-based survey that operated from January - March 2010. Measures included the Yale-Brown Obsessive Compulsive Scale Modified for ORS (ORS-YBOCS), Work and Social Adjustment Scale (WSAS), Depression Anxiety Stress Scales (DASS), and symptom specific questionnaires developed for this study. Results: Individuals reported, on average, moderately severe ORS symptoms. The average age of onset of ORS symptoms was 21.1 years, with 54% reporting a chronic, unremitting course. Individuals endorsed a lifetime average of two malodorous preoccupations, most commonly stool, garbage, and ammonia. Odors were most often reported to emanate from the armpits, feet, and breasts. Nearly all participants engaged in time-consuming rituals to try to hide or fix their perceived malodor (e.g., checking and camouflaging). Eighteen percent reported poor or delusional insight and 64.0% reported ideas or delusions of reference. More severe ORS symptoms were moderately associated with female gender, poorer insight, and higher levels of impairment (in work, social leisure, ability to maintain close relationships, and consecutive days housebound). Conclusion: This is the largest study on ORS to date. Results underscore the clinical significance and psychosocial impact of this understudied disorder, and highlight the need for subsequent research to examine clinical features and inform treatment. (C) 2015 Elsevier Inc. All rights reserved. C1 [Greenberg, Jennifer L.; Shaw, Ashley M.; Reuman, Lillian; Schwartz, Rachel; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenberg, Jennifer L.; Shaw, Ashley M.; Reuman, Lillian; Schwartz, Rachel] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Greenberg, Jennifer L.; Shaw, Ashley M.; Reuman, Lillian; Schwartz, Rachel] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Shaw, Ashley M.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Reuman, Lillian] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Schwartz, Rachel] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. RP Greenberg, JL (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM jlgreenberg@mgh.harvard.edu; a.shaw6@umiami.edu; reuman@unc.edu; raschw@mail.med.upenn.edu; swilhelm@mgh.harvard.edu NR 42 TC 1 Z9 1 U1 5 U2 53 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JAN PY 2016 VL 80 BP 11 EP 16 DI 10.1016/j.jpsychores.2015.11.001 PG 6 WC Psychiatry SC Psychiatry GA DB2FO UT WOS:000368323900002 PM 26721542 ER PT J AU Eed, HR Abdel-Kader, NS El Tahan, MH Dai, TH Amin, R AF Eed, Heba Ramadan Abdel-Kader, Nora S. El Tahan, Mahmoud Helmy Dai, Tianhong Amin, Rehab TI Bioluminescence-Sensing Assay for Microbial Growth Recognition SO JOURNAL OF SENSORS LA English DT Article AB The conventional methods for microbial viability quantification require cultivation and are laborious. There is consequently a widespread need for cultivation-free methods. The adenosine triphosphate (ATP) bioluminescence-sensing assay is considered an extremely effective biosensor; hence ATP is the energy currency of all living microbes and can be used as a rapid indicator of microbial viability. We developed an ATP bioluminescence-sensing assay to detect microbial viability. A bioluminescent recombinant E. coli strain was used with luciferase extracted from transformed bacteria. Results showed that there is a direct correlation between the bioluminescence intensity of the ATP bioluminescence-sensing assay and the microbial viability. Bacterial counts from food samples were detected using the developed sensing assay and validated by the traditional plate-counting method. Compared with the plate-counting method, ATP bioluminescence-sensing assay is a more rapid and efficient approach for detecting microbial viability. C1 [Eed, Heba Ramadan; El Tahan, Mahmoud Helmy] ARC, RCFF, Giza 12619, Egypt. [Abdel-Kader, Nora S.] Cairo Univ, Dept Chem, Fac Sci, Giza 12613, Egypt. [Dai, Tianhong; Amin, Rehab] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Amin, Rehab] Cairo Univ, Natl Inst Laser Enhanced Sci, Giza 12613, Egypt. RP Amin, R (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rehabamin@niles.edu.eg FU Center for Special Studies and Programs (CSSP), Bibliotheca Alexandrina FX This study was supported by a grant from the Center for Special Studies and Programs (CSSP), Bibliotheca Alexandrina. The authors would like to thank Dr. Richard Weiss, Professor at Department of Molecular Biology, Salzburg University, Austria, for providing them with the vector pET28b. NR 16 TC 0 Z9 0 U1 0 U2 10 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 1687-725X EI 1687-7268 J9 J SENSORS JI J. Sens. PY 2016 AR 1492467 DI 10.1155/2016/1492467 PG 5 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA DB1QC UT WOS:000368282700001 ER PT J AU Gross, DJ Golijanin, P Dumont, GD Parada, SA Vopat, BG Reinert, SE Romeo, AA Provencher, CDRMT AF Gross, Daniel J. Golijanin, Petar Dumont, Guillaume D. Parada, Stephen A. Vopat, Bryan G. Reinert, Steven E. Romeo, Anthony A. Provencher, C. D. R. Matthew T. TI The effect of sagittal rotation of the glenoid on axial glenoid width and glenoid version in computed tomography scan imaging SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Computed tomography; shoulder; glenohumeral; glenoid; version; scapula; 3D ID ANTERIOR SHOULDER INSTABILITY; BONE LOSS; ROENTGENOGRAPHIC EVALUATION; GLENOHUMERAL INSTABILITY; AXILLARY VIEW; SCAPULAR Y; DISLOCATION; ACCURACY; DEFECTS; FAILURE AB Background: Computed tomography (CT) scans of the shoulder are often not well aligned to the axis of the scapula and glenoid. The purpose of this paper was to determine the effect of sagittal rotation of the glenoid on axial measurements of anterior-posterior (AP) glenoid width and glenoid version attained by standard CT scan. In addition, we sought to define the angle of rotation required to correct the CT scan to optimal positioning. Methods: A total of 30 CT scans of the shoulder were reformatted using OsiriX software multiplanar reconstruction. The uncorrected (UNCORR) and corrected (CORR) CT scans were compared for measurements of both (1) axial AP glenoid width and (2) glenoid version at 5 standardized axial cuts. Results: The mean difference in glenoid version was 2.6% (2 degrees +/- 0.1 degrees; P = .0222) and the mean difference in AP glenoid width was 5.2% (1.2 +/- 0.42 mm; P = .0026) in comparing the CORR and UNCORR scans. The mean angle of correction required to align the sagittal plane was 20.1 degrees of rotation (range, 9 degrees-39 degrees; standard error of mean, 1.2 degrees). Conclusion: These findings demonstrate that UNCORR CT scans of the glenohumeral joint do not correct for the sagittal rotation of the glenoid, and this affects the characteristics of the axial images. Failure to align the sagittal image to the 12-o'clock to 6-o'clock axis results in measurement error in both glenoid version and AP glenoid width. Use of UNCORR CT images may have notable implications for decision-making and surgical treatment. (C) 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Gross, Daniel J.; Golijanin, Petar; Dumont, Guillaume D.; Vopat, Bryan G.; Provencher, C. D. R. Matthew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Sports Med & Surg, Boston, MA USA. [Parada, Stephen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston Shoulder Inst, Boston, MA USA. [Reinert, Steven E.] Lifespan Rhode Isl Hosp, Informat Serv, Providence, RI USA. [Romeo, Anthony A.] Rush Univ, Med Ctr, Midwest Orthopaed, Chicago, IL 60612 USA. RP Provencher, CDRMT (reprint author), MGH Sports Med Ctr, 175 Cambridge St,4th Floor, Boston, MA 02114 USA. EM mattprovencher@gmail.com NR 31 TC 2 Z9 2 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 JAN PY 2016 VL 25 IS 1 BP 61 EP 68 DI 10.1016/j.jse.2015.06.017 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA DB0XR UT WOS:000368232000014 PM 26423023 ER PT J AU Oflazoglu, K Menendez, ME Ring, D O'Brien, TM Archibald, JD AF Oflazoglu, Kamilcan Menendez, Mariano E. Ring, David O'Brien, Todd M. Archibald, Jason D. TI Axillary artery injury associated with subpectoral biceps tenodesis: a case report SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Editorial Material ID LONG HEAD; TENOTOMY; OUTCOMES; STRENGTH; RISK C1 [Oflazoglu, Kamilcan; Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [O'Brien, Todd M.; Archibald, Jason D.] North Shore Med Ctr, Dept Orthopaed Surg, Danvers, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,Yawkey Ctr,Ste 2100, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 16 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 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JAN PY 2016 VL 25 IS 1 BP E25 EP E28 DI 10.1016/j.jse.2015.09.021 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA DB0XR UT WOS:000368232000005 PM 26687475 ER PT J AU Streiff, MB Agnelli, G Connors, JM Crowther, M Eichinger, S Lopes, R McBane, RD Moll, S Ansell, J AF Streiff, Michael B. Agnelli, Giancarlo Connors, Jean M. Crowther, Mark Eichinger, Sabine Lopes, Renato McBane, Robert D. Moll, Stephan Ansell, Jack TI Guidance for the treatment of deep vein thrombosis and pulmonary embolism SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Anticoagulant therapy; Venous thromboembolism; Deep vein thrombosis; Pulmonary embolism; NOACs; DOACs ID RECURRENT VENOUS THROMBOEMBOLISM; MOLECULAR-WEIGHT HEPARIN; ORAL ANTICOAGULANT-THERAPY; VENA-CAVA FILTERS; RIGHT-VENTRICULAR DYSFUNCTION; RANDOMIZED-CONTROLLED-TRIALS; CLINICAL-PRACTICE GUIDELINES; PATIENT-LEVEL METAANALYSIS; POPULATION-BASED COHORT; BONE-MINERAL DENSITY AB This guidance document focuses on the diagnosis and treatment of venous thromboembolism (VTE). Efficient, cost effective diagnosis of VTE is facilitated by combining medical history and physical examination with pre-test probability models, D dimer testing and selective use of confirmatory imaging. Clinical prediction rules, biomarkers and imaging can be used to tailor therapy to disease severity. Anticoagulation options for acute VTE include unfractionated heparin, low molecular weight heparin, fondaparinux and the direct oral anticoagulants (DOACs). DOACs are as effective as conventional therapy with LMWH and vitamin K antagonists. Thrombolytic therapy is reserved for massive pulmonary embolism (PE) or extensive deep vein thrombosis (DVT). Inferior vena cava filters are reserved for patients with acute VTE and contraindications to anticoagulation. Retrievable filters are strongly preferred. The possibility of thoracic outlet syndrome and May-Thurner syndrome should be considered in patients with subclavian/axillary and left common iliac vein DVT, respectively in absence of identifiable triggers. The optimal duration of therapy is dictated by the presence of modifiable thrombotic risk factors. Long term anticoagulation should be considered in patients with unprovoked VTE as well as persistent prothrombotic risk factors such as cancer. Short-term therapy is sufficient for most patients with VTE associated with transient situational triggers such as major surgery. Biomarkers such as D dimer and risk assessment models such the Vienna risk prediction model offer the potential to customize VTE therapy for the individual patient. Insufficient data exist to support the integration of bleeding risk models into duration of therapy planning. C1 [Streiff, Michael B.] Johns Hopkins Univ, Sch Med, Dept Pathol & Med, Div Hematol, Baltimore, MD 21218 USA. [Agnelli, Giancarlo] Univ Perugia, Dept Internal Med, Stroke Unit, I-06100 Perugia, Italy. [Connors, Jean M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Hematol Div,Brigham & Womens Hosp, Boston, MA 02115 USA. [Crowther, Mark] McMaster Univ, Dept Med & Pathol & Mol Med, Hamilton, ON, Canada. [Eichinger, Sabine] Med Univ Vienna, Dept Med, Vienna, Austria. [Lopes, Renato] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [McBane, Robert D.] Mayo Clin, Dept Med, Div Cardiovasc, Rochester, MN USA. [Moll, Stephan] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Ansell, Jack] Hofstra North Shore LIJ Sch Med, Dept Med, Hempstead, NY USA. RP Streiff, MB (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol & Med, Div Hematol, Baltimore, MD 21218 USA. EM mstreif@jhmi.edu FU Boehringer Ingelheim; Daiichi Sankyo; Janssen Pharmaceuticals FX We wish to acknowledge the support provided by Myelin and Associates with the preparation of this manuscript for submission. The work contained in this manuscript was partially funded by support from the following companies: Boehringer Ingelheim, Daiichi Sankyo and Janssen Pharmaceuticals. This guidance document is endorsed by the Anticoagulation Forum's Board of Directors: Mark Crowther, MD, MSc, FRCPC, Jack E. Ansell, MD, Allison Burnett, PharmD, Nathan Clark, PharmD, Adam Cuker, MD, David Garcia, MD, Scott Kaatz, DO, MSc, FACP, Renato D. Lopes, MD, PhD, Tracy Minichiello, MD, Edith Nutescu, PharmD, FCCP, Lynn Oertel, MS, ANP, CACP, Eva Kline-Rogers, MS, RN, NP, Terri Schnurr, RN, CCRC, Michael Streiff, MD, Diane Wirth, ANP, CACP, BCPS, CACP, Daniel Witt, Pharm D, Ann Wittkowsky, PharmD, CACP, FASHP, FCCP. NR 151 TC 10 Z9 10 U1 2 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JAN PY 2016 VL 41 IS 1 SI SI BP 32 EP 67 DI 10.1007/s11239-015-1317-0 PG 36 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DB0ID UT WOS:000368190900004 PM 26780738 ER PT J AU Burnett, AE Mahan, CE Vazquez, SR Oertel, LB Garcia, DA Ansell, J AF Burnett, Allison E. Mahan, Charles E. Vazquez, Sara R. Oertel, Lynn B. Garcia, David A. Ansell, Jack TI Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE DOACs; NOACs; Direct thrombin inhibitors; Factor Xa inhibitors; Antidotes; Care transitions; Bridging anticoagulation; Drug interactions ID ACUTE VENOUS THROMBOEMBOLISM; NONVALVULAR ATRIAL-FIBRILLATION; PROTHROMBIN COMPLEX CONCENTRATE; MOLECULAR-WEIGHT HEPARIN; DRUG-DRUG INTERACTION; ACTIVATED FACTOR-VII; RANDOMIZED CLINICAL-TRIALS; ACUTE CORONARY SYNDROME; VITAMIN-K ANTAGONISTS; DABIGATRAN ETEXILATE AB The authors of this manuscript first developed a list of pivotal practical questions related to real-world clinical scenarios involving the use of DOACs for VTE treatment. We then performed a PubMed search for topics and key words including, but not limited to, apixaban, antidote, bridging, cancer, care transitions, dabigatran, direct oral anticoagulant, deep vein thrombosis, edoxaban, interactions, measurement, perioperative, pregnancy, pulmonary embolism, reversal, rivaroxaban, switching, \thrombophilia, venous thromboembolism, and warfarin to answer these questions. Non- English publications and publications > 10 years old were excluded. In an effort to provide practical information about the use of DOACs for VTE treatment, answers to each question are provided in the form of guidance statements, with the intent of high utility and applicability for frontline clinicians across a multitude of care settings. C1 [Burnett, Allison E.] Univ New Mexico, Univ New Mexico Hosp, Inpatient Antithrombosis Serv, Coll Pharm, Albuquerque, NM 87106 USA. [Mahan, Charles E.] Univ New Mexico, Presbyterian Healthcare Serv, Coll Pharm, Albuquerque, NM 87106 USA. [Vazquez, Sara R.] Univ Utah, Hlth Care Thrombosis Ctr, Salt Lake City, UT USA. [Oertel, Lynn B.] Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA. [Garcia, David A.] Univ Washington, Sch Med, Div Hematol, Seattle, WA USA. [Ansell, Jack] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. RP Burnett, AE (reprint author), Univ New Mexico, Univ New Mexico Hosp, Inpatient Antithrombosis Serv, Coll Pharm, 2211 Lomas Blvd NE, Albuquerque, NM 87106 USA. EM aburnett@salud.unm.edu FU Boehringer Ingelheim; Daiichi Sankyo; Janssen Pharmaceuticals FX We wish to acknowledge the support provided by Myelin and Associates with the preparation of this manuscript for submission. The work contained in this manuscript was partially funded by support from the following companies: Boehringer Ingelheim, Daiichi Sankyo and Janssen Pharmaceuticals. This guidance document is endorsed by the Anticoagulation Forum's Board of Directors: Mark Crowther, MD, MSc, FRCPC, Jack E. Ansell, MD, Allison Burnett, PharmD, Nathan Clark, PharmD, Adam Cuker, MD, David Garcia, MD, Scott Kaatz, DO, MSc, FACP, Renato D. Lopes, MD, PhD, Tracy Minichiello, MD, Edith Nutescu, PharmD, FCCP, Lynn Oertel, MS, ANP, CACP, Eva Kline-Rogers, MS, RN, NP, Terri Schnurr, RN, CCRC, Michael Streiff, MD, Diane Wirth, ANP, CACP, BCPS, CACP, Daniel Witt, Pharm D, Ann Wittkowsky, PharmD, CACP, FASHP, FCCP. NR 127 TC 11 Z9 12 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JAN PY 2016 VL 41 IS 1 SI SI BP 206 EP 232 DI 10.1007/s11239-015-1310-7 PG 27 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DB0ID UT WOS:000368190900013 PM 26780747 ER PT J AU Dariushnia, SR Haskal, ZJ Midia, M Martin, LG Walker, TG Kalva, SP Clark, TWI Ganguli, S Krishnamurthy, V Saiter, CK Nikolic, B AF Dariushnia, Sean R. Haskal, Ziv J. Midia, Mehran Martin, Louis G. Walker, T. Gregory Kalva, Sanjeeva P. Clark, Timothy W. I. Ganguli, Suvranu Krishnamurthy, Venkataramu Saiter, Cindy K. Nikolic, Boris CA Soc Interventional Radiology Stand TI Quality Improvement Guidelines for Transjugular lntrahepatic Portosystemic Shunts SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID BUDD-CHIARI-SYNDROME; PORTAL-VEIN THROMBOSIS; REFRACTORY HEPATIC HYDROTHORAX; INTRAHEPATIC PORTACAVAL-SHUNT; LIVER-TRANSPLANT RECIPIENTS; ACUTE VARICEAL HEMORRHAGE; SINGLE-CENTER EXPERIENCE; LONG-TERM; CIRRHOTIC-PATIENTS; CLINICAL-OUTCOMES C1 [Dariushnia, Sean R.] Emory Univ, Sch Med, Dept Radiol Intervent Radiol & Image Guided Med, Atlanta, GA USA. [Haskal, Ziv J.] Univ Virginia, Dept Radiol & Med Imaging, Charlottesville, VA USA. [Midia, Mehran] McMaster Univ, Dept Diagnost Imaging, Hamilton, ON, Canada. [Martin, Louis G.] Emory Univ Hosp, Dept Radiol, Atlanta, GA 30322 USA. [Walker, T. Gregory] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Ganguli, Suvranu] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ganguli, Suvranu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Image Guided Canc Therapy, Boston, MA USA. [Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Div Intervent Radiol, Dept Radiol, Dallas, TX 75390 USA. [Clark, Timothy W. I.] Penn Presbyterian Med Ctr, Sect Intervent Radiol, Philadelphia, PA USA. [Krishnamurthy, Venkataramu] Univ Michigan, Med Ctr, Dept Radiol, Div Vasc & Intervent Radiol, Ann Arbor, MI 48109 USA. [Saiter, Cindy K.] Radiol Associates, Pensacola, FL USA. [Nikolic, Boris] Stratton Med Ctr, Dept Radiol, Albany, NY USA. RP Dariushnia, SR (reprint author), Care of SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM dariushnia1@yahoo.com FU Celanova Biosciences (San Antonio, TX); Koo Foundation (Taipei, Taiwan) FX S.P.K. received royalties from Springer (Berlin, Germany) and Elsevier (Philadelphia, PA), as well as personal fees from Celanova Biosciences (San Antonio, TX) and the Koo Foundation (Taipei, Taiwan). None of the other authors have identified a conflict of interest. NR 119 TC 3 Z9 3 U1 2 U2 3 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 JAN PY 2016 VL 27 IS 1 BP 1 EP 7 DI 10.1016/j.jvir.2015.09.018 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DA7DA UT WOS:000367963600001 PM 26614596 ER PT J AU Barczynski, M Randolph, GW Cernea, C AF Barczynski, Marcin Randolph, Gregory W. Cernea, Claudio CA Int Neural Monitoring Study Grp TI International Survey on the Identification and Neural Monitoring of the EBSLN During Thyroidectomy SO LARYNGOSCOPE LA English DT Article DE Thyroid surgery; external branch of the superior laryngeal nerve; intraoperative neural monitoring ID SUPERIOR LARYNGEAL NERVE; EXTERNAL BRANCH; PARATHYROID SURGERY AB Objectives/Hypothesis: Surgical management of the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy is complex. We hypothesized that there exist variations in surgical behaviors patterns in the management of the EBSLN during thyroidectomy. Study Design: A prospective Web-based anonymous survey (www.surveymonkey.com). Methods: The survey, consisting of 22 questions including surgeon demographics, laryngeal examination before and after surgery, and utilization of intraoperative neuromonitoring (IONM) for the management of the recurrent laryngeal nerve (RLN) and the EBSLN, was sent to 673 surgeons worldwide with known interest in thyroid surgery. Results: A total of 170/673 (25.3%) surgeons from five continents with low-volume (11.2%), moderate-volume (27.2%), and high-volume practices (61.5%) completed the survey. Laryngeal preoperative examination was performed by 94% of respondents. IONM was utilized in the RLN management by 95% of respondents. IONM was used for identification of the EBSLN by 26.3% of low-volume versus 68.4% of high-volume surgeons (P = .004), and 93% of respondents felt EBSLN identification with IONM as necessary in voice professionals. Staged thyroidectomy was performed for benign disease by 89.5% of low-volume versus 63.2% of high-volume surgeons (P =.031). Post-thyroid surgery laryngeal examination was performed by 36.8% of low-volume versus 64.9% of high-volume surgeons (P = .032). Conclusions: Laryngeal examination and IONM is used frequently. However, the exact pattern of utilization varies notably with demographic information. Generally, high-volume surgeons, those with otolaryngology background, and younger surgeons more commonly utilize IONM according to existing international neural monitoring study group guidelines. Prospective multicenter studies are needed to guide an evidence-based management of the EBSLN during thyroidectomy. C1 [Barczynski, Marcin] Jagiellonian Univ, Coll Med, Chair Gen Surg 3, Dept Endocrine Surg, PL-31202 Krakow, Poland. [Randolph, Gregory W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Otol & Laryngol,Div Thyroid & Parathyroid Su, Boston, MA USA. [Randolph, Gregory W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Surg, Massachusetts Eye & Ear Infirm,Div Surg Oncol, Boston, MA USA. [Cernea, Claudio] Univ Sao Paulo, Sch Med, Dept Head & Neck Surg, Sao Paulo, Brazil. RP Barczynski, M (reprint author), Jagiellonian Univ, Coll Med, Chair Gen Surg 3, Dept Endocrine Surg, 37 Pradnicka St, PL-31202 Krakow, Poland. EM marbar@mp.pl RI Cernea, Claudio/F-5610-2016 NR 17 TC 3 Z9 3 U1 0 U2 2 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 JAN PY 2016 VL 126 IS 1 BP 285 EP 291 DI 10.1002/lary.25548 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA DA9LT UT WOS:000368131000054 PM 26452247 ER PT J AU Lee, LY Harberg, C Matkowskyj, KA Cook, S Roenneburg, D Werner, S Johnson, J Foley, DP AF Lee, Lung-Yi Harberg, Calvin Matkowskyj, Kristina A. Cook, Shelly Roenneburg, Drew Werner, Sabine Johnson, Jeffrey Foley, David P. TI Overactivation of the Nuclear Factor (Erythroid-Derived 2)-Like 2-Antioxidant Response Element Pathway in Hepatocytes Decreases Hepatic Ischemia/Reperfusion Injury in Mice SO LIVER TRANSPLANTATION LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; LIVER ISCHEMIA; REACTIVE OXYGEN; RISK-FACTORS; APOPTOSIS; NRF2; ACTIVATION; PROTECTS; NECROSIS; RATS AB Hepatic ischemia/reperfusion injury (IRI) is a critical component of hepatic surgery. Oxidative stress has long been implicated as a key player in IRI. In this study, we examine the cell-specific role of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-antioxidant response element pathway in warm hepatic IRI. Nrf2 knockout (KO) and wild-type (WT) animals and novel transgenic mice expressing a constitutively active nuclear factor (erythroid-derived 2)-like 2 (caNrf2) mutant in hepatocytes (AlbCre+/caNrf2+) and their littermate controls underwent partial hepatic ischemia or sham surgery. The animals were killed 6 hours after reperfusion, and their serum and tissue were collected for analysis. As compared to WT animals after ischemia/reperfusion (IR), Nrf2 KO mice had increased hepatocellular injury with increased serum alanine aminotransferase and aspartate aminotransferase, Suzuki score, apoptosis, an increased inflammatory infiltrate, and enhanced inflammatory cytokine expression. On the other hand, AlbCre+/caNrf2+ that underwent IR had significantly reduced serum transaminases, less necrosis on histology, and a less pronounced inflammatory infiltrate and inflammatory cytokine expression as compared to the littermate controls. However, there were no differences in apoptosis. Taken together, Nrf2 plays a critical role in our murine model of warm hepatic IRI, with Nrf2 deficiency exacerbating hepatic IRI and hepatocyte-specific Nrf2 overactivation providing protection against warm hepatic IRI. (C) 2015 AASLD. C1 [Lee, Lung-Yi; Harberg, Calvin; Roenneburg, Drew; Foley, David P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Matkowskyj, Kristina A.; Cook, Shelly] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA. [Johnson, Jeffrey] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53792 USA. [Johnson, Jeffrey] Univ Wisconsin, Mol & Environm Toxicol Ctr, Madison, WI 53792 USA. [Johnson, Jeffrey] Univ Wisconsin, Ctr Neurosci, Madison, WI 53792 USA. [Johnson, Jeffrey] Univ Wisconsin, Waisman Ctr, Madison, WI 53792 USA. [Matkowskyj, Kristina A.] US Dept Vet Affairs, William S Middleton Mem Hosp, Pathol Serv, Madison, WI USA. [Foley, David P.] US Dept Vet Affairs, William S Middleton Mem Hosp, Surg Serv, Madison, WI USA. [Werner, Sabine] Swiss Fed Inst Technol, Inst Mol Hlth Sci, Dept Biol, Zurich, Switzerland. RP Foley, DP (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, 600 Highland Ave,Clin Sci Ctr H4-766, Madison, WI 53792 USA. EM foley@surgery.wisc.edu FU Clinical and Translational Science Award program through the National Institutes of Health Center for Advancing Translational Sciences [UL1TR000427]; American Society of Transplant Surgeons-Pfizer Mid-Level Faculty Award; National Institutes of Health [T32 CA0900217]; Swiss National Science Foundation [310030_132884] FX The project was supported by the Clinical and Translational Science Award program through the National Institutes of Health Center for Advancing Translational Sciences (UL1TR000427) for David P. Foley. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The project was also supported by the American Society of Transplant Surgeons-Pfizer Mid-Level Faculty Award for David P. Foley, National Institutes of Health (T32 CA0900217) for Lung-Yi Lee, and the Swiss National Science Foundation (310030_132884) for Sabine Werner. NR 33 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD JAN PY 2016 VL 22 IS 1 BP 91 EP 102 DI 10.1002/lt.24303 PG 12 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA DA9PA UT WOS:000368140500011 PM 26285140 ER PT J AU Williams, GR Bethard, JR Berkaw, MN Nagel, AK Luttrell, LM Ball, LE AF Williams, Grace R. Bethard, Jennifer R. Berkaw, Mary N. Nagel, Alexis K. Luttrell, Louis M. Ball, Lauren E. TI Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics SO METHODS LA English DT Article DE G protein-coupled receptor; Mass spectrometry; Parathyroid hormone receptor; Phosphoproteomics; Osteoblast ID REVERSED-PHASE CHROMATOGRAPHY; IN-VIVO; QUANTITATIVE PROTEOMICS; MASS-SPECTROMETRY; POSTTRANSLATIONAL MODIFICATIONS; PHOSPHORYLATION NETWORKS; FRACTION CONCATENATION; FUNCTIONAL SELECTIVITY; SITE LOCALIZATION; MC3T3-E1 CELLS AB The type 1 parathyroid hormone receptor (PTH1R) is a key regulator of calcium homeostasis and bone turnover. Here, we employed SILAC-based quantitative mass spectrometry and bioinformatic pathways analysis to examine global changes in protein phosphorylation following short-term stimulation of endogenously expressed PTH1R in osteoblastic cells in vitro. Following 5 min exposure to the conventional agonist, PTH(1-34), we detected significant changes in the phosphorylation of 224 distinct proteins. Kinase substrate motif enrichment demonstrated that consensus motifs for PKA and CAMK2 were the most heavily upregulated within the phosphoproteome, while consensus motifs for mitogen-activated protein kinases were strongly downregulated. Signaling pathways analysis identified ERK1/2 and ART as important nodal kinases in the downstream network and revealed strong regulation of small GTPases involved in cytoskeletal rearrangement, cell motility, and focal adhesion complex signaling. Our data illustrate the utility of quantitative mass spectrometry in measuring dynamic changes in protein phosphorylation following GPCR activation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Williams, Grace R.; Bethard, Jennifer R.; Berkaw, Mary N.; Nagel, Alexis K.; Ball, Lauren E.] Med Univ S Carolina, Dept Mol & Cellular Pharmacol, Charleston, SC 29425 USA. [Nagel, Alexis K.; Ball, Lauren E.] Med Univ S Carolina, Dept Oral Hlth Sci, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Ball, LE (reprint author), Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, 173 Ashley Ave,BSB 358,MSC 509, Charleston, SC 29425 USA. EM ballle@musc.edu OI Ball, Lauren/0000-0001-6780-1679 FU University Research Resource Facility [P20 GM103542]; [R01 DE020925]; [S10 D010731]; [R01 DK055524]; [R01 GM095497] FX The authors thank Susana Comte-Walters, Michael Schilling and Benjamin Neely for assistance. Mass spectrometry was performed in the MUSC Mass Spectrometry Facility, a University Research Resource Facility funded through the Office of the Provost and the SC COBRE in Oxidants, Redox Balance and Signaling (P20 GM103542). This work was supported by grants R01 DE020925 (LEB), S10 D010731 (LEB), R01 DK055524 (LML) and R01 GM095497 (LML). NR 94 TC 1 Z9 1 U1 4 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD JAN 1 PY 2016 VL 92 BP 36 EP 50 DI 10.1016/j.ymeth.2015.06.022 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DB0QL UT WOS:000368212500005 PM 26160508 ER PT J AU Cacciottolo, M Christensen, A Moser, A Liu, JH Pike, CJ Smith, C Ladu, MJ Sullivan, PM Morgan, TE Dolzhenko, E Charidimou, A Wahlund, LO Wiberg, MK Shams, S Chiang, GCY Finch, CE AF Cacciottolo, Mafalda Christensen, Amy Moser, Alexandra Liu, Jiahui Pike, Christian J. Smith, Conor LaDu, Mary Jo Sullivan, Patrick M. Morgan, Todd E. Dolzhenko, Egor Charidimou, Andreas Wahlund, Lars-Olof Wiberg, Maria Kristofferson Shams, Sara Chiang, Gloria Chia-Yi Finch, Caleb E. CA Alzheimer's Dis Neuroimaging TI The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's Disease Neuroimaging Initiative (ADNI); Alzheimer's disease (AD); Amyloid beta-peptide (A beta); Apolipoprotein E (APOE); Cerebral amyloid angiopathy (CAA); EFAD mice; Karolinska Imaging Dementia Study (KIDS); Microbleeds; Cerebral microbleeds or microhemorrhages; Sex bias ID CEREBRAL AMYLOID ANGIOPATHY; APOLIPOPROTEIN-E GENOTYPE; TRANSGENIC MOUSE MODEL; PRECURSOR PROTEIN; RISK-FACTORS; COGNITIVE IMPAIRMENT; BETA-PEPTIDE; 3XTG-AD MICE; OLDER-ADULTS; BRAIN AB The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD(+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Ab also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Ab load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. (C) 2016 Elsevier Inc. All rights reserved. C1 [Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J.; Morgan, Todd E.; Finch, Caleb E.] Univ So Calif, Davis Sch Gerontol, Dornsife Coll, Los Angeles, CA 90089 USA. [Smith, Conor; LaDu, Mary Jo] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL USA. [Sullivan, Patrick M.] Duke Univ, Dept Med, Durham VA Med Ctr, Durham, NC USA. [Sullivan, Patrick M.] GRECC, Durham, NC USA. [Dolzhenko, Egor; Finch, Caleb E.] Univ So Calif, Dept Mol & Computat Biol, Los Angeles, CA USA. [Charidimou, Andreas] Harvard Univ, Sch Med, Hemorrhag Stroke Res Program,Dept Neurol, Massachusetts Gen Hosp,Ctr Stroke Res, Boston, MA 02115 USA. [Wahlund, Lars-Olof] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Wahlund, Lars-Olof] Karolinska Univ Hosp, Div Clin Geriatr, Stockholm, Sweden. [Wiberg, Maria Kristofferson; Shams, Sara] Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Wiberg, Maria Kristofferson; Shams, Sara] Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden. [Chiang, Gloria Chia-Yi] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Finch, Caleb E.] Univ So Calif, Dept Biol Sci, Dornsife Coll, Los Angeles, CA USA. RP Finch, CE (reprint author), Univ So Calif, Davis Sch Gerontol, Dornsife Coll, Los Angeles, CA 90089 USA. EM cefinch@usc.edu OI Christensen, Amy/0000-0002-3357-0523; wahlund, lars-olof/0000-0002-9905-8426 FU NIA [R21-AG040683, P01-AG026572, P01AG044682, R21AG030128, R21AG048498, UL1RR029879, P01-AG05142, ADDF]; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; Bio-Clinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly; EuroImmun; F. Hoffmann-La Roche Ltd.; Genentech; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research Development; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals; Pfizer Inc.; Piramal Imaging; Servier; Synarc; Takeda Pharmaceutical Company FX Experimental studies on mice were supported by the NIA: R21-AG040683 (CEF); P01-AG026572 (R.D. Brinton): Project 2 (CEF), Project 3 (CJP), P01AG044682 (MJL), R21AG030128 (MJL), R21AG048498 (MJL), UL1RR029879 (CCTS), ADDF (MJL). Imaging studies were supported by the NIA: P01-AG05142 (H. Chui). Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIA U01 AG024904; DOD W81XWH-12-2e0012). ADNI is also funded by the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; Bio-Clinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly; EuroImmun; F. Hoffmann-La Roche Ltd. and Genentech; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals; Pfizer Inc.; Piramal Imaging; Servier; Synarc; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research funds ADNI sites in Canada. Private contributions are facilitated by the Foundation for the NIH (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education. The study is coordinated by the Alzheimer's Disease Cooperative Study at UC San Diego. ADNI data are disseminated by the Laboratory for NeuroImaging at USC. Valuable comments were provided by Luigi Ferrucci, MD, PhD (NIA, Baltimore, MD). NR 86 TC 8 Z9 8 U1 2 U2 10 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 JAN PY 2016 VL 37 BP 47 EP 57 DI 10.1016/j.neurobiolaging.2015.10.010 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA DA8DD UT WOS:000368033900007 PM 26686669 ER PT J AU Cheng, YS Kozin, ED Remenschneider, AK Nakajima, HH Lee, DJ AF Cheng, Yew Song Kozin, Elliott D. Remenschneider, Aaron K. Nakajima, Hideko Heidi Lee, Daniel J. TI Characteristics of Wax Occlusion in the Surgical Repair of Superior Canal Dehiscence in Human Temporal Bone Specimens SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Superior canal dehiscence bone wax; Superior canal dehiscence occlusion; Superior canal dehiscence plugging; Superior canal dehiscence repair; Superior semicircular canal dehiscence ID HEARING OUTCOMES; MANAGEMENT; SYMPTOMS; SURGERY; SIZE AB Hypothesis:Superior canal dehiscence (SCD) repair using surgical bone wax may result in variable outcomes if large wax volumes are applied.Background:SCD is a disorder characterized by a pathologic defect in the bony labyrinth of the superior semicircular canal (SSC), resulting in vestibular and/or auditory symptoms. Repair of SCD using bone wax can provide symptomatic relief, but surgical outcomes are variable. These observations may be associated with the inconsistency in the position and extension of intralabyrinthine bone wax during surgical repair.Methods:A pathological model of SCD was created using cadaveric human temporal bones and a microdrill. Defects in the arcuate eminence 0.5 to 3.5mm in length were repaired by surgical occlusion with bone wax. The volume of wax used in the repair was quantified. The position of bone wax was evaluated by direct visualization and imaging (computed tomography [CT]). To visualize wax on CT, specimens were repaired using radiopaque wax.Results:Exceedingly small volumes of bone wax (3.0-5.0mm(2)) reliably occluded the canal lumen. Multiple wax applications resulted in extension into the common crus and ampulla. The length of this extension was related to the number of applications.Conclusions:Repair of SCD with bone wax occludes the bony defect completely in most patients. Wax can extend along the lumen of the superior canal beyond the limits of the dehiscence to reach the sensory neuroepithelium of the vestibular end organs. Limiting the number of wax applications is essential to avoid inadvertent injury to the delicate neurosensory systems. C1 [Cheng, Yew Song; Kozin, Elliott D.; Remenschneider, Aaron K.; Nakajima, Hideko Heidi; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Cheng, Yew Song; Kozin, Elliott D.; Remenschneider, Aaron K.; Nakajima, Hideko Heidi; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_lee@meei.harvard.edu FU American Otological Society; [R01 DC004797] FX This study was supported by R01 DC004797 and the American Otological Society. NR 30 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2016 VL 37 IS 1 BP 83 EP 88 DI 10.1097/MAO.0000000000000916 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DA7XM UT WOS:000368018900014 PM 26649609 ER PT J AU O'Malley, JT Nadol, JB McKenna, MJ AF O'Malley, Jennifer T. Nadol, Joseph B., Jr. McKenna, Michael J. TI Anti CD163(+), Iba1(+), and CD68(+) Cells in the Adult Human Inner Ear: Normal Distribution of an Unappreciated Class of Macrophages/Microglia and Implications for Inflammatory Otopathology in Humans SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Inflammation; Innate immunity; Inner ear; Macrophages/microglia ID HEMOGLOBIN SCAVENGER RECEPTOR; HUMAN ENDOLYMPHATIC SAC; MICROGLIA-LIKE CELLS; MACROPHAGE ACTIVITY; TISSUE MACROPHAGES; SURFACE EXPRESSION; ACOUSTIC TRAUMA; CROSS-LINKING; IN-VIVO; COCHLEA AB Hypothesis:Identification, characterization, and location of cells involved in the innate immune defense system of the human inner ear may lead to a better understanding of many otologic diseases and new treatments for hearing and balance-related disorders.Background:Many otologic disorders are thought to have, as part of their disease process, an immune component. Although resident macrophages are known to exist in the mouse inner ear, the innate immune cells in the human inner ear are, to date, unknown.Methods:Primary antibodies against CD163, Iba1, and CD68 (markers known to be specific for macrophages/microglia) were used to immunohistochemically stain celloidin embedded archival temporal bone tissue of normal individuals with no known otologic disorders other than changes associated with age.Results:Cells were positively stained throughout the temporal bone within the connective tissue and supporting cells with all three markers. They were often associated with neurons and on occasion entered the sensory cell areas of the auditory and vestibular epithelium.Conclusions:We have immunohistochemically identified an unappreciated class of cells in the normal adult inner ear consistent in staining characteristics and morphology with macrophages/microglia. As in other organ systems, it is likely these cells play an essential role in organ homeostasis that has not yet been elucidated within the ear. C1 [O'Malley, Jennifer T.; Nadol, Joseph B., Jr.; McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Otopathol Lab, Dept Otolaryngol, Boston, MA 02114 USA. [Nadol, Joseph B., Jr.; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP O'Malley, JT (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Jennifer_O'Malley@MEEI.Harvard.edu FU NIDCD FX The authors thank Diane Jones, Barbara Burgess, and MengYu Zhu for careful, thoughtful, and expert preparation of the temporal bone specimens used in this study. The authors also thank Dr. Anat Stemmer-Rachamimov, M.D., for consultations, slide reviews, and suggestions of antibodies. They thank their temporal bone donors whose gifts are so very precious and integral to authors' research and understanding of otologic disorders. And the authors are very grateful for the continued financial support of the NIDCD. NR 49 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2016 VL 37 IS 1 BP 99 EP 108 DI 10.1097/MAO.0000000000000879 PG 10 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DA7XM UT WOS:000368018900016 PM 26485593 ER PT J AU Bourne, SK Duhaime, AC AF Bourne, Sarah K. Duhaime, Ann-Christine TI Transient Horizontal Gaze Palsy in a One-Month-Old Boy after a Fall SO PEDIATRIC NEUROSURGERY LA English DT Article DE Development; Gaze palsy; Frontal eye fields; Head trauma ID FRONTAL-LOBE EPILEPSY; BLUNT HEAD TRAUMA; INTRACRANIAL HEMORRHAGE; CHILDREN; ELECTROENCEPHALOGRAPHY; OUTCOMES; AGE AB A 1-month-old boy was evaluated after a fall from a height of 3 feet and found to have right parietal skull fracture as well as right and left frontal traumatic hemorrhage. Ten days after the injury, he represented with a persistent left gaze preference. Further workup including MRI and EEG determined that this finding was most likely due to a small, focal, left-frontal eye field lesion. We review the horizontal gaze pathway and demonstrate that this is present at this very young age, and that a very focal and relatively minor injury can cause gaze disturbance. (C) 2015 S. Karger AG, Basel C1 [Bourne, Sarah K.; Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Bourne, SK (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St, Boston, MA 02114 USA. EM sbourne@partners.org NR 25 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 EI 1423-0305 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PY 2016 VL 51 IS 1 BP 42 EP 47 DI 10.1159/000441680 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA DA8UM UT WOS:000368081900007 PM 26636750 ER PT J AU Lupo, PJ Robinson, JO Diamond, PM Jamal, L Danysh, HE Blumenthal-Barby, J Lehmann, LS Vassy, JL Christensen, KD Green, RC McGuire, AL AF Lupo, Philip J. Robinson, Jill O. Diamond, Pamela M. Jamal, Leila Danysh, Heather E. Blumenthal-Barby, Jennifer Lehmann, Lisa Soleymani Vassy, Jason L. Christensen, Kurt D. Green, Robert C. McGuire, Amy L. CA MedSeq Project Team TI Patients' perceived utility of whole-genome sequencing for their healthcare: findings from the MedSeq project SO PERSONALIZED MEDICINE LA English DT Article DE clinical utility; patient perspectives; perceived utility; personal utility; whole-genome sequencing ID MEDICINE; PERSPECTIVES; FRAMEWORK AB Aim: To evaluate patients' expectations regarding the perceived utility of whole-genome sequencing (WGS). Materials & methods: We used latent class analysis to characterize individuals enrolled in the MedSeq Project based on their perceived utility of WGS. Multinomial logistic regression was used to evaluate associations between participant characteristics and latent classes. Results: Findings characterized participants into one of three perceived utility groups: enthusiasts, who had a high probability of agreement with all utility items (23%); health conscious, who perceived utility in medically related areas (60%) or skeptics, who had a low probability of agreement with utility items (17%). Trust significantly predicted latent class. Conclusion: Understanding differences in perceived utility of WGS may inform strategies for uptake of this technology. C1 [Lupo, Philip J.; Danysh, Heather E.] Baylor Coll Med, Dept Pediat, Sect Hematol Oncol, Houston, TX 77030 USA. [Robinson, Jill O.; Jamal, Leila; Blumenthal-Barby, Jennifer; McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Diamond, Pamela M.] Univ Texas Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77030 USA. [Lehmann, Lisa Soleymani; Vassy, Jason L.; Christensen, Kurt D.; Green, Robert C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lehmann, Lisa Soleymani; Vassy, Jason L.] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 20115 USA. [Vassy, Jason L.] VA Boston Healthcare Syst, Sect Gen Internal Med, Boston, MA 02130 USA. [Christensen, Kurt D.; Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. RP Lupo, PJ (reprint author), Baylor Coll Med, Dept Pediat, Sect Hematol Oncol, Houston, TX 77030 USA. EM philip.lupo@bcm.edu FU US NIH [U01HG006500]; NIH; DOD; Illumina FX This work was supported by the US NIH (U01HG006500). RC Green's research is supported by grants from NIH, DOD and Illumina. RC Green has received compensation for advisory services or speaking from Invitae, Prudential, Arivale, Illumina, AIA, Helix and Roche. Clinical Trials Registration: ClinicalTrials.gov #NCT01736566. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 18 TC 4 Z9 4 U1 2 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PY 2016 VL 13 IS 1 BP 13 EP 20 DI 10.2217/pme.15.45 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DA9XP UT WOS:000368163400004 PM 27019659 ER PT J AU Elbasha, EH Chhatwal, J AF Elbasha, Elamin H. Chhatwal, Jagpreet TI Myths and Misconceptions of Within-Cycle Correction: A Guide for Modelers and Decision Makers SO PHARMACOECONOMICS LA English DT Article ID COST-EFFECTIVENESS ANALYSIS; DISCRETE-EVENT SIMULATION; LIFE TABLE METHOD; CONTINUOUS-TIME AB Commonly used decision-analytic models for cost-effectiveness analysis simulate time in discrete steps. Use of discrete-time steps can introduce errors when calculating cumulative outcomes such as costs and quality-adjusted life-years. There are a number of myths or misconceptions concerning how to correct these errors and the need to do so. This tutorial shows that, by neglecting to apply within-cycle (sometimes referred to as half-cycle or continuity) correction methods to the results of discrete-time models, the analyst may arrive at the wrong recommendation regarding the use of a technology. We show that the standard half-cycle correction method results in the same cumulative outcome as the trapezoidal rule and life-table method. However, the trapezoidal rule has the added advantage of applying the correction at each cycle, not just the initial and final cycle. We further show that the Simpson's 1/3 rule is more accurate than the trapezoidal rule. We recommend using the Simpson's 1/3 rule in the base-case analysis and, if needed, showing the results with other methods in the sensitivity analysis. We also demonstrate that both the trapezoidal and Simpson's rules can easily be implemented in commonly used software. C1 [Elbasha, Elamin H.] Merck & Co Inc, Kenilworth, NJ 07033 USA. [Chhatwal, Jagpreet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Elbasha, Elamin H.] Merck & Co Inc, Merck Res Labs, N Wales, PA 19454 USA. RP Elbasha, EH (reprint author), Merck & Co Inc, Kenilworth, NJ 07033 USA. EM elamin_elbasha@merck.com NR 24 TC 0 Z9 0 U1 1 U2 3 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1170-7690 EI 1179-2027 J9 PHARMACOECONOMICS JI Pharmacoeconomics PD JAN PY 2016 VL 34 IS 1 BP 13 EP 22 DI 10.1007/s40273-015-0337-0 PG 10 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA DA9XL UT WOS:000368163000003 PM 26643402 ER PT J AU Caplan, D Waters, G Bertram, J Ostrowski, A Michaud, J AF Caplan, David Waters, Gloria Bertram, Julia Ostrowski, Adam Michaud, Jennifer TI Effects of Written and Auditory Language-Processing Skills on Written Passage Comprehension in Middle and High School Students SO READING RESEARCH QUARTERLY LA English DT Article DE Assessment; Diagnostic; Screening; Standards-based; To inform instruction; as inquiry; Comprehension; Depth of (higher level; literal level; etc; ); Listening; Making inferences; Text features; text structure; Decoding; High-frequency words; Morphemic analysis; Polysyllabic analysis; Sight words; word recognition; Structural analysis; Literature; Nonfiction; Theoretical perspectives; Cognitive; Linguistics; Psycholinguistic; Vocabulary; Affixes; Morphology; Word structure; Early adolescence; Adolescence ID INFERENTIAL MEDIATION MODEL; READING-COMPREHENSION; SYNTACTIC COMPREHENSION; POOR READERS; FIT INDEXES; SAMPLE-SIZE; KNOWLEDGE; LITERACY; TEXT; ABILITY AB The authors assessed 4,865 middle and high school students for the ability to recognize and understand written and spoken morphologically simple words, morphologically complex words, and the syntactic structure of sentences and for the ability to answer questions about facts presented in a written passage and to make inferences based on those facts. Factor analysis of combined accuracy and reaction time results for the tests of simple words, complex words, and sentences resulted in three factors in both the auditory and written modalities, reflecting recognition of forms of simple and complex words, understanding of simple and complex words, and recognition of the structure and understanding the meaning of sentences. Structural equation models showed direct effects of these factors in both modalities on written passage comprehension. The results provide evidence that skills in processing language in the written modality are separate from, although related to, skills in auditory language processing and are important determinants of comprehension of written passages in middle and high school. C1 [Caplan, David; Waters, Gloria; Bertram, Julia; Ostrowski, Adam] Boston Univ, Dept Speech Language & Hearing Sci, Coll Hlth & Rehabil Sci, Sargent Coll, Boston, MA 02215 USA. [Caplan, David] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Neurol, Boston, MA 02114 USA. [Caplan, David] Harvard Univ, Neuropsychol Lab, Neurol, Sch Med, Boston, MA USA. [Waters, Gloria] Boston Univ, Res, Boston, MA 02215 USA. [Michaud, Jennifer] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Boston Univ, Dept Speech Language & Hearing Sci, Coll Hlth & Rehabil Sci, Sargent Coll, Boston, MA 02215 USA. EM dcaplan@partners.org; gwaters@bu.edu; jbertram@bu.edu; adamost@bu.edu; jmichaud1@partners.org FU Institute for Educational Sciences (IES/DoE) [R305A100261] FX The research reported here was supported by a grant from the Institute for Educational Sciences (IES/DoE R305A100261) to Gloria Waters and David Caplan. NR 66 TC 1 Z9 1 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0034-0553 EI 1936-2722 J9 READ RES QUART JI Read. Res. Q. PD JAN-MAR PY 2016 VL 51 IS 1 BP 67 EP 92 DI 10.1002/rrq.126 PG 26 WC Education & Educational Research; Psychology, Educational SC Education & Educational Research; Psychology GA DB0YI UT WOS:000368234100004 ER PT J AU Ling, XX Liu, Y Huang, Z Shah, PK Li, C AF Ling, Xiaoxi Liu, Yu Huang, Zhen Shah, Parantu K. Li, Cheng TI A graphical article-level metric for intuitive comparison of large-scale literatures SO SCIENTOMETRICS LA English DT Article DE Graphical article-level metrics; Visualization; Science navigation map ID CITATIONS AB With the advances of all research fields, the volume of scientific literature has grown exponentially over the past decades, and the management and exploration of scientific literature is becoming an increasingly complicated task. It calls for a tool that combines scientific impacts and social focuses to visualize relevant papers from a specific research area and time period, and to find important and interesting papers. Therefore, we propose a graphical article-level metric (gALM), which captures the impact and popularity of papers from scientific and social aspects. These two dimensions are combined and visualized graphically as a circular map. The map is divided into sectors of papers belonging to a publication year, and each block represents a paper's journal citations by block size and readerships in Mendeley by block color. In this graphical way, gALM provides a more intuitive comparison of large-scale literatures. In addition, we also design an online Web server, Science Navigation Map (SNM), which not only visualizes the gALM but provides it with interactive features. Through an interactive visualization map of article-level metrics on scientific impact and social popularity in Mendeley, users can intuitively make a comparison of papers as well as explore and filter important and relevant papers by these metrics. We take the journal PLoS Biology as an example and visualize all the papers published in PLoS Biology during 2003 and 2014 by SNM. From this map, one can easily and intuitively find basic statistics of papers, such as the most cited papers and the most popular papers in Mendeley during a time period. SNM on the journal PLoS Biology is publicly available at http://www.linkscholar.org/plosbiology/. C1 [Ling, Xiaoxi; Liu, Yu; Huang, Zhen] Dalian Univ Technol, Sch Software, Dalian, Liaoning, Peoples R China. [Shah, Parantu K.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Shah, Parantu K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Cheng] Peking Univ, Sch Life Sci, Peking Tsinghua Ctr Life Sci, Ctr Stat Sci, Beijing 100871, Peoples R China. RP Liu, Y (reprint author), Dalian Univ Technol, Sch Software, Dalian, Liaoning, Peoples R China. EM lxx2260@126.com; yuliu@dlut.edu.cn; kobehz24@gmail.com; parantu.shah@gmail.com; lch3000@gmail.com FU Natural Science Foundation of China [U1233110]; Fundamental Research Funds for the Central Universities [DUT13JR01] FX This work was supported by grants from the Natural Science Foundation of China (No. U1233110) and the Fundamental Research Funds for the Central Universities (No. DUT13JR01). NR 28 TC 0 Z9 0 U1 5 U2 26 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0138-9130 EI 1588-2861 J9 SCIENTOMETRICS JI Scientometrics PD JAN PY 2016 VL 106 IS 1 BP 41 EP 50 DI 10.1007/s11192-015-1782-4 PG 10 WC Computer Science, Interdisciplinary Applications; Information Science & Library Science SC Computer Science; Information Science & Library Science GA DA8SG UT WOS:000368075800003 ER PT J AU Haugen, BR Alexander, EK Bible, KC Doherty, GM Mandel, SJ Nikiforov, YE Pacini, F Randolph, GW Sawka, AM Schlumberger, M Schuff, KG Sherman, SI Sosa, JA Steward, DL Tuttle, RM Wartofsky, L AF Haugen, Bryan R. Alexander, Erik K. Bible, Keith C. Doherty, Gerard M. Mandel, Susan J. Nikiforov, Yuri E. Pacini, Furio Randolph, Gregory W. Sawka, Anna M. Schlumberger, Martin Schuff, Kathryn G. Sherman, Steven I. Sosa, Julie Ann Steward, David L. Tuttle, R. Michael Wartofsky, Leonard TI 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer SO THYROID LA English DT Article ID FINE-NEEDLE-ASPIRATION; RECOMBINANT HUMAN THYROTROPIN; WHOLE-BODY SCAN; LYMPH-NODE DISSECTION; LOW-RISK PATIENTS; POSITRON-EMISSION-TOMOGRAPHY; QUALITY-OF-LIFE; CENTRAL NECK DISSECTION; RADIOIODINE REMNANT ABLATION; RADIOACTIVE IODINE THERAPY AB Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders. C1 [Haugen, Bryan R.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Alexander, Erik K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Bible, Keith C.] Mayo Clin, Rochester, MN USA. [Doherty, Gerard M.] Boston Med Ctr, Boston, MA USA. [Mandel, Susan J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Nikiforov, Yuri E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Pacini, Furio] Univ Siena, I-53100 Siena, Italy. [Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Sawka, Anna M.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Schlumberger, Martin] Inst Gustave Roussy, Villejuif, France. [Schlumberger, Martin] Univ Paris 11, Villejuif, France. [Schuff, Kathryn G.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sosa, Julie Ann] Duke Univ, Sch Med, Durham, NC USA. [Steward, David L.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wartofsky, Leonard] MedStar Washington Hosp Ctr, Washington, DC USA. RP Haugen, BR (reprint author), Univ Colorado, Sch Med, Aurora, CO 80045 USA. EM bryan.haugen@ucdenver.edu OI Sherman, Steven/0000-0002-3079-5153 FU ATA; ThyCa: Thyroid Cancer Survivors' Association, Inc. FX The task force wishes to thank Ms. Bobbi Smith, Executive Director, ATA, and Ms. Sharleene Cano, Assistant to the Taskforce, for their constant help and support, as well as Ms. Vicki Wright (Division of Endocrinology, University of Colorado School of Medicine) for her assistance in manuscript preparation. We thank Dr. Joshua Klopper (Division of Endocrinology, University of Colorado School of Medicine) on behalf of the CAC Quality Of Life Task Force for the contribution of the Survivorship Care section [D9]. We also thank Dr. Irwin Klein (North Shore University Hospital, Manhasset, New York) for his input on TSH targets for long-term thyroid hormone therapy (Table 15). We would like to thank the ATA members who responded to our survey in preparation for this iteration of the guidelines as well as manuscript review prior to journal submission, and the leadership of ThyCa: Thyroid Cancer Survivors' Association, Inc. and Thyroid Cancer Canada who provided written feedback on our survey. A.M.S. holds a Cancer Care Ontario Health Services Research Chair, which enabled protected time for research and contribution to these guidelines. These guidelines were funded by the ATA without support from any commercial sources. The patient organization, ThyCa: Thyroid Cancer Survivors' Association, Inc., contributed an unrestricted educational grant toward the development of the thyroid nodules and differentiated thyroid cancer guidelines. NR 1071 TC 466 Z9 504 U1 22 U2 62 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN 1 PY 2016 VL 26 IS 1 BP 1 EP 133 DI 10.1089/thy.2015.0020 PG 133 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DA7YT UT WOS:000368022200001 PM 26462967 ER PT J AU Ceccaldi, R Rondinelli, B D'Andrea, AD AF Ceccaldi, Raphael Rondinelli, Beatrice D'Andrea, Alan D. TI Repair Pathway Choices and Consequences at the Double-Strand Break SO TRENDS IN CELL BIOLOGY LA English DT Review ID DNA END RESECTION; CHROMOSOMAL TRANSLOCATION FORMATION; CTIP-MEDIATED RESECTION; HOMOLOGOUS-RECOMBINATION; SACCHAROMYCES-CEREVISIAE; GENOMIC INSTABILITY; CELL-CYCLE; MAMMALIAN-CELLS; DAMAGE RESPONSE; CANCER AB DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genomic integrity. Failure to repair a DSB has deleterious consequences, including genomic instability and cell death. Indeed, misrepair of DSBs can lead to inappropriate end-joining events, which commonly underlie oncogenic transformation due to chromosomal translocations. Typically, cells employ two main mechanisms to repair DSBs: homologous recombination (HR) and classical nonhomologous end joining (C-NHEJ). In addition, alternative error-prone DSB repair pathways, namely alternative end joining (alt-EJ) and single-strand annealing (SSA), have been recently shown to operate in many different conditions and to contribute to genome rearrangements and oncogenic transformation. Here, we review the mechanisms regulating DSB repair pathway choice, together with the potential interconnections between HR and the annealing-dependent error-prone DSB repair pathways. C1 [Ceccaldi, Raphael; Rondinelli, Beatrice; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu FU Ovarian Cancer Research Fellowship (OCRF); Italian Association for Cancer Research (AIRC) Fellowships for Abroad; National Institutes of Health (NIH) [P50CA168504, R01HL52725]; OCRF; Breast Cancer Research Foundation (BCRF) FX We would like to thank Jessica C. Liu and Prabha Sarangl for editing the manuscript and helpful discussions. RC. is a recipient of the Ovarian Cancer Research Fellowship (OCRF). B.R. is a recipient of the Italian Association for Cancer Research (AIRC) Fellowships for Abroad. This work was supported by National Institutes of Health (NIH) grants P50CA168504 and R01HL52725 and by grants from the OCRF and Breast Cancer Research Foundation (BCRF) to A.D.D. NR 77 TC 63 Z9 67 U1 21 U2 66 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JAN PY 2016 VL 26 IS 1 SI SI BP 52 EP 64 DI 10.1016/j.tcb.2015.07.009 PG 13 WC Cell Biology SC Cell Biology GA DB0NY UT WOS:000368206000007 PM 26437586 ER PT J AU Swirski, FK Robbins, CS Nahrendorf, M AF Swirski, Filip K. Robbins, Clinton S. Nahrendorf, Matthias TI Development and Function of Arterial and Cardiac Macrophages SO TRENDS IN IMMUNOLOGY LA English DT Review ID TISSUE-RESIDENT MACROPHAGES; HEMATOPOIETIC STEM-CELLS; HUMAN ATHEROSCLEROTIC PLAQUES; STEADY-STATE; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; IN-VIVO; CIRCULATING MONOCYTES; TRANSGENIC MICE; INFLAMMATION AB Macrophages inhabit all major organs, and are capable of adapting their functions to meet the needs of their home tissues. The recent recognition that tissue macrophages derive from different sources, coupled with the notion that environmental cues and inflammatory stimuli can sculpt and agitate homeostasis, provides a frame of reference from which we can decipher the breadth and depth of macrophage activity. Here we discuss macrophages residing in the cardiovascular system, focusing particularly on their development and function in steady state and disease. Central to our discussion is the tension between macrophage ontogeny as a determinant of macrophage function, and the idea that tissues condition macrophage activities and supplant the influence of macrophage origins in favor of environmental demands. C1 [Swirski, Filip K.; Nahrendorf, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Robbins, Clinton S.] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto Gen Res Inst, Dept Immunol, Toronto, ON M5G 1L7, Canada. [Robbins, Clinton S.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1L7, Canada. RP Swirski, FK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu FU Massachusetts General Hospital Research Scholar Award [R01HL117829, R01NS084863]; Howard M. Goodman Fellowship; [R01HL095612]; [R01HL128264] FX This work was supported by grants R01HL117829, R01NS084863, a Massachusetts General Hospital Research Scholar Award (to M.N.), and R01HL095612, R01HL128264, and Howard M. Goodman Fellowship (to F.K.S.). C.S.R. (clint.robbins@utoronto.ca) and M.N. (mnahrendorf@mgh.harvard.edu) may also be contacted to discuss this article. NR 87 TC 3 Z9 3 U1 2 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD JAN PY 2016 VL 37 IS 1 BP 32 EP 40 DI 10.1016/j.it.2015.11.004 PG 9 WC Immunology SC Immunology GA DB0OW UT WOS:000368208400005 PM 26748179 ER PT J AU McKee, AC Cairns, NJ Dickson, DW Folkerth, RD Keene, CD Litvan, I Perl, DP Stein, TD Vonsattel, JP Stewart, W Tripodis, Y Crary, JF Bieniek, KF Dams-O'Connor, K Alvarez, VE Gordon, WA AF McKee, Ann C. Cairns, Nigel J. Dickson, Dennis W. Folkerth, Rebecca D. Keene, C. Dirk Litvan, Irene Perl, Daniel P. Stein, Thor D. Vonsattel, Jean-Paul Stewart, William Tripodis, Yorghos Crary, John F. Bieniek, Kevin F. Dams-O'Connor, Kristen Alvarez, Victor E. Gordon, Wayne A. CA TBI CTE Grp TI The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy SO ACTA NEUROPATHOLOGICA LA English DT Article DE Chronic traumatic encephalopathy; Traumatic brain injury; Tauopathy; Brain trauma; Neurodegenerative disorders ID PROGRESSIVE SUPRANUCLEAR PALSY; REPETITIVE HEAD-INJURY; FOOTBALL-LEAGUE PLAYER; CORTICOBASAL DEGENERATION; NEUROFIBRILLARY TANGLES; DEMENTIA-PUGILISTICA; ALZHEIMERS-DISEASE; PUNCH-DRUNK; TAUOPATHY; PATHOLOGY AB Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer's disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen's kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen's kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II-III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies. C1 [McKee, Ann C.; Alvarez, Victor E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McKee, Ann C.; Stein, Thor D.; Alvarez, Victor E.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [McKee, Ann C.; Stein, Thor D.; Tripodis, Yorghos; Alvarez, Victor E.] Boston Univ, Sch Med, Alzheimers Dis Ctr, CTE Program, Boston, MA 02118 USA. [McKee, Ann C.; Stein, Thor D.; Alvarez, Victor E.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [McKee, Ann C.; Stein, Thor D.] Dept Veteran Affairs Med Ctr, Bedford, MA 01730 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Dickson, Dennis W.; Bieniek, Kevin F.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Folkerth, Rebecca D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Keene, C. Dirk] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Litvan, Irene] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Perl, Daniel P.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Dept Pathol, Bethesda, MD 20814 USA. [Vonsattel, Jean-Paul] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Stewart, William] Univ Glasgow, Inst Neurosci & Psychol, Dept Neuropathol, Glasgow G51 4TF, Lanark, Scotland. [Stewart, William] Queen Elizabeth Univ Hosp, Glasgow G51 4TF, Lanark, Scotland. [Tripodis, Yorghos] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Crary, John F.] Icahn Sch Med Mt Sinai Sch, Ronald M Loeb Ctr Alzheimers Dis, Friedman Brain Inst, Fishberg Dept Neurosci,Dept Pathol, New York, NY 10029 USA. [Dams-O'Connor, Kristen; Gordon, Wayne A.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. RP McKee, AC (reprint author), Boston Univ, Sch Med, Dept Neurol, 72 East Concord St, Boston, MA 02118 USA. EM amckee@bu.edu RI Keene, Christopher/N-1806-2015; OI Tripodis, Yorghos/0000-0003-2190-7608; Bieniek, Kevin/0000-0003-4922-864X; Stewart, William/0000-0003-2199-2582; Litvan, Irene/0000-0002-3485-3445 FU National Institute of Neurological Disorders and Stroke [1U01NS086659-01, R01NS078337, R56NS078337, R01NS095252]; Department of Defense [W81XWH-13-2-0064, W81XWH-14-1-0399]; Department of Veterans Affairs, the Veterans Affairs Biorepository [CSP 501]; National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846, supplement 0572063345-5]; Department of Defense Peer Reviewed Alzheimer's Research Program (DoD-PRARP) [13267017]; National Institute of Aging Boston University Framingham Heart Study [R01AG1649]; National Operating Committee on Standards for Athletic Equipment; Concussion Legacy Foundation; Andlinger Foundation; World Wrestling Entertainment; National Football League; National Institute on Aging (NJC) [P50 AG05681, P01 AG03991] FX The authors gratefully acknowledge the use of the resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA, USA), the Boston University School of Medicine, and the Mayo Clinic Jacksonville. We also gratefully acknowledge the help of all members of the Chronic Traumatic Encephalopathy Program at Boston University School of Medicine, the Boston VA, as well as the individuals and families whose participation and contributions made this work possible. This work was supported by the National Institute of Neurological Disorders and Stroke (1U01NS086659-01, R01NS078337, R56NS078337, R01NS095252), Department of Defense (W81XWH-13-2-0064, W81XWH-14-1-0399), Department of Veterans Affairs, the Veterans Affairs Biorepository (CSP 501), the National Institute of Aging Boston University Alzheimer's Disease Center (P30AG13846; supplement 0572063345-5), Department of Defense Peer Reviewed Alzheimer's Research Program (DoD-PRARP # 13267017), the National Institute of Aging Boston University Framingham Heart Study (R01AG1649), the National Operating Committee on Standards for Athletic Equipment and the Concussion Legacy Foundation. This work was also supported by unrestricted gifts from the Andlinger Foundation, the World Wrestling Entertainment and the National Football League. This work was supported by grants P50 AG05681 and P01 AG03991 from the National Institute on Aging (NJC). NR 48 TC 41 Z9 41 U1 6 U2 28 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JAN PY 2016 VL 131 IS 1 BP 75 EP 86 DI 10.1007/s00401-015-1515-z PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DA2CB UT WOS:000367601800005 PM 26667418 ER PT J AU Shankar, GM Lelic, N Gill, CM Thorner, AR Van Hummelen, P Wisoff, JH Loeffler, JS Brastianos, PK Shin, JH Borges, LF Butler, WE Zagzag, D Brody, RI Duhaime, AC Taylor, MD Hawkins, CE Louis, DN Cahill, DP Curry, WT Meyerson, M AF Shankar, Ganesh M. Lelic, Nina Gill, Corey M. Thorner, Aaron R. Van Hummelen, Paul Wisoff, Jeffrey H. Loeffler, Jay S. Brastianos, Priscilla K. Shin, John H. Borges, Lawrence F. Butler, William E. Zagzag, David Brody, Rachel I. Duhaime, Ann-Christine Taylor, Michael D. Hawkins, Cynthia E. Louis, David N. Cahill, Daniel P. Curry, William T. Meyerson, Matthew TI BRAF alteration status and the histone H3F3A gene K27M mutation segregate spinal cord astrocytoma histology SO ACTA NEUROPATHOLOGICA LA English DT Letter ID LOW-GRADE GLIOMAS; GLIOBLASTOMA; SUBGROUPS; TUMORS; H3.3 C1 [Shankar, Ganesh M.; Brastianos, Priscilla K.; Meyerson, Matthew] Broad Inst, Canc Program, Cambridge, MA USA. [Shankar, Ganesh M.; Lelic, Nina; Shin, John H.; Borges, Lawrence F.; Butler, William E.; Duhaime, Ann-Christine; Cahill, Daniel P.; Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Gill, Corey M.; Brastianos, Priscilla K.] Massachusetts Gen Hosp, Div Neurooncol, Boston, MA 02114 USA. [Thorner, Aaron R.; Van Hummelen, Paul; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Thorner, Aaron R.; Van Hummelen, Paul; Meyerson, Matthew] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Wisoff, Jeffrey H.; Zagzag, David] NYU, Dept Neurosurg, Langone Med Ctr, New York, NY 10016 USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hawkins, Cynthia E.] Univ Toronto, Dept Pediat Lab Med, Toronto, ON, Canada. [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brody, Rachel I.] NYU, Dept Pathol, Langone Med Ctr, New York, NY 10016 USA. [Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Div Neurosurg, Toronto, ON M5G 1X8, Canada. [Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Cahill, DP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 32 Fruit St,YAW-9-9040, Boston, MA 02114 USA. EM cahill@mgh.harvard.edu; wcurry@mgh.harvard.edu; Matthew_Meyerson@dfci.harvard.edu OI Wisoff, Jeffrey/0000-0003-3303-2220; Shin, John/0000-0001-7490-8108 FU NINDS NIH HHS [NS065743, R25 NS065743] NR 19 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JAN PY 2016 VL 131 IS 1 BP 147 EP 150 DI 10.1007/s00401-015-1492-2 PG 4 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DA2CB UT WOS:000367601800010 PM 26487540 ER PT J AU Muyanja, D Muzoora, C Muyingo, A Muyindike, W Siedner, MJ AF Muyanja, Daniel Muzoora, Conrad Muyingo, Anthony Muyindike, Winnie Siedner, Mark J. TI High Prevalence of Metabolic Syndrome and Cardiovascular Disease Risk Among People with HIV on Stable ART in Southwestern Uganda SO AIDS PATIENT CARE AND STDS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; INFECTED PATIENTS; HYPERTENSION; ADULTS; EPIDEMIOLOGY; MORTALITY; STROKE AB The objectives of this study were to determine the epidemiology and correlates of cardiovascular disease (CVD) risk among Ugandans on first-line antiretroviral therapy (ART). We conducted a cross-sectional study at an HIV clinic in southwestern Uganda. We enrolled adult patients on non-nucleoside-based ART regimens for a minimum of 2 years. We collected anthropometric and clinical measurements, smoking history, and blood for fasting lipid profile and blood sugar (FBS). Outcomes of interest were (1) presence of metabolic syndrome (at least two of the following: FBS >100mg/dL, blood pressure of 130/85mmHg, triglycerides 150mg/dL, HDL <40mg/DL, or waist circumference 94cm in males or 80cm in females); and (2) a Framingham score correlating to >5% 10-year CVD risk. Of the 250 participants enrolled, metabolic syndrome was detected in 145/250 (58%) of participants (62% in females and 50% in males). Forty-three participants (17%) had a Framingham risk correlating to a 5% or greater risk for CVD within 10 years (26% in males and 13% in females). In multivariate analyses, being female (AOR 3.13; 95% CI: 1.0-9.70; p=0.04) and over 40 years of age (AOR 1.78; 95% CI: 1.00-3.17; p=0.05) was independently associated with having metabolic syndrome. We found no independent risk factors for a Framingham risk score 10-year risk exceeding 5%, or associations between ART regimen and CVD risk profiles. We conclude that metabolic abnormalities are common among patients on first-line ART in rural Uganda, and appear to be more common in women than men. C1 [Muyanja, Daniel; Muzoora, Conrad; Muyingo, Anthony] Mbarara Univ Sci & Technol, Dept Internal Med, Mbarara 256, Uganda. [Muyindike, Winnie] Mbarara Reg Referral Hosp, Dept Internal Med, Mbarara, Uganda. [Siedner, Mark J.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. [Siedner, Mark J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Siedner, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. RP Muyanja, D (reprint author), Mbarara Univ Sci & Technol, POB 1410, Mbarara 256, Uganda. EM mdmuyanja@gmail.com FU Joint Clinical Research Center in Kampala Uganda; NIH [K23MH 099916]; Harvard Center for AIDS Research FX The source of funding for the study was the Joint Clinical Research Center in Kampala Uganda. MJS receives research funding from the NIH (K23MH 099916) and the Harvard Center for AIDS Research. NR 42 TC 5 Z9 5 U1 1 U2 3 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 JAN 1 PY 2016 VL 30 IS 1 BP 4 EP 10 DI 10.1089/apc.2015.0213 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DA5EG UT WOS:000367824900002 PM 26683587 ER PT J AU Gandhi, TK Abookire, SA Kachalia, A Sands, K Mort, E Bommarito, G Gagne, J Sato, L Weingart, SN AF Gandhi, Tejal K. Abookire, Susan A. Kachalia, Allen Sands, Kenneth Mort, Elizabeth Bommarito, Grace Gagne, Jane Sato, Luke Weingart, Saul N. TI Design and Implementation of the Harvard Fellowship in Patient Safety and Quality SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE patient safety; medical education; postgraduate training; quality ID EXPERIENCE AB The Harvard Fellowship in Patient Safety and Quality is a 2-year physician-oriented training program with a strong operational orientation, embedding trainees in the quality departments of participating hospitals. It also integrates didactic and experiential learning and offers the option of obtaining a master's degree in public health. The program focuses on methodologically rigorous improvement and measurement, with an emphasis on the development and implementation of innovative practice. The operational orientation is intended to foster the professional development of future quality and safety leaders. The purpose of this article is to describe the design and development of the fellowship. C1 [Gandhi, Tejal K.] Natl Patient Safety Fdn, Boston, MA 02210 USA. [Abookire, Susan A.] Houston Methodist, Houston, TX USA. [Kachalia, Allen] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sands, Kenneth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mort, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bommarito, Grace] Partners HealthCare Syst, Boston, MA USA. [Gagne, Jane; Sato, Luke] Harvard Med Inst Inc CRICO, Risk Management Fdn, Cambridge, MA USA. [Weingart, Saul N.] Tufts Med Ctr, Boston, MA USA. RP Gandhi, TK (reprint author), Natl Patient Safety Fdn, 268 Summer St, Boston, MA 02210 USA. EM tgandhi@npsf.org FU CRICO, Boston, MA FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Supported by a grant from CRICO, Boston, MA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD JAN-FEB PY 2016 VL 31 IS 1 BP 22 EP 26 DI 10.1177/1062860614549183 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DA5BU UT WOS:000367817900003 PM 25184234 ER PT J AU Abookire, SA Gandhi, TK Kachalia, A Sands, K Mort, E Bommarito, G Gagne, J Sato, L Weingart, SN AF Abookire, Susan A. Gandhi, Tejal K. Kachalia, Allen Sands, Kenneth Mort, Elizabeth Bommarito, Grace Gagne, Jane Sato, Luke Weingart, Saul N. TI Creating a Fellowship Curriculum in Patient Safety and Quality SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE patient safety; medical education; postgraduate training; quality AB The authors sought to create a curriculum suitable for a newly created clinical fellowship curriculum across Harvard Medical School-affiliated teaching hospitals as part of a newly created 2-year quality and safety fellowship program described in the companion article Design and Implementation of the Harvard Fellowship in Patient Safety and Quality. The aim of the curriculum development process was to define, coordinate, design, and implement a set of essential skills for future physician-scholars of any specialty to lead operational quality and patient safety efforts. The process of curriculum development and the ultimate content are described in this article. C1 [Abookire, Susan A.] Houston Methodist, Houston, TX USA. [Gandhi, Tejal K.] Natl Patient Safety Fdn, Boston, MA USA. [Kachalia, Allen] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sands, Kenneth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mort, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bommarito, Grace] Partners HealthCare Syst, Boston, MA USA. [Gagne, Jane; Sato, Luke] Harvard Med Inst Inc CRICO, Risk Management Fdn, Cambridge, MA USA. [Weingart, Saul N.] Tufts Med Ctr, Boston, MA USA. RP Gandhi, TK (reprint author), Natl Patient Safety Fdn, 268 Summer St, Boston, MA 02210 USA. EM tgandhi@npsf.org FU Risk Management Foundation of the Harvard Medical Institutions, Inc. (CRICO), Cambridge, MA FX The authors received the following financial support for the research, authorship, and/or publication of this article: Supported by a grant from Risk Management Foundation of the Harvard Medical Institutions, Inc. (CRICO), Cambridge, MA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD JAN-FEB PY 2016 VL 31 IS 1 BP 27 EP 30 DI 10.1177/1062860614549012 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DA5BU UT WOS:000367817900004 PM 25184235 ER PT J AU Bilousova, T Miller, CA Poon, WW Vinters, HV Corrada, M Kawas, C Hayden, EY Tepow, DB Glabe, C Albay, R Cole, GM Teng, E Gylys, KH AF Bilousova, Tina Miller, Carol. A. Poon, Wayne W. Vinters, Harry V. Corrada, Maria Kawas, Claudia Hayden, Eric Y. Tepow, David B. Glabe, Charles Albay, Ricardo, III Cole, Gregory M. Teng, Edmond Gylys, Karen H. TI Synaptic Amyloid-beta Oligomers Precede p-Tau and Differentiate High Pathology Control Cases SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOSOMAL-LYSOSOMAL SYSTEM; ALZHEIMERS-DISEASE CORTEX; INTRANEURONAL A-BETA; TRANSGENIC RAT MODEL; IN-VIVO; MOUSE MODEL; NEUROFIBRILLARY TANGLES; COGNITIVE IMPAIRMENT; SOLUBLE OLIGOMERS; SENILE PLAQUES AB Amyloid-beta (A beta) and hyperphosphorylated tau (p-tau) aggregates form the two discrete pathologies of Alzheimer disease (AD), and oligomeric assemblies of each protein are localized to synapses. To determine the sequence by which pathology appears in synapses, A beta and p-tau were quantified across AD disease stages in parietal cortex. Nondemented cases with high Levels of AD-related pathology were included to determine factors that confer protection from clinical symptoms. Flow cytometric analysis of synaptosome preparations was used to quantify A beta and p-tau in Large populations of individual synaptic terminals. Soluble A beta oligomers were assayed by a single antibody sandwich enzyme-Linked immunosorbent assay. Total in situ A beta was elevated in patients with early- and late-stage AD dementia, but not in high pathology nondemented controls compared with age-matched normal controls. However, soluble A beta oligomers were highest in early AD synapses, and this assay distinguished early AD cases from high pathology controls. Overall, synapse-associated p-tau did not increase until Late-stage disease in human and transgenic rat cortex, and p-tau was elevated in individual A beta-positive synaptosomes in early AD. These results suggest that soluble oligomers in surviving neocortical synaptic terminals are associated with dementia onset and suggest an amyloid cascade hypothesis in which oligomeric All drives phosphorylated tau accumulation and synaptic spread. These results indicate that antiamyloid therapies will be less effective once p-tau pathology is developed. C1 [Bilousova, Tina; Gylys, Karen H.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Bilousova, Tina; Hayden, Eric Y.; Tepow, David B.; Cole, Gregory M.; Teng, Edmond; Gylys, Karen H.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Res, Los Angeles, CA USA. [Vinters, Harry V.; Hayden, Eric Y.; Tepow, David B.; Cole, Gregory M.; Teng, Edmond] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. [Vinters, Harry V.] Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. [Cole, Gregory M.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Miller, Carol. A.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Miller, Carol. A.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Miller, Carol. A.] Univ So Calif, Keck Sch Med, Program Neurosci, Los Angeles, CA 90033 USA. [Poon, Wayne W.; Corrada, Maria; Kawas, Claudia] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA USA. [Corrada, Maria; Kawas, Claudia] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Kawas, Claudia] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92717 USA. [Glabe, Charles; Albay, Ricardo, III] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. [Cole, Gregory M.; Teng, Edmond] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Gylys, KH (reprint author), Box 956919,Factor Bldg, Los Angeles, CA 90095 USA. EM kgylys@sonnet.ucla.edu FU NIH [AG27465, NS038328, AG041295, CA16042, AI 28697]; National Institute on Aging (NIA) [AG18879, AG34628]; NIA [R01AG21055]; American Federation for Aging Research; John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation; Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers; University of California Los Angeles Clinical and Translational Science Institute (UCLA CTSI) grant [UL1TR000124]; UCLA Older Americans Independence Center grant [P30 AG028748]; Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine; AD Research Center Neuropathology Cores NIA grants [P50 AG05142, P50 AG16970, P50 AG16573] FX Supported by NIH grants AG27465 (K.H.G.), NS038328 (D.B.T.), and AG041295 (D.B.T.); National Institute on Aging (NIA) grants AG18879 (C.A.M.) and AG34628 (jointly sponsored by the NIA, American Federation for Aging Research, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation, and an anonymous donor; to E.T.); the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers (D.B.T.); University of California Los Angeles Clinical and Translational Science Institute (UCLA CTSI) grant UL1TR000124 (U.Y.H.); UCLA Older Americans Independence Center grant P30 AG028748 (E.Y.H.); and the Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine (H.V.V.). Tissue was obtained from the AD Research Center Neuropathology Cores NIA grants P50 AG05142 (USC), P50 AG16970 (UCLA), and P50 AG16573 (UC Irvine). Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility, supported by NIH grants CA16042 and AI 28697 and by the JCCC, the UCLA AIDS Institute, the David Geffen School of Medicine, and the Chancellor's Office at UCLA. Diagnosis, characterization, and follow-up of >90 study subjects was supported by NIA grant R01AG21055. NR 88 TC 7 Z9 7 U1 5 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2016 VL 186 IS 1 BP 185 EP 198 DI 10.1016/j.ajpath.2015.09.018 PG 14 WC Pathology SC Pathology GA DA3NV UT WOS:000367705300018 PM 26718979 ER PT J AU Grishchuk, Y Stember, KG Matsunaga, A Olivares, AM Cruz, NM King, VE Humphrey, DM Wang, SL Muzikansky, A Betensky, RA Thoreson, WB Haider, N Slaugenhaupt, SA AF Grishchuk, Yulia Stember, Katherine G. Matsunaga, Aya Olivares, Ana M. Cruz, Nelly M. King, Victoria E. Humphrey, Daniel M. Wang, Shirley L. Muzikansky, Alona Betensky, Rebecca A. Thoreson, Wallace B. Haider, Neena Slaugenhaupt, Susan A. TI Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RECEPTOR POTENTIAL CHANNEL; LYSOSOMAL TRAFFICKING; TARGETED DISRUPTION; MEMBRANE-PROTEIN; CATION CHANNEL; TRP CHANNEL; GENE; MICE; DISEASE; CELLS AB Mucolipidosis IV is a debilitating developmental Lysosomal storage disorder characterized by severe neuromotor retardation and progressive loss of vision, Leading to blindness by the second decade of Life. Mucolipidosis IV is caused by Loss-of-function mutations in the MCOLN1 gene, which encodes the transient receptor potential channel protein mucolipin-1. Ophthalmic pathology in patients includes corneal haze and progressive retinal and optic nerve atrophy. Herein, we report ocular pathology in Mcoln1(-/-) mouse, a good phenotypic model of the disease. Early, but non-progressive, thinning of the photoreceptor layer, reduced levels of rhodopsin, disrupted rod outer segments, and widespread accumulation of the typical storage inclusion bodies were the major histological findings in the Mcoln1(-/-) retina. Electroretinograms showed significantly decreased functional response (scotopic a- and b-wave amplitudes) in the Mcoln1(-/-) mice. At the ultrastructural level, we observed formation of axonal spheroids and decreased density of axons in the optic nerve of the aged (6-month-old) Mcoln1(-/-) mice, which indicates progressive axonal degeneration. Our data suggest that mucolipin-1 plays a role in postnatal development of photoreceptors and provides a set of outcome measures that can be used for ocular therapy development for mucolipidosis IV. C1 [Grishchuk, Yulia; Stember, Katherine G.; Matsunaga, Aya; King, Victoria E.; Humphrey, Daniel M.; Wang, Shirley L.; Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Olivares, Ana M.; Cruz, Nelly M.; Haider, Neena] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. [Thoreson, Wallace B.] Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE USA. RP Grishchuk, Y (reprint author), Harvard Univ, Sch Med, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM ygrishchuk@mgh.harvard.edu FU ML4 Foundation; Research to Prevent Blindness Senior Scientific Investigator Award; NIH National Eye Institute [P30EY003790]; NIH [8UL1TR000170-05]; Harvard University; Harvard NeuroDiscovery Center and Harvard Catalyst (National Center for Advancing Translational Sciences, NIH) [8UL1TR000170-05]; NIH NEI Core grant [P30EY003790] FX Supported by an ML4 Foundation grant (Y.G. and S.A.S.), a Research to Prevent Blindness Senior Scientific Investigator Award (W.B.T.), NIH National Eye Institute core grant (P30EY003790), NIH Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic health care centers. Statistical analysis was conducted with support from Harvard NeuroDiscovery Center and Harvard Catalyst (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic health care centers). SERI electron microscopy core is supported through an NIH NEI Core grant (P30EY003790). NR 53 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2016 VL 186 IS 1 BP 199 EP 209 DI 10.1016/j.ajpath.2015.09.017 PG 11 WC Pathology SC Pathology GA DA3NV UT WOS:000367705300019 PM 26608452 ER PT J AU Brady, KT McCauley, JL Back, SE AF Brady, Kathleen T. McCauley, Jenna L. Back, Sudie E. TI Prescription Opioid Misuse, Abuse, and Treatment in the United States: An Update SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; BUPRENORPHINE-NALOXONE TREATMENT; DRUG-ABUSE; MAINTENANCE TREATMENT; ADDICTION TREATMENT; SCREENING-TEST; USE DISORDERS; CHRONIC PAIN; RISK TOOL; OVERDOSE AB Objective: Prescription opioid abuse and dependence have escalated rapidly in the United States over the past 20 years, leading to high rates of overdose deaths and a dramatic increase in the number of people seeking treatment for opioid dependence. The authors review the scope of the abuse and overdose epidemic, prescription practices, and the assessment, treatment, and prevention of prescription opioid misuse and dependence. Method: The authors provide an overview of the literature from 2006 to the present, with the twin goals of highlighting advances in prevention and treatment and identifying remaining gaps in the science. Results: A number of policy and educational initiatives at the state and federal government level have been undertaken in the past 5 years to help providers and consumers, respectively, prescribe and use opioids more responsibly. Initial reports suggest that diversion and abuse levels have begun to plateau, likely as a result of these initiatives. While there is a large body of research suggesting that opioid substitution coupled with psychosocial interventions is the best treatment option for heroin dependence, there is limited research focusing specifically on the treatment of prescription opioid dependence. In particular, the treatment of chronic pain in individuals with prescription opioid use disorders is underexplored. Conclusions: While policy and educational initiatives appear to be effective in decreasing prescription opioid abuse and misuse, research focusing on the development and evaluation of treatments specific to prescription opioid dependence and its common comorbidities (e.g., chronic pain, depression) is critically needed. C1 [Brady, Kathleen T.] Med Univ S Carolina, Addict Sci Div, Inst Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Brady, KT (reprint author), Med Univ S Carolina, Addict Sci Div, Inst Psychiat & Behav Sci, Charleston, SC 29425 USA. EM bradyk@musc.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [2 P50 DA016511]; NIDA [5 U10 DA013727, 1 K23 DA036566] FX Supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grant 2 P50 DA016511 and NIDA grants 5 U10 DA013727 and 1 K23 DA036566. NR 59 TC 14 Z9 14 U1 18 U2 51 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 JAN PY 2016 VL 173 IS 1 BP 18 EP 26 DI 10.1176/appi.ajp.2015.15020262 PG 9 WC Psychiatry SC Psychiatry GA DA2QK UT WOS:000367640700008 PM 26337039 ER PT J AU England, BR Sayles, H Michaud, K Caplan, L Davis, LA Cannon, GW Sauer, BC Solow, EB Reimold, AM Kerr, GS Schwab, P Baker, JF Mikuls, TR AF England, Bryant R. Sayles, Harlan Michaud, Kaleb Caplan, Liron Davis, Lisa A. Cannon, Grant W. Sauer, Brian C. Solow, Elizabeth B. Reimold, Andreas M. Kerr, Gail S. Schwab, Pascale Baker, Josh F. Mikuls, Ted R. TI Cause-Specific Mortality in Male US Veterans With Rheumatoid Arthritis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID DISEASE-ACTIVITY; INFLAMMATORY POLYARTHRITIS; CARDIOVASCULAR-DISEASE; LUNG-DISEASE; POPULATION; ASSOCIATION; CANCER; COHORT; INDEX; METHOTREXATE AB Objective. There has been limited investigation into cause-specific mortality and the associated risk factors in men with rheumatoid arthritis (RA). We investigated all-cause and cause-specific mortality in men with RA, examining determinants of survival. Methods. Men from a longitudinal RA registry were followed from enrollment until death or through 2013. Vital status and cause of death were determined using the National Death Index. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all-cause, cardiovascular disease (CVD), cancer, and respiratory mortality. Associations with all-cause and cause-specific mortality were examined using multivariable Cox proportional hazards and competing-risks regression. Results. There were 1,652 men with RA and 332 deaths. The leading causes of death were CVD (31.6%; SMR 1.77 [95% confidence interval (95% CI) 1.46-2.14]), cancer (22.9%; SMR 1.50 [95% CI 1.20-1.89]), and respiratory disease (15.1%; SMR 2.90 [95% CI 2.20-3.83]). Factors associated with all-cause mortality included older age, white race, smoking, low body weight, comorbidity, disease activity, and prednisone use. Rheumatoid factor concentration and nodules were associated with CVD mortality. There were no associations of methotrexate or biologic agent use with all-cause or cause-specific mortality. Conclusion. Men in this RA cohort experienced increased all-cause and cause-specific mortality, with a 3-fold risk of respiratory-related deaths compared to age-matched men in the general population. Further studies are needed in order to examine whether interventions targeting potentially modifiable correlates of mortality might lead to improved long-term survival in men with RA. C1 [England, Bryant R.; Sayles, Harlan; Mikuls, Ted R.] Vet Affairs Nebraska Western Iowa Hlth Care Syst, Omaha, NE USA. [England, Bryant R.; Sayles, Harlan; Mikuls, Ted R.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Michaud, Kaleb] Univ Nebraska, Med Ctr, Vet Affairs Nebraska Western Iowa Hlth Care Syst, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Caplan, Liron; Davis, Lisa A.] Denver VAMC, Denver, CO USA. [Caplan, Liron; Davis, Lisa A.] Univ Colorado, Denver, CO 80202 USA. [Davis, Lisa A.] Denver Hlth Med Ctr, Denver, CO USA. [Cannon, Grant W.; Sauer, Brian C.] Vet Affairs Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Cannon, Grant W.; Sauer, Brian C.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Solow, Elizabeth B.; Reimold, Andreas M.] Dallas Vet Affairs, Dallas, TX USA. [Solow, Elizabeth B.; Reimold, Andreas M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kerr, Gail S.] Vet Affairs Med Ctr & Georgetown, Washington, DC USA. [Kerr, Gail S.] Howard Univ, Washington, DC 20059 USA. [Schwab, Pascale] Portland Vet Affairs Hlth Care Syst, Portland, OR USA. [Schwab, Pascale] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Baker, Josh F.] Philadelphia VAMC, Philadelphia, PA USA. [Baker, Josh F.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Mikuls, TR (reprint author), 986270 Nebraska Med Ctr, Omaha, NE 68198 USA. EM tmikuls@unmc.edu OI England, Bryant R./0000-0002-9649-3588 FU Rheumatology Research Foundation Resident Research Preceptorship; Rheumatology Research Foundation Investigator Award; Rheumatology Research Foundation Scientific Development Award; Veterans Affairs Merit Award FX Dr. England's work was supported by a Rheumatology Research Foundation Resident Research Preceptorship. Dr. Michaud's work was supported by a Rheumatology Research Foundation Investigator Award. Dr. Davis' work was supported by a Rheumatology Research Foundation Scientific Development Award. Dr. Mikuls' work was supported by a Veterans Affairs Merit Award. NR 39 TC 7 Z9 7 U1 0 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 JAN PY 2016 VL 68 IS 1 BP 36 EP 45 DI 10.1002/acr.2264 PG 10 WC Rheumatology SC Rheumatology GA DA3FQ UT WOS:000367682800003 PM 26097231 ER PT J AU Rosen, AK Mull, HJ AF Rosen, Amy K. Mull, Hillary J. TI Identifying adverse events after outpatient surgery: improving measurement of patient safety SO BMJ QUALITY & SAFETY LA English DT Editorial Material DE Adverse events; epidemiology and detection; Surgery; Patient safety; Quality measurement ID GLOBAL TRIGGER TOOL; HOSPITALIZED-PATIENTS; DRUG EVENTS; AMBULATORY SURGERY; OLDER-ADULTS; PRIMARY-CARE; SURVEILLANCE; COMPLICATIONS; INDICATORS; PROGRAM C1 [Rosen, Amy K.; Mull, Hillary J.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Mull, Hillary J.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. RP Rosen, AK (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. EM akrosen@bu.edu OI Mull, Hillary/0000-0002-4484-0445 NR 38 TC 0 Z9 1 U1 2 U2 4 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 JAN PY 2016 VL 25 IS 1 BP 3 EP 5 DI 10.1136/bmjqs-2015-004752 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DA5IH UT WOS:000367836200002 PM 26453634 ER PT J AU Menendez, ME Janssen, SJ Ring, D AF Menendez, Mariano E. Janssen, Stein J. Ring, David TI Electronic health record-based triggers to detect adverse events after outpatient orthopaedic surgery SO BMJ QUALITY & SAFETY LA English DT Article DE Trigger tools; Surgery; Quality improvement ID PATIENT SAFETY; DRUG EVENTS; HOSPITALS; RATES; HARM; CARE; TOOL AB Background Adverse events (AEs) after outpatient orthopaedic surgery are common, but difficult to detect. Electronic health records facilitate abstraction of large quantities of data, and may allow automated identification of triggers' or clues indicating the possibility of an AE. We evaluated electronic health record-based triggers to detect AEs after outpatient orthopaedic surgery. Methods The medical records of 1464 patients undergoing outpatient surgical procedures in one of five orthopaedic services at our institution were manually reviewed for the occurrence of 90-day postoperative AEs. We used electronic health records to identify triggers suggestive of an AE. Each trigger was evaluated for positive predictive value (PPV). We constructed a logistic regression model to determine triggers associated with AEs and used the beta coefficients derived from the model to produce a formula for the likelihood of identifying an AE in the medical record. Results The overall rate of 90-day AEs was 10%, with surgical site infection being the most common (3.3%). Electronic triggers with the highest PPVs for the occurrence of 90-day AEs were antibiotic prescription (75%), emergency department visit (41%), bone/joint or blood culture (41%), repeat surgery (39%) and consult with infectious disease specialist (33%). Using our formula to predict the likelihood of identifying an AE in the medical record, a predicted probability of >0.10 had a specificity of 80% and sensitivity of 53% for actual AE. Conclusions Electronic health record-based triggers may facilitate quality-improvement efforts to monitor morbidity after outpatient orthopaedic surgery. Further research is needed to understand the optimal use of electronic triggers as surgical quality indicators and as screening tools to flag cases for manual review. Level of evidence Level III, prognostic study. C1 [Menendez, Mariano E.; Janssen, Stein J.; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM marianofurrer@gmail.com NR 17 TC 2 Z9 2 U1 1 U2 3 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 JAN PY 2016 VL 25 IS 1 BP 25 EP 30 DI 10.1136/bmjqs-2015-004332 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DA5IH UT WOS:000367836200006 PM 26359272 ER PT J AU Cheng, A Owens, D AF Cheng, Andrew Owens, David TI Marfan syndrome, inherited aortopathies and exercise: What is the right answer? SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID ARTERIAL BLOOD-PRESSURE; SUDDEN CARDIAC DEATH; AORTIC DISSECTION; CARDIOVASCULAR-DISEASE; HEMODYNAMIC-RESPONSE; SPORTS PARTICIPATION; RESISTANCE EXERCISE; PHYSICAL-ACTIVITY; RECOMMENDATIONS; MANAGEMENT AB Exercise recommendations for those who have Marfan syndrome or other genetic predisposition for thoracic aortic disease remain controversial and at times ambiguous. There are no outcomes studies to help guide recommendations. In this review, we examine the guidelines regarding exercise and inherited aortic conditions, the theoretical reasoning and circumstantial evidence that support the guidelines, as well as the knowledge gaps that continue to exist. C1 [Cheng, Andrew] VA Puget Sound, Dept Cardiol, Seattle, WA 98108 USA. [Cheng, Andrew; Owens, David] Univ Washington, Dept Cardiol, Seattle, WA 98195 USA. RP Cheng, A (reprint author), VA Puget Sound, Dept Cardiol, 1660 South Columbian Way, Seattle, WA 98108 USA. EM ACheng@cardiology.washington.edu OI Owens, David/0000-0002-7293-9688 NR 38 TC 0 Z9 0 U1 1 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 EI 1473-0480 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD JAN PY 2016 VL 50 IS 2 BP 100 EP + DI 10.1136/bjsports-2014-306440rep PG 6 WC Sport Sciences SC Sport Sciences GA DA2FB UT WOS:000367609600009 PM 26729892 ER PT J AU Shapiro, M Nandi, B Pai, C Samur, MK Pelluru, D Fulciniti, M Prabhala, RH Munshi, NC Gold, JS AF Shapiro, Mia Nandi, Bisweswar Pai, Christine Samur, Mehmet K. Pelluru, Dheeraj Fulciniti, Mariateresa Prabhala, Rao H. Munshi, Nikhil C. Gold, Jason S. TI Deficiency of IL-17A, but not the prototypical Th17 transcription factor ROR gamma t, decreases murine spontaneous intestinal tumorigenesis SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE ROR gamma t; IL-17A; Th17; Carcinogenesis; Adenoma; Colorectal neoplasms ID PREVENT COLORECTAL ADENOMAS; INNATE LYMPHOID-CELLS; APC(MIN/+) MICE; RANDOMIZED-TRIAL; AUTOIMMUNE INFLAMMATION; HELPER-CELLS; TUMOR-GROWTH; MAST-CELLS; CANCER; DIFFERENTIATION AB While inflammation has been associated with the development and progression of colorectal cancer, the exact role of the inflammatory Th17 pathway remains unclear. In this study, we aimed to determine the relative importance of IL-17A and the master regulator of the Th17 pathway, the transcription factor ROR gamma t, in the sporadic intestinal neoplasia of APC(MIN/+) mice and in human colorectal cancer. We show that levels of IL-17A are increased in human colon cancer as compared to adjacent uninvolved colon. Similarly, na < ve helper T cells from colorectal cancer patients are more inducible into the Th17 pathway. Furthermore, IL-17A, IL-21, IL-22, and IL-23 are all demonstrated to be directly mitogenic to human colorectal cancer cell lines. Nevertheless, deficiency of IL-17A but not ROR gamma t is associated with decreased spontaneous intestinal tumorigenesis in the APC(MIN/+) mouse model, despite the fact that helper T cells from ROR gamma t-deficient APC(MIN/+) mice do not secrete IL-17A when subjected to Th17-polarizing conditions and that Il17a expression is decreased in the intestine of ROR gamma t-deficient APC(MIN/+) mice. Differential expression of Th17-associated cytokines between IL-17A-deficient and ROR gamma t-deficient APC(MIN/+) mice may explain the difference in adenoma development. C1 [Shapiro, Mia; Nandi, Bisweswar; Pai, Christine; Pelluru, Dheeraj; Prabhala, Rao H.] VA Boston Healthcare Syst, Res Serv, West Roxbury, MA 02132 USA. [Shapiro, Mia; Nandi, Bisweswar; Samur, Mehmet K.; Fulciniti, Mariateresa; Prabhala, Rao H.; Munshi, Nikhil C.; Gold, Jason S.] Harvard Univ, Sch Med, Boston, MA USA. [Samur, Mehmet K.; Pelluru, Dheeraj; Fulciniti, Mariateresa; Prabhala, Rao H.; Munshi, Nikhil C.] Dana Farber Canc Ctr, Boston, MA USA. [Munshi, Nikhil C.] VA Boston Healthcare Syst, Med Serv, West Roxbury, MA USA. [Gold, Jason S.] VA Boston Healthcare Syst 112, Surg Serv, Boston, MA 02132 USA. [Gold, Jason S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Gold, JS (reprint author), VA Boston Healthcare Syst, Res Serv, West Roxbury, MA 02132 USA. EM jgold4@partners.org FU United States Department of Veteran Affairs Office of Research and Development Career Development Award-2 FX This work was supported by a United States Department of Veteran Affairs Office of Research and Development Career Development Award-2 (Jason S. Gold). NR 51 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2016 VL 65 IS 1 BP 13 EP 24 DI 10.1007/s00262-015-1769-2 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA DA3GY UT WOS:000367686400002 PM 26559812 ER PT J AU Maxson, JE Abel, ML Wang, JH Deng, XM Reckel, S Luty, SB Sun, HH Gorenstein, J Hughes, SB Bottomly, D Wilmot, B McWeeney, SK Radich, J Hantschel, O Middleton, RE Gray, NS Druker, BJ Tyner, JW AF Maxson, Julia E. Abel, Melissa L. Wang, Jinhua Deng, Xianming Reckel, Sina Luty, Samuel B. Sun, Huahang Gorenstein, Julie Hughes, Seamus B. Bottomly, Daniel Wilmot, Beth McWeeney, Shannon K. Radich, Jerald Hantschel, Oliver Middleton, Richard E. Gray, Nathanael S. Druker, Brian J. Tyner, Jeffrey W. TI Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis SO CANCER RESEARCH LA English DT Article ID EGF RECEPTOR; CANCER GENOMICS; PROSTATE-CANCER; SH2 DOMAIN; ACK1; RESISTANCE; ACTIVATION; PHOSPHORYLATION; TUMOR; AMPLIFICATION AB The amount of genomic information about leukemia cells currently far exceeds our overall understanding of the precise genetic events that ultimately drive disease development and progression. Effective implementation of personalized medicine will require tools to distinguish actionable genetic alterations within the complex genetic landscape of leukemia. In this study, we performed kinase inhibitor screens to predict functional gene targets in primary specimens from patients with acute myeloid leukemia and chronic myelomonocytic leukemia. Deep sequencing of the same patient specimens identified genetic alterations that were then integrated with the functionally important targets using the HitWalker algorithm to prioritize the mutant genes that most likely explain the observed drug sensitivity patterns. Through this process, we identified tyrosine kinase nonreceptor 2 (TNK2) point mutations that exhibited oncogenic capacity. Importantly, the integration of functional and genomic data using HitWalker allowed for prioritization of rare oncogenic mutations that may have been missed through genomic analysis alone. These mutations were sensitive to the multikinase inhibitor dasatinib, which antagonizes TNK2 kinase activity, as well as novel TNK2 inhibitors, XMD8-87 and XMD16-5, with greater target specificity. We also identified activating truncation mutations in other tumor types that were sensitive to XMD8-87 and XMD16-5, exemplifying the potential utility of these compounds across tumor types dependent on TNK2. Collectively, our findings highlight a more sensitive approach for identifying actionable genomic lesions that may be infrequently mutated or overlooked and provide a new method for the prioritization of candidate genetic mutations. (C) 2015 AACR. C1 [Maxson, Julia E.; Abel, Melissa L.; Luty, Samuel B.; Bottomly, Daniel; Wilmot, Beth; McWeeney, Shannon K.; Druker, Brian J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Maxson, Julia E.; Abel, Melissa L.; Luty, Samuel B.; Druker, Brian J.; Tyner, Jeffrey W.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Maxson, Julia E.; Hughes, Seamus B.; Radich, Jerald] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Wang, Jinhua; Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Reckel, Sina; Hantschel, Oliver] Ecole Polytech Fed Lausanne, Sch Life Sci, ISREC, Lausanne, Switzerland. [Sun, Huahang; Gorenstein, Julie; Middleton, Richard E.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Bottomly, Daniel; Wilmot, Beth; McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97239 USA. [Wilmot, Beth; McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Div Bioinformat & Computat Biol, Portland, OR 97239 USA. [Druker, Brian J.] Howard Hughes Med Inst, Portland, OR USA. [Tyner, Jeffrey W.] Oregon Hlth & Sci Univ, Cell Dev & Canc Biol, Portland, OR 97239 USA. RP Tyner, JW (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM tynerj@ohsu.edu RI Hantschel, Oliver/H-4705-2013 OI Hantschel, Oliver/0000-0001-8569-8169 FU Howard Hughes Medical Institute; Leukemia & Lymphoma Society; Leukemia & Lymphoma Society Fellow Award; Medical Research Foundation Early Clinical Investigator Award; NCI [K99 CA190605-01, 5R00CA151457-04, 1R01CA183947-01]; V Foundation for Cancer Research; Gabrielle's Angel Foundation for Cancer Research; NIH [5 R01 CA173469-02] FX This work was supported by Howard Hughes Medical Institute and The Leukemia & Lymphoma Society. J.E. Maxson is supported by a Leukemia & Lymphoma Society Fellow Award and a Medical Research Foundation Early Clinical Investigator Award, and NCI K99 CA190605-01. J.W. Tyner is supported by grants from the V Foundation for Cancer Research, the Gabrielle's Angel Foundation for Cancer Research, and the NCI (5R00CA151457-04; 1R01CA183947-01). N.S. Gray, X. Deng, and J. Wang are supported by NIH grant (5 R01 CA173469-02). NR 40 TC 2 Z9 2 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2016 VL 76 IS 1 BP 127 EP 138 DI 10.1158/0008-5472.CAN-15-0817 PG 12 WC Oncology SC Oncology GA DA1KE UT WOS:000367553900017 PM 26677978 ER PT J AU Canaipa, R Treister, R Lang, M Moreira, JM Castro-Caldas, A AF Canaipa, Rita Treister, Roi Lang, Magdalena Moreira, Joao M. Castro-Caldas, Alexandre TI Feeling Hurt Pain Sensitivity is Correlated With and Modulated by Social Distress SO CLINICAL JOURNAL OF PAIN LA English DT Article DE pain; social distress; social rejection; Cyberball ID PHYSICAL PAIN; NEURAL RESPONSES; EXCLUSION; REJECTION; FMRI; STRESS; HYPERALGESIA; THRESHOLD; BEHAVIOR AB Objectives:Social distress, resulting from loss or threat to social relationships, shares similar psychological and neuronal processes with physical pain. Recent evidence demonstrated that social distress may have an impact on pain. The current study aimed to further assess the relationship between these 2 phenomena.Materials and Methods:Sixty healthy participants were randomly assigned to inclusion, noninclusion, or exclusion conditions of Cyberball, a virtual ball tossing game used to induce social distress. Pain and unpleasantness in response to noxious electrical stimuli were assessed before and after Cyberball manipulation. Psychological characteristics were evaluated by the Experiences in Close Relationships Questionnaire and the neuroticism scale of Big Five Inventory.Results:Significant correlations were found between social distress and pre-Cyberball unpleasantness thresholds: those who perceived the Cyberball task as more distressing demonstrated lower unpleasantness thresholds. Post-Cyberball manipulation pain intensity ratings, but not unpleasantness ratings, were lower in the inclusion condition. No associations were found between the psychological characteristic and the effects of Cyberball on pain or unpleasantness ratings.Discussion:The current study results indicate that participants' pre-Cyberball unpleasantness threshold is related to their responsiveness to social distress and that physical pain may be modulated by social events. Further studies are needed to clarify the clinical relevance of these results. C1 [Canaipa, Rita] Univ Lisbon, Fac Med, P-1699 Lisbon, Portugal. [Moreira, Joao M.] Univ Lisbon, Dept Psychol, P-1699 Lisbon, Portugal. [Canaipa, Rita; Castro-Caldas, Alexandre] Portuguese Catholic Univ, Hlth Sci Inst, P-1649023 Lisbon, Portugal. [Treister, Roi; Lang, Magdalena] Harvard Univ, Sch Med, Dept Neurol, Nerve Injury Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Canaipa, R (reprint author), Portuguese Catholic Univ, Hlth Sci Inst, Edificio Biblioteca Joao Paulo 2,5 Piso, P-1649023 Lisbon, Portugal. EM rita.canaipa@gmail.com RI Castro-Caldas, Alexandre/M-4156-2013; OI Castro-Caldas, Alexandre/0000-0002-9148-3719; Canaipa, Rita/0000-0003-2437-7825 FU Portuguese Foundation for Science and Technology, Lisbon, Portugal PhD Grant [SFRH/BD/42709/2008] FX Supported by a Portuguese Foundation for Science and Technology, Lisbon, Portugal PhD Grant SFRH/BD/42709/2008 to R.C. The authors declare no conflict of interest. NR 32 TC 0 Z9 0 U1 6 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0749-8047 EI 1536-5409 J9 CLIN J PAIN JI Clin. J. Pain PD JAN PY 2016 VL 32 IS 1 BP 14 EP 19 DI 10.1097/AJP.0000000000000220 PG 6 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DA2AG UT WOS:000367597100003 PM 25654536 ER PT J AU Liang, KV Sileanu, FE Clermont, G Murugan, R Pike, F Palevsky, PM Kellum, JA AF Liang, Kelly V. Sileanu, Florentina E. Clermont, Gilles Murugan, Raghavan Pike, Francis Palevsky, Paul M. Kellum, John A. TI Modality of RRT and Recovery of Kidney Function after AKI in Patients Surviving to Hospital Discharge SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RENAL REPLACEMENT THERAPY; CRITICALLY-ILL PATIENTS; CONTINUOUS VENOVENOUS HEMODIAFILTRATION; INTENSIVE-CARE-UNIT; RANDOMIZED CLINICAL-TRIAL; INTERMITTENT HEMODIALYSIS; RETROSPECTIVE COHORT; MULTIPLE-ORGAN; FAILURE; INJURY AB Background and objectives Observational evidence has suggested that RRT modality may affect recovery after AKI. It is unclear whether initial choice of intermittent hemodialysis or continuous RRT affects renal recovery, survival, or development of ESRD in critically ill patients when modality choice is made primarily on hemodynamics. Design, setting, participants, & measurements We performed a retrospective cohort study examining adults (>= 18 years old) admitted to intensive care units from 2000 to 2008 who received RRT for AKI and survived to hospital discharge or 90 days. We analyzed renal recovery (alive and not requiring RRT) and reasons for non-recovery (death or ESRD) at 90 and 365 days. Conditional multivariable logistic regression was used to assess differences in renal recovery at 90 and 365 days between continuous RRT and intermittent hemodialysis. Models were stratified by propensity for continuous RRT and adjusted for age and reference creatinine. Results Of 4738 patients with Kidney Disease Improving Global Outcomes stage 3 AKI, 1338 (28.2%) received RRT, and 638 (47.7%) survived to hospital discharge (353 intermittent hemodialysis and 285 continuous RRT). Recovery from AKI was lower for intermittent hemodialysis versus continuous RRT at 90 days (66.6% intermittent hemodialysis versus 75.4% continuous RRT; P=0.02) but similar at 365 days (54.1% intermittent hemodialysis versus 59.6% continuous RRT; P=0.17). In multivariable analysis, there was no difference in odds of recovery at 90 or 365 days for patients initially treated with continuous RRT versus intermittent hemodialysis (90 days: odds ratio, 1.19; 95% confidence interval, 0.91 to 1.55; P=0.20; 365 days: odds ratio, 0.93; 95% confidence interval, 0.72 to 1.2; P=0.55). Conclusions We found no significant difference in hazards for nonrecovery or reasons for nonrecovery (mortality or ESRD) with intermittent hemodialysis versus continuous RRT. These results suggest that, when initial RRT modality is chosen primarily on hemodynamics, renal recovery and clinical outcomes in survivors are similar between intermittent hemodialysis and continuous RRT. C1 [Liang, Kelly V.; Palevsky, Paul M.; Kellum, John A.] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Sileanu, Florentina E.; Murugan, Raghavan; Pike, Francis; Palevsky, Paul M.; Kellum, John A.] Univ Pittsburgh, Sch Med, Ctr Crit Care Nephol, Dept Crit Care Med, Pittsburgh, PA USA. [Sileanu, Florentina E.; Murugan, Raghavan; Pike, Francis; Palevsky, Paul M.; Kellum, John A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Sileanu, Florentina E.; Clermont, Gilles; Murugan, Raghavan; Pike, Francis; Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness Ctr, Pittsburgh, PA USA. [Sileanu, Florentina E.; Pike, Francis] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Kellum, JA (reprint author), Ctr Crit Care Nephrol, Dept Crit Care Med, 604 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kellumja@ccm.upmc.edu FU Gambro/Baxter, Waukegan, IL FX This work was supported by Gambro/Baxter, Waukegan, IL. NR 50 TC 5 Z9 5 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 JAN PY 2016 VL 11 IS 1 BP 30 EP 38 DI 10.2215/CJN.01290215 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA DA4JM UT WOS:000367766200008 PM 26681135 ER PT J AU Hoffman, W Lakkis, FG Chalasani, G AF Hoffman, William Lakkis, Fadi G. Chalasani, Geetha TI B Cells, Antibodies, and More SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RENAL-ALLOGRAFT REJECTION; GERMINAL CENTER B; IDIOPATHIC MEMBRANOUS NEPHROPATHY; MIXED CRYOGLOBULINEMIA VASCULITIS; DEPLETING INDUCTION THERAPY; RANDOMIZED CONTROLLED-TRIAL; INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; ANCA-ASSOCIATED VASCULITIS AB B cells play a central role in the immunopathogenesis of glomerulonephritides and transplant rejection. B cells secrete antibodies that contribute to tissue injury via multiple mechanisms. In addition, B cells contribute to disease pathogenesis in autoimmunity and alloimmunity by presenting antigens as well as providing costimulation and cytokines to T cells. B cells also play an immunomodulatory role in regulating the immune response by secreting cytokines that inhibit disease onset and/or progression. B cell-targeted approaches for treating immune diseases of the kidney and other organs have gained significant momentum. However, much remains to be understood about B-cell biology in order to determine the timing, duration, and context of optimal therapeutic response to B cell-targeted approaches. In this review, we discuss the multifaceted roles of B cells as enhancers and regulators of immunity with relevance to kidney disease and transplantation. C1 [Hoffman, William; Lakkis, Fadi G.; Chalasani, Geetha] Univ Pittsburgh, Sch Med, Dept Med Renal Electrolyte, Pittsburgh, PA 15261 USA. [Lakkis, Fadi G.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15261 USA. [Lakkis, Fadi G.; Chalasani, Geetha] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA 15261 USA. [Lakkis, Fadi G.; Chalasani, Geetha] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15261 USA. [Chalasani, Geetha] Vet Affairs Pittsburgh Hlth Care Syst, Renal Sect, Pittsburgh, PA 15261 USA. RP Chalasani, G (reprint author), Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Hlth Care Syst, Thomas E Starzl Transplantat Inst, 200 Lothrop St,W1554 Biomed Sci Tower, Pittsburgh, PA 15261 USA. EM gec12@pitt.edu FU National Institutes of Health [R01 AI079177] FX This work was supported by funds from National Institutes of Health grant R01 AI079177 (G.C.). NR 192 TC 6 Z9 6 U1 0 U2 8 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 JAN PY 2016 VL 11 IS 1 BP 137 EP 154 DI 10.2215/CJN.09430915 PG 18 WC Urology & Nephrology SC Urology & Nephrology GA DA4JM UT WOS:000367766200020 PM 26700440 ER PT J AU Pavone, KJ Akeju, O Sampson, AL Ling, K Purdon, PL Brown, EN AF Pavone, Kara J. Akeju, Oluwaseun Sampson, Aaron L. Ling, Kelly Purdon, Patrick L. Brown, Emery N. TI Nitrous oxide-induced slow and delta oscillations SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Slow waves; EEG; General anesthesia; NMDA-receptor blockade; Parabrachial nucleus ID INDUCED ALPHA-RHYTHM; BURST-SUPPRESSION; PARABRACHIAL NUCLEUS; GENERAL-ANESTHESIA; HYPNOTIC RESPONSE; GABA(A) RECEPTORS; LOCUS-COERULEUS; PROPOFOL; ELECTROENCEPHALOGRAM; DEXMEDETOMIDINE AB Objectives: Switching from maintenance of general anesthesia with an ether anesthetic to maintenance with high-dose (concentration >50% and total gas flow rate >4 liters per minute) nitrous oxide is a common practice used to facilitate emergence from general anesthesia. The transition from the ether anesthetic to nitrous oxide is associated with a switch in the putative mechanisms and sites of anesthetic action. We investigated whether there is an electroencephalogram (EEG) marker of this transition. Methods: We retrospectively studied the ether anesthetic to nitrous oxide transition in 19 patients with EEG monitoring receiving general anesthesia using the ether anesthetic sevoflurane combined with oxygen and air. Results: Following the transition to nitrous oxide, the alpha (8-12 Hz) oscillations associated with sevoflurane dissipated within 3-12 min (median 6 min) and were replaced by highly coherent large-amplitude slow-delta (0.1-4 Hz) oscillations that persisted for 2-12 min (median 3 min). Conclusions: Administration of high-dose nitrous oxide is associated with transient, large amplitude slow-delta oscillations. Significance: We postulate that these slow-delta oscillations may result from nitrous oxide-induced blockade of major excitatory inputs (NMDA glutamate projections) from the brainstem (parabrachial nucleus and medial pontine reticular formation) to the thalamus and cortex. This EEG signature of high-dose nitrous oxide may offer new insights into brain states during general anesthesia. (C) 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. C1 [Pavone, Kara J.; Akeju, Oluwaseun; Sampson, Aaron L.; Ling, Kelly; Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Akeju, Oluwaseun; Purdon, Patrick L.; Brown, Emery N.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Brown, EN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB 444, Boston, MA 02114 USA. EM enb@neurostat.mit.edu FU National Institutes of Health - United States, Bethesda, Maryland [DP1-OD003646, DP2-OD006454, TR01-GM104948]; Foundation for Anesthesia Education and Research Award, Rochester, Minnesota; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital - United States, Boston, Massachusetts FX Supported by grants DP1-OD003646 (to ENB), DP2-OD006454 (to PLP) and TR01-GM104948 (to ENB) from the National Institutes of Health - United States, Bethesda, Maryland; Foundation for Anesthesia Education and Research Award (to OA), Rochester, Minnesota; funds from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital - United States, Boston, Massachusetts. NR 64 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JAN PY 2016 VL 127 IS 1 BP 556 EP 564 DI 10.1016/j.clinph.2015.06.001 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA1FD UT WOS:000367540800067 PM 26118489 ER PT J AU Hermans, MC Westover, MB van Putten, MJAM Hirsch, LJ Gaspard, N AF Hermans, Mathilde C. Westover, M. Brandon van Putten, Michel J. A. M. Hirsch, Lawrence J. Gaspard, Nicolas TI Quantification of EEG reactivity in comatose patients SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG reactivity; Coma; Automated analysis; Quantitative EEG; tBSI ID CARDIAC-ARREST; SUBARACHNOID HEMORRHAGE; THERAPEUTIC HYPOTHERMIA; INTERRATER RELIABILITY; AMERICAN ACADEMY; POSTANOXIC COMA; BRAIN; PREDICTION; AGREEMENT; TERMINOLOGY AB Objective: EEG reactivity is an important predictor of outcome in comatose patients. However, visual analysis of reactivity is prone to subjectivity and may benefit from quantitative approaches. Methods: In EEG segments recorded during reactivity testing in 59 comatose patients, 13 quantitative EEG parameters were used to compare the spectral characteristics of 1-minute segments before and after the onset of stimulation (spectral temporal symmetry). Reactivity was quantified with probability values estimated using combinations of these parameters. The accuracy of probability values as a reactivity classifier was evaluated against the consensus assessment of three expert clinical electroencephalographers using visual analysis. Results: The binary classifier assessing spectral temporal symmetry in four frequency bands (delta, theta, alpha and beta) showed best accuracy (Median AUC: 0.95) and was accompanied by substantial agreement with the individual opinion of experts (Gwet's AC1: 65-70%), at least as good as inter-expert agreement (AC1: 55%). Probability values also reflected the degree of reactivity, as measured by the inter-experts' agreement regarding reactivity for each individual case. Conclusion: Automated quantitative EEG approaches based on probabilistic description of spectral temporal symmetry reliably quantify EEG reactivity. Significance: Quantitative EEG may be useful for evaluating reactivity in comatose patients, offering increased objectivity. (C) 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Hermans, Mathilde C.] Univ Twente, Dept Tech Med, NL-7500 AE Enschede, Netherlands. [Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [van Putten, Michel J. A. M.] Univ Twente, Dept Neurol & Clin Neurophysiol, Medisch Spectrum Twente & Clin Neurophysiol Grp, NL-7500 AE Enschede, Netherlands. [Hermans, Mathilde C.; Hirsch, Lawrence J.; Gaspard, Nicolas] Yale Univ, Sch Med, Comprehens Epilepsy Ctr, Dept Neurol, New Haven, CT 06520 USA. [Gaspard, Nicolas] Univ Libre Bruxelles, Dept Neurol, Comprehens Epilepsy Ctr, Hop Erasme, B-1070 Brussels, Belgium. RP Gaspard, N (reprint author), Univ Libre Bruxelles, Dept Neurol, Comprehens Epilepsy Ctr, Hop Erasme, Route Lennik 808, B-1070 Brussels, Belgium. OI van Putten, Michel/0000-0001-8319-3626 FU Dutch Heart Organization; National Institute of Health (NIH-NINDS) [1K23NS090900-01]; Andrew David Heitman Neuroendovascular Research Fund; UCB-Pharma; Upsher-Smith; Lundbeck.; Eisai; Sunovion; Neuropace; Allergan; Lundbeck FX M.H. was the recipient of a grant from the Dutch Heart Organization. M.B.W. received research support from the National Institute of Health (NIH-NINDS, 1K23NS090900-01), the, and the Andrew David Heitman Neuroendovascular Research Fund.; M.vP. is a co-founder of Clinical Science Systems (www.clinicalscienceystems.com). L.J.H. received support for investigator-initiated studies from UCB-Pharma, Upsher-Smith, Lundbeck., Eisai and Sunovion and consultation fees from Lundbeck, Upsher-Smith, Neuropace, and Allergan. Besides, L.J.H. received honoraria for speaking from Natus and Neuropace. L.J.G. was author of chapters of UpToDate-Neurology and co-author of the book "Atlas of EEG in Critical Care'', by Hirsch and Brenner, 2010. N.G. is a Clinical Master Specialist of the Belgian Fund for Scientific Research - FNRS and received honoraria from UpToDate. NR 40 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JAN PY 2016 VL 127 IS 1 BP 571 EP 580 DI 10.1016/j.clinph.2015.06.024 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA1FD UT WOS:000367540800069 PM 26183757 ER PT J AU Zhang, DF Melikian, R Papavassiliou, E AF Zhang, Dafang Melikian, Rojeh Papavassiliou, Efstathios TI Chiari I Malformation Presenting as Shoulder Pain, Weakness, and Muscle Atrophy in a Collegiate Athlete SO CURRENT SPORTS MEDICINE REPORTS LA English DT Review ID CLINICAL ARTICLE; DECOMPRESSION; SYRINGOMYELIA; ADULTS; LIFE C1 [Zhang, Dafang; Melikian, Rojeh] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Papavassiliou, Efstathios] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA. [Zhang, Dafang; Melikian, Rojeh; Papavassiliou, Efstathios] Harvard Univ, Sch Med, Boston, MA USA. RP Zhang, DF (reprint author), BIDMC, Dept Orthopaed Surg, 10th Floor,Stoneman Bldg,330 Brookline Ave, Boston, MA 02215 USA. EM dzhang9@partners.org NR 22 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1537-890X EI 1537-8918 J9 CURR SPORT MED REP JI Curr. Sport. Med. Rep. PD JAN-FEB PY 2016 VL 15 IS 1 BP 10 EP 12 DI 10.1249/JSR.0000000000000217 PG 3 WC Sport Sciences SC Sport Sciences GA DA5DO UT WOS:000367822800005 PM 26745162 ER PT J AU Tsai, J Sippel, LM Mota, N Southwick, SM Pietrzak, RH AF Tsai, Jack Sippel, Lauren M. Mota, Natalie Southwick, Steven M. Pietrzak, Robert H. TI LONGITUDINAL COURSE OF POSTTRAUMATIC GROWTH AMONG US MILITARY VETERANS: RESULTS FROM THE NATIONAL HEALTH AND RESILIENCE IN VETERANS STUDY SO DEPRESSION AND ANXIETY LA English DT Article DE posttraumatic stress disorder; resilience; stress; spirituality; quality of life ID BREAST-CANCER; HAPPINESS; SYMPTOMS; ALTRUISM; STRESS; TRAUMA; WAR; BIBLIOTHERAPY; SATISFACTION; METAANALYSIS AB BackgroundPosttraumatic growth (PTG) is increasingly recognized as an important psychosocial phenomenon, but few studies have evaluated the longitudinal course of PTG. This study identified courses of PTG over a 2-year period in a contemporary, nationally representative sample of U.S. military veterans, and examined sociodemographic, military, trauma, medical, and psychosocial predictors of PTG course. Methods Data were based on a Web-based survey of a nationally representative sample of 1,838 U.S. veterans who reported at least one potentially traumatic event and provided data at two time points (October-December 2011 and September-October 2013). Results Five different courses of PTG were identifiedConsistently Low (33.6%), Moderately Declining (19.4%), Increasing PTG (16.8%), Dramatically Declining (15.7%), and Consistently High (14.5%). More than half (59.4%) of veterans who reported at least moderate PTG maintained that level of PTG 2 years later. Posttraumatic stress disorder symptoms, medical conditions, purpose in life, altruism, gratitude, religiosity, and an active reading lifestyle predicted maintenance or increase in PTG. Conclusions PTG has a heterogeneous course and is not only common, but can persist over time especially in the presence of posttraumatic stress and certain psychosocial factors. Clinicians and researchers should consider the personal growth that can result from trauma and help trauma survivors find ways to maintain this growth over time. C1 [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT 06516 USA. [Tsai, Jack; Sippel, Lauren M.; Mota, Natalie; Southwick, Steven M.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Sippel, Lauren M.; Mota, Natalie; Southwick, Steven M.; Pietrzak, Robert H.] US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, 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 FU United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder; United States Department of Veterans Affairs, Office of Research and Development FX This work was supported in part by the United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, the United States Department of Veterans Affairs, Office of Research and Development, and a private donation. 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. None of the authors report any conflicts of interest with this work. NR 47 TC 3 Z9 3 U1 4 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2016 VL 33 IS 1 BP 9 EP 18 DI 10.1002/da.22371 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DA3TX UT WOS:000367722900001 PM 25914061 ER PT J AU Olvet, DM Delaparte, L Yeh, FC DeLorenzo, C McGrath, PJ Weissman, MM Adams, P Fava, M Deckersbach, T McInnis, MG Carmody, TJ Cooper, CM Kurian, BT Lu, HZ Toups, MS Trivedi, MH Parsey, RV AF Olvet, Doreen M. Delaparte, Lauren Yeh, Fang-Cheng DeLorenzo, Christine McGrath, Patrick J. Weissman, Myrna M. Adams, Phillip Fava, Maurizio Deckersbach, Thilo McInnis, Melvin G. Carmody, Thomas J. Cooper, Crystal M. Kurian, Benji T. Lu, Hanzhang Toups, Marisa S. Trivedi, Madhukar H. Parsey, Ramin V. TI A COMPREHENSIVE EXAMINATION OF WHITE MATTER TRACTS AND CONNECTOMETRY IN MAJOR DEPRESSIVE DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE depression; brain imaging; neuroimaging; mood disorders; diffusion tensor imaging; white matter tracts; connectometry; fractional anisotropy; multisite study ID ORBITOFRONTAL CORTEX; DIFFUSION MRI; SPATIAL STATISTICS; TREATMENT-NAIVE; YOUNG-ADULTS; LIFE-SPAN; TRACTOGRAPHY; INTEGRITY; ABNORMALITIES; 1ST-EPISODE AB BackgroundMajor depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI). Methods139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract-based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD. ResultsThere were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry. ConclusionsThe lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts. C1 [Olvet, Doreen M.; DeLorenzo, Christine; Parsey, Ramin V.] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. [Delaparte, Lauren] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Yeh, Fang-Cheng] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. [Parsey, Ramin V.] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. [McGrath, Patrick J.; Weissman, Myrna M.; Adams, Phillip] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Fava, Maurizio; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [McInnis, Melvin G.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Carmody, Thomas J.; Cooper, Crystal M.; Kurian, Benji T.; Lu, Hanzhang; Toups, Marisa S.; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. RP Olvet, DM (reprint author), SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. EM doreen.olvet@stonybrookmedicine.edu RI Parsey, Ramin/J-8254-2014; OI Yeh, Fang-Cheng/0000-0002-7946-2173 FU National Institute of Mental Health [U01-MH092250] FX Contract grant sponsor: National Institute of Mental Health; Contract grant number: U01-MH092250. NR 57 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2016 VL 33 IS 1 BP 56 EP 65 DI 10.1002/da.22445 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DA3TX UT WOS:000367722900006 PM 26477532 ER PT J AU Jahangiri, L Sharpe, M Novikov, N Gonzalez-Rosa, JM Borikova, A Nevis, K Paffett-Lugassy, N Zhao, L Adams, M Guner-Ataman, B Burns, CE Burns, CG AF Jahangiri, Leila Sharpe, Michka Novikov, Natasha Gonzalez-Rosa, Juan Manuel Borikova, Asya Nevis, Kathleen Paffett-Lugassy, Noelle Zhao, Long Adams, Meghan Guner-Ataman, Burcu Burns, Caroline E. Burns, C. Geoffrey TI The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field SO DEVELOPMENT LA English DT Article DE AP-1; Fosl2; Cardiac development; Heart; Second heart field; Zebrafish ID OUTFLOW TRACT; CARDIOMYOCYTE DIFFERENTIATION; SECONDARY HEART; ARTERIAL POLE; PROGENITOR SPECIFICATION; RESTRICTED EXPRESSION; DISTINCT PHASES; SMOOTH-MUSCLE; CELLS; REGENERATION AB The vertebrate heart forms through successive phases of cardiomyocyte differentiation. Initially, cardiomyocytes derived from first heart field (FHF) progenitors assemble the linear heart tube. Thereafter, second heart field (SHF) progenitors differentiate into cardiomyocytes that are accreted to the poles of the heart tube over a well-defined developmental window. Although heart tube elongation deficiencies lead to life-threatening congenital heart defects, the variables controlling the initiation, rate and duration of myocardial accretion remain obscure. Here, we demonstrate that the AP-1 transcription factor, Fos-like antigen 2 (Fosl2), potentiates the rate of myocardial accretion from the zebrafish SHF. fosl2 mutants initiate accretion appropriately, but cardiomyocyte production is sluggish, resulting in a ventricular deficit coupled with an accumulation of SHF progenitors. Surprisingly, mutant embryos eventually correct the myocardial deficit by extending the accretion window. Overexpression of Fosl2 also compromises production of SHF-derived ventricular cardiomyocytes, a phenotype that is consistent with precocious depletion of the progenitor pool. Our data implicate Fosl2 in promoting the progenitor to cardiomyocyte transition and uncover the existence of regulatory mechanisms to ensure appropriate SHF-mediated cardiomyocyte contribution irrespective of embryonic stage. C1 [Jahangiri, Leila; Sharpe, Michka; Novikov, Natasha; Gonzalez-Rosa, Juan Manuel; Borikova, Asya; Nevis, Kathleen; Paffett-Lugassy, Noelle; Zhao, Long; Adams, Meghan; Guner-Ataman, Burcu; Burns, Caroline E.; Burns, C. Geoffrey] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Jahangiri, Leila; Sharpe, Michka; Novikov, Natasha; Gonzalez-Rosa, Juan Manuel; Borikova, Asya; Nevis, Kathleen; Paffett-Lugassy, Noelle; Zhao, Long; Adams, Meghan; Guner-Ataman, Burcu; Burns, Caroline E.; Burns, C. Geoffrey] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Burns, Caroline E.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Burns, CE (reprint author), Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM cburns6@partners.org; gburns@cvrc.mgh.harvard.edu RI Zhao, Long/A-6439-2014 FU National Science Foundation; Cell and Molecular Training for Cardiovascular Biology [T32HL007208]; EMBO Long-Term Fellowship [ALTF 253-2014]; National Institutes of Health National Research Service Award [1F32HL110627, 1F32HL112579]; Harvard Stem Cell Institute Training Grant [5HL087735]; MGH Tosteson Award; AHA Post-doctoral Fellowship [14POST20380738]; American Heart Association (AHA) Post-doctoral Fellowship [10POST4170037]; AHA Scientist Development Grant [14SDG19020018]; National Institutes of Health [5R01HL096816] FX M.S. was supported by a National Science Foundation Graduate Research Fellowship. N.N., A.B. and M.A. were supported by the Cell and Molecular Training for Cardiovascular Biology [T32HL007208 (PI: Gerszten)] grant awarded to Massachusetts General Hospital. J.M.G.-R. was supported by an EMBO Long-Term Fellowship [ALTF 253-2014]. K.R.N. was supported by a National Institutes of Health National Research Service Award [1F32HL110627]. N.P.-L. was supported by the Harvard Stem Cell Institute Training Grant [5HL087735], a National Institutes of Health National Research Service Award [1F32HL112579] and an MGH Tosteson Award. L.Z. was supported by an AHA Post-doctoral Fellowship [14POST20380738]. B.G.-A. was supported by an American Heart Association (AHA) Post-doctoral Fellowship [10POST4170037] and an AHA Scientist Development Grant [14SDG19020018]. This work was supported by an R01 award to C.G.B. [5R01HL096816] from the National Institutes of Health. Deposited in PMC for release after 12 months. NR 64 TC 0 Z9 0 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD JAN 1 PY 2016 VL 143 IS 1 BP 113 EP 122 DI 10.1242/dev.126136 PG 10 WC Developmental Biology SC Developmental Biology GA DA2IJ UT WOS:000367618200012 PM 26732840 ER PT J AU Kaz, AM Dominitz, JA AF Kaz, Andrew M. Dominitz, Jason A. TI Can individuals with colonic polyposis be managed safely with colonoscopic surveillance? SO ENDOSCOPY LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; APC C1 [Kaz, Andrew M.; Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA 98108 USA. [Kaz, Andrew M.; Dominitz, Jason A.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kaz, Andrew M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Kaz, AM (reprint author), VA Puget Sound Hlth Care Syst, Gastroenterol Sect, 1660 S Columbian Way,S-111-Gastro, Seattle, WA 98108 USA. EM Andrew.Kaz@va.gov FU VA Puget Sound Health Care System FX This material is the result of work supported in part by resources from the VA Puget Sound Health Care System. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 12 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PD JAN PY 2016 VL 48 IS 1 BP 7 EP 8 DI 10.1055/s-0034-1393637 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CZ9YU UT WOS:000367454600003 PM 26710280 ER PT J AU Papakostas, TD Lim, L van Zyl, T Miller, JB Modjtahedi, BS Andreoli, CM Wu, D Young, LH Kim, IK Vavvas, DG Esmaili, DD Husain, D Eliott, D Kim, LA AF Papakostas, T. D. Lim, L. van Zyl, T. Miller, J. B. Modjtahedi, B. S. Andreoli, C. M. Wu, D. Young, L. H. Kim, I. K. Vavvas, D. G. Esmaili, D. D. Husain, D. Eliott, D. Kim, L. A. TI Intravitreal aflibercept for macular oedema secondary to central retinal vein occlusion in patients with prior treatment with bevacizumab or ranibizumab SO EYE LA English DT Article ID VEGF TRAP; PHASE-III; DEGENERATION; TRIAL; INJECTION; OUTCOMES; THERAPY; GALILEO; EYE AB Purpose To report the visual and anatomic outcomes in eyes with macular oedema (MO) secondary to central retinal vein occlusion (CRVO) that were switched from either intravitreal bevacizumab or ranibizumab to intravitreal aflibercept. Methods Two-center retrospective chart review. Eyes with MO secondary to CRVO that received a minimum of three intravitreal injections of bevacizumab or ranibizumab and were switched to intravitreal aflibercept for persistent or recurrent MO not responding to either bevacizumab and/or ranibizumab. Results In all 42 eyes of 42 patients were included in the study. The median visual acuity before the switch was 20/126, 1 month after the first injection of aflibercept 20/89 (P=0.0191), and at the end of the follow-up 20/100 (P=0.2724). The median CRT before the switch was 536 mu m, 1 month after the first injection of aflibercept 293.5 mu m (P=0.0038), and at the end of the follow-up 279 mu m (P=0.0013 compared to before the switch). The median number of weeks between injections before the switch was 5.6 and after the switch was 7.6 (P < 0.0001). Conclusion Converting eyes with refractory MO due to CRVO to aflibercept can result in stabilization of the vision, improved macular anatomy, and extension of the injection interval. C1 [Papakostas, T. D.; Lim, L.; van Zyl, T.; Miller, J. B.; Modjtahedi, B. S.; Wu, D.; Young, L. H.; Kim, I. K.; Vavvas, D. G.; Husain, D.; Eliott, D.; Kim, L. A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. [Andreoli, C. M.] Harvard Vanguard Med Associates, Boston, MA USA. [Esmaili, D. D.] Retina Vitreous Associates Med Grp, Los Angeles, CA USA. RP Eliott, D (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu; leo_kim@meei.harvard.edu FU NEI NIH HHS [K12 EY016335] NR 21 TC 6 Z9 6 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD JAN PY 2016 VL 30 IS 1 BP 79 EP 84 DI 10.1038/eye.2015.175 PG 6 WC Ophthalmology SC Ophthalmology GA DA5PW UT WOS:000367856000012 PM 26449196 ER PT J AU Saigusa, T Dang, YJ Mullick, AE Yeh, ST Zile, MR Baicu, CF Bell, PD AF Saigusa, Takamitsu Dang, Yujing Mullick, Adam E. Yeh, Steve T. Zile, Michael R. Baicu, Catalin F. Bell, P. Darwin TI Suppressing angiotensinogen synthesis attenuates kidney cyst formation in a Pkd1 mouse model SO FASEB JOURNAL LA English DT Article DE renin angiotensin system; antisense oligonucleotide; polycystic kidney disease; hypertension ID BLOOD-PRESSURE; ANTISENSE OLIGODEOXYNUCLEOTIDES; IN-VIVO; DISEASE; RENIN; SYSTEM; INHIBITOR; CELL; HYPERTENSION; RATS AB Activation of the intrarenal renin angiotensin system(RAS) is believed to play an important role in the development of hypertension and cystogenesis in autosomal dominant polycystic kidney disease (ADPKD). Results of clinical studies testing RAS inhibitors in slowing the progression of cystic disease in ADPKD are inconclusive, and we hypothesized that current RAS inhibitors do not adequately suppress intrarenal RAS. For this study, we compared a novel Gen 2 antisense oligonucleotide (ASO) that inhibits angiotensinogen (Agt) synthesis to lisinopril in adult conditional Pkd1 systemic-knockout mice, a model of ADPKD. Six weeks after Pkd1 global gene knockout, the mice were treated with Agt-ASO (66 mg/kg/wk), lisinopril (100 mg/kg/d), PBS (control), or scrambled ASO (66 mg/kg/wk) for 10 wk, followed by tissue collection. Agt ASO resulted in significant reduction in plasma, liver, and kidney Agt, and increased kidney renin compared with control treatments. Kidneys from Agt-ASO-treated mice were not as enlarged and showed reduced cystic volume compared with lisinopril or control treatments. Blood pressure was better controlled with lisinopril than with Agt-ASO. Agt-ASO suppressed cell proliferation in both cystic and noncystic cells compared with lisinopril and control treatments. However, Agt-ASO did not reduce cell proliferation in liver, which indicates that Agt-ASO targets cell signaling pathways that specifically suppresses cystogenesis in the kidney. These data suggest that Agt-ASO effectively attenuates intrarenal RAS and therefore can be a novel and effective agent for treating ADPKD. C1 [Saigusa, Takamitsu; Dang, Yujing; Bell, P. Darwin] Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. [Zile, Michael R.; Baicu, Catalin F.] Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA. [Saigusa, Takamitsu; Dang, Yujing; Zile, Michael R.; Baicu, Catalin F.; Bell, P. Darwin] Ralph Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Mullick, Adam E.; Yeh, Steve T.] ISIS Pharmaceut, Carlsbad, CA 92008 USA. RP Saigusa, T (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,CSB 829, Charleston, SC 29425 USA. EM saigusa@musc.edu; bellpd@musc.edu OI Mullick, Adam/0000-0003-4600-961X FU U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [K08DK106465, P30 DK074038]; U.S. Department of Veterans Affairs Merit Award; Dialysis Clinic, Inc. (Nashville, TN, USA) FX This work was supported by U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Grants K08DK106465 (to T.S.) and P30 DK074038 (to P.D.B.); U.S. Department of Veterans Affairs Merit Award (to P.D.B.); and a Dialysis Clinic, Inc. (Nashville, TN, USA) grant (to T.S. and P.D.B.). The authors declare no conflicts of interest. NR 42 TC 4 Z9 4 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2016 VL 30 IS 1 BP 370 EP 379 DI 10.1096/fj.15-279299 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA DA2JL UT WOS:000367621000035 PM 26391272 ER PT J AU Fan, Y Bi, RY Densmore, MJ Sato, T Kobayashi, T Yuan, Q Zhou, XD Erben, RG Lanske, B AF Fan, Yi Bi, Ruiye Densmore, Michael J. Sato, Tadatoshi Kobayashi, Tatsuya Yuan, Quan Zhou, Xuedong Erben, Reinhold G. Lanske, Beate TI Parathyroid hormone 1 receptor is essential to induce FGF23 production and maintain systemic mineral ion homeostasis SO FASEB JOURNAL LA English DT Article DE calcium/phosphate metabolism; kidney-bone mineral diseases; Galnt3 ID FIBROBLAST GROWTH FACTOR-23; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; FAMILIAL TUMORAL CALCINOSIS; PTH/PTHRP RECEPTOR; INDIAN HEDGEHOG; METAPHYSEAL CHONDRODYSPLASIA; BLOMSTRAND-CHONDRODYSPLASIA; HYPOPHOSPHATEMIC RICKETS; TARGETED EXPRESSION; IN-VIVO AB Parathyroid-hormone-type 1 receptor (PTH1R) is extensively expressed in key regulatory organs for systemic mineral ion homeostasis, including kidney and bone. We investigated the bone-specific functions of PTH1R in modulating mineral ion homeostasis by generating a novel mouse model in which PTH1R is ablated in the limb mesenchyme using Prx1Cre transgenic mice. Such ablation decreased FGF23 protein and serum levels by 50%, despite normal Fgf23 mRNA levels in long bones. Circulating calcium and PTH levels were unchanged, but inorganic phosphate and 1,25(OH)(2)D-3 levels were significantly decreased and accompanied by elevated urinary calcium and phosphate wasting. Key renal genes for balancing mineral ion homeostasis, calbindin D-28k, Klotho, and Napi2a were suppressed by 30-40%. Intermittent hPTH(1-34) injections increased Fgf23 mRNA (7.3-fold), Nurr1 mRNA(3.1-fold), and serum intact-FGF23 (1.6-fold) in controls, but failed to induce Fgf23, Nurr1 mRNA, or intact FGF23 production in mutants. Moreover, a significant elevation in serum C-terminal-FGF23 levels (4-fold) was detected in both genotypes. PTH markedly down-regulated Galnt3 expression (2.7-fold) in controls but not in mutants. These results demonstrate the pivotal role of PTH1R in long bones to regulate systemic mineral ion homeostasis and the direct induction of FGF23 by PTH1R signaling. C1 [Fan, Yi; Densmore, Michael J.; Sato, Tadatoshi; Lanske, Beate] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Fan, Yi; Bi, Ruiye; Yuan, Quan; Zhou, Xuedong] Sichuan Univ, State Key Lab Oral Dis, West China Hosp Stomatol, Chengdu 610064, Sichuan, Peoples R China. [Bi, Ruiye] Sichuan Univ, West China Sch Stomatol, Chengdu 610064, Sichuan, Peoples R China. [Bi, Ruiye; Kobayashi, Tatsuya; Lanske, Beate] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bi, Ruiye; Kobayashi, Tatsuya; Lanske, Beate] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Erben, Reinhold G.] Univ Vet Med, Inst Physiol Pathophysiol & Biophys, Dept Biomed Sci, Vienna, Austria. RP Lanske, B (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Res & Educ Bldg,Room 303,188 Longwood Ave, Boston, MA 02115 USA. EM beate_lanske@hsdm.harvard.edu FU U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases [DK097105]; Harvard School of Dental Medicine; State Key Laboratory of Oral Diseases [SKLOD2015OF01] FX The authors thank Amgen for providing the FGF23 antibody and The Center for Skeletal Research Core for the measurement of urinary cAMP levels. Study design: Y.F. and B.L; study conduct: Y.F., R.B., T.S., R.E., and M.D; data collection: Y.F., T.S., R.B., and T.K; data interpretation: Y.F., T.K., Q.Y., X.Z., and B.L; manuscript draft: Y.F; and manuscript revision: M.D. B.L. This work was supported by U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases Grant DK097105 (to B.L.), the Harvard School of Dental Medicine, and by State Key Laboratory of Oral Diseases Open Funding Grant SKLOD2015OF01. The authors declare no conflicts of interest. NR 47 TC 4 Z9 4 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2016 VL 30 IS 1 BP 428 EP 440 DI 10.1096/fj.15-278184 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA DA2JL UT WOS:000367621000040 PM 26428657 ER PT J AU Seidel, JL Escartin, C Ayata, C Bonvento, G Shuttleworth, CW AF Seidel, Jessica L. Escartin, Carole Ayata, Cenk Bonvento, Gilles Shuttleworth, C. William TI Multifaceted Roles for Astrocytes in Spreading Depolarization: A Target for Limiting Spreading Depolarization in Acute Brain Injury? SO GLIA LA English DT Review DE spreading depression; migraine; stroke; traumatic brain injury; reactive astrocyte; Ca2+; waves; adenosine; glutamate; neurovascular coupling ID CEREBRAL-BLOOD-FLOW; CENTRAL-NERVOUS-SYSTEM; FIBRILLARY ACIDIC PROTEIN; IN-VIVO; RAT-BRAIN; SYNAPTIC-TRANSMISSION; CORTICAL DEPRESSION; RECEPTOR ACTIVATION; ENERGY-METABOLISM; GLUTAMATE RELEASE AB Spreading depolarizations (SDs) are coordinated waves of synchronous depolarization, involving large numbers of neurons and astrocytes as they spread slowly through brain tissue. The recent identification of SDs as likely contributors to pathophysiology in human subjects has led to a significant increase in interest in SD mechanisms, and possible approaches to limit the numbers of SDs or their deleterious consequences in injured brain. Astrocytes regulate many events associated with SD. SD initiation and propagation is dependent on extracellular accumulation of K+ and glutamate, both of which involve astrocytic clearance. SDs are extremely metabolically demanding events, and signaling through astrocyte networks is likely central to the dramatic increase in regional blood flow that accompanies SD in otherwise healthy tissues. Astrocytes may provide metabolic support to neurons following SD, and may provide a source of adenosine that inhibits neuronal activity following SD. It is also possible that astrocytes contribute to the pathophysiology of SD, as a consequence of excessive glutamate release, facilitation of NMDA receptor activation, brain edema due to astrocyte swelling, or disrupted coupling to appropriate vascular responses after SD. Direct or indirect evidence has accumulated implicating astrocytes in many of these responses, but much remains unknown about their specific contributions, especially in the context of injury. Conversion of astrocytes to a reactive phenotype is a prominent feature of injured brain, and recent work suggests that the different functional properties of reactive astrocytes could be targeted to limit SDs in pathophysiological conditions. C1 [Seidel, Jessica L.; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA. [Escartin, Carole; Bonvento, Gilles] Univ Paris Saclay, Univ Paris 11,DSV,CNRS,UMR 9199, Commissariat Energie Atom & Energies Alternat CEA, Inst Imagerie Biomed I2BM,Mol Imaging Ctr MIRCen, F-92260 Fontenay Aux Roses, France. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv & Neurosci Intens Care Unit,Dept Neur, Charlestown, MA USA. [Shuttleworth, C. William] Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA. RP Shuttleworth, CW (reprint author), Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA. EM bshuttleworth@salud.unm.edu RI Escartin, Carole/A-1952-2010; Bonvento, Gilles/F-6023-2013 OI Escartin, Carole/0000-0003-3613-4118; Bonvento, Gilles/0000-0002-2886-4228 FU NIH [NS051288]; Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA); Centre National de la Recherche Scientifique (CNRS) FX Supported by NIH grant NS051288 (C.W.S) & Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA; http://www.cea.fr/) and Centre National de la Recherche Scientifique (CNRS; http://www.cnrs.fr/) (G.B.). NR 168 TC 7 Z9 7 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-1491 EI 1098-1136 J9 GLIA JI Glia PD JAN PY 2016 VL 64 IS 1 BP 5 EP 20 DI 10.1002/glia.22824 PG 16 WC Neurosciences SC Neurosciences & Neurology GA DA3DU UT WOS:000367677600001 PM 26301517 ER PT J AU Liu, J Konstantinopoulos, PA Matulonis, UA AF Liu, Joyce Konstantinopoulos, Panagiotis A. Matulonis, Ursula A. TI Genomic testing and precision medicine What does this mean for gynecologic oncology?* SO GYNECOLOGIC ONCOLOGY LA English DT Article ID OVARIAN-CANCER; CELL CARCINOMA; MUTATIONS; WOMEN; INHIBITORS; GERMLINE; SURVIVAL; GENES C1 [Liu, Joyce; Konstantinopoulos, Panagiotis A.; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Gynecol Oncol Program, Boston, MA 02215 USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ursula_matulonis@dfci.harvard.edu FU AstraZeneca; Genentech/Roche; Boston Biomedical; Atara Biotherapeutics; Merrimack Pharmaceuticals FX Ursula Matulonis: consultant for Astrazeneca, Tesaro, and Genentech/Roche. Joyce Liu: consultant for Astrazeneca and Genentech/Roche and conducted clinical research on trials sponsored by AstraZeneca, Genentech/Roche, Boston Biomedical, Atara Biotherapeutics, and Merrimack Pharmaceuticals. Panagiotis A. Konstantinopoulos: Advisory Board for Vertex Inc. NR 22 TC 1 Z9 1 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 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2016 VL 140 IS 1 BP 3 EP 5 DI 10.1016/j.ygyno.2015.12.001 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DA5UW UT WOS:000367869100002 PM 26657840 ER PT J AU Mitra, D Klopp, AH Viswanathan, AN AF Mitra, Devarati Klopp, Ann H. Viswanathan, Akila N. TI Pros and cons of vaginal brachytherapy after external beam radiation therapy in endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Endometrial cancer; Vaginal brachytherapy; External beam radiation therapy ID GYNECOLOGIC-ONCOLOGY-GROUP; QUALITY-OF-LIFE; CERVICAL STROMAL INVASION; LONG-TERM SURVIVAL; PHASE-III TRIAL; STAGE-I; ADJUVANT RADIOTHERAPY; POSTOPERATIVE RADIOTHERAPY; PELVIC RADIOTHERAPY; RANDOMIZED-TRIAL AB A large number of studies have looked at the role of radiation therapy in the treatment of endometrial cancer. One particular radiation strategy in common practice is the use of adjuvant external beam (EB) radiotherapy followed by vaginal brachytherapy (VB). While the addition of VB to EB provides a theoretical benefit of a localized boost with higher focused dose to an area of potentially high recurrence risk, a randomized clinical trial to compare outcomes and toxicities of EB + VB vs. EB alone is lacking. The goal of this review is to present the current data for and against the use of this combined radiation modality and to provide some preliminary evidence regarding which patient populations may be most likely to benefit. (C) 2015 Elsevier Inc. All rights reserved. C1 [Mitra, Devarati; Viswanathan, Akila N.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mitra, Devarati; Viswanathan, Akila N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Klopp, Ann H.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. RP Viswanathan, AN (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU NCI NIH HHS [P30 CA008748] NR 55 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2016 VL 140 IS 1 BP 167 EP 175 DI 10.1016/j.ygyno.2015.09.084 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DA5UW UT WOS:000367869100029 PM 26432041 ER PT J AU Kehr, E Masry, P Lis, R Loda, M Taplin, ME Hirsch, MS AF Kehr, Elizabeth Masry, Paul Lis, Rosina Loda, Massimo Taplin, Mary-Ellen Hirsch, Michelle S. TI Detecting metastatic prostate carcinoma in pelvic lymph nodes following neoadjuvant hormone therapy: the eyes have it! SO HISTOPATHOLOGY LA English DT Article DE abiaterone; androgen receptor; keratin; lymph node; neoadjuvant treatment; NKX3.1; prostate cancer; prostatectomy; PSA ID ANDROGEN-DEPRIVATION THERAPY; CANCER; MICROMETASTASES; MELANOMA AB Aims: Residual cancer morphology in radical prostatectomies (RPs) after neoadjuvant hormone therapy includes inconspicuous cytology, and treated tumour cells can be difficult to identify in lymph nodes. The aim of this study was to evaluate the role of immunohistochemistry (IHC) in identifying occult lymph node metastases following neoadjuvant hormone treatment of prostate cancer. Methods and results: One hundred and twenty-eight lymph nodes from 24 patients treated with neoadjuvant hormone therapy, including abiraterone acetate alone or combined with leuprolide, were stained with antibodies against keratin AE1/AE3, prostate-specific antigen (PSA), prostate-specific acid phosphatase (PrAP), androgen receptor (AR), and NKX3.1. IHC slides were scored 'blind', and then retrospectively compared with haematoxylin and eosin (H&E)-stained slides and pathology reports. IHC identified carcinoma in six lymph nodes from three patients. All metastases were positive for NKX3.1 and AR, five of six were positive for AE1/AE3, and three of six were positive for PSA; PrAP was negative in all metastatic foci. All six lymph node metastases had been identified by H&E staining at the time of RP. Conclusions: These findings suggest that routine use of IHC on lymph nodes from neoadjuvant-treated prostate carcinomas is not necessary. Nevertheless, for suspicious small foci of atypical cells in neoadjuvant-treated lymph nodes, NKX3.1 and AR appear to have the greatest sensitivity. C1 [Kehr, Elizabeth; Masry, Paul; Loda, Massimo; Hirsch, Michelle S.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kehr, Elizabeth; Masry, Paul; Loda, Massimo; Taplin, Mary-Ellen; Hirsch, Michelle S.] Harvard Univ, Sch Med, Boston, MA USA. [Lis, Rosina; Loda, Massimo; Taplin, Mary-Ellen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Hirsch, MS (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA. EM mhirsch1@partners.org FU Janssen Pharmaceuticals, Inc. FX The authors wish to acknowledge, from the BWH Department of Pathology, Mr Mark Buchanan for his assistance with tissue block sectioning, and all members of the department of immunohistochemistry laboratory for immunostaining of lymph nodes. Janssen Pharmaceuticals, Inc. provided financial support for the abiraterone clinical trial. This work was presented in part at the 103rd Annual Meeting of the United States and Canadian Academy of Pathology in San Diego, California, 2014. NR 17 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 EI 1365-2559 J9 HISTOPATHOLOGY JI Histopathology PD JAN PY 2016 VL 68 IS 2 BP 303 EP 307 DI 10.1111/his.12739 PG 5 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DA5DU UT WOS:000367823500014 PM 26018610 ER PT J AU Partovi, S Reiber, JHC Ghoshhajra, BB AF Partovi, Sasan Reiber, Johan H. C. Ghoshhajra, Brian B. TI Topical issue: multimodality imaging in atherosclerosis SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Editorial Material DE Special issue; Atherosclerosis; Computed tomography; Magnetic resonance imaging; Contrast-enhanced ultrasound; Hybrid imaging C1 [Partovi, Sasan] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Radiol, Cleveland, OH 44106 USA. [Reiber, Johan H. C.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Ghoshhajra, BB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM bghoshhajra@mgh.harvard.edu NR 21 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2016 VL 32 IS 1 SI SI BP 1 EP 3 DI 10.1007/s10554-015-0774-z PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DA5QD UT WOS:000367856700001 PM 26438168 ER PT J AU Takx, RAP Partovi, S Ghoshhajra, BB AF Takx, Richard A. P. Partovi, Sasan Ghoshhajra, Brian B. TI Imaging of atherosclerosis SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Atherosclerosis; Cardiovascular disease; Ultrasound; CTA; MRA; PET ID PERIPHERAL ARTERIAL-DISEASE; OPTICAL COHERENCE TOMOGRAPHY; FRACTIONAL FLOW RESERVE; CORONARY CT ANGIOGRAPHY; COMPUTED-TOMOGRAPHY; ISCHEMIC-STROKE; MR-ANGIOGRAPHY; INTRAVASCULAR ULTRASOUND; FUNCTIONAL SEVERITY; CARDIOVASCULAR RISK AB Cardiovascular disease (CVD) is a major health concern worldwide and atherosclerosis is the main cause of CVD. Atherosclerosis is a systemic and chronic inflammatory disease, which is characterized by plaque formation and can affect different vascular beds. Imaging of atherosclerosis could guide therapeutic interventions. Ultrasound, computed tomography, magnetic resonance imaging (MRI), positron emission tomography (PET) and interventional angiography are the main imaging modalities available for the assessment of atherosclerotic burden and for potential prediction of future events. In addition, the introduction of new hybrid imaging techniques like PET/MRI allow for the simultaneous evaluation of anatomical and metabolic characteristics tissues. This article provides an overview of coronary and non-coronary atherosclerosis and summarizes the current understanding of different available imaging techniques. The integration of these techniques in clinical practice may allow for superior risk stratification and therapeutic planning as well as monitoring of interventional and medication based treatment strategies. C1 [Takx, Richard A. P.; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Takx, Richard A. P.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands. [Partovi, Sasan] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. RP Ghoshhajra, BB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM BGHOSHHAJRA@mgh.harvard.edu NR 68 TC 2 Z9 2 U1 3 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2016 VL 32 IS 1 SI SI BP 5 EP 12 DI 10.1007/s10554-015-0730-y PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DA5QD UT WOS:000367856700002 PM 26239134 ER PT J AU Young, JY Schaefer, PW AF Young, Joseph Yeen Schaefer, Pamela Whitney TI Acute ischemic stroke imaging: a practical approach for diagnosis and triage SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Stroke; Imaging; MRI; CT ID MIDDLE CEREBRAL-ARTERY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; ATTENUATED INVERSION-RECOVERY; TISSUE-PLASMINOGEN ACTIVATOR; TRACT FRACTIONAL ANISOTROPY; ADMISSION CT PERFUSION; DIFFUSION-WEIGHTED MRI; SUSPECTED ACUTE STROKE; INTRAVENOUS T-PA; COMPUTED-TOMOGRAPHY AB Ischemic stroke is a prevalent disease with significant associated morbidity and healthcare costs. There are currently effective intravenous and endovascular therapies that have the potential to improve functional outcome when used in the appropriate patient population. The utilization of various imaging modalities has been shown to be crucial in identifying which patients may benefit from these therapies. Therefore, a thorough understanding of the role that imaging plays in guiding therapeutic decisions in acute ischemic stroke patients is important. C1 [Young, Joseph Yeen; Schaefer, Pamela Whitney] Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02114 USA. RP Young, JY (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, 55 Fruit St,Gray 273A, Boston, MA 02114 USA. EM jyyoung@partners.org NR 129 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2016 VL 32 IS 1 SI SI BP 19 EP 33 DI 10.1007/s10554-015-0757-0 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DA5QD UT WOS:000367856700004 PM 26362874 ER PT J AU Celeng, C Vadvala, H Puchner, S Pursnani, A Sharma, U Kovacs, A Maurovich-Horvat, P Hoffmann, U Ghoshhajra, B AF Celeng, Csilla Vadvala, Harshna Puchner, Stefan Pursnani, Amit Sharma, Umesh Kovacs, Attila Maurovich-Horvat, Pal Hoffmann, Udo Ghoshhajra, Brian TI Defining the optimal systolic phase targets using absolute delay time for reconstructions in dual-source coronary CT angiography SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Coronary CT angiography; Dual-source CT; Systolic phase targets; Absolute delay time ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; HEART-RATE; IMAGE-QUALITY; ARTERY STENOSES; MR-ANGIOGRAPHY; DIASTOLE; MOTION; BLOCKADE; DURATION; VALVE AB To define the optimal systolic phase for dual-source computed tomography angiography using an absolute reconstruction delay time after the R-R interval based on the coronary artery motion, we analyzed images reconstructed between 200 and 420 miliseconds (ms) after the R wave at 20 ms increments in 21 patients. Based on the American Heart Association coronary segmentation guidelines, the origin of six coronary artery landmarks (RCA, AM1, PDA, LM, OM1, and D2) were selected to calculate the coronary artery motion velocity. The velocity of the given landmark was defined as the quotient of the route and the length of the time interval. The x, y and z-coordinates of the selected landmark were recorded, and were used for the calculation of the 3D route of coronary artery motion by using a specific equation. Differences in velocities were assessed by analysis of variance for repeated measures; Bonferroni post hoc tests were used for multiple pair wise comparisons. 1488 landmarks were measured (6 locations at 12 systolic time points) in 21 patients and were analyzed. The mean values of the minimum velocities were calculated separately for each heart rate group (i.e. < 65; 65-80; and > 80 bpm). The mean lowest coronary artery velocities in each segment occurred in the middle period of each time interval of the acquired systolic phase i.e. 280-340 ms. No differences were found in the minimal coronary artery velocities between the three HR groups, with the exception of the AM1 branch (p = 0.00495) between < 65 and > 80 bpm (p = 0.03), and at HRs of 65-80 versus > 80 bpm (p = 0.006). During an absolute delay of 200-420 ms after the R-wave, the ideal reconstruction interval varies significantly among coronary artery segments. Decreased velocities occur between 280 to 340 ms. Therefore a narrow range of systolic intervals, rather than a single phase, should be acquired. C1 [Celeng, Csilla; Vadvala, Harshna; Puchner, Stefan; Pursnani, Amit; Sharma, Umesh; Hoffmann, Udo; Ghoshhajra, Brian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR PET CT Program,Cardiovasc, Boston, MA 02114 USA. [Celeng, Csilla; Kovacs, Attila; Maurovich-Horvat, Pal] Semmelweis Univ, Heart & Vasc Ctr, MTA SE Cardiovasc Imaging Res Grp, H-1122 Budapest, Hungary. RP Ghoshhajra, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR PET CT Program,Cardiovasc, 55 Fruit St, Boston, MA 02114 USA. EM celengcsilla@gmail.com; hvadvala@partners.org; Stefan.puchner@meduniwien.ac.at; amit.pursnani@gmail.com; umeshsharmaphd@yahoo.com; kovatti@gmail.com; maurovich.horvat@gmail.com; uhoffmann@partners.org; bghoshhajra@mgh.harvard.edu OI Kovacs, Attila/0000-0003-2320-6434 FU NHLBI NIH HHS [K24 HL113128] NR 34 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2016 VL 32 IS 1 SI SI BP 91 EP 100 DI 10.1007/s10554-015-0755-2 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DA5QD UT WOS:000367856700010 PM 26335369 ER PT J AU Joseph, P Ishai, A MacNabb, M Abdelbaky, A Lavender, ZR Ruskin, J Nahrendorf, M Tawakol, A AF Joseph, Philip Ishai, Amorina MacNabb, Megan Abdelbaky, Amr Lavender, Zachary R. Ruskin, Jeremy Nahrendorf, Matthias Tawakol, Ahmed TI Atrial fibrillation is associated with hematopoietic tissue activation and arterial inflammation SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Atrial fibrillation; Hematopoietic activation; Positron emission tomography ID ENDOTHELIAL PROGENITOR CELLS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; RISK; ATHEROSCLEROSIS; MONOCYTES; STRESS AB Inflammation is associated with the development of atrial fibrillation (AF). Activity in hematopoietic tissues, which produce inflammatory leukocytes, is closely related to systemic inflammation, arterial inflammation and cardiovascular events, but its relationship to AF is unknown. Using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging, we examined the relationships between AF, splenic metabolic activity and vascular inflammation. We conducted a cross sectional study of 70 participants: 35 with AF, who were matched (by age, sex and history of active cancer) to 35 controls without AF. Splenic metabolic activity and vascular aortic inflammation were measured by the mean FDG maximum standard uptake values (SUV Max) by PET. We examined (1) the association between AF and splenic activity, and (2) AF and aortic inflammation. The mean age of the population was 68.13 (standard deviation (SD) 8.98) years and 46 (65 %) participants were male. Splenic activity was higher in AF participants [2.31 (SD 0.45) vs. 2.07 (SD 0.37), p = 0.024], and remained significant after adjusting for demographic and clinical covariates. Aortic inflammation was also higher in AF participants [2.22 (SD 0.44) vs. 1.91 (SD 0.44), p = 0.004], and remained significant on multivariable analysis. Aortic inflammation and splenic activity were highly correlated (Pearson R = 0.61, p < 0.001). Atrial fibrillation is associated with higher hematopoietic tissue activation and arterial inflammation. Further studies are needed to clarify the mechanisms by which this cardio-splenic axis is implicated in AF. C1 [Joseph, Philip; Ishai, Amorina; MacNabb, Megan; Abdelbaky, Amr; Lavender, Zachary R.; Ruskin, Jeremy; Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiac Imaging, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Joseph, Philip; Ishai, Amorina; MacNabb, Megan; Abdelbaky, Amr; Lavender, Zachary R.; Ruskin, Jeremy; Nahrendorf, Matthias; Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Joseph, Philip] McMaster Univ, Hamilton, ON, Canada. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Div Cardiac Imaging, Cardiac MR PET CT Program, Suite 400-165 Cambridge St, Boston, MA 02114 USA. EM atawakol@partners.org FU NHLBI NIH HHS [R01 HL122177] NR 23 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2016 VL 32 IS 1 SI SI BP 113 EP 119 DI 10.1007/s10554-015-0766-z PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DA5QD UT WOS:000367856700012 PM 26411879 ER PT J AU Prabhakar, AM Staziaki, PV Takx, RAP Ghoshhajra, BB AF Prabhakar, Anand M. Staziaki, Pedro V. Takx, Richard A. P. Ghoshhajra, Brian B. TI Preoperative evaluation for coronary atherosclerosis with computed tomography angiography in intravenous drug users: an emerging indication in the face of a growing threat SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Coronary CTA; Drug abuse; Endocarditis ID INFECTIVE ENDOCARDITIS; CT ANGIOGRAPHY; ECHOCARDIOGRAPHY; COMPLICATIONS; GUIDELINES; STENOSIS; DISEASE AB The purpose of this study was to describe the application of coronary computed tomography angiography (CCTA) in evaluation of patients with history of intravenous drug use (IDU). An IRB approved retrospective review was performed of all patients who had a prior history of IDU and presenting with endocarditis who had undergone CCTA. Demographic characteristics and cardiovascular risk factors were collected. In addition, we reviewed CCTA reports for dosimetric parameters, calcium score, and atherosclerotic burden. There were 32 patients (25 males) included in this study with a mean age of 38 +/- A 10.8 years. The average BMI for the study group was 26.5 +/- A 4.9. 44 % of patients had evidence of atherosclerotic disease on coronary CTA. Mean calcium score was 175 +/- A 487. Median total exam effective dose was 4.8 mSv (range: 3.3-7.3 mSv). In spite of their relatively young age and BMI at the upper limits of normal, patients with history of IDU have atherosclerosis and coronary CTA can be utilized to screen these patients and may be helpful for risk stratification prior to noncoronary surgical procedures. Given the recent rise in IDU, this may become a growing indication for CCTA. C1 [Prabhakar, Anand M.; Staziaki, Pedro V.; Takx, Richard A. P.; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiovasc Imaging,Dept Radiol, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiovasc Imaging,Dept Radiol, 55 Fruit St,Gray 2, Boston, MA 02114 USA. EM aprabhakar@mgh.harvard.edu OI Staziaki, Pedro/0000-0003-3219-3815 NR 17 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2016 VL 32 IS 1 SI SI BP 131 EP 135 DI 10.1007/s10554-015-0719-6 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DA5QD UT WOS:000367856700014 PM 26208684 ER PT J AU Partovi, S Ghoshhajra, BB Walker, TG AF Partovi, Sasan Ghoshhajra, Brian B. Walker, T. Gregory TI Beyond stenotic degree assessment in carotid atherosclerotic lesions: single catheter near-infrared spectroscopy and intravascular ultrasound SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article ID LIPID-CORE PLAQUES; CORONARY-ARTERIES; RISK; IVUS; NIRS; MRI; FIBROATHEROMAS; ANGIOGRAPHY; STENOSIS C1 [Partovi, Sasan] Case Western Reserve Univ, Dept Radiol, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Ghoshhajra, Brian B.; Walker, T. Gregory] Harvard Univ, Div Vasc Imaging & Intervent, Dept Radiol, Med Sch,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Walker, TG (reprint author), Harvard Univ, Div Vasc Imaging & Intervent, Dept Radiol, Med Sch,Massachusetts Gen Hosp, 55 Fruit St GRB 290A, Boston, MA 02114 USA. EM TGWALKER@mgh.harvard.edu NR 19 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2016 VL 32 IS 1 SI SI BP 201 EP 203 DI 10.1007/s10554-015-0729-4 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DA5QD UT WOS:000367856700022 PM 26245472 ER PT J AU Bartonicek , J Kozanek, M Jupiter, JB AF Bartonicek, Jan Kozanek, Michal Jupiter, Jesse B. TI Early history of scapular fractures SO INTERNATIONAL ORTHOPAEDICS LA English DT Review DE Scapular fracture; History of treatment of scapular fractures; Scapula; History AB The first to use the term Scapula was Vesalius (1514-1564) and thus it has remained ever since. Probably the oldest injured scapula, from 250 million years ago, was described by Chinese authors of a skeletal examination of a fossilised remains of a dinosaur Yangchuanosaurus hepingensis. In humans, the oldest known scapular fractures date back to the prehistoric and early historic times. In ancient times, a fracture of acromion was described in the treatises of Hippocrates. Early modern history of the treatment of scapular fractures is closely interlinked with the history of the French surgery. The first to point out the existence of these fractures were Petit, Du Verney and Desault in the 18th century. The first study devoted solely to scapular fractures was published by Traugott Karl August Vogt in 1799. Thomas Callaway published in 1849 an extensive dissertation on injuries to the shoulder girdle, in which he discussed a number of cases known at that time. The first radiograph of a scapular fracture was published by Petty in 1907. Mayo Robson (1884), Lambotte (1913) and Lane (1914) were pioneers in the surgical treatment of these fractures, followed in 1923 by the French surgeons Lenormat, Dujarrier and Basset. The first internal fixation of the glenoid fossa, including a radiograph, was published by Fischer in 1939. C1 [Bartonicek, Jan] Charles Univ Prague, Fac Med 1, Dept Orthopaed, Prague 16902 6, Czech Republic. [Bartonicek, Jan] Cent Mil Hosp Prague, Prague 16902 6, Czech Republic. [Kozanek, Michal; Jupiter, Jesse B.] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Kozanek, Michal] Comenius Univ, Fac Med, Bratislava, Slovakia. RP Bartonicek , J (reprint author), Charles Univ Prague, Fac Med 1, Dept Orthopaed, U Vojenske Nemocnice 1 200, Prague 16902 6, Czech Republic. EM bartonicek.jan@seznam.cz; kozanek.michael@mhg.harvard.edu; jjupiter@mgh.harvard.edu RI Bartonicek, Jan/E-8217-2017 OI Bartonicek, Jan/0000-0002-2228-1443 FU [IGA MZ CR NT/14092] FX The study was prepared under the Grant IGA MZ CR NT/14092: Diagnostics and operative treatment of displaced intraarticular fractures of the scapula. The authors wish to thank Mirka Plecita and Ludmila Frajerova for assistance in tracing the original documents, and Professor Chris Colton and Ludmila Bebarova for their assistance in preparation of the manuscript. NR 69 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 EI 1432-5195 J9 INT ORTHOP JI Int. Orthop. PD JAN PY 2016 VL 40 IS 1 BP 213 EP 222 DI 10.1007/s00264-015-2821-8 PG 10 WC Orthopedics SC Orthopedics GA DA4WR UT WOS:000367803400031 PM 26133287 ER PT J AU Barry, MJ Palmer, WE Petruska, AJ AF Barry, Michael J. Palmer, William E. Petruska, Alex J. TI A Proximal Hamstring Injury-Getting Off a Slippery Slope SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID OUTCOMES C1 [Barry, Michael J.] Massachusetts Gen Hosp, Div Gen Med, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Palmer, William E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Petruska, Alex J.] Massachusetts Gen Hosp, Sports Phys Therapy Serv, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, John D Stoeckle Ctr Primary Care Innovat, 50 Staniford St,Eighth Floor, Boston, MA 02114 USA. EM mbarry@partners.org NR 5 TC 1 Z9 1 U1 1 U2 2 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 JAN PY 2016 VL 176 IS 1 BP 15 EP 16 DI 10.1001/jamainternmed.2015.6795 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DA1II UT WOS:000367549100005 PM 26618607 ER PT J AU Good, CB Gellad, WF AF Good, Chester B. Gellad, Walid F. TI Off-label Drug Use and Adverse Drug Events Turning up the Heat on Off-label Prescribing SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Good, Chester B.] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. [Good, Chester B.; Gellad, Walid F.] Univ Pittsburgh, Dept Med, Div Gen Med, Pittsburgh, PA USA. [Good, Chester B.; Gellad, Walid F.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Good, Chester B.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. RP Good, CB (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Room 2A135,Univ Dr C, Pittsburgh, PA 15240 USA. EM chester.good@va.gov NR 9 TC 2 Z9 2 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2016 VL 176 IS 1 BP 63 EP 64 DI 10.1001/jamainternmed.2015.6068 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DA1II UT WOS:000367549100016 PM 26524668 ER PT J AU Shah, RV Murthy, VL Colangelo, LA Reis, J Venkatesh, BA Sharma, R Abbasi, SA Goff, DC Carr, JJ Rana, JS Terry, JG Bouchard, C Sarzynski, MA Eisman, A Neilan, T Das, S Jerosch-Herold, M Lewis, CE Carnethon, M Lewis, GD Lima, JAC AF Shah, Ravi V. Murthy, Venkatesh L. Colangelo, Laura A. Reis, Jared Venkatesh, Bharath Ambale Sharma, Ravi Abbasi, Siddique A. Goff, David C., Jr. Carr, J. Jeffrey Rana, Jamal S. Terry, James G. Bouchard, Claude Sarzynski, Mark A. Eisman, Aaron Neilan, Tomas Das, Saumya Jerosch-Herold, Michael Lewis, Cora E. Carnethon, Mercedes Lewis, Gregory D. Lima, Joao A. C. TI Association of Fitness in Young Adulthood With Survival and Cardiovascular Risk The Coronary Artery Risk Development in Young Adults (CARDIA) Study SO JAMA INTERNAL MEDICINE LA English DT Article ID SOCIETY-OF-CARDIOLOGY; LEFT-VENTRICULAR MASS; HEALTHY LIFE-STYLE; CARDIORESPIRATORY FITNESS; HEART-FAILURE; ATHEROSCLEROSIS MESA; PHYSICAL-ACTIVITY; MIDDLE-AGE; DISEASE; CALCIFICATION AB IMPORTANCE Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear. OBJECTIVE To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD). DESIGN, SETTING, AND PARTICIPANTS Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up. MAIN OUTCOMES AND MEASURES The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated. RESULTS Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P <.001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P =.002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (beta = -0.24; 95% CI, -0.45 to -0.03; P =.02) and significantly better lobal longitudinal strain (beta = -0.09; 95% CI, -0.14 to -0.05; P <.001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P =.002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P =.006), respectively, along with a more impaired strain (beta = 0.15; 95% CI, 0.08-0.23; P <.001). No association between change in fitness and CAC was found. CONCLUSIONS AND RELEVANCE Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated withmyocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis. C1 [Shah, Ravi V.; Das, Saumya] Beth Israel Deaconess Med Ctr, Cardiovasc Div, Dept Med, Boston, MA 02215 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Med, Cardiovasc Med Div, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA. [Colangelo, Laura A.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Reis, Jared] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Venkatesh, Bharath Ambale; Sharma, Ravi; Lima, Joao A. C.] Johns Hopkins Univ, Johns Hopkins Med Inst, Inst Heart & Vasc, Dept Med & Cardiol, Baltimore, MD 21287 USA. [Abbasi, Siddique A.] Brown Univ, Rhode Isl Hosp, Dept Internal Med, Div Cardiol, Providence, RI 02912 USA. [Goff, David C., Jr.] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Carr, J. Jeffrey; Terry, James G.] Vanderbilt Univ, Dept Epidemiol, Nashville, TN 37235 USA. [Rana, Jamal S.] Kaiser Permanente No Calif, Dept Cardiol, Oakland, CA USA. [Rana, Jamal S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Bouchard, Claude; Sarzynski, Mark A.; Lewis, Gregory D.] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA. [Eisman, Aaron; Neilan, Tomas] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Noninvas Cardiovasc Imaging Sect, Boston, MA 02115 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Div Preventat Med, Birmingham, AL USA. [Carnethon, Mercedes] Northwestern Univ, Feinberg Sch Med, Dept Preventat Med, Chicago, IL 60611 USA. RP Lima, JAC (reprint author), Johns Hopkins Univ, Inst Heart & Vasc, Johns Hopkins Med Inst, 600 N Wolfe St,Blalock 524, Baltimore, MD 21287 USA. EM jlima@jhmi.edu RI Sarzynski, Mark/A-9798-2014; Ambale Venkatesh, Bharath/F-4941-2016; Bouchard, Claude/A-7637-2009; OI Ambale Venkatesh, Bharath/0000-0002-2330-2373; Murthy, Venkatesh/0000-0002-7901-1321 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95168, N01-HC-95169, HL098445-05, AG0005]; National Center for Research Resources [UL1-TR-000040, UL1-RR-025005]; Fellow-to-Faculty Award from the American Heart Association; Centers of Biomedical Research Excellence from the National Institute of General Medical Sciences, National Institutes of Health [8P20 GM-1033528]; NHLBI, the Intramural Research Program of the National Institute on Aging (NIA) [HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268200900041C]; NIA [AG0005]; NHLBI [AG0005] FX This study was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95168, N01-HC-95169, and HL098445-05 from the National Heart, Lung, and Blood Institute (NHLBI) (Dr Carr); by grants UL1-TR-000040 and UL1-RR-025005 from the National Center for Research Resources; by a Fellow-to-Faculty Award from the American Heart Association (Dr Shah); by Centers of Biomedical Research Excellence grant 8P20 GM-1033528 from the National Institute of General Medical Sciences, National Institutes of Health (Dr Sarzynski); and by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the NHLBI, the Intramural Research Program of the National Institute on Aging (NIA), and intra-agency agreement AG0005 between the NIA and NHLBI (Coronary Artery Risk Development in Young Adults [CARDIA] study). NR 41 TC 15 Z9 15 U1 2 U2 9 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 JAN PY 2016 VL 176 IS 1 BP 87 EP 95 DI 10.1001/jamainternmed.2015.6309 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DA1II UT WOS:000367549100021 PM 26618471 ER PT J AU Ishida, JH Johansen, KL AF Ishida, Julie H. Johansen, Kirsten L. TI Exclusion of Patients With Kidney Disease From Cardiovascular Trials SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Ishida, Julie H.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94121 USA. [Ishida, Julie H.; Johansen, Kirsten L.] San Francisco VA Med Ctr, Dept Med, Div Nephrol, San Francisco, CA USA. RP Johansen, KL (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol, 4150 Clement St,Box 111J, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU NIDDK NIH HHS [K24 DK085153, K24DK085153, K23 DK103963, K23DK103963] NR 6 TC 2 Z9 2 U1 0 U2 2 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 JAN PY 2016 VL 176 IS 1 BP 124 EP 125 DI 10.1001/jamainternmed.2015.6403 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DA1II UT WOS:000367549100034 PM 26618994 ER PT J AU Pino, RM AF Pino, Richard M. TI The Safe Use of Propofol SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Pino, Richard M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Pino, Richard M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pino, Richard M.] Massachusetts Gen Hosp, Surg Intens Care Unit, Boston, MA 02114 USA. RP Pino, RM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM rpino@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 2 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 JAN PY 2016 VL 176 IS 1 BP 140 EP 140 DI 10.1001/jamainternmed.2015.7198 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DA1II UT WOS:000367549100044 PM 26747670 ER PT J AU Hoang, TD Reis, J Zhu, N Jacobs, DR Launer, LJ Whitmer, RA Sidney, S Yaffe, K AF Hoang, Tina D. Reis, Jared Zhu, Na Jacobs, David R., Jr. Launer, Lenore J. Whitmer, Rachel A. Sidney, Stephen Yaffe, Kristine TI Effect of Early Adult Patterns of Physical Activity and Television Viewing on Midlife Cognitive Function SO JAMA PSYCHIATRY LA English DT Article ID YOUNG-ADULTS; SEDENTARY BEHAVIOR; ALZHEIMERS-DISEASE; OLDER-ADULTS; EXECUTIVE FUNCTION; RISK DEVELOPMENT; TEMPORAL TRENDS; LIFE-COURSE; MIDDLE-AGE; TIME USE AB IMPORTANCE Sedentary behaviors and physical inactivity are not only increasing worldwide but also are critical risk factors for adverse health outcomes. Yet, few studies have examined the effects of sedentary behavior on cognition or the long-term role of either behavior in early to middle adulthood. OBJECTIVE To investigate the association between 25-year patterns of television viewing and physical activity and midlife cognition. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 3247 adults (black and white races; aged 18-30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (March 25, 1985, to August 31, 2011). Data analysis was performed June 1, 2014, through April 15, 2015. MAIN OUTCOMES AND MEASURES We assessed television viewing and physical activity at repeated visits (>= 3 assessments) over 25 years using a validated questionnaire. A 25-year pattern of high television viewing was defined as watching TV above the upper baseline quartile (>3 hours/d) for more than two-thirds of the visits, and a 25-year pattern of low physical activity was defined as activity levels below the lower, sex-specific baseline quartile for more than two-thirds of the of the visits. We evaluated cognitive function at year 25 using the Digit Symbol Substitution Test (DSST), Stroop test, and Rey Auditory Verbal Learning Test. RESULTS At baseline, the mean (SD) age of the 3247 study participants was 25.1 (3.6) years, 1836 (56.5%) were female, 1771 (54.5%) were white, and 3015 (92.9%) had completed at least high school. Compared with participants with low television viewing, those with high television viewing during 25 years (353 of 3247 [10.9%]) were more likely to have poor cognitive performance (<1 SD below the race-specific mean) on the DSST and Stroop test, with findings reported as adjusted odds ratio (95% CI): DSST, 1.64 (1.21-2.23) and Stroop test, 1.56 (1.13-2.14), but not the Rey Auditory Verbal Learning Test, adjusted for age, race, sex, educational level, smoking, alcohol use, body mass index, and hypertension. Low physical activity during 25 years in 528 of 3247 participants (16.3%) was significantly associated with poor performance on the DSST, 1.47 (1.14-1.90). Compared with participants with low television viewing and high physical activity, the odds of poor performance were almost 2 times higher for adults with both high television viewing and low physical activity in 107 of 3247 (3.3%) (DSST, 1.95 [1.19-3.22], and Stroop test, 2.20 [1.36-3.56]). CONCLUSIONS AND RELEVANCE High television viewing and low physical activity in early adulthood were associated with worse midlife executive function and processing speed. This is one of the first studies to demonstrate that these risk behaviors may be critical targets for prevention of cognitive aging even before middle age. C1 [Hoang, Tina D.] Northern Calif Inst Res & Educ, San Francisco, CA 94121 USA. [Reis, Jared] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Zhu, Na; Jacobs, David R., Jr.] Univ Minnesota, Div Epidemiol, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Whitmer, Rachel A.; Sidney, Stephen] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Hoang, TD (reprint author), Northern Calif Inst Res & Educ, Vet Affairs Med Ctr, 4150 Clement St,116-H, San Francisco, CA 94121 USA. EM tina.hoang@va.gov RI Dey, Kamalesh/E-6568-2017 FU National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging (NIA); NIA [AG0005, K24 AG031155]; NHLBI [AG0005, HL122658] FX The Coronary Artery Risk Development in Young Adults (CARDIA) Study is conducted and supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and the Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between the NIA and NHLBI (AG0005). The CARDIA Cognitive Function Ancillary Study is supported by grant HL122658 from the NHLBI. Dr Yaffe is also supported by grant K24 AG031155 from the NIA. NR 66 TC 2 Z9 2 U1 4 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JAN PY 2016 VL 73 IS 1 BP 73 EP 79 DI 10.1001/jamapsychiatry.2015.2468 PG 7 WC Psychiatry SC Psychiatry GA DA5CP UT WOS:000367820000012 PM 26629780 ER PT J AU Wu, CS Zou, L AF Wu, Ching-Shyi Zou, Lee TI The SUMO (Small Ubiquitin-like Modifier) Ligase PIAS3 Primes ATR for Checkpoint Activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE checkpoint control; DNA damage response; DNA repair; DNA replication; small ubiquitin-like modifier (SUMO) ID DNA-DAMAGE; E3 LIGASE; INDUCED SUMOYLATION; REPAIR; PATHWAY; PCNA; REPLICATION; RESPONSES; COMPLEX; PROTEIN AB The maintenance of genomic stability relies on the concerted action of DNA repair and DNA damage signaling pathways. The PIAS (protein inhibitor of activated STAT) family of SUMO (small ubiquitin-like modifier) ligases has been implicated in DNA repair, but whether it plays a role in DNA damage signaling is still unclear. Here, we show that the PIAS3 SUMO ligase is important for activation of the ATR (ataxia telangiectasia and Rad3 related)-regulated DNA damage signaling pathway. PIAS3 is the only member of the PIAS family that is indispensable for ATR activation. In response to different types of DNA damage and replication stress, PIAS3 plays multiple roles in ATR activation. In cells treated with camptothecin (CPT), PIAS3 contributes to formation of DNA double-stranded breaks. In UV (ultraviolet light)- or HU (hydroxyurea)-treated cells, PIAS3 is required for efficient ATR autophosphorylation, one of the earliest events during ATR activation. Although PIAS3 is dispensable for ATRIP (ATR-interacting protein) SUMOylation and the ATR-ATRIP interaction, it is required for maintaining the basal kinase activity of ATR prior to DNA damage. In the absence of PIAS3, ATR fails to display normal kinase activity after DNA damage, which accompanies with reduced phosphorylation of ATR substrates. Together, these results suggest that PIAS3 primes ATR for checkpoint activation by sustaining its basal kinase activity, revealing a new function of the PIAS family in DNA damage signaling. C1 [Wu, Ching-Shyi; Zou, Lee] Harvard Univ, Sch Med, MGH Canc Ctr, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zou, L (reprint author), Harvard Univ, Sch Med, MGH Canc Ctr, Bldg 149-7408,13th St, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu OI Wu, Ching-Shyi/0000-0001-9800-9844 FU NIH [GM076388, CA197779] FX This work was supported by NIH Grants GM076388 and CA197779 (to L. Z.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 40 TC 3 Z9 3 U1 1 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 1 PY 2016 VL 291 IS 1 BP 279 EP 290 DI 10.1074/jbc.M115.691170 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA1XP UT WOS:000367589500022 PM 26565033 ER PT J AU Schafer, AL AF Schafer, Anne L. TI Decline in Bone Mass During Weight Loss: A Cause for Concern? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; OBESE OLDER-ADULTS; OVERWEIGHT POSTMENOPAUSAL WOMEN; LONG-DURATION SPACEFLIGHT; LIFE-STYLE INTERVENTION; MIDDLE-AGED NORWEGIANS; GASTRIC BYPASS-SURGERY; MINERAL DENSITY; HIP FRACTURE; CALORIC RESTRICTION C1 [Schafer, Anne L.] San Francisco VA Med Ctr, Endocrine Res Unit, San Francisco, CA 94158 USA. [Schafer, Anne L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Schafer, Anne L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Schafer, AL (reprint author), San Francisco VA Med Ctr, Endocrine Res Unit, 1700 Owens St,Room 367, San Francisco, CA 94158 USA. EM anne.schafer@ucsf.edu FU CSRD VA [IK2 CX000549] NR 56 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2016 VL 31 IS 1 BP 36 EP 39 DI 10.1002/jbmr.2754 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DA3JP UT WOS:000367693300003 PM 26595270 ER PT J AU Mihos, CG Larrauri-Reyes, M Santana, O AF Mihos, Christos G. Larrauri-Reyes, Maiteder Santana, Orlando TI A Meta-Analysis of Ring Annuloplasty Versus Combined Ring Annuloplasty and Subvalvular Repair for Moderate-to-Severe Functional Mitral Regurgitation SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID DILATED CARDIOMYOPATHY; MIDTERM OUTCOMES; HEART-FAILURE; RECURRENCE; RISK AB BackgroundA ring annuloplasty (Ring) for moderate-to-severe functional mitral regurgitation (MR) is associated with suboptimal outcomes, and adjunctive subvalvular repair techniques (Ring+Subvalvular) have been advocated to improve repair durability. However, the outcomes of this strategy are not clearly defined. MethodsA systematic review was performed to identify studies that compared a Ring versus Ring+Subvalvular repair for the treatment of moderate-to-severe functional MR. A meta-analysis was conducted on clinical outcomes and echocardiographic measures of follow-up MR and left ventricular reverse remodeling. Risk ratio (RR) and mean difference (MD) were calculated by the Mantel-Haenszel and Inverse Variance methods under a fixed or random effects model, as appropriate. ResultsSeven non-randomized studies were identified, with a total of 531 patients (Ring=301, Ring+Subvalvular=230). At follow-up (range 30-47 months), a Ring+Subvalvular repair was associated with a lower mortality (RR=0.59, 95%confidence interval [CI] 0.37-0.94, p=0.03), greater freedom from moderate or greater MR (RR=0.44, 95%CI 0.27-0.72, p=0.001), and improved left ventricular end-diastolic diameter (MD=-3.49mm, 95%CI -5.45 to -1.53, p=0.0005) and New York Heart Association functional class (MD=-0.25, 95%CI -0.42 to -0.08, p=0.004). A trend toward a reduced risk of reoperation for recurrent MR was noted with a combined Ring+Subvalvular repair (RR=0.28, 95%CI 0.06-1.22, p=0.09). Finally, a Ring+Subvalvular repair did not impact operative mortality or follow-up left ventricular ejection fraction. ConclusionA combined Ring+Subvalvular repair for moderate-to-severe functional MR can be safely performed, and may improve mid-term outcomes, as compared with Ring alone. doi: 10.1111/jocs.12662 (J Card Surg 2016;31:31-37) C1 [Mihos, Christos G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Larrauri-Reyes, Maiteder; Santana, Orlando] Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Miami Beach, FL USA. RP Mihos, CG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. EM cmihos@mgh.harvard.edu NR 25 TC 3 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0886-0440 EI 1540-8191 J9 J CARDIAC SURG JI J. Card. Surg. PD JAN PY 2016 VL 31 IS 1 BP 31 EP 37 DI 10.1111/jocs.12662 PG 7 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA DA5NW UT WOS:000367850800006 PM 26626776 ER PT J AU Zou, CB Synan, MJ Li, J Xiong, S Manni, ML Liu, Y Chen, BB Zhao, YT Shiva, S Tyurina, YY Jiang, JF Lee, JS Das, S Ray, A Ray, P Kagan, VE Mallampalli, RK AF Zou, Chunbin Synan, Matthew J. Li, Jin Xiong, Sheng Manni, Michelle L. Liu, Yuan Chen, Bill B. Zhao, Yutong Shiva, Sruti Tyurina, Yulia Y. Jiang, Jianfei Lee, Janet S. Das, Sudipta Ray, Anuradha Ray, Prabir Kagan, Valerian E. Mallampalli, Rama K. TI LPS impairs oxygen utilization in epithelia by triggering degradation of the mitochondrial enzyme Alcat1 SO JOURNAL OF CELL SCIENCE LA English DT Article DE Degradation; Mitochondria; Ubiquitin ID PLURIPOTENT STEM-CELL; BARTH-SYNDROME; HISTONE DEACETYLASE; LYSOCARDIOLIPIN ACYLTRANSFERASE; CARDIOLIPIN DEFICIENCY; SUBSTRATE RECOGNITION; UBIQUITIN LIGASE; LIVER-MITOCHONDRIA; OXIDATIVE STRESS; LUNG INJURY AB Cardiolipin (also known as PDL6) is an indispensable lipid required for mitochondrial respiration that is generated through de novo synthesis and remodeling. Here, the cardiolipin remodeling enzyme, acyl-CoA:lysocardiolipin-acyltransferase-1 (Alcat1; SwissProt ID, Q6UWP7) is destabilized in epithelia by lipopolysaccharide (LPS) impairing mitochondrial function. Exposure to LPS selectively decreased levels of carbon 20 (C-20)-containing cardiolipin molecular species, whereas the content of C-18 or C-16 species was not significantly altered, consistent with decreased levels of Alcat1. Alcat1 is a labile protein that is lysosomally degraded by the ubiquitin E3 ligase Skp-Cullin-F-box containing the Fbxo28 subunit (SCF-Fbxo28) that targets Alcat1 for monoubiquitylation at residue K183. Interestingly, K183 is also an acetylation-acceptor site, and acetylation conferred stability to the enzyme. Histone deacetylase 2 (HDAC2) interacted with Alcat1, and expression of a plasmid encoding HDAC2 or treatment of cells with LPS deacetylated and destabilized Alcat1, whereas treatment of cells with a pan-HDAC inhibitor increased Alcat1 levels. Alcat1 degradation was partially abrogated in LPS-treated cells that had been silenced for HDAC2 or treated with MLN4924, an inhibitor of Cullin-RING E3 ubiquitin ligases. Thus, LPS increases HDAC2-mediated Alcat1 deacetylation and facilitates SCF-Fbxo28-mediated disposal of Alcat1, thus impairing mitochondrial integrity. C1 [Zou, Chunbin; Synan, Matthew J.; Li, Jin; Manni, Michelle L.; Liu, Yuan; Chen, Bill B.; Zhao, Yutong; Lee, Janet S.; Das, Sudipta; Ray, Anuradha; Ray, Prabir; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Xiong, Sheng] Jinan Univ, Inst Biomed, Coll Life Sci & Technol, Guangzhou 510630, Guangdong, Peoples R China. [Xiong, Sheng] Jinan Univ, Natl Engn Res Ctr Genet Med, Coll Life Sci & Technol, Guangzhou 510630, Guangdong, Peoples R China. [Shiva, Sruti; Kagan, Valerian E.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. [Tyurina, Yulia Y.; Jiang, Jianfei; Kagan, Valerian E.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol & Bioengn, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, 930 Scaife Hall, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; Merit Review Award from the US Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174, HL081784, 1UH2HL123502, P01HL114453, ES020693, U19AIO68021, CA 165065, OH008282]; Human Frontier Science Program [HFSPRGP0013/2014, HL116472, HL01916, HL112791, HL125435, 12SDG12040330]; MOST of China [2012ZX09103-301-033, 2012ZX09202-301-001] FX This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs; National Institutes of Health [R01 grant numbers HL096376, HL097376, HL098174, HL081784, 1UH2HL123502 and P01HL114453 to R.K.M.; and ES020693, U19AIO68021, CA 165065, OH008282 (to V.E.K.)]; and Human Frontier Science Program [grant numbers HFSPRGP0013/2014 (to V.E.K.); HL116472 (to B.B.C.); HL01916 and HL112791 (to Y.Z.); and HL125435 and 12SDG12040330 (to C.Z.)]. S.X. was supported from the MOST of China [grant number 2012ZX09103-301-033 and 2012ZX09202-301-001]. The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. Deposited in PMC for release after 12 months. NR 93 TC 3 Z9 3 U1 1 U2 11 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD JAN 1 PY 2016 VL 129 IS 1 BP 51 EP 64 DI 10.1242/jcs.176701 PG 14 WC Cell Biology SC Cell Biology GA DA1LI UT WOS:000367556900006 PM 26604221 ER PT J AU Denechaud, PD Lopez-Mejia, IC Giralt, A Lai, QW Blanchet, E Delacuisine, B Nicolay, BN Dyson, NJ Bonner, C Pattou, F Annicotte, JS Fajas, L AF Denechaud, Pierre-Damien Lopez-Mejia, Isabel C. Giralt, Albert Lai, Qiuwen Blanchet, Emilie Delacuisine, Brigitte Nicolay, Brandon N. Dyson, Nicholas J. Bonner, Caroline Pattou, Francois Annicotte, Jean-Sebastien Fajas, Lluis TI E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ELEMENT-BINDING PROTEIN-1C; FATTY-ACID SYNTHESIS; INSULIN-RESISTANCE; TRANSCRIPTION FACTOR; MOUSE MODEL; ER STRESS; LIVER; MICE; METABOLISM; ACTIVATION AB E2F transcription factors are known regulators of the cell cycle, proliferation, apoptosis, and differentiation. Here, we reveal that E2F1 plays an essential role in liver physiopathology through the regulation of glycolysis and lipogenesis. We demonstrate that E2F1 deficiency leads to a decrease in glycolysis and de nova synthesis of fatty acids in hepatocytes. We further demonstrate that E2F1 directly binds to the promoters of key lipogenic genes, including Fasn, but does not bind directly to genes encoding glycolysis pathway components, suggesting an indirect effect. In murine models, E2F1 expression and activity increased in response to feeding and upon insulin stimulation through canonical activation of the CDK4/pRB pathway. Moreover, E2F1 expression was increased in liver biopsies from obese, glucose-intolerant humans compared with biopsies from lean subjects. Finally, E2f1 deletion completely abrogated hepatic steatosis in different murine models of nonalcoholic fatty liver disease (NAFLD). In conclusion, our data demonstrate that E2F1 regulates lipid synthesis and glycolysis and thus contributes to the development of liver pathology. C1 [Denechaud, Pierre-Damien; Lopez-Mejia, Isabel C.; Giralt, Albert; Lai, Qiuwen; Delacuisine, Brigitte; Fajas, Lluis] Univ Lausanne UNIL, Dept Physiol, Lausanne, Switzerland. [Blanchet, Emilie; Annicotte, Jean-Sebastien] Univ Montpellier, Inst Genet Mol Montpellier, F-34059 Montpellier, France. [Nicolay, Brandon N.; Dyson, Nicholas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol Oncol,Canc Ctr, Charlestown, MA USA. [Bonner, Caroline; Pattou, Francois] European Genom Inst Diabet, Lille, France. [Bonner, Caroline; Pattou, Francois] INSERM, UMR 1190, F-59045 Lille, France. [Bonner, Caroline; Pattou, Francois] Ctr Hosp Reg Univ, Lille, France. [Annicotte, Jean-Sebastien] Univ Lille Nord France, CNRS, UMR 8199, European Genom Inst Diabet, Lille, France. RP Fajas, L (reprint author), Univ Lausanne, Dept Physiol, CH-1005 Lausanne, Switzerland. EM Iluis.fajas@unil.ch RI Pierre-Damien, Denechaud/M-5650-2016 OI Pierre-Damien, Denechaud/0000-0003-3502-4814 FU Swiss Ligue Contre le Cancer; French Ligue Contre le Cancer; Swiss National Science Foundation; Fondation de France FX We acknowledge the members of the Fajas laboratory for their support and discussions. We thank A. Chanthany and A.C. Thomas for their technical support. We also thank Jacques Rougemont, Marion Leleu, and Sara Benmohammed of the BBCF at the EPFL for their assistance with ChIP-seq analysis. This work was supported by grants from the Swiss Ligue Contre le Cancer, the French Ligue Contre le Cancer, the Swiss National Science Foundation, and the Fondation de France. NR 41 TC 5 Z9 5 U1 3 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2016 VL 126 IS 1 BP 137 EP 150 DI 10.1172/JCI81542 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DA4JG UT WOS:000367765600016 PM 26619117 ER PT J AU Lagarrigue, S Lopez-Mejia, IC Denechaud, PD Escote, X Castillo-Armengo, J Jimenez, V Chavey, C Giralt, A Lai, QW Zhang, LJ Martinez-Carreres, L Delacuisine, B Annicotte, JS Blanchet, E Hure, S Abella, A Tinahones, FJ Vendrell, J Dubus, P Bosch, F Kahn, CR Fajas, L AF Lagarrigue, Sylviane Lopez-Mejia, Isabel C. Denechaud, Pierre-Damien Escote, Xavier Castillo-Armengo, Judit Jimenez, Veronica Chavey, Carine Giralt, Albert Lai, Qiuwen Zhang, Lianjun Martinez-Carreres, Laia Delacuisine, Brigitte Annicotte, Jean-Sebastien Blanchet, Emilie Hure, Sebastien Abella, Anna Tinahones, Francisco J. Vendrell, Joan Dubus, Pierre Bosch, Fatima Kahn, C. Ronald Fajas, Lluis TI CDK4 is an essential insulin effector in adipocytes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CYCLIN-DEPENDENT KINASES; BREAST-CANCER; CELL-CYCLE; MEDIATED PHOSPHORYLATION; PROMOTES ADIPOGENESIS; LIPID-METABOLISM; ADIPOSE-TISSUE; MICE; INHIBITORS; TRANSCRIPTION AB Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4(R24C)). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT. C1 [Lagarrigue, Sylviane; Lopez-Mejia, Isabel C.; Denechaud, Pierre-Damien; Escote, Xavier; Castillo-Armengo, Judit; Giralt, Albert; Lai, Qiuwen; Martinez-Carreres, Laia; Delacuisine, Brigitte; Hure, Sebastien; Fajas, Lluis] Univ Lausanne, Dept Physiol, CH-1005 Lausanne, Switzerland. [Lagarrigue, Sylviane; Chavey, Carine; Annicotte, Jean-Sebastien; Blanchet, Emilie; Hure, Sebastien; Fajas, Lluis] Univ Montpellier, IGMM, F-34059 Montpellier, France. [Jimenez, Veronica; Bosch, Fatima] Univ Autonoma Barcelona, Sch Vet Med, Ctr Anim Biotechnol & Gene Therapy, Bellaterra, Spain. [Jimenez, Veronica; Bosch, Fatima] Univ Autonoma Barcelona, Sch Vet Med, Dept Biochem & Mol Biol, Bellaterra, Spain. [Jimenez, Veronica; Bosch, Fatima] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona, Spain. [Zhang, Lianjun] Univ Lausanne, Ludwig Ctr Canc Res, Translat Tumor Immunol, CH-1066 Epalinges, Switzerland. [Annicotte, Jean-Sebastien] Univ Lille Nord France, European Genom Inst Diabet, CNRS, UMR 8199, Lille, France. [Abella, Anna] INSERM, U834, Montpellier, France. [Tinahones, Francisco J.] Hosp Univ Virgen de la Victoria, Unidad Gest Clin Endocrinol & Nutr, Malaga, Spain. [Tinahones, Francisco J.] Inst Salud Carlos III, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Madrid, Spain. [Vendrell, Joan] Univ Rovira & Virgili, Inst Invest Pere Virgil, CIBERDEM, Hosp Univ Joan 23, E-43007 Tarragona, Spain. [Dubus, Pierre] Univ Bordeaux, Histol & Pathol Mol Tumeurs, EA2406, Bordeaux, France. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. RP Fajas, L (reprint author), Univ Lausanne, Dept Physiol, CH-1005 Lausanne, Switzerland. EM lluis.fajas@unil.ch RI Pierre-Damien, Denechaud/M-5650-2016; Escote, Xavier/G-3440-2015; OI Pierre-Damien, Denechaud/0000-0003-3502-4814; Escote, Xavier/0000-0003-1172-3995; BOSCH, FATIMA/0000-0002-7705-5515 FU ICREA Academia; Generalitat de Catalunya, Spain; Ministerio de Economia y Cornpetitividad, Spain [SAF 2014-54866-R]; Swiss Ligue Contre le Cancer; French Ligue Contre le Cancer; Swiss National Science Foundation FX Members of the Fajas laboratory are acknowledged for support and discussions. We thank M. Barbacid for providing Cdk4R24C/R24C and Cdk4nc mice. We thank A.-C. Thomas and F. Thevenaz for technical support. We thank J.-C. Stehle from the Mouse Pathology Facility. F. Bosch is the recipient of an award from the ICREA Academia, Generalitat de Catalunya, Spain. Vector generation and production were funded by Ministerio de Economia y Cornpetitividad (SAF 2014-54866-R), Spain. This work was supported by grants from the Swiss Ligue Contre le Cancer, the French Ligue Contre le Cancer, and the Swiss National Science Foundation. S. Lagarrigue was supported by a grant from the French Ligue Contre le Cancer and the Swiss National Science Foundation. NR 45 TC 4 Z9 4 U1 1 U2 6 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 JAN PY 2016 VL 126 IS 1 BP 335 EP 348 DI 10.1172/JCI81480 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DA4JG UT WOS:000367765600030 PM 26657864 ER PT J AU Li, X Rhee, DK Malhotra, R Mayeur, C Hurst, LA Ager, E Shelton, G Kramer, Y McCulloh, D Keefe, D Bloch, KD Bloch, DB Peterson, RT AF Li, Xiang Rhee, David K. Malhotra, Rajeev Mayeur, Claire Hurst, Liam A. Ager, Emily Shelton, Georgia Kramer, Yael McCulloh, David Keefe, David Bloch, Kenneth D. Bloch, Donald B. Peterson, Randall T. TI Progesterone receptor membrane component-1 regulates hepcidin biosynthesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEME-BINDING PROTEIN; SYSTEMIC IRON BALANCE; BETA-THALASSEMIA; HORMONE HEPCIDIN; GENE-EXPRESSION; CELL VIABILITY; SERUM HEPCIDIN; MOUSE MODEL; IN-VIVO; ACTIVATION AB Iron homeostasis is tightly regulated by the membrane iron exporter ferroportin and its regulatory peptide hormone hepcidin. The hepcidin/ferroportin axis is considered a promising therapeutic target for the treatment of diseases of iron overload or deficiency. Here, we conducted a chemical screen in zebrafish to identify small molecules that decrease ferroportin protein levels. The chemical screen led to the identification of 3 steroid molecules, epitiostanol, progesterone, and mifepristone, which decrease ferroportin levels by increasing the biosynthesis of hepcidin. These hepcidin-inducing steroids (HISs) did not activate known hepcidin-inducing pathways, including the BMP and JAK/STAT3 pathways. Progesterone receptor membrane component-1 (PGRMC1) was required for HIS-dependent increases in hepcidin biosynthesis, as PGRMC1 depletion in cultured hepatoma cells and zebrafish blocked the ability of HISs to increase hepcidin mRNA levels. Neutralizing antibodies directed against PGRMC1 attenuated the ability of HISs to induce hepcidin gene expression. Inhibiting the kinases of the SRC family, which are downstream of PGRMC1, blocked the ability of HISs to increase hepcidin mRNA levels. Furthermore, HIS treatment increased hepcidin biosynthesis in mice and humans. Together, these data indicate that PGRMC1 regulates hepcidin gene expression through an evolutionarily conserved mechanism. These studies have identified drug candidates and potential therapeutic targets for the treatment of diseases of abnormal iron metabolism. C1 [Li, Xiang; Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Syst Biol, Boston, MA USA. [Li, Xiang; Peterson, Randall T.] Broad Inst, Cambridge, MA USA. [Rhee, David K.; Malhotra, Rajeev; Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Rhee, David K.; Malhotra, Rajeev; Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Mayeur, Claire; Hurst, Liam A.; Ager, Emily; Shelton, Georgia; Kramer, Yael; Bloch, Kenneth D.; Bloch, Donald B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, Boston, MA USA. [McCulloh, David; Keefe, David] NYU, Langone Med Ctr, Dept Obstet & Gynecol, New York, NY USA. [Bloch, Donald B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA. RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,4-101A, Charlestown, MA 02129 USA. EM bloch@helix.mgh.harvard.edu; peterson@cvrc.mgh.harvard.edu OI Malhotra, Rajeev/0000-0003-0120-4630 FU NIH grant [R01DK082971]; National Heart, Lung, and Blood Institute (NHLBI) training grant [T32HL007208]; John S. LaDue Memorial Fellowship from Harvard Medical School; NHLBI grant [K08HL111210]; Charles and Ann Sanders Massachusetts General Hospital Scholar Award; Leducq Foundation FX Support was provided by NIH grant R01DK082971 (to K.D. Bloch, D.B. Bloch, and R.T. Peterson), National Heart, Lung, and Blood Institute (NHLBI) training grant T32HL007208 (to D.K. Rhee), the John S. LaDue Memorial Fellowship from Harvard Medical School (to D.K. Rhee), NHLBI grant K08HL111210 (to R. Malhotra), the Charles and Ann Sanders Massachusetts General Hospital Scholar Award (to R.T. Peterson), and the Leducq Foundation (to C. Mayeur, L.A. Hurst, G. Shelton, D.B. Bloch, and K.D. Bloch). NR 64 TC 12 Z9 12 U1 4 U2 14 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 JAN PY 2016 VL 126 IS 1 BP 389 EP 401 DI 10.1172/JCI83831 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DA4JG UT WOS:000367765600034 PM 26657863 ER PT J AU Lo, WK Goldberg, HJ Wee, J Fisichella, PM Chan, WW AF Lo, Wai-Kit Goldberg, Hilary J. Wee, Jon Fisichella, P. Marco Chan, Walter W. TI Both Pre-Transplant and Early Post-Transplant Antireflux Surgery Prevent Development of Early Allograft Injury After Lung Transplantation SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Antireflux surgery; Lung transplantation; Allograft injury ID GASTROESOPHAGEAL-REFLUX DISEASE; BRONCHOALVEOLAR LAVAGE FLUID; FUNDOPLICATION; ASPIRATION; DYSFUNCTION; PEPSIN; BRONCHIOLITIS; RECIPIENTS; REJECTION; COMPLICATIONS AB Background Antireflux surgery (ARS) has been associated with improved lung transplant outcomes. Pre-transplant ARS has been shown in small studies to improve pulmonary function among transplant candidates with gastroesophageal reflux disease (GERD). Although early post-transplant ARS has been shown to be effective in reducing chronic rejection, the optimal timing of ARS in transplant recipients remains unclear. The aim of this study is to evaluate the time to early allograft injury among lung transplant recipients by timing of ARS. Methods This was a retrospective cohort study of lung transplant recipients undergoing ARS before or after transplantation at a tertiary care center since 2007, with at least 1-year follow-up. Early allograft injury was defined clinically and histologically as acute rejection or lymphocytic bronchiolitis, occurring within the first year after transplantation. In accordance with prior studies, the cutoff between early and late post-transplant ARS was set at 6 months. Time-to-event analysis using the Cox proportional hazards model was applied to assess the relationship between timing of surgery and early allograft injury. Subjects not meeting this outcome were censored at 1 year in the time-to-event analysis. Fisher's exact test for binary variables and Student's t test for continuous variables were performed to assess for differences among the three groups: ARS pre-transplant, ARS early post-transplant, and ARS late post-transplant. Results Forty-eight subjects (60 % men, mean age 55) met the inclusion criteria for the study. Patient demographics, pre-transplant cardiopulmonary function, BMI, CMV status, and PPI exposure were similar between groups. Kaplan-Meier analysis demonstrated significantly increased early allograft injury in late post-transplant ARS patients compared with both pre-transplant (log-rank p = 0.007) and early post-transplant (log-rank p = 0.05) patients, as well as a significant trend across groups (log-rank p = 0.005). No significant difference between pre- and early post-transplant groups was noted. Three ARS failures were noted in the pre- and late post-transplant groups. Complications included one death due to aspiration pneumonia in a late post-transplant ARS recipient. No early post-transplant ARS patients experienced ARS failure or complications. Conclusion Late post-lung transplant ARS resulted in increased risk of early allograft injury compared to pre-transplant and early post-transplant ARS. Both pre- and early post-transplant ARS appear equally safe and effective in improving lung transplant outcomes. These findings support consideration of aggressive reflux testing and application of antireflux measures before or soon after transplantation to minimize the impact of reflux on allograft injury. C1 [Lo, Wai-Kit; Chan, Walter W.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Lo, Wai-Kit] Boston VA Healthcare Syst, Dept Gastroenterol, Boston, MA USA. [Lo, Wai-Kit; Goldberg, Hilary J.; Wee, Jon; Fisichella, P. Marco; Chan, Walter W.] Harvard Univ, Sch Med, Boston, MA USA. [Goldberg, Hilary J.] Brigham & Womens Hosp, Div Pulm Med, Boston, MA 02115 USA. [Wee, Jon] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. [Fisichella, P. Marco] Boston VA Healthcare Syst, Dept Surg, Boston, MA USA. RP Chan, WW (reprint author), Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA. EM wwchan@partners.org NR 31 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN PY 2016 VL 20 IS 1 BP 111 EP 118 DI 10.1007/s11605-015-2983-0 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DA0XK UT WOS:000367520700035 PM 26493975 ER PT J AU Fuentes, E Ahmad, R Hong, TS Clark, JW Kwak, EL Rattner, DW Mullen, JT AF Fuentes, Eva Ahmad, Rima Hong, Theodore S. Clark, Jeffrey W. Kwak, Eunice L. Rattner, David W. Mullen, John T. TI Adjuvant Therapy Completion Rates in Patients with Gastric Cancer Undergoing Perioperative Chemotherapy Versus a Surgery-First Approach SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Gastric cancer; Adjuvant therapy completion; Perioperative chemotherapy; Surgery first ID PREOPERATIVE CHEMORADIOTHERAPY; GASTROESOPHAGEAL JUNCTION; TOTAL GASTRECTOMY; MORTALITY; ADENOCARCINOMA; MORBIDITY; STOMACH; TRIAL AB Delayed recovery after gastrectomy may preclude the administration of adjuvant therapy in a significant percentage of patients who undergo elective gastrectomy as the initial therapy for gastric cancer. Clinicopathologic and treatment variables of 155 patients undergoing potentially curative gastrectomy for stages Ib-IIIc gastric adenocarcinoma from 2001 to 2014 were analyzed, and rates of receipt of chemotherapy and radiotherapy in patients treated with either a surgery-first approach (SURG) or neoadjuvant therapy followed by surgery followed by postoperative therapy (PERIOP) were compared. SURG patients (n = 93) were older and more likely to have distal tumors and to undergo distal gastrectomy and D1 lymphadenectomy than PERIOP patients (n = 62). The distribution of ASA scores was similar between groups. SURG patients were less likely than PERIOP patients to complete at least one cycle of chemotherapy (56 vs 100 %, P = 0.001) and all recommended chemotherapy and radiation therapy (44 vs 66 %, P = 0.013). These findings were consistent for SURG patients treated during different time periods throughout the study and for patients of poorer performance status. A significantly higher percentage of gastric cancer patients treated with perioperative chemotherapy receive some or all of the recommended components of multimodality therapy than patients treated with a surgery-first approach. C1 [Fuentes, Eva; Ahmad, Rima; Rattner, David W.; Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Clark, Jeffrey W.; Kwak, Eunice L.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jmullen@partners.org NR 15 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN PY 2016 VL 20 IS 1 BP 172 EP 179 DI 10.1007/s11605-015-2954-5 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DA0XK UT WOS:000367520700059 PM 26394879 ER PT J AU Haas, JS Sprague, BL Klabunde, CN Tosteson, ANA Chen, JS Bitton, A Beaber, EF Onega, T Kim, JJ MacLean, CD Harris, K Yamartino, P Howe, K Pearson, L Feldman, S Brawarsky, P Schapira, MM AF Haas, Jennifer S. Sprague, Brian L. Klabunde, Carrie N. Tosteson, Anna N. A. Chen, Jane S. Bitton, Asaf Beaber, Elisabeth F. Onega, Tracy Kim, Jane J. MacLean, Charles D. Harris, Kimberly Yamartino, Phillip Howe, Kathleen Pearson, Loretta Feldman, Sarah Brawarsky, Phyllis Schapira, Marilyn M. CA PROSPR Population-Based Res Optimi TI Provider Attitudes and Screening Practices Following Changes in Breast and Cervical Cancer Screening Guidelines SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE breast cancer screening; cervical cancer screening; provider practice patterns; primary care; clinical practice guidelines ID PRIMARY-CARE-PHYSICIANS; SERVICES TASK-FORCE; UNITED-STATES; MAMMOGRAPHY; RECOMMENDATIONS; CONSISTENT; ADHERENCE; SOCIETY; MODEL AB Changes to national guidelines for breast and cervical cancer screening have created confusion and controversy for women and their primary care providers. To characterize women's primary health care provider attitudes towards screening and changes in practice in response to recent revisions in guidelines for breast and cervical cancer screening. In 2014, we distributed a confidential web and mail survey to 668 women's health care providers affiliated with the four clinical care networks participating in the three PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium breast cancer research centers (385 respondents; response rate 57.6 %). We assessed self-reported attitudes toward breast and cervical cancer screening, as well as practice changes in response to the most recent revisions of the U.S. Preventive Services Task Force (USPSTF) recommendations. The majority of providers believed that mammography screening was effective for reducing cancer mortality among women ages 40-74 years, and that Papanicolaou (Pap) testing was very effective for women ages 21-64 years. While the USPSTF breast and cervical cancer screening recommendations were widely perceived by the respondents as influential, 75.7 and 41.2 % of providers (for mammography and cervical cancer screening, respectively) reported screening practices in excess of those recommended by USPSTF. Provider-reported barriers to concordance with guideline recommendations included: patient concerns (74 and 36 % for breast and cervical, respectively), provider disagreement with the recommendations (50 and 14 %), health system measurement of a provider's screening practices that use conflicting measurement criteria (40 and 21 %), concern about malpractice risk (33 and 11 %), and lack of time to discuss the benefits and harms with their patients (17 and 8 %). Primary care providers do not consistently follow recent USPSTF breast and cervical cancer screening recommendations, despite noting that these guidelines are influential. C1 [Haas, Jennifer S.; Chen, Jane S.; Bitton, Asaf; Harris, Kimberly; Feldman, Sarah; Brawarsky, Phyllis] Brigham & Womens Hosp, Boston, MA 02120 USA. [Haas, Jennifer S.; Bitton, Asaf; Feldman, Sarah] Harvard Univ, Sch Med, Boston, MA USA. [Sprague, Brian L.; MacLean, Charles D.; Howe, Kathleen] Univ Vermont, Burlington, VT USA. [Tosteson, Anna N. A.; Onega, Tracy; Pearson, Loretta] Geisel Sch Med Dartmouth, Lebanon, NH USA. [Tosteson, Anna N. A.; Onega, Tracy; Pearson, Loretta] Norris Cotton Canc Ctr, Lebanon, NH USA. [Klabunde, Carrie N.] NIH, Off Dis Prevent, Off Director, Bethesda, MD 20892 USA. [Beaber, Elisabeth F.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kim, Jane J.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Yamartino, Phillip; Schapira, Marilyn M.] Univ Penn, Philadelphia, PA 19104 USA. [Yamartino, Phillip; Schapira, Marilyn M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA. RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St, Boston, MA 02120 USA. EM jhaas@partners.org FU National Cancer Institute-funded consortium, Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) [U54 CA163307, U54 CA 163313, U54 CA163303, U01CA163304, U54CA164336] FX We appreciate the input of Alan Waxman, MD, on the development of the survey. This study was conducted as part of the National Cancer Institute-funded consortium, Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) (grant numbers U54 CA163307, U54 CA 163313, U54 CA163303, U01CA163304, U54CA164336). A list of PROSPR investigators and contributing research staff is provided at: http://healthcaredelivery.cancer.gov/prospr/ NR 27 TC 6 Z9 6 U1 4 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 JAN PY 2016 VL 31 IS 1 BP 52 EP 59 DI 10.1007/s11606-015-3449-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DA1FB UT WOS:000367540600013 PM 26129780 ER PT J AU Berchuck, JE Patel, S AF Berchuck, Jacob E. Patel, Shalini TI An Often-Overlooked Etiology of Pleuritic Chest Pain SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE Clinical image; Diagnosis; Cardiovascular disease; Pulmonary disease C1 [Berchuck, Jacob E.; Patel, Shalini] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Patel, Shalini] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Berchuck, JE (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,Room M-987, San Francisco, CA 94143 USA. EM jacob.berchuck@ucsf.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2016 VL 31 IS 1 BP 138 EP 138 DI 10.1007/s11606-015-3316-4 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DA1FB UT WOS:000367540600034 PM 25869019 ER PT J AU Lapps, J Flansbaum, B Leykum, L Boswell, J Haines, L AF Lapps, Joshua Flansbaum, Bradley Leykum, Luci Boswell, Josh Haines, Luigi TI Updating threshold-based identification of hospitalists in 2012 Medicare pay data SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CARE AB In the absence of a unique identifier, it is difficult to assess the number of practicing hospitalists. We use a variety of thresholds of billing activity to identify hospitalists in a dataset of publicly released 2012 Medicare physician pay data. Our study updates previous estimates of the number of hospitalists practicing nationwide in 2012 and suggests the field continues to grow. This research also highlights a need for a more precise system of identifying hospitalists. Journal of Hospital Medicine 2016;11:45-47. (c) 2015 Society of Hospital Medicine C1 [Lapps, Joshua; Boswell, Josh] Soc Hosp Med, Govt Relat Dept, Philadelphia, PA 19130 USA. [Flansbaum, Bradley] Lenox Hill Hosp, North Shore Long Isl Jewish Hlth Syst, New York, NY 10021 USA. [Leykum, Luci] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Leykum, Luci] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Haines, Luigi] Soc Hosp Med, Dept Informat Technol, Philadelphia, PA 19130 USA. [Haines, Luigi] Adv Solut Int Inc, Austin, TX USA. RP Lapps, J (reprint author), Soc Hosp Med, 1500 Spring Garden St,Suite 501, Philadelphia, PA 19130 USA. EM jlapps@hospitalmedicine.org FU Department of Veterans Affairs, Veterans Health Administration; South Texas Veterans Health Care System FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration. Investigator salary support is provided through the South Texas Veterans Health Care System. 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. The authors report no conflicts of interest. NR 9 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2016 VL 11 IS 1 BP 45 EP 47 DI 10.1002/jhm.2480 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DA3VR UT WOS:000367728300006 PM 26381496 ER PT J AU Rao, K Safdar, N AF Rao, Krishna Safdar, Nasia TI Fecal microbiota transplantation for the treatment of Clostridium difficile infection SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID ULCERATIVE-COLITIS; INTESTINAL MICROBIOTA; BACTERIOTHERAPY; HEALTH; METAANALYSIS; DISEASE; COLONIZATION; EPIDEMIOLOGY; VANCOMYCIN; RESISTANCE AB Clostridium difficile, a major cause of healthcare-associated diarrhea due to perturbation of the normal gastrointestinal microbiome, is responsible for significant morbidity, mortality, and healthcare expenditures. The incidence and severity of C difficile infection (CDI) is increasing, and recurrent disease is common. Recurrent infection can be difficult to manage with conventional antibiotic therapy. Fecal microbiota transplantation (FMT), which involves instillation of stool from a healthy donor into the gastrointestinal tract of the patient, restores the gut microbiome to a healthy state. FMT has emerged as a promising new treatment for CDI. There are limited data on FMT for treatment of primary CDI, but FMT appears safe and effective for recurrent CDI. The safety and efficacy of FMT in patients with severe primary or severe recurrent CDI has not been established. Patients with inflammatory bowel disease (IBD) who undergo FMT for CDI may be at increased risk of IBD flare, and caution should be exercised with use of FMT in that population. The long-term safety of FMT is unknown; thus, rigorously conducted prospective studies are needed. Journal of Hospital Medicine 2016;11:56-61. (c) 2015 Society of Hospital Medicine C1 [Rao, Krishna] Univ Michigan, Dept Internal Med, Div Infect Dis, Ann Arbor, MI 48109 USA. [Rao, Krishna] Vet Affairs Ann Arbor Healthcare Syst, Div Infect Dis, Ann Arbor, MI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med & Publ Hlth, Infect Dis Sect, Dept Med, Madison, WI 53705 USA. RP Safdar, N (reprint author), Univ Wisconsin, Infect Dis Sect, Dept Med, Sch Med & Publ Hlth,MFCB, 1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu FU Claude D. Pepper Older Americans Independence Center [AG-024824]; Michigan Institute for Clinical and Health Research [2UL1TR000433]; VA MERIT award FX K.R. is supported by grants from the Claude D. Pepper Older Americans Independence Center (grant number AG-024824) and the Michigan Institute for Clinical and Health Research (grant number 2UL1TR000433). N.S. is supported by a VA MERIT award. The contents of this article do not necessarily represent the views of the Department of Veterans Affairs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors report no conflicts of interest. NR 65 TC 9 Z9 9 U1 4 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2016 VL 11 IS 1 BP 56 EP 61 DI 10.1002/jhm.2449 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DA3VR UT WOS:000367728300009 PM 26344412 ER PT J AU Silvestri, MT Bongiovanni, TR Glover, JG Gross, CP AF Silvestri, Mark T. Bongiovanni, Tasce R. Glover, Janis G. Gross, Cary P. TI Impact of price display on provider ordering: A systematic review SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID EMERGENCY-DEPARTMENT; HEALTH-CARE; LABORATORY TESTS; COST; INFORMATION; PHYSICIANS; BEHAVIOR; TRANSPARENCY; SERVICES; CHARGES AB BACKGROUNDDisplaying order prices to physicians is 1 potential strategy to reduce unnecessary health expenditures, but its impact on patterns of care is unclear. OBJECTIVETo review characteristics of previous price display interventions, impact on order costs and volume, effects on patient safety, acceptability to physicians, and the quality of this evidence. DESIGNSystematic review of studies that showed numeric prices of laboratory tests, imaging studies, or medications to providers in real time during the ordering process and evaluated the impact on provider ordering. Two investigators independently extracted data for each study and evaluated study quality using a modified Downs and Black checklist. RESULTSOf 1494 studies reviewed, 19 met inclusion criteria, including 5 randomized trials, 13 pre-post intervention studies, and 1 time series analysis. Studies were published between 1983 and 2014. Of 15 studies reporting the quantitative impact of price display on aggregate order costs or volume, 10 demonstrated a statistically significant decrease in the intervention group. Price display was found to decrease aggregate order costs (9 of 13 studies) more frequently than order volume (3 of 8 studies). Patient safety was evaluated in 5 studies and was unaffected by price display. Provider acceptability tended to be positive, although evidence was limited. Study quality was mixed, with checklist scores ranging from 5/21 to 20/21. CONCLUSIONSProvider price display likely reduces order costs to a modest degree. Patient safety appeared unchanged, though evidence was limited. More high-quality evidence is needed to confirm these findings within a modern context. Journal of Hospital Medicine 2016;11:65-76. (c) 2015 Society of Hospital Medicine C1 [Silvestri, Mark T.; Bongiovanni, Tasce R.; Gross, Cary P.] Yale Univ, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, New Haven, CT USA. [Bongiovanni, Tasce R.] US Dept Vet Affairs, Connecticut Healthcare Syst, West Haven, CT USA. [Glover, Janis G.] Yale Univ, Harvey Cushing John Hay Whitney Med Lib, New Haven, CT USA. [Gross, Cary P.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Silvestri, MT (reprint author), Robert Wood Johnson Fdn, Clin Scholars Program, POB 208088,333 Cedar St,SHM IE-61, New Haven, CT 06520 USA. EM mark.silvestri@yale.edu FU Johnson Johnson; Medtronic Inc.; 21st Century Oncology; Fair Health Inc.; ASTRO FX Dr. Silvestri, Dr. Bongiovanni, and Ms. Glover have nothing to disclose. Dr. Gross reports grants from Johnson & Johnson, Medtronic Inc., and 21st Century Oncology during the conduct of this study. In addition, he received payment from Fair Health Inc. and ASTRO outside the submitted work. NR 32 TC 2 Z9 2 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2016 VL 11 IS 1 BP 65 EP 76 DI 10.1002/jhm.2500 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA DA3VR UT WOS:000367728300011 PM 26498736 ER PT J AU Gordon, D Gardella, C Eschenbach, D Mitchell, CM AF Gordon, Dina Gardella, Carolyn Eschenbach, David Mitchell, Caroline M. TI High Prevalence of Sexual Dysfunction in a Vulvovaginal Specialty Clinic SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE sexual dysfunction; vulvovaginitis; vulvar pain; dyspareunia ID OLDER WOMEN; DEPRESSION; VAGINITIS; SEROTONIN; PSORIASIS; LIFE AB Objective Our study evaluated the presence and predictors of sexual dysfunction in a vulvovaginal specialty clinic population. Materials and Methods Women who presented to a vulvovaginal specialty clinic were eligible to enroll. The participants completed a questionnaire, including Female Sexual Function Index to assess sexual dysfunction and Patient Health Questionnaire (PHQ)-9 depression screen, and underwent a standardized physical examination, with vaginal swabs collected for wet mount and culture. Logistic regression assessed the relationship between sexual dysfunction and clinical diagnosis. Results We enrolled 161 women, aged 18 to 80 years (median,36 years), presenting with vulvovaginal complaints. Median symptom duration was 24 months; 131 women (81%) reported chronic symptoms (12 months). By PHQ-9, 28 women (17%) met depression criteria. In the month before assessment, 86 women (53%) experienced sexual dysfunction. Women had a primary diagnosis of vaginitis (n = 46 [29%]), vestibulodynia/vulvitis (n = 70 [43%]), lichen planus or lichen sclerosus (n = 24 [15%]). Controlling for age, we found that sexual dysfunction did not correlate with chronic symptoms (incidence rate ratio [IRR], 0.86; 95% confidence interval [CI], 0.50-1.48), depression (IRR, 1.24; 95% CI, 0.59-2.58), or presence of any of the 3 main diagnoses (IRR, 1.16; 95% CI, 0.47-2.88). Discussion Sexual dysfunction is present in more than half of women presenting to a vulvovaginitis referral clinic, more than twice the rate in the wider population. C1 [Gordon, Dina; Gardella, Carolyn; Eschenbach, David] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Mitchell, Caroline M.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Mitchell, CM (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, 55 Fruit St, Boston, MA 02114 USA. EM cmmitchell@partners.org FU Career Development Awards from NIAID [1K08AI087969 - 01]; Doris Duke Charitable Foundation FX Dr. Mitchell is supported by Career Development Awards from NIAID (1K08AI087969 - 01) and the Doris Duke Charitable Foundation. NR 21 TC 0 Z9 0 U1 6 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1089-2591 EI 1526-0976 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD JAN PY 2016 VL 20 IS 1 BP 80 EP 84 DI 10.1097/LGT.0000000000000085 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DA2AJ UT WOS:000367597400016 PM 25259664 ER PT J AU Rowe, SP Macura, KJ Ciarallo, A Mena, E Blackford, A Nadal, R Antonarakis, ES Eisenberger, MA Carducci, MA Ross, AE Kantoff, PW Holt, DP Dannals, RF Mease, RC Pomper, MG Cho, SY AF Rowe, Steven P. Macura, Katarzyna J. Ciarallo, Anthony Mena, Esther Blackford, Amanda Nadal, Rosa Antonarakis, Emmanuel S. Eisenberger, Mario A. Carducci, Michael A. Ross, Ashley E. Kantoff, Philip W. Holt, Daniel P. Dannals, Robert F. Mease, Ronnie C. Pomper, Martin G. Cho, Steve Y. TI Comparison of Prostate-Specific Membrane Antigen Based F-18-DCFBC PET/CT to Conventional Imaging Modalities for Detection of Hormone-Naive and Castration-Resistant Metastatic Prostate Cancer SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE prostate-specific membrane antigen; metastatic prostate cancer; positron emission tomography; computed tomography; bone scan ID POSITRON-EMISSION-TOMOGRAPHY; ANTI-1-AMINO-3-F-18-FLUOROCYCLOBUTANE-1-CARBOXYLIC ACID; UP-REGULATION; EXPRESSION; PSMA; CARCINOMA; BIODISTRIBUTION; C-11-ACETATE; METAANALYSIS; INHIBITORS AB Conventional imaging modalities (CIMs) have limited sensitivity and specificity for detection of metastatic prostate cancer. We examined the potential of a first-in-class radiofluorinated small-molecule inhibitor of prostate-specific membrane antigen (PSMA), N-[N-[(S)-1,3-dicarboxypropyfIcarbamoyl]-4-F-18-fluorobenzyl-L-cysteine (F-18-DCFBC), to detect metastatic hormone-naive (HNPC) and castration-resistant prostate cancer (CRPC). Methods: Seventeen patients were prospectively enrolled (9 HNPC and 8 CRPC); 16 had CIM evidence of new or progressive metastatic prostate cancer and 1 had high clinical suspicion of metastatic disease. F-18-DCFBC PET/CT imaging was obtained with 2 successive PET scans starting at 2 h after injection. Patients were imaged with CIM at approximately the time of PET. A lesion-by-lesion analysis of PET to CIM was performed in the context of either HNPC or CRPC. The patients were followed with available clinical imaging as a reference standard to determine the true nature of identified lesions on PET and CIM. Results: On the lesion-by-lesion analysis, F-18-DCFBC PET was able to detect a larger number of lesions (592 positive with 63 equivocal) than CIM (520 positive with 61 equivocal) overall, in both HNPC and CRPC patients. F-18-DCFBC PET detection of lymph nodes, bone lesions, and visceral lesions was superior to CIM. When intrapatient clustering effects were considered, F-18-DCFBC PET was estimated to be positive in a large proportion of lesions that would be negative or equivocal on CIM (0.45). On follow-up, the sensitivity of F-18-DCFBC PET (0.92) was superior to CIM (0.71). 18F-DCFBC tumor uptake was increased at the later PET time point (similar to 2.5 h after injection), with background uptake showing a decreasing trend on later PET. Conclusion: PET imaging with F-18-DCFBC, a small-molecule PSMA-targeted radiotracer, detected more lesions than CIM and promises to diagnose and stage patients with metastatic prostate cancer more accurately than current imaging methods. C1 [Rowe, Steven P.; Macura, Katarzyna J.; Ciarallo, Anthony; Mena, Esther; Holt, Daniel P.; Dannals, Robert F.; Mease, Ronnie C.; Pomper, Martin G.; Cho, Steve Y.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. [Macura, Katarzyna J.; Blackford, Amanda; Nadal, Rosa; Antonarakis, Emmanuel S.; Eisenberger, Mario A.; Carducci, Michael A.] Johns Hopkins Med Inst, Dept Med Oncol, Baltimore, MD 21205 USA. [Macura, Katarzyna J.; Ross, Ashley E.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Macura, Katarzyna J.; Ross, Ashley E.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cho, SY (reprint author), 1111 Highland Ave,WIMR1 Rm 7139, Madison, WI 53705 USA. EM scho@uwhealth.org FU Prostate Cancer Foundation Young Investigator Award; RSNA Research & Education Foundation Research Scholar Award [EB006351, CA184228, CA183031, CA134675] FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. We acknowledge funding from the Prostate Cancer Foundation Young Investigator Award, RSNA Research & Education Foundation Research Scholar Award, EB006351, CA184228, CA183031, and CA134675. No other potential conflict of interest relevant to this article was reported. NR 40 TC 14 Z9 15 U1 6 U2 11 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2016 VL 57 IS 1 BP 46 EP 53 DI 10.2967/jnumed.115.163782 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DA5SL UT WOS:000367862700010 PM 26493203 ER PT J AU As-Sanie, S Kim, J Schmidt-Wilcke, T Sundgren, PC Clauw, DJ Napadow, V Harris, RE AF As-Sanie, Sawsan Kim, Jieun Schmidt-Wilcke, Tobias Sundgren, Pia C. Clauw, Daniel J. Napadow, Vitaly Harris, Richard E. TI Functional Connectivity Is Associated With Altered Brain Chemistry in Women With Endometriosis-Associated Chronic Pelvic Pain SO JOURNAL OF PAIN LA English DT Article DE Endometriosis; chronic pelvic pain; neuroimaging; glutamate; functional connectivity ID DEFAULT MODE NETWORK; INSULAR CORTEX; ANTERIOR INSULA; RESPONSE FUNCTION; CONTROLLED-TRIAL; CLINICAL PAIN; BOLD SIGNAL; FIBROMYALGIA; FMRI; GLUTAMATE AB In contrast to women with relatively asymptomatic endometriosis, women with endometriosis-associated chronic pelvic pain (CPP) exhibit nonpelvic hyperalgesia and decreased gray matter volume in key neural pain processing regions. Although these findings suggest central pain amplification in endometriosis-associated CPP, the underlying changes in brain chemistry and function associated with central pain amplification remain unknown. We performed proton spectroscopy and seed-based resting functional connectivity magnetic resonance imaging to determine whether women with endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions. Relative to age-matched pain-free controls, women with endometriosis-associated CPP displayed increased levels of combined glutamine-glutamate (Glx) within the anterior insula and greater anterior insula connectivity to the medial prefrontal cortex (mPFC). Increased connectivity between these regions was positively correlated with anterior insula Glx concentrations (r = .87), as well as clinical anxiety (r = .61, P = .02), depression (r = .60, P = .03), and pain intensity (r = .55, P = .05). There were no significant differences in insula metabolite levels or resting-state connectivity in endometriosis patients without CPP versus controls. We conclude that enhanced anterior insula glutamatergic neurotransmission and connectivity with the mPFC, key regions of the salience and default mode networks, may play a role in the pathophysiology of CPP independent of the presence of endometriosis. Perspective: Similar to other chronic pain conditions, endometriosis-associated pelvic pain is associated with altered brain chemistry and function in pain processing regions. These findings support central pain amplification as a mechanism of chronic pelvic pain, and clinicians should consider the use of adjunctive therapies that target central pain dysfunction in these women. (C) 2016 by the American Pain Society C1 [As-Sanie, Sawsan] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Sundgren, Pia C.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Kim, Jieun; Napadow, Vitaly] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Schmidt-Wilcke, Tobias; Clauw, Daniel J.; Harris, Richard E.] Univ Michigan Hlth Syst, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. RP As-Sanie, S (reprint author), Univ Michigan Hlth Syst, Womens Hosp L4100, Dept Obstet & Gynecol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM sassanie@med.umich.edu OI As-Sanie, Sawsan/0000-0002-7166-1979 FU NIH [K12HD001438, UL1RR024986, 1S10OD012240-01A1, 1R01 AT007550]; Bayer Droegemueller Award in Clinical Research; DFG (Deutsche Forschungsgemeinschaft) [GZ: SchM 2665/1]; NCCAM, NIH [P01-AT006663, R01-AT007550]; NIAMS, NIH [R01-AR064367]; Dana Foundation; Department of Defense (Army grant) [DAMD-W81XWH-07-2-0050]; GCRC [M01-RR-01066]; Korea Institute of Oriental Medicine [K15050]; Pfizer, Inc; Forest Laboratories FX This study was funded by NIH K12HD001438, NIH UL1RR024986, NIH 1S10OD012240-01A1, and the Bayer Droegemueller Award in Clinical Research. T.S.-W. was supported by a grant from the DFG (Deutsche Forschungsgemeinschaft, GZ: SchM 2665/1). V.N. was supported by NCCAM, NIH: P01-AT006663, R01-AT007550; NIAMS, NIH: R01-AR064367. R.E.H. was supported by the Dana Foundation, the Department of Defense (Army grant: DAMD-W81XWH-07-2-0050), GCRC M01-RR-01066, and NIH: 1R01 AT007550. J.K. was supported by a grant of the Korea Institute of Oriental Medicine (K15050). R.E.H. has previously consulted for Pfizer, Inc. D.J.C. has received grants/research support from Pfizer, Inc and Forest Laboratories. He has been a consultant for and served on advisory boards for Pfizer, Inc, Eli Lilly and Company, Forest Laboratories, Inc, Cypress Bioscience, Inc, Pierre Fabre Pharmaceuticals, UCB, and AstraZeneca. All other authors have no conflicts of interest to disclose. NR 70 TC 5 Z9 5 U1 1 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JAN PY 2016 VL 17 IS 1 BP 1 EP 13 DI 10.1016/j.jpain.2015.09.008 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA5VI UT WOS:000367870300001 PM 26456676 ER PT J AU Castillo-Saavedra, L Gebodh, N Bikson, M Diaz-Cruz, C Brandao, R Coutinho, L Truong, D Datta, A Shani-Hershkovich, R Weiss, M Laufer, I Reches, A Peremen, Z Geva, A Parra, LC Fregni, F AF Castillo-Saavedra, Laura Gebodh, Nigel Bikson, Marom Diaz-Cruz, Camilo Brandao, Rivail Coutinho, Livia Truong, Dennis Datta, Abhishek Shani-Hershkovich, Revital Weiss, Michal Laufer, Ilan Reches, Amit Peremen, Ziv Geva, Amir Parra, Lucas C. Fregni, Felipe TI Clinically Effective Treatment of Fibromyalgia Pain With High-Definition Transcranial Direct Current Stimulation: Phase II Open-Label Dose Optimization SO JOURNAL OF PAIN LA English DT Article DE Fibromyalgia; pain; noninvasive brain stimulation; high-definition transcranial direct current stimulation; motor cortex ID ELECTRICAL BRAIN-STIMULATION; PRIMARY MOTOR CORTEX; NEUROPATHIC PAIN; PLACEBO-RESPONSE; MAGNETIC STIMULATION; TENDER POINTS; HD-TDCS; PREDICTORS; PERCEPTION; TRIALS AB Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported. Online Registration: Registered in Clinicaltrials.gov under registry number NCT01842009. Perspective: In this article, an optimized protocol for the treatment of fibromyalgia pain with targeted subthreshold brain stimulation using high-definition transcranial direct current stimulation is outlined. (C) 2016 by the American Pain Society C1 [Castillo-Saavedra, Laura; Gebodh, Nigel; Diaz-Cruz, Camilo; Brandao, Rivail; Coutinho, Livia; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat,Dept Phys Med & Rehabil, Boston, MA USA. [Castillo-Saavedra, Laura; Gebodh, Nigel; Diaz-Cruz, Camilo; Brandao, Rivail; Coutinho, Livia; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gebodh, Nigel; Bikson, Marom; Truong, Dennis; Datta, Abhishek; Parra, Lucas C.] CUNY City Coll, Dept Biomed Engn, New York, NY 10031 USA. [Brandao, Rivail] Univ Fed Bahia, Postgrad Program Interact Processes Organs & Syst, Salvador, BA, Brazil. [Datta, Abhishek] Soterix Med Inc, New York, NY USA. [Shani-Hershkovich, Revital; Weiss, Michal; Laufer, Ilan; Reches, Amit; Peremen, Ziv; Geva, Amir] ElMindA Ltd, Herzliyya, Israel. [Peremen, Ziv] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Geva, Amir] Ben Gurion Univ Negev, Beer Sheva, Israel. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Spaulding Neuromodulat Ctr, 79-96 13th St, Boston, MA 02163 USA. EM ffregni@mgh.harvard.edu FU Elminda, Ltd; Coulter Foundation [75969-00-02]; National Institutes of Health (NIH) [5U54CA132378-08]; National Institutes of Health (NIH/NSF) [5R01MH092926-05]; United States Department of Defense [FA9550-13-1-0073] FX This research was supported in part by grants from Elminda, Ltd, Coulter Foundation (grant 75969-00-02), the National Institutes of Health (NIH grant 5U54CA132378-08, NIH/NSF grant 5R01MH092926-05) and the United States Department of Defense (grant FA9550-13-1-0073). The City University of New York owns patents on High-Definition tDCS with M.B., L.C.P., and A.D. as inventor. M.B., L.C.P., and A.D. have equity in Soterix Medical Inc. NR 48 TC 9 Z9 9 U1 1 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JAN PY 2016 VL 17 IS 1 BP 14 EP 26 DI 10.1016/j.jpain.2015.09.009 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA5VI UT WOS:000367870300002 PM 26456677 ER PT J AU Treister, R Nielsen, CS Stubhaug, A Farrar, JT Pud, D Sawilowsky, S Oaklander, AL AF Treister, Roi Nielsen, Christopher S. Stubhaug, Audun Farrar, John T. Pud, Dorit Sawilowsky, Shlomo Oaklander, Anne Louise TI Response to the Letter to the Editor: Experimental Comparison of Parametric Versus Non parametric Analyses of Data From the Cold Pressor Test SO JOURNAL OF PAIN LA English DT Letter C1 [Treister, Roi; Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Treister, Roi; Oaklander, Anne Louise] Harvard Univ, Sch Med, Boston, MA USA. [Nielsen, Christopher S.] Norwegian Inst Publ Hlth, Div Mental Hlth, Oslo, Norway. [Stubhaug, Audun] Oslo Univ Hosp, Dept Pain Management & Res, N-0450 Oslo, Norway. [Farrar, John T.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Pud, Dorit] Univ Haifa, Fac Social Welf & Hlth Sci, IL-31999 Haifa, Israel. [Sawilowsky, Shlomo] Wayne State Univ, Coll Educ, Detroit, MI USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. RP Treister, R (reprint author), Massachusetts Gen Hosp, Dept Neurol, 275 Charles St Warren Bldg 310, Boston, MA 02114 USA. EM treister.roi@gmail.com NR 5 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JAN PY 2016 VL 17 IS 1 BP 128 EP 129 DI 10.1016/j.jpain.2015.10.004 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA5VI UT WOS:000367870300013 PM 26721380 ER PT J AU McCaslin, SE Maguen, S Metzler, T Bosch, J Neylan, TC Marmar, CR AF McCaslin, Shannon E. Maguen, Shira Metzler, Thomas Bosch, Jeane Neylan, Thomas C. Marmar, Charles R. TI Assessing posttraumatic stress related impairment and well-being: The Posttraumatic Stress Related Functioning Inventory (PRFI) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE PTSD; Functioning; Veterans; Assessment; Outcomes ID MALE VIETNAM VETERANS; ABUSE SCREENING-TEST; QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES; INTERPERSONAL VIOLENCE; DISORDER SYMPTOMS; HEALTH; WAR; TRAUMA; IRAQ AB Posttraumatic stress symptoms are associated with poorer social and occupational functioning and quality of life. However, general assessments of functioning do not determine the extent to which these difficulties are directly related to PTSD symptoms. This study examines the psychometric properties of a self-report measure, the 27-item Posttraumatic Stress Related Functioning Inventory (PRFI), which was developed to provide a self-report tool for clinicians and researchers to better understand the perceived impact of PTSD symptoms on functioning. The psychometric properties of the PRFI were examined utilizing data collected within a larger study examining quality of life and functioning in 251 veterans who had served in OEF/OIF/OND and endorsed the presence of subsyndromal or greater levels of PTSD symptoms at screening. One-year test-retest reliability of the measure was examined in a subset of the baseline sample who received a second administration of the PRFI (n = 109). Higher levels of PTSD symptoms were associated with poorer functioning in all domains. The PRFI demonstrated convergent validity with a measure of PTSD symptoms and was less correlated with measures of alcohol and drug use, good internal consistency and test-retest reliability from baseline to one-year follow-up. The PRFI provides self-report information regarding several domains of functioning. This initial examination of psychometric properties of the scale indicated that it may be useful for efficiently eliciting information about the ways in which PTSD symptoms in veterans impact everyday functioning. Published by Elsevier Ltd. C1 [McCaslin, Shannon E.] Natl Ctr PTSD, Disseminat & Training Div, Menlo Pk, CA USA. [McCaslin, Shannon E.; Maguen, Shira; Metzler, Thomas; Neylan, Thomas C.] San Francisco Vet Adm Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [McCaslin, Shannon E.; Maguen, Shira; Metzler, Thomas; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Bosch, Jeane] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. [Marmar, Charles R.] NYU, Steven & Alexandra Cohen Vet Ctr, New York, NY USA. [Marmar, Charles R.] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10016 USA. RP McCaslin, SE (reprint author), VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Disseminat & Training Div, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM Shannon.McCaslin@va.gov FU United States (U.S.) Department of Veterans Affairs, Clinical Sciences Research and Development Service [CDA-2-032-06F]; United States (U.S.) Department of Veterans Affairs, Health Services Research and Development Service [RCD 06-042] FX This work was supported by Career Development Award (CDA-2-032-06F: McCaslin) from the United States (U.S.) Department of Veterans Affairs, Clinical Sciences Research and Development Service and Career Development Award (RCD 06-042: Maguen) from the United States (U.S.) Department of Veterans Affairs, Health Services Research and Development Service.The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 35 TC 0 Z9 0 U1 1 U2 5 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 JAN PY 2016 VL 72 BP 104 EP 111 DI 10.1016/j.jpsychires.2015.10.016 PG 8 WC Psychiatry SC Psychiatry GA DA0KB UT WOS:000367484900016 PM 26615453 ER PT J AU Kaura, D Blickman, JG Boland, GW AF Kaura, Deepak Blickman, Johan G. Boland, Giles W. TI The Haptic Radiologist: Being There, Always SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Kaura, Deepak] Sidra Med & Res Ctr, Doha, Qatar. [Blickman, Johan G.] Univ Rochester, Coll Med, Rochester, NY USA. [Boland, Giles W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kaura, D (reprint author), Sidra Med & Res Ctr, POB 26999, Doha, Qatar. EM dkaura@sidra.org NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2016 VL 13 IS 1 BP 104 EP 105 DI 10.1016/j.jacr.2015.10.010 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DA5VL UT WOS:000367870600028 PM 26614411 ER PT J AU Erpenbeck, L Demers, M Zsengeller, ZK Gallant, M Cifuni, SM Stillman, IE Karumanchi, SA Wagner, DD AF Erpenbeck, Luise Demers, Melanie Zsengeller, Zsuzsanna K. Gallant, Maureen Cifuni, Stephen M. Stillman, Isaac E. Karumanchi, S. Ananth Wagner, Denisa D. TI ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor-Induced Thrombotic Microangiopathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; HEMOLYTIC-UREMIC SYNDROME; ANTI-VEGF THERAPY; RENAL-CELL CARCINOMA; THROMBOCYTOPENIC PURPURA; DEFICIENT ACTIVITY; BLOOD-PRESSURE; MOUSE MODEL; PREECLAMPSIA AB Thrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor-related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor-related TMA. ADAMTS13(-/-) mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor-related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13(-/-) mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition. C1 [Erpenbeck, Luise; Demers, Melanie; Gallant, Maureen; Cifuni, Stephen M.; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Erpenbeck, Luise; Demers, Melanie; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Zsengeller, Zsuzsanna K.; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Zsengeller, Zsuzsanna K.; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Zsengeller, Zsuzsanna K.; Stillman, Isaac E.; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, 3 Blackfan Circle,Third Floor, Boston, MA 02115 USA. EM Denisa.Wagner@childrens.harvard.edu FU National Heart, Lung, and Blood Institute of National Institutes of Health [R01-HL102101]; Deutsche Akademie der Naturforscher Leopoldina (Nationale Akademie der Wissenschaften) FX The authors thank L. Cowan for help with the preparation of the manuscript and K. Martinod and S.L. Wong for critical input and discussions. This research was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health grant R01-HL102101 (to D.D.W.). L.E. is a recipient of a fellowship of the Deutsche Akademie der Naturforscher Leopoldina (Nationale Akademie der Wissenschaften). S.A.K. is an investigator of the Howard Hughes Medical Institute. NR 67 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2016 VL 27 IS 1 BP 120 EP 131 DI 10.1681/ASN.2014121165 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA DA2NH UT WOS:000367632400016 PM 26038528 ER PT J AU Mohler, JL Armstrong, AJ Bahnson, RR D'Amico, AV Davis, BJ Eastham, JA Enke, CA Farrington, TA Higano, CS Horwitz, EM Hurwitz, M Kane, CJ Kawachi, MH Kuettel, M Lee, RJ Meeks, JJ Penson, DF Plimack, ER Pow-Sang, JM Raben, D Richey, S Roach, M Rosenfeld, S Schaeffer, E Skolarus, TA Small, EJ Sonpavde, G Srinivas, S Strope, SA Tward, J Shead, DA Freedman-Cass, DA AF Mohler, James L. Armstrong, Andrew J. Bahnson, Robert R. D'Amico, Anthony Victor Davis, Brian J. Eastham, James A. Enke, Charles A. Farrington, Thomas A. Higano, Celestia S. Horwitz, Eric M. Hurwitz, Michael Kane, Christopher J. Kawachi, Mark H. Kuettel, Michael Lee, Richard J. Meeks, Joshua J. Penson, David F. Plimack, Elizabeth R. Pow-Sang, Julio M. Raben, David Richey, Sylvia Roach, Mack, III Rosenfeld, Stan Schaeffer, Edward Skolarus, Ted A. Small, Eric J. Sonpavde, Guru Srinivas, Sandy Strope, Seth A. Tward, Jonathan Shead, Dorothy A. Freedman-Cass, Deborah A. TI Prostate Cancer, Version 1.2016 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID BEAM RADIATION-THERAPY; MITOXANTRONE PLUS PREDNISONE; RISK CLASSIFICATION-SYSTEM; CYCLE PROGRESSION SCORE; NEEDLE-BIOPSY COHORT; RADICAL PROSTATECTOMY; ACTIVE SURVEILLANCE; GENOMIC CLASSIFIER; PRETREATMENT NOMOGRAM; PROGNOSTIC VALUE AB The NCCN Guidelines for Prostate Cancer address staging and risk assessment after an initial diagnosis of prostate cancer and management options for localized, regional, and metastatic disease. Recommendations for disease monitoring, treatment of recurrent disease, and systemic therapy for metastatic castration-recurrent prostate cancer also are included. This article summarizes the NCCN Prostate Cancer Panel's most significant discussions for the 2016 update of the guidelines, which include refinement of risk stratification methods and new options for the treatment of men with high-risk and very-high-risk disease and progressive castration-naive disease. C1 [Mohler, James L.; Kawachi, Mark H.] Roswell Park Canc Inst, Buffalo, NY 14263 USA. [Armstrong, Andrew J.] Duke Canc Inst, Durham, NC USA. [Bahnson, Robert R.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bahnson, Robert R.] Solove Res Inst, Columbus, OH USA. [D'Amico, Anthony Victor] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Davis, Brian J.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Eastham, James A.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Enke, Charles A.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Farrington, Thomas A.] PHEN, Phnom Penh, Cambodia. [Higano, Celestia S.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98109 USA. [Horwitz, Eric M.; Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Hurwitz, Michael] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Kane, Christopher J.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Kawachi, Mark H.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Lee, Richard J.] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. [Meeks, Joshua J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Penson, David F.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Pow-Sang, Julio M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Raben, David] Univ Colorado, Canc Ctr, Boulder, CO 80309 USA. [Richey, Sylvia] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Roach, Mack, III; Small, Eric J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Rosenfeld, Stan] Univ Calif San Francisco, Patient Serv Comm Chair, San Francisco, CA 94143 USA. [Schaeffer, Edward] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Skolarus, Ted A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Sonpavde, Guru] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Srinivas, Sandy] Stanford Canc Inst, Stanford, CA USA. [Strope, Seth A.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Strope, Seth A.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Tward, Jonathan] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Shead, Dorothy A.; Freedman-Cass, Deborah A.] Natl Comprehens Canc Network, Ft Washington, PA USA. RP Mohler, JL (reprint author), Roswell Park Canc Inst, Buffalo, NY 14263 USA. FU AstraZeneca; Bayer Healthcare Pharmaceuticals Inc.; Bristol-Myers Squibb; Clovis Oncology; Genentech; Novartis Oncology; Otsuka America Pharmaceutical, Inc.; Seattle Genetics, Inc.; Takeda Oncology; Actelion Pharmaceuticals US, Inc.; Astellas; Medivation, Inc. FX This activity is supported by educational grants from AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Clovis Oncology, Genentech, Novartis Oncology, Otsuka America Pharmaceutical, Inc., Seattle Genetics, Inc., and Takeda Oncology; support provided by Actelion Pharmaceuticals US, Inc.; and by an independent educational grant from Astellas and Medivation, Inc. NR 64 TC 54 Z9 55 U1 5 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 JAN PY 2016 VL 14 IS 1 BP 19 EP 30 PG 12 WC Oncology SC Oncology GA DA2MN UT WOS:000367629000005 PM 26733552 ER PT J AU Levy, M Smith, T Alvarez-Perez, A Back, A Baker, JN Beck, AC Block, S Dalal, S Dans, M Fitch, TR Kapo, J Kutner, JS Kvale, E Misra, S Mitchell, W Portman, DG Sauer, TM Spiegel, D Sutton, L Szmuilowicz, E Taylor, RM Temel, J Tickoo, R Urba, SG Weinstein, E Zachariah, F Bergman, MA Scavone, JL AF Levy, Michael Smith, Thomas Alvarez-Perez, Amy Back, Anthony Baker, Justin N. Beck, Anna C. Block, Susan Dalal, Shalini Dans, Maria Fitch, Thomas R. Kapo, Jennifer Kutner, Jean S. Kvale, Elizabeth Misra, Sumathi Mitchell, William Portman, Diane G. Sauer, Todd M. Spiegel, David Sutton, Linda Szmuilowicz, Eytan Taylor, Robert M. Temel, Jennifer Tickoo, Roma Urba, Susan G. Weinstein, Elizabeth Zachariah, Finly Bergman, Mary Anne Scavone, Jillian L. TI Palliative Care Version 1.2016 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID OPIOID-INDUCED CONSTIPATION; CELL LUNG-CANCER; MALIGNANT BOWEL OBSTRUCTION; RESTLESS LEGS SYNDROME; CHEMOTHERAPY-INDUCED NAUSEA; PLACEBO-CONTROLLED TRIAL; HIGH-DOSE METOCLOPRAMIDE; CENTRAL ANTICHOLINERGIC SYNDROME; RANDOMIZED CONTROLLED-TRIAL; ANOREXIA-CACHEXIA SYNDROME AB The NCCN Guidelines for Palliative Care provide interdisciplinary recommendations on palliative care for patients with cancer. The NCCN Guidelines are intended to provide guidance to the primary oncology team on the integration of palliative care into oncology. The NCCN Palliative Care Panel's recommendations seek to ensure that each patient experiences the best quality of life possible throughout the illness trajectory. Accordingly, the NCCN Guidelines outline best practices for screening, assessment, palliative care interventions, reassessment, and after-death care. C1 [Levy, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Smith, Thomas] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Alvarez-Perez, Amy] Roswell Pk Canc Inst, Buffalo, NY USA. [Back, Anthony] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Baker, Justin N.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Beck, Anna C.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Block, Susan] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Dalal, Shalini] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Dans, Maria] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Dans, Maria] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Fitch, Thomas R.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Kapo, Jennifer] Smilow Canc Hosp, Yale Canc Center, New Haven, CT USA. [Kutner, Jean S.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Kvale, Elizabeth] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Misra, Sumathi] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Mitchell, William] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Portman, Diane G.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Sauer, Todd M.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Spiegel, David] Stanford Canc Inst, Stanford, CA USA. [Sutton, Linda] Duke Canc Inst, Durham, NC USA. [Szmuilowicz, Eytan] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Taylor, Robert M.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Taylor, Robert M.] Solove Res Inst, Columbus, OH USA. [Temel, Jennifer] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Tickoo, Roma] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Weinstein, Elizabeth] Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA. [Weinstein, Elizabeth] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA. [Zachariah, Finly] City Hope Comprehens Canc Ctr, Duarte, CA USA. RP Levy, M (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 187 TC 4 Z9 5 U1 2 U2 3 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 JAN PY 2016 VL 14 IS 1 BP 82 EP 113 PG 32 WC Oncology SC Oncology GA DA2MN UT WOS:000367629000010 PM 26733557 ER PT J AU Sillesen, M Bambakidis, T Dekker, SE Fabricius, R Svenningsen, P Bruhn, PJ Svendsen, LB Hillingso, J Alam, HB AF Sillesen, Martin Bambakidis, Ted Dekker, Simone E. Fabricius, Rasmus Svenningsen, Peter Bruhn, Peter James Svendsen, Lars Bo Hillingso, Jens Alam, Hasan B. TI Histone deactylase gene expression profiles are associated with outcomes in blunt trauma patients SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Trauma; histone deacetylase; complications; biomarkers ID LONG-TERM SURVIVAL; SUBEROYLANILIDE HYDROXAMIC ACID; LETHAL 2-HIT MODEL; PHARMACOLOGICAL RESUSCITATION; DEACETYLASE INHIBITORS; SEPTIC SHOCK; PRO-SURVIVAL; BRAIN-INJURY; PHENOTYPE; MODULATION AB BACKGROUND Treatment with histone deacetylase (HDAC) inhibitors, such as valproic acid, increases survival in animal models of trauma and sepsis. Valproic acid is a pan-inhibitor that blocks most of the known HDAC isoforms. Targeting individual HDAC isoforms may increase survival and reduce complications, but little is known of the natural history of HDAC gene expression following trauma. We hypothesized that distinct HDAC isoform gene expression patterns would be associated with differences in outcomes following trauma. METHODS Twenty-eight-day longitudinal HDAC leukocyte gene expression profiles in 172 blunt trauma patients were extracted from the Inflammation and the Host Response to Injury (Glue Grant) data set. Outcome was classified as complicated (death or no recovery by Day 28, n = 51) or uncomplicated (n = 121). Mixed modeling was used to compare the HDAC expression trajectories between the groups, corrected for Injury Severity Score (ISS), base deficit, and volume of blood products transfused during the initial 12 hours following admission. Weighted gene correlation network analysis identified modules of genes with significant coexpression, and HDAC genes were mapped to these modules. Biologic function of these modules was investigated using the Gene Ontology database. RESULTS Elevated longitudinal HDAC expression trajectories for HDAC1, HDAC3, HDAC6, and HDAC11 were associated with complicated outcomes. In contrast, suppressed expression of Sirtuin 3 (SIRT3) was associated with adverse outcome (p < 0.01). Weighted gene correlation network analysis identified significant coexpression of HDAC and SIRT genes with genes involved in ribosomal function and down-regulation of protein translation in response to stress (HDAC1), T-cell signaling, and T-cell selection (HDAC3) as well as coagulation and hemostasis (SIRT3). No coexpression of HDAC11 was identified. CONCLUSION Expression trajectories of HDAC1, HDAC3, HDAC6, HDAC11, and SIRT3 correlate with outcomes following trauma and may potentially serve as biomarkers. They may also be promising targets for pharmacologic intervention. The effects of HDAC and SIRT gene expression in trauma may be mediated through pathways involved in ribosomal and T-cell function as well as coagulation and hemostasis. C1 [Sillesen, Martin; Svenningsen, Peter; Bruhn, Peter James; Svendsen, Lars Bo; Hillingso, Jens] Copenhagen Univ Hosp, Rigshosp, Dept Surg Gastroenterol, Copenhagen, Denmark. [Fabricius, Rasmus] Copenhagen Univ Hosp, Rigshosp, Dept Surg, Copenhagen, Denmark. [Sillesen, Martin] Copenhagen Univ Hosp, Rigshosp, Inst Inflammat Res, Copenhagen, Denmark. [Sillesen, Martin] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Bambakidis, Ted; Dekker, Simone E.; Alam, Hasan B.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Dekker, Simone E.] Vrije Univ Amsterdam Med Ctr, Inst Cardiovasc Res, Dept Anesthesiol, Amsterdam, Netherlands. RP Alam, HB (reprint author), Univ Michigan Hlth Syst, 2920 Taubman Ctr 5331,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu NR 28 TC 0 Z9 0 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JAN PY 2016 VL 80 IS 1 BP 26 EP 33 DI 10.1097/TA.0000000000000896 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA DA1GN UT WOS:000367544400004 PM 26517778 ER PT J AU Zhu, B Witzel, T Jiang, S Huang, SY Rosen, BR Wald, LL AF Zhu, Bo Witzel, Thomas Jiang, Shan Huang, Susie Y. Rosen, Bruce R. Wald, Lawrence L. TI Selective Magnetic Resonance Imaging of Magnetic Nanoparticles by Acoustically Induced Rotary Saturation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MR contrast agent; molecular imaging; contrast mechanism; positive contrast/spin-lock ID IRON-OXIDE NANOPARTICLES; CONTRAST AGENTS; ELASTOGRAPHY; VISUALIZATION; CURRENTS; THERAPY; MODEL; MRI AB Purpose: The goal of this study was to introduce a new method to selectively detect iron oxide contrast agents using an acoustic wave to perturb the spin-locked water signal in the vicinity of the magnetic particles. The acoustic drive can be modulated externally to turn the effect on and off, allowing sensitive and quantitative statistical comparison and removal of confounding image background variations. Methods: We demonstrated the effect in spin-locking experiments using piezoelectric actuators to generate vibrational displacements of iron oxide samples. We observed a resonant behavior of the signal changes with respect to the acoustic frequency where iron oxide is present. We characterized the effect as a function of actuator displacement and contrast agent concentration. Results: The resonant effect allowed us to generate block-design "modulation response maps" indicating the contrast agent's location, as well as positive contrast images with suppressed background signal. We found that the acoustically induced rotary saturation (AIRS) effect stayed approximately constant across acoustic frequency and behaved monotonically over actuator displacement and contrast agent concentration. Conclusion: AIRS is a promising method capable of using acoustic vibrations to modulate the contrast from iron oxide nanoparticles and thus perform selective detection of the contrast agents, potentially enabling more accurate visualization of contrast agents in clinical and research settings. (C) 2014 Wiley Periodicals, Inc. C1 [Zhu, Bo; Witzel, Thomas; Huang, Susie Y.; Rosen, Bruce R.; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Jiang, Shan] MIT, Dept Chem Engn, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Rosen, Bruce R.] Kyung Hee Univ, East West Med Res Inst, Collaborating Ctr Traditi Med, Dept Meridian & Acupuncture, Seoul, South Korea. [Rosen, Bruce R.] Kyung Hee Univ, Sch Korean Med, Seoul, South Korea. [Zhu, Bo; Rosen, Bruce R.; Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Zhu, B (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM boz@mit.edu RI Wald, Lawrence/D-4151-2009 FU National Institute of Biomedical Imaging and Bioengineering [T32-EB001680] FX Grant sponsor: National Institute of Biomedical Imaging and Bioengineering; Grant number: T32-EB001680. NR 28 TC 1 Z9 1 U1 0 U2 8 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 JAN PY 2016 VL 75 IS 1 BP 97 EP 106 DI 10.1002/mrm.25522 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DA3ZF UT WOS:000367739200010 PM 25537578 ER PT J AU Stockmann, JP Witzel, T Keil, B Polimeni, JR Mareyam, A LaPierre, C Setsompop, K Wald, LL AF Stockmann, Jason P. Witzel, Thomas Keil, Boris Polimeni, Jonathan R. Mareyam, Azma LaPierre, Cristen Setsompop, Kawin Wald, Lawrence L. TI A 32-Channel Combined RF and B-0 Shim Array for 3T Brain Imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE multi-coil shimming; RF receive arrays; echo planar imaging; geometric distortion; brain MRI ID PARALLEL RECEPTION; 7 TESLA; COIL; ACQUISITION; DESIGN; ORDER AB Purpose: We add user-controllable direct currents (DC) to the individual elements of a 32-channel radio-frequency (RF) receive array to provide B-0 shimming ability while preserving the array's reception sensitivity and parallel imaging performance. Methods: Shim performance using constrained DC current (+/- 2.5A) is simulated for brain arrays ranging from 8 to 128 elements. A 32-channel 3-tesla brain array is realized using inductive chokes to bridge the tuning capacitors on each RF loop. The RF and B-0 shimming performance is assessed in bench and imaging measurements. Results: The addition of DC currents to the 32-channel RF array is achieved with minimal disruption of the RF performance and/or negative side effects such as conductor heating or mechanical torques. The shimming results agree well with simulations and show performance superior to third-order spherical harmonic (SH) shimming. Imaging tests show the ability to reduce the standard frontal lobe susceptibility-induced fields and improve echo planar imaging geometric distortion. The simulation of 64- and 128-channel brain arrays suggest that even further shimming improvement is possible (equivalent to up to 6th-order SH shim coils). Conclusion: Including user-controlled shim currents on the loops of a conventional highly parallel brain array coil is feasible with modest current levels and produces improved B-0 shimming performance over standard second-order SH shimming. (C) 2015 Wiley Periodicals, Inc. C1 [Stockmann, Jason P.; Witzel, Thomas; Keil, Boris; Polimeni, Jonathan R.; Mareyam, Azma; LaPierre, Cristen; Setsompop, Kawin; Wald, Lawrence L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Witzel, Thomas; Keil, Boris; Polimeni, Jonathan R.; Setsompop, Kawin; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Stockmann, JP (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM jaystock@nmr.mgh.harvard.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU NIH NIBIB [R21EB017338, P41EB015896] FX Grant sponsor: NIH NIBIB; Grant number: R21EB017338 and P41EB015896. NR 36 TC 8 Z9 8 U1 4 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 JAN PY 2016 VL 75 IS 1 BP 441 EP 451 DI 10.1002/mrm.25587 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DA3ZF UT WOS:000367739200045 PM 25689977 ER PT J AU Bardia, A Keenan, TE Ebbert, JO Lazovich, D Wang, AH Vierkant, RA Olson, JE Vachon, CM Limburg, PJ Anderson, KE Cerhan, JR AF Bardia, Aditya Keenan, Tanya E. Ebbert, Jon O. Lazovich, DeAnn Wang, Alice H. Vierkant, Robert A. Olson, Janet E. Vachon, Celine M. Limburg, Paul J. Anderson, Kristin E. Cerhan, James R. TI Personalizing Aspirin Use for Targeted Breast Cancer Chemoprevention in Postmenopausal Women SO MAYO CLINIC PROCEEDINGS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIAL; HORMONE-RECEPTOR STATUS; NSAID USE; VITAMIN-E; CONSENSUS STATEMENT; PRIMARY PREVENTION; COLORECTAL-CANCER; PROSTATE-CANCER; RISK-FACTORS AB Objective: To evaluate the association of aspirin and other nonsteroidal anti-inflammatory drugs with the incidence of postmenopausal breast cancer for risk subgroups defined by selected nonmodifiable or difficult to modify breast cancer risk factors in order to better understand the potential risk-benefit ratio for targeted chemoprevention. Patients and Methods: Postmenopausal women with no history of cancer on July 1, 1992 (N = 26,580), were prospectively followed up through December 31, 2005, for breast cancer incidence (N = 1581). Risk subgroups were defined on the basis of family history of breast cancer, age at menarche, age at menopause, parity/age at first live birth, personal history of benign breast disease, and body mass index. Hazard ratios (HRs) and 95% CIs adjusted for other breast cancer risk factors were estimated using Cox models. Results: Aspirin use was associated with a lower incidence of breast cancer for women with a family history of breast cancer (HR, 0.62 for 6 or more times per week vs never use; 95% CI, 0.41-0.93) and those with a personal history of benign breast disease (HR, 0.69; 95% CI, 0.50-0.95) but not for women in higher-risk subgroups for age at menarche, age at menopause, parity/age at first live birth, or body mass index. In contrast, inverse associations with aspirin use were observed in all lower-risk subgroups. Nonsteroidal anti-inflammatory drug use had no association with breast cancer incidence. Conclusion: On the basis of their increased risk of breast cancer, postmenopausal women with a family history of breast cancer or a personal history of benign breast disease could potentially be targeted for aspirin chemoprevention studies. Future studies are needed to confirm these findings. (C) 2016 Mayo Foundation for Medical Education and Research C1 [Bardia, Aditya; Keenan, Tanya E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Ebbert, Jon O.; Limburg, Paul J.] Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA. [Wang, Alice H.; Vierkant, Robert A.; Olson, Janet E.; Vachon, Celine M.; Cerhan, James R.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Lazovich, DeAnn; Anderson, Kristin E.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Cerhan, JR (reprint author), Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA. EM cerhan.james@mayo.edu FU National Institutes of Health [R01 CA39742] FX This work was supported by grant R01 CA39742 from the National Institutes of Health. NR 61 TC 4 Z9 5 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2016 VL 91 IS 1 BP 71 EP 80 DI 10.1016/j.mayocp.2015.10.018 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DA3KX UT WOS:000367696700015 PM 26678006 ER PT J AU Ganna, A Fall, T Salihovic, S Lee, W Broeckling, CD Kumar, J Hagg, S Stenemo, M Magnusson, PKE Prenni, JE Lind, L Pawitan, Y Ingelsson, E AF Ganna, Andrea Fall, Tove Salihovic, Samira Lee, Woojoo Broeckling, Corey D. Kumar, Jitender Hagg, Sara Stenemo, Markus Magnusson, Patrik K. E. Prenni, Jessica E. Lind, Lars Pawitan, Yudi Ingelsson, Erik TI Large-scale non-targeted metabolomic profiling in three human population-based studies SO METABOLOMICS LA English DT Article DE Metabolomics; Epidemiology; Annotation; Cohort ID MASS-SPECTROMETRY; RISK; BIOMARKERS; ALIGNMENT; DESIGN AB Non-targeted metabolomic profiling is used to simultaneously assess a large part of the metabolome in a biological sample. Here, we describe both the analytical and computational methods used to analyze a large UPLC-Q-TOF MS-based metabolomic profiling effort using plasma and serum samples from participants in three Swedish population-based studies of middle-aged and older human subjects: TwinGene, ULSAM and PIVUS. At present, more than 200 metabolites have been manually annotated in more than 3600 participants using an in-house library of standards and publically available spectral databases. Data available at the metabolights repository include individual raw unprocessed data, processed data, basic demographic variables and spectra of annotated metabolites. Additional phenotypical and genetic data is available upon request to cohort steering committees. These studies represent a unique resource to explore and evaluate how metabolic variability across individuals affects human diseases. C1 [Ganna, Andrea] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Ganna, Andrea] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA. [Ganna, Andrea] Harvard Univ, Sch Med, Boston, MA USA. [Ganna, Andrea; Fall, Tove; Salihovic, Samira; Kumar, Jitender; Stenemo, Markus; Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, SE-75141 Uppsala, Sweden. [Ganna, Andrea; Pawitan, Yudi] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Lee, Woojoo] Inha Univ, Dept Stat, Inchon, South Korea. [Broeckling, Corey D.; Prenni, Jessica E.] Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA. [Prenni, Jessica E.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. [Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Ingelsson, Erik] Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA. RP Fall, T (reprint author), Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Box 1115, SE-75141 Uppsala, Sweden. EM tove.fall@medsci.uu.se RI Magnusson, Patrik/C-4458-2017; OI Prenni, Jessica/0000-0002-0337-8450 FU Knut och Alice Wallenberg Foundation; European Research Council [335395]; Swedish Diabetes Foundation [2013-024]; Swedish Heart-Lung Foundation [20120197]; Family Ernfors Fund; Swedish Government's strategic research area EXODIAB (Excellence of Diabetes Research in Sweden); Swedish Research Council [2012-1397] FX This study was supported by grants from Knut och Alice Wallenberg Foundation (Wallenberg Academy Fellow), European Research Council (ERC-2013-StG; Grant No. 335395), Swedish Diabetes Foundation (Grant No. 2013-024), Swedish Heart-Lung Foundation (Grant No. 20120197), the Family Ernfors Fund, the Swedish Government's strategic research area EXODIAB (Excellence of Diabetes Research in Sweden), and Swedish Research Council (Grant No. 2012-1397). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 1 Z9 1 U1 9 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 EI 1573-3890 J9 METABOLOMICS JI Metabolomics PD JAN PY 2016 VL 12 IS 1 DI 10.1007/s11306-015-0893-5 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ9OJ UT WOS:000367426600004 ER PT J AU Oliva, E AF Oliva, Esther TI Practical issues in uterine pathology from banal to bewildering: the remarkable spectrum of smooth muscle neoplasia SO MODERN PATHOLOGY LA English DT Article ID SEX-CORD TUMORS; ENDOMETRIAL STROMAL TUMORS; INFLAMMATORY MYOFIBROBLASTIC TUMOR; PROGESTERONE-RECEPTOR EXPRESSION; EPITHELIOID TROPHOBLASTIC TUMOR; MITOTICALLY ACTIVE LEIOMYOMAS; UNUSUAL HISTOLOGIC FEATURES; CYCLE REGULATORY MARKERS; CELL CARCINOMA SYNDROME; FEMALE GENITAL-TRACT AB Among mesenchymal tumors of the uterus, smooth muscle neoplasms are most common. The wide morphologic spectrum, especially within the category of leiomyomas, is responsible for diagnostic problems more frequently with leiomyosarcoma (including mitotically active, apoplectic, and leiomyoma with bizarre nuclei) but also with endometrial stromal tumors. In the former scenario, clinical information, gross appearance as well as strict utilization of morphologic criteria including cytologic atypia, mitotic activity, and tumor cell necrosis are clues in establishing the correct diagnosis. It is important to keep in mind that mitotic rate thresholds vary for the different subtypes of leiomyosarcoma. Of note, p16 should be used with caution in supporting a diagnosis of leiomyosarcoma as it is often positive in leiomyomas with bizarre nuclei and leiomyomas with apoplectic change (in the latter most frequently and more intense near areas of necrosis). MED12 mutations have also a very limited role in this differential diagnosis. Endometrial stromal tumors are by far, less common than smooth muscle tumors, but can be confused with leiomyosarcomas if they are associated with an undifferentiated uterine sarcoma and the low-grade component is overlooked or they have a myxoid/fibroblastic morphology. The differential diagnosis may be confounded if the latter is associated with a high-grade endometrial stromal sarcoma. It is important to highlight that CD10 is not a reliable marker in these differentials and should be used as a part of a panel of antibodies that also includes desmin and h-caldesmon. Two other recently categorized tumors in the uterus that merit special mention are PEComa and inflammatory myofibroblastic tumor as they enter in the differential diagnosis of smooth muscle tumors. PEComa may be part of the tuberous sclerosis syndrome and may show either a predominantly epithelioid or spindle morphology or combination thereof. Rarely, it may contain melanin pigment. There is variable positivity for HMB-45, MelanA, MiTF, and CathepsinK, and some tumors have been shown to express TFE-3 especially when associated with "clear cell" morphology. Patients with adverse outcome have tumors with >= 2 of the following features: >= 5 cm, infiltration, high-grade cytologic features, mitotic rate >= 1/50 high-power fields, necrosis, or lymphovascular invasion. Inflammatory myofibroblastic tumor is important to recognize as it often mimics myxoid smooth muscle tumors, either benign or malignant. The presence of an associated lymphoplasmacytic infiltrate should alert to that possibility and ALK studies (immunostain or FISH) are helpful in establishing this diagnosis. These tumors can behave in a malignant manner if large, associated with abundant myxoid change, brisk mitotic rate or show tumor cell necrosis. C1 [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM eoliva@mgh.harvard.edu NR 124 TC 2 Z9 2 U1 3 U2 4 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 JAN PY 2016 VL 29 SU 1 BP S104 EP S120 DI 10.1038/modpathol.2015.139 PG 17 WC Pathology SC Pathology GA DA0PH UT WOS:000367499100008 PM 26715170 ER PT J AU Wilbur, DC AF Wilbur, David C. TI Practical issues related to uterine pathology: in situ and invasive cervical glandular lesions and their benign mimics: emphasis on cytology-histology correlation and interpretive pitfalls SO MODERN PATHOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ENDOCERVICAL ADENOCARCINOMA; UNITED-STATES; CANCER; TRENDS; WOMEN; HPV AB In situ and invasive neoplastic glandular lesions of the uterine have cytologic correlates that must be distinguished from a variety of benign and reactive conditions. Careful study of the cytologic features allows discrimination in the majority of cases; however, the designation of 'atypical glandular cells' is reserved for equivocal cases that cannot be readily resolved. In this article, the cytologic features of endocervical adenocarcinoma in situ and invasive endocervical adenocarcinoma will be presented, highlighting their correlation to the well-known histologic features. Variants of the usual type of endocervical neoplasms that have important clinical and differential diagnostic features, including mucinous adenocarcinoma and clear-cell carcinoma, will be discussed. There are a number of common cytologic mimics of endocervical neoplasms, including tubal metaplasia, directly sampled (abraded) endometrium, and high-grade squamous intraepithelial lesion involving endocervical glands. The cytologic features of these entities and their differentiation from endocervical neoplasia will be explored. Finally, the role of ancillary studies such as human papillomavirus testing in the management of glandular lesions of the cervix will be integrated into the discussion. C1 [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Lab Pathol,Dept Pathol, Boston, MA 02114 USA. RP Wilbur, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Lab Pathol,Dept Pathol, 55 Fruit St,Warren 120, Boston, MA 02114 USA. EM dwilbur@mgh.harvard.edu NR 26 TC 1 Z9 1 U1 0 U2 0 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 JAN PY 2016 VL 29 SU 1 BP S1 EP S11 DI 10.1038/modpathol.2015.138 PG 11 WC Pathology SC Pathology GA DA0PH UT WOS:000367499100001 PM 26715169 ER PT J AU Winkler, EA Yue, JK McAllister, TW Temkin, NR Oh, SS Burchard, EG Hu, DL Ferguson, AR Lingsma, HF Burke, JF Sorani, MD Rosand, J Yuh, EL Barber, J Tarapore, PE Gardner, RC Sharma, S Satris, GG Eng, C Puccio, AM Wang, KKW Mukherjee, P Valadka, AB Okonkwo, DO Diaz-Arrastia, R Manley, GT AF Winkler, Ethan A. Yue, John K. McAllister, Thomas W. Temkin, Nancy R. Oh, Sam S. Burchard, Esteban G. Hu, Donglei Ferguson, Adam R. Lingsma, Hester F. Burke, John F. Sorani, Marco D. Rosand, Jonathan Yuh, Esther L. Barber, Jason Tarapore, Phiroz E. Gardner, Raquel C. Sharma, Sourabh Satris, Gabriela G. Eng, Celeste Puccio, Ava M. Wang, Kevin K. W. Mukherjee, Pratik Valadka, Alex B. Okonkwo, David O. Diaz-Arrastia, Ramon Manley, Geoffrey T. CA TRACK-TBI Investigators TI COMT Val (158) Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury SO NEUROGENETICS LA English DT Article DE Traumatic brain injury; Genetic factors; Cognitive function; Outcome measures; Human studies ID COMMON DATA ELEMENTS; CATECHOL-O-METHYLTRANSFERASE; VERBAL-LEARNING TEST; WORKING-MEMORY; GENE POLYMORPHISMS; PREFRONTAL CORTEX; PERFORMANCE; GENOTYPE; RECOMMENDATIONS; RESILIENCE AB Mild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed, and its role in mTBI has not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val (158) Met polymorphism influences outcome on a cognitive battery 6 months following mTBI-Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1-5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13-15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of a parts per thousand yen3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met (158) /Met (158) 29 %, Met (158) /Val (158) 47 %, Val (158) /Val (158) 24 %) show that the COMT Met (158) allele (mean 101.6 +/- SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val (158) /Val (158) homozygotes (93.8 +/- SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p = 0.017). The COMT Val (158) Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val (158) Met may preferentially modulate nonverbal cognition following uncomplicated mTBI. Registry: ClinicalTrials.gov Identifier NCT01565551. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94110 USA. [Winkler, Ethan A.; Yue, John K.; Ferguson, Adam R.; Burke, John F.; Sorani, Marco D.; Yuh, Esther L.; Tarapore, Phiroz E.; Sharma, Sourabh; Satris, Gabriela G.; Mukherjee, Pratik; Manley, Geoffrey T.] San Francisco Gen Hosp, Brain & Spinal Injury Ctr, San Francisco, CA 94110 USA. [McAllister, Thomas W.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Temkin, Nancy R.; Barber, Jason] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Temkin, Nancy R.; Barber, Jason; Eng, Celeste] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Oh, Sam S.; Burchard, Esteban G.; Hu, Donglei; Eng, Celeste] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94110 USA. [Lingsma, Hester F.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Rosand, Jonathan; Gardner, Raquel C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Rosand, Jonathan] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Yuh, Esther L.; Mukherjee, Pratik] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94110 USA. [Gardner, Raquel C.] San Francisco Vet Adm Med Ctr, Dept Neurol, San Francisco, CA USA. [Puccio, Ava M.; Okonkwo, David O.] Univ Pittsburgh, Med Ctr, Dept Neurol Surg, Pittsburgh, PA USA. [Wang, Kevin K. W.] Univ Florida, Dept Psychiat, Ctr Neuroprote & Biomarkers Res, Gainesville, FL 32611 USA. [Wang, Kevin K. W.] Univ Florida, Dept Neurosci, Ctr Neuroprote & Biomarkers Res, Gainesville, FL 32610 USA. [Valadka, Alex B.] Seton Brain & Spine Inst, Austin, TX USA. [Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. [Diaz-Arrastia, Ramon] Ctr Neurosci & Regenerat Med, Bethesda, MD USA. RP Manley, GT (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 1001 Potrero Ave,Bldg 1,Room 101, San Francisco, CA 94110 USA. EM manleyg@neurosurg.ucsf.edu RI Yue, John/P-1348-2015 OI Yue, John/0000-0001-9694-7722 FU NIH [RC2 NS069409, RC2 NS069409-02S1, U01 NS086090-01]; DOD [USAMRAAW81XWH-13-1-0441, W81XWH-14-2-0176] FX This work was supported by the following grants: NIH RC2 NS069409, NIH RC2 NS069409-02S1, NIH U01 NS086090-01, DOD USAMRAAW81XWH-13-1-0441, DOD W81XWH-14-2-0176 NR 68 TC 2 Z9 3 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1364-6745 EI 1364-6753 J9 NEUROGENETICS JI Neurogenetics PD JAN PY 2016 VL 17 IS 1 BP 31 EP 41 DI 10.1007/s10048-015-0467-8 PG 11 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA DA3KJ UT WOS:000367695300005 PM 26576546 ER PT J AU Kozin, ED Sethi, RK Herr, M Shrime, MG Rocco, JW Lin, D Deschler, DG Emerick, KS AF Kozin, Elliott D. Sethi, Rosh K. Herr, Marc Shrime, Mark G. Rocco, James W. Lin, Derrick Deschler, Daniel G. Emerick, Kevin S. TI Comparison of Perioperative Outcomes between the Supraclavicular Artery Island Flap and Fasciocutaneous Free Flap SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE supraclavicular artery island flap; head and neck reconstruction; total laryngectomy; outcomes ID ORGAN PRESERVATION THERAPY; ADVANCED LARYNGEAL-CANCER; NECK RECONSTRUCTION; HEAD; COMPLICATIONS; CHEMOTHERAPY; RADIOTHERAPY; LIMITATIONS; RADIATION; SURGERY AB Objective Outcomes of the supraclavicular artery island flap (SCAIF) have not been extensively studied in comparison with free tissue transfer (FTT) flaps for head and neck reconstruction. We hypothesize that the pedicled SCAIF has decreased operating room time, length of stay, time to wound healing of recipient site, complications, and hospital charges as compared with FTT. Study Design Case series with chart review. Setting Tertiary care teaching hospital. Subjects and Methods Medical records were reviewed for patients who underwent SCAIF (n = 45) or FTT (n = 28) reconstruction between 2011 and 2013. Results Total operating room time was significantly lower for the SCAIF group vs the FTT group (6.7 vs 8.1 hours, P = .002). Procedural time was 5.7 hours for the SCAIF group, as compared with 7.2 hours for FTT group (P = .0015). Mean area for SCAIF donor site was 63.89 cm(2) vs 81.8 cm(2) for the radial forearm free flap group (P = .015). There was no significant difference in mean length of stay between SCAIF (8.8 days) and FTT (11 days, P = .12). Mean length of time to wound healing of the recipient site was similar in the SCAIF group vs the FTT group (17.3 vs 22.1 days, P = .071). Ratio of total hospital charges for SCAIF were 32% lower than that of FTT (P = .0001). Conclusion This is among the first studies to compare SCAIF with FTT in a large cohort analysis. We find decreased operating room times for SCAIF vs FTT, with similar length of stay and wound healing. Other outcomes between SCAIF and FTT were also comparable. C1 [Kozin, Elliott D.; Sethi, Rosh K.; Herr, Marc; Shrime, Mark G.; Lin, Derrick; Deschler, Daniel G.; Emerick, Kevin S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kozin, Elliott D.; Sethi, Rosh K.; Herr, Marc; Shrime, Mark G.; Lin, Derrick; Deschler, Daniel G.; Emerick, Kevin S.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. [Rocco, James W.] Ohio State Univ, Wexner Med Ctr, Dept Otolaryngol Head & Neck Surg, Columbus, OH 43210 USA. RP Kozin, ED (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Elliott_Kozin@meei.harvard.edu NR 28 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2016 VL 154 IS 1 BP 66 EP 72 DI 10.1177/0194599815607345 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DA4BS UT WOS:000367745700011 PM 26467355 ER PT J AU Shenoy-Bhangle, AS Nimkin, K Aranson, T Gee, MS AF Shenoy-Bhangle, Anuradha S. Nimkin, Katherine Aranson, Thomas Gee, Michael S. TI Value of diffusion-weighted imaging when added to magnetic resonance enterographic evaluation of Crohn disease in children SO PEDIATRIC RADIOLOGY LA English DT Article DE Children; Crohn disease; Diffusion-weighted imaging; Histology; Magnetic resonance enterography ID INFLAMMATORY-BOWEL-DISEASE; MR ENTEROGRAPHY; WALL; MANIFESTATIONS; FEASIBILITY; MODALITY; ABDOMEN; PELVIS; RISK; CT AB MR enterography is increasingly utilized for noninvasive evaluation of disease activity in young patients with Crohn disease and has great impact on clinical management. Diffusion-weighted imaging (DWI) is a rapid MR imaging technique that measures molecular diffusion of water and is sensitive to the inflammatory process; however, its value to MR enterography has not been rigorously evaluated. To determine whether the addition of DWI to MR enterography is helpful in evaluating Crohn disease activity in young patients when compared to a histological reference. In this single-institution retrospective study, we searched an imaging database for the period January 2010 to December 2012 to identify patients age 19 years and younger who had MR enterography with diffusion-weighted imaging (DWI). We used an electronic medical record search to identify those who had MR enterography and colonoscopy performed within 28 days of each other. All MR enterography scans were performed on a 1.5-T or 3-T clinical MR scanner with phased-array torso coil configuration using standard pulse sequences as well as axial DWI with b values of 50, 400 and 800. Bowel segments were evaluated for disease activity based on standard MR enterography sequences; in addition, segmental apparent diffusion coefficient (ADC) values were calculated based on DWI. Histological reference for disease activity was based on assessment for mucosal inflammatory changes on endoscopic biopsy. MR enterography and DWI evaluation were performed in a blinded fashion with respect to histological results. We included imaging of 78 bowel segments from 27 patients (mean age 14.5 +/- 3.02 years) with known Crohn disease in the study. The mean ADC for bowel segments with active disease was 1.56 +/- 0.7 x 10(3) mm(2)/s compared with 2.58 +/- 1.4 x 10(3) mm(2)/s for segments without active disease, a difference that was statistically significant (P < 0.01, Student's t-test). Using a threshold value of 2.0 x 10(3) mm(2)/s, DWI demonstrated lower accuracy (64.1%) but higher sensitivity (78.8%) for detecting active disease compared with standard MR enterography (69.2% and 54.6%, respectively). Combining DWI with MR enterography, using DWI as the initial screen and MR enterography afterward to reduce false negativity, led to a significant increase in accuracy (76.9%; P = 0.03, McNemar's test) compared with either imaging technique alone. Although DWI does not perform as well as standard MR enterography for detection of active Crohn disease, the combination of DWI and MR enterography increases imaging accuracy for determining disease activity compared with either technique alone. These results indicate that DWI adds value to MR enterography and supports the incorporation of DWI into MR enterography protocols for evaluation of Crohn disease in young patients. C1 [Shenoy-Bhangle, Anuradha S.] Beth Israel Deaconess Med Ctr, Shapiro Clin Ctr, Div Abdominal Imaging Community Radiol, Boston, MA 02215 USA. [Nimkin, Katherine; Gee, Michael S.] Massachusetts Gen Hosp Children, Dept Radiol, Div Pediat Imaging, Boston, MA USA. [Aranson, Thomas] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Gee, Michael S.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA 02114 USA. RP Shenoy-Bhangle, AS (reprint author), Beth Israel Deaconess Med Ctr, Shapiro Clin Ctr, Div Abdominal Imaging Community Radiol, 330 Brookline Ave,4th Floor, Boston, MA 02215 USA. EM abhangle@bidmc.harvard.edu NR 30 TC 8 Z9 8 U1 1 U2 1 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 JAN PY 2016 VL 46 IS 1 BP 34 EP 42 DI 10.1007/s00247-015-3438-1 PG 9 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA DA4XN UT WOS:000367806200005 PM 26238966 ER PT J AU Bouchard, LC Antoni, MH Blomberg, BB Stagl, JM Gudenkauf, LM Jutagir, DR Diaz, A Lechner, S Gluck, S Derhagopian, RP Carver, CS AF Bouchard, Laura C. Antoni, Michael H. Blomberg, Bonnie B. Stagl, Jamie M. Gudenkauf, Lisa M. Jutagir, Devika R. Diaz, Alain Lechner, Suzanne Glueck, Stefan Derhagopian, Robert P. Carver, Charles S. TI Postsurgical Depressive Symptoms and Proinflammatory Cytokine Elevations in Women Undergoing Primary Treatment for Breast Cancer SO PSYCHOSOMATIC MEDICINE LA English DT Article DE breast cancer; depression; proinflammatory cytokines ID C-REACTIVE PROTEIN; QUALITY-OF-LIFE; RATING-SCALE; STRESS; INFLAMMATION; DISORDER; FATIGUE; METAANALYSIS; PROGRESSION; REMISSION AB Objective Depression and inflammation may independently promote breast cancer (BCa) disease progression and poorer clinical outcomes. Depression has been associated with increased levels of inflammatory markers in medically healthy individuals and patients with cancer. However, inconsistencies in study time frames complicate interpretation of results within specific cancer types. This study examined relationships between depressive symptoms and inflammation in women with early-stage BCa before beginning adjuvant treatment. Methods Women with Stage 0-III BCa were recruited approximately 4 to 8 weeks after surgery. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression, and blood samples were collected to quantify circulating levels of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF-) by enzyme-linked immunosorbent assay. Analyses of covariance were used to test for group differences (elevated versus low depressive symptoms) in levels of cytokines. Multiple regression analyses were used to examine relationships between continuous severity of depressive symptoms and levels of cytokines adjusting for relevant biobehavioral covariates. Results Thirty-six (40%) of 89 patients showed elevated levels of depressive symptoms and, in adjusted models, had marginally higher levels of IL-1 (mean [M] = 14.49 [95% confidence interval {CI} = 6.11-32.65] versus M = 4.68 [95% CI = 1.96-9.86] and IL-6 [M = 88.74 {95% CI = 33.28-233.96} versus M = 61.52 {95% CI = 27.44-136.40}]) significantly higher levels of TNF- (M = 17.07 [95% CI = 8.27-34.32] versus M = 6.94 [95% CI = 3.58-12.80]) than did women with low depressive symptoms. Across the spectrum of depressive symptoms, greater magnitude of depressive symptoms was related to greater levels of IL-1 ( = 0.06, p = .006, R-2 = 0.25) and TNF- ( = 0.06, p = .003, R-2 = 0.27). Conclusions Postsurgery and preadjuvant treatment for early-stage BCa, depressive symptoms covary with elevated levels of multiple proinflammatory cytokines. Findings have implications for psychosocial and biological interventions concurrently focusing on depression and inflammation. Trial Registration: NCT01422551. C1 [Bouchard, Laura C.; Antoni, Michael H.; Gudenkauf, Lisa M.; Jutagir, Devika R.; Carver, Charles S.] Univ Miami, Dept Psychol, Miami, FL USA. [Antoni, Michael H.; Lechner, Suzanne] Univ Miami, Miller Sch Med, Dept Psychiat Behav Sci, Miami, FL 33136 USA. [Blomberg, Bonnie B.; Diaz, Alain] Univ Miami, Miller Sch Med, Dept Microbiol Immunol, Miami, FL 33136 USA. [Antoni, Michael H.; Blomberg, Bonnie B.; Diaz, Alain; Lechner, Suzanne; Carver, Charles S.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Stagl, Jamie M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Glueck, Stefan] Celgene Corp, Global Med Affairs, Summit, NJ USA. [Derhagopian, Robert P.] Baptist Hlth Breast Ctr, Miami, FL USA. RP Bouchard, LC (reprint author), Univ Miami, Dept Psychol, 5665 Ponce De Leon Blvd, Coral Gables, FL 33146 USA. EM l.bouchard@umail.miami.edu OI Jacobs, Jamie M./0000-0001-9740-624X; carver, charles/0000-0002-3688-8545 FU National Cancer Institute of the National Institutes of Health [5R01 CA64710] FX Michael H. Antoni, the principal investigator of this study, as well as Bonnie B. Blomberg, Alain Diaz, Suzanne Lechner, Stefan Gluck, and Charles S. Carver received funding for this study through the National Cancer Institute of the National Institutes of Health (5R01 CA64710). The authors report no conflicts of interest. NR 46 TC 3 Z9 3 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2016 VL 78 IS 1 BP 26 EP 37 DI 10.1097/PSY.0000000000000261 PG 12 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DA5DT UT WOS:000367823400004 PM 26569533 ER PT J AU Auvergne, L Bortsov, AV Ulirsch, JC Peak, DA Jones, JS Swor, RA Domeier, RM Lee, DC Rathlev, NK Hendry, PL McLean, SA AF Auvergne, Lauriane Bortsov, Andrey V. Ulirsch, Jacob C. Peak, David A. Jones, Jeffrey S. Swor, Robert A. Domeier, Robert M. Lee, David C. Rathlev, Niels K. Hendry, Phyllis L. McLean, Samuel A. TI Association of Epidemiologic Factors and Genetic Variants Influencing Hypothalamic-Pituitary-Adrenocortical Axis Function With Postconcussive Symptoms After Minor Motor Vehicle Collision SO PSYCHOSOMATIC MEDICINE LA English DT Article DE postconcussive symptoms; minor traumatic brain injury; FKBP5; stress response ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; PERITRAUMATIC DISTRESS INVENTORY; CONCUSSION SYMPTOMS; FKBP5 POLYMORPHISMS; UNITED-STATES; CHRONIC PAIN; HEAD-INJURY; DEPRESSION; ANXIETY AB Objectives To determine the influence of epidemiologic factors and the influence of genetic variants affecting FKBP5, a protein known to modulate hypothalamic-pituitary-adrenocortical axis function, on the severity of somatic symptoms commonly termed postconcussive 6 and 12 months after motor vehicle collision (MVC). Methods European Americans 18 to 65 years of age who presented to one of eight emergency departments (EDs) after MVC were enrolled. Exclusion criteria included hospital admission. Blood samples were collected in the ED for genotyping. Participants completed evaluations including an adapted Rivermead Post-Concussive Symptoms Questionnaire in the ED and at 6 weeks, 6 months, and 1 year. Repeated-measures analysis of covariance was used to evaluate the association between epidemiologic factors (sociodemographic, pre-MVC health, collision characteristics, head injury, peritraumatic pain, and stress), FKBP5 genetic variants, and postconcussive symptom severity. Results Among 943 patients recruited in the ED, follow-up was completed on 835 (88%) at 6 months and 857 (90%) at 1 year. Self-reported head impact during collision was not associated with chronic postconcussive symptom severity. After correction for multiple testing, three FKBP5 single-nucleotide polymorphisms (rs3800373, rs7753746, and rs9380526) predicted chronic postconcussive symptom severity, with an average symptom severity of 1.10 (95% confidence interval = 0.96-1.24), 1.36 (1.21-1.51), and 1.55 (1.23-1.88) for one, two, or three copies of minor allele at rs3800373 (p = .001). Similar effect sizes were observed for the minor alleles of rs7753746 and rs9380526. Conclusions Postconcussive symptoms after minor MVC are not generally related to the severity of mild brain injury. This study shows that neurobiologic stress systems may play a role in the pathogenesis of postconcussive symptoms. C1 [Auvergne, Lauriane; Bortsov, Andrey V.; Ulirsch, Jacob C.; McLean, Samuel A.] Univ N Carolina, Sch Med, Dept Anesthesiol, Chapel Hill, NC 27599 USA. [McLean, Samuel A.] Univ N Carolina, Sch Med, Dept Emergency Med, Chapel Hill, NC 27599 USA. [Bortsov, Andrey V.; Ulirsch, Jacob C.; McLean, Samuel A.] TRYUMPH Res Program, Chapel Hill, NC USA. [Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jones, Jeffrey S.] Spectrum Hlth Hosp Butterworth, Dept Emergency Med, Grand Rapids, MI USA. [Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. [Domeier, Robert M.] St Joseph Mercy Hosp, Dept Emergency Med, Ann Arbor, MI 48104 USA. [Lee, David C.] North Shore Univ, Dept Emergency Med, Manhasset, NY USA. [Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Hendry, Phyllis L.] Univ Florida, Hlth Sci Ctr, Dept Emergency Med, Jacksonville, FL 32209 USA. RP McLean, SA (reprint author), Univ N Carolina, Sch Med, Wing C CB 7010, Chapel Hill, NC 27599 USA. EM smclean@aims.unc.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health [1RO1 AR056328]; University of North Carolina School of Medicine FX Dr. McLean received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, under Award Number 1RO1 AR056328. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Auvergne received funding through the Scott Neil Schwirck Research Fellowship at the University of North Carolina School of Medicine. Dr. McLean had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. No conflicts of interest exist for any of the authors. NR 64 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2016 VL 78 IS 1 BP 68 EP 78 DI 10.1097/PSY.0000000000000253 PG 11 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DA5DT UT WOS:000367823400008 PM 26588823 ER PT J AU Van Eylen, L Boets, B Steyaert, J Evers, K Wagemans, J Noens, U AF Van Eylen, Lien Boets, Bart Steyaert, Jean Evers, Kris Wagemans, Johan Noens, Ilse TI Cognitive flexibility in autism spectrum disorder: Explaining the inconsistencies? (vol 5, pg 1390, 2011) SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Correction C1 [Van Eylen, Lien; Noens, Ilse] Katholieke Univ Leuven KU Leuven, Parenting & Special Educ Res Grp, Leuven, Belgium. [Van Eylen, Lien; Boets, Bart; Steyaert, Jean; Evers, Kris] UPC KU Leuven, Dept Child Psychiat, Leuven, Belgium. [Van Eylen, Lien; Evers, Kris; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, Leuven, Belgium. [Van Eylen, Lien; Boets, Bart; Steyaert, Jean; Evers, Kris; Wagemans, Johan; Noens, Ilse] Katholieke Univ Leuven, Leuven Autism Res LAuRes, Leuven, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. RP Van Eylen, L (reprint author), Katholieke Univ Leuven KU Leuven, Parenting & Special Educ Res Grp, Leuven, Belgium. EM Lien.VanEylen@ped.kuleuven.be NR 1 TC 0 Z9 0 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-4222 J9 RES DEV DISABIL JI Res. Dev. Disabil. PD JAN PY 2016 VL 48 BP R1 EP R1 DI 10.1016/j.ridd.2015.12.008 PG 1 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA DA4JL UT WOS:000367766100009 ER PT J AU Greenwood, TA Lazzeroni, LC Calkins, ME Freedman, R Green, MF Gur, RE Gur, RC Light, GA Nuechterlein, KH Olincy, A Radant, AD Seidman, LJ Siever, LJ Silverman, JM Stone, WS Sugar, CA Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL AF Greenwood, Tiffany A. Lazzeroni, Laura C. Calkins, Monica E. Freedman, Robert Green, Michael F. Gur, Raquel E. Gur, Ruben C. Light, Gregory A. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Sugar, Catherine A. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. TI Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Endophenotype; Genetics; Schizophrenia; Association; Linkage; Heritability ID GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; TRAIT LINKAGE ANALYSIS; BIPOLAR-DISORDER; DOPAMINE TRANSPORTER; SUSTAINED ATTENTION; CANDIDATE GENES; SCHIZOAFFECTIVE DISORDER; INTELLECTUAL DISABILITY; 1ST-DEGREE RELATIVES AB The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation. (C) 2015 Elsevier B. V. All rights reserved. C1 [Greenwood, Tiffany A.; Light, Gregory A.; Swerdlow, Neal R.; Tsuang, Ming T.; Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Light, Gregory A.; Braff, David L.] VA San Diego Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, San Diego, CA 92161 USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Greenwood, TA (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0689, La Jolla, CA 92093 USA. EM tgreenwood@ucsd.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Greenwood, Tiffany/0000-0002-6080-6503 FU National Institute of Mental Health [R01-MH065571, R01-MH065588, R01-MH065562, R01-MH065707, R01-MH065554, R01-MH065578, R01-MH065558, R01 MH86135, K01-MH087889]; National Institutes of Health [HHSN268200782096C] FX The authors wish to thank all of the participants and support staff that made this study possible. This study was supported by grants R01-MH065571, R01-MH065588, R01-MH065562, R01-MH065707, R01-MH065554, R01-MH065578, R01-MH065558, R01 MH86135, and K01-MH087889 (TAG) from the National Institute of Mental Health. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract Number HHSN268200782096C. COGS website: http://www.npistat.com/cogs/. NR 100 TC 6 Z9 6 U1 2 U2 12 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 JAN PY 2016 VL 170 IS 1 BP 30 EP 40 DI 10.1016/j.schres.2015.11.008 PG 11 WC Psychiatry SC Psychiatry GA DA1DC UT WOS:000367535500003 PM 26597662 ER PT J AU Lizano, PL Keshavan, MS Tandon, N Mathew, IT Mothi, SS Montrose, DM Yao, JK AF Lizano, Paulo L. Keshavan, Matcheri S. Tandon, Neeraj Mathew, Ian T. Mothi, Suraj Sarvode Montrose, Debra M. Yao, Jeffrey K. TI Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE High risk; First episode psychosis; Soluble fms-like tyrosine kinase; Angiogenesis; Inflammation/immune ID ENDOTHELIAL GROWTH-FACTOR; 1ST EPISODE PSYCHOSIS; CYTOKINE ALTERATIONS; INTERFERON-GAMMA; SCHIZOPHRENIA; VEGF; SYMPTOMS; RECEPTOR; FLT-1; SFLT1 AB Schizophrenia (SZ) is a heterogeneous disorder that presents in adolescence, persists into adulthood, and has many clinical features. Recent evidence suggests that abnormalities in inflammatory, neurotrophic, and angiogenic processes may play a role in the etiology of SZ. The identification of molecular biomarkers early in the course of disease is crucial to transforming diagnostic and therapeutic avenues. We investigated 14 molecular analytes focusing on inflammatory, neurotrophic and angiogenic pathways from the plasma of antipsychotic-naive familial high risk for SZ (FHR; n = 35) and first-episode psychosis (FEP; n = 45) subjects, in comparison to healthy controls (HC, n = 39). We identified distinct alterations in molecular signatures in young relatives at FHR for SZ prior to psychosis onset and FEP subjects. Firstly, the expression of soluble fms-like tyrosine kinase (sFlt-1), an anti-angiogenic factor that binds vascular endothelial growth factor (VEGF), was significantly increased in the FHR group compared to HC, but not in FEP. Secondly, interferon gamma (IFN gamma) was significantly reduced in the FEP group compared to HC. Thirdly, network analysis revealed a positive correlation between sFlt-1 and VEGF, suggesting an activation of the angiogenic cascade in the FHR group, which persists in FEP. Our results indicate an angiogenesis and immunological dysfunction early in the course of disease, shifting the balance towards anti-angiogenesis and inflammation. Published by Elsevier B.V. C1 [Lizano, Paulo L.; Keshavan, Matcheri S.; Tandon, Neeraj; Mathew, Ian T.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Lizano, Paulo L.; Keshavan, Matcheri S.; Mothi, Suraj Sarvode] Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02115 USA. [Keshavan, Matcheri S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Keshavan, Matcheri S.; Montrose, Debra M.; Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Tandon, Neeraj] Baylor Coll Med, Houston, TX 77030 USA. [Yao, Jeffrey K.] Med Res Serv, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. RP Yao, JK (reprint author), VA Pittsburg Healthcare Syst, B-1-2E-140,Univ Dr C, Pittsburgh, PA 15240 USA. EM jkyao@pitt.edu FU Department of Veterans Affairs; VA Pittsburgh Healthcare System; National Institute of Health [MH58141, MH64023, KO2 MH 01180, MH45156, c UL1 RR024153]; National Institute of Health, NIH/NCRR/GCRC [M01 RR00056]; Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst, The Harvard Clinical