FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rider, JR Fiorentino, M Kelly, R Gerke, T Jordahl, K Sinnott, JA Giovannucci, EL Loda, M Mucci, LA Finn, S AF Rider, Jennifer R. Fiorentino, Michelangelo Kelly, Rachel Gerke, Travis Jordahl, Kristina Sinnott, Jennifer A. Giovannucci, Edward L. Loda, Massimo Mucci, Lorelei A. Finn, Stephen CA Transdisciplinary Prostate Canc Pa TI Tumor expression of adiponectin receptor 2 and lethal prostate cancer SO CARCINOGENESIS LA English DT Article ID ACTIVATED PROTEIN-KINASE; INSULIN SENSITIVITY; SERUM ADIPONECTIN; BREAST-CANCER; CARDIOVASCULAR-DISEASE; AFRICAN-AMERICANS; PHYSICIANS HEALTH; COLORECTAL-CANCER; ENDOTHELIAL-CELLS; TISSUE EXPRESSION AB To investigate the role of adiponectin receptor 2 (AdipoR2) in aggressive prostate cancer we used immunohistochemistry to characterize AdipoR2 protein expression in tumor tissue for 866 men with prostate cancer from the Physicians' Health Study and the Health Professionals Follow-up Study. AdipoR2 tumor expression was not associated with measures of obesity, pathological tumor stage or prostate-specific antigen (PSA) at diagnosis. However, AdipoR2 expression was positively associated with proliferation as measured by Ki-67 expression quartiles (P-trend < 0.0001), with expression of fatty acid synthase (P-trend = 0.001), and with two measures of angiogenesis (P-trend < 0.1). An inverse association was observed with apoptosis as assessed by the TUNEL assay (P-trend = 0.006). Using Cox proportional hazards regression and controlling for age at diagnosis, Gleason score, year of diagnosis category, cohort and baseline BMI, we identified a statistically significant trend for the association between quartile of AdipoR2 expression and lethal prostate cancer (P-trend = 0.02). The hazard ratio for lethal prostate cancer for the two highest quartiles, as compared to the two lowest quartiles, of AdipoR2 expression was 1.9 (95% confidence interval [CI]: 1.2-3.0). Results were similar when additionally controlling for categories of PSA at diagnosis and Ki-67 expression quartiles. These results strengthen the evidence for the role of AdipoR2 in prostate cancer progression. C1 [Rider, Jennifer R.; Giovannucci, Edward L.; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Rider, Jennifer R.; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fiorentino, Michelangelo] S Orsola Malphighi Hosp, Addarii Inst Oncol, Pathol Unit, I-40126 Bologna, Italy. Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Finn, Stephen] Univ Dublin Trinity Coll, Dept Pathol, Dublin 8, Ireland. RP Rider, JR (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. EM rider@hsph.harvard.edu OI Rider, Jennifer/0000-0002-2637-6036; Finn, Stephen/0000-0002-8628-5814 FU Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence program in Prostate Cancer [5P50CA090381-08]; National Cancer Institute [T32 CA009001, CA55075, CA141298, CA13389, CA-34944, CA-40360, CA-097193, PO1 CA055075]; National Heart, Lung, and Blood Institute [HL-26490, HL-34595] FX Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence program in Prostate Cancer (5P50CA090381-08); the National Cancer Institute (T32 CA009001, CA55075, CA141298, CA13389, CA-34944, CA-40360, CA-097193 and PO1 CA055075); the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595). J.R.R., L.A.M. and S.F. are Prostate Cancer Foundation Young Investigators. NR 50 TC 3 Z9 3 U1 1 U2 3 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 JUN PY 2015 VL 36 IS 6 BP 639 EP 647 DI 10.1093/carcin/bgv048 PG 9 WC Oncology SC Oncology GA CK4GK UT WOS:000356181700005 PM 25863129 ER PT J AU Ni, J Auriel, E Jindal, J Ayres, A Schwab, KM Martinez-Ramirez, S Gurol, EM Greenberg, SM Viswanathan, A AF Ni, Jun Auriel, Eitan Jindal, Jenelle Ayres, Alison Schwab, Kristin M. Martinez-Ramirez, Sergi Gurol, Edip M. Greenberg, Steven M. Viswanathan, Anand TI The Characteristics of Superficial Siderosis and Convexity Subarachnoid Hemorrhage and Clinical Relevance in Suspected Cerebral Amyloid Angiopathy SO CEREBROVASCULAR DISEASES LA English DT Article DE Superficial siderosis; Convexity subarachnoid hemorrhage; Cerebral amyloid angiopathy; Transient focal neurological episode; Intracerebral hemorrhage ID RECURRENT INTRACEREBRAL HEMORRHAGE; LOBAR HEMORRHAGE; SPECTRUM; PREVALENCE; MECHANISMS; COHORT; RISK AB Background and Aims: Systematic studies of superficial siderosis (SS) and convexity subarachnoid hemorrhage (cSAH) in patients with suspected cerebral amyloid angiopathy (CAA) without lobar intracerebral hemorrhage (ICH) are lacking. We sought to determine the potential anatomic correlation between SS/cSAH and transient focal neurological episodes (TFNE) and whether SS/cSAH is predictor of future cerebral hemorrhagic events in these patients. Methods: We enrolled 90 consecutive patients with suspected CAA (due to the presence of strictly lobar microbleeds (CMBs) and/or SS/cSAH) but without the history of symptomatic lobar ICH who underwent brain MRI including T2*-weighted, diffusion-weighted imaging and fluid-attenuated inversion recovery sequences from an ongoing single center CAA cohort from 1998 to 2012. Evaluation of SS, cSAH and CMBs was performed. Medical records and follow-up information were obtained from prospective databases and medical charts. TFNE was defined according to published criteria and electroencephalogram reports were reviewed. Results: Forty-one patients (46%) presented with SS and/or cSAH. The prevalence of TFNE was significantly higher in those with SS/cSAH (61 vs. 10%; p < 0.001) and anatomically correlated with the location of cSAH, but not SS. The majority of TFNE in patients with SS/cSAH presented with spreading sensory symptoms. Intermittent focal slowing on electroencephalogram was present in the same area as SS/cSAH in 6 patients, but no epileptiform activity was found in any patients. Among those with available clinical follow-up (76/90 patients, 84%), ten patients with SS/cSAH (29%, median time from the scan for all patients with SS/cSAH: 21 months) had a symptomatic cerebral bleeding event on follow up (average time to events: 34 months) compared with only 1 event (2.4%, 25 months from the scan) in patients without SS/cSAH (time to event: 25 months) (p = 0.001). The location of hemorrhages on follow-up scan was not in the same location of previously noted SS/cSAH in 9 of 10 patients. Follow-up imaging was obtained in 9 of 17 patients with cSAH and showed evidence of SS in the same location as initial cSAH in all these 9 cases. Conclusions: SS/cSAH is common in patients with suspected CAA without lobar intracerebral hemorrhage and may have a significantly higher risk of future cerebral bleeding events, regardless of the severity of the baseline CMB burden. The findings further highlight a precise anatomical correlation between TFNE and cSAH, but not SS. Distinct from transient ischemic attack or seizure, the majority of TFNE caused by SS/cSAH appear to present with spreading sensory symptoms. (c) 2015 S. Karger AG, Basel C1 [Ni, Jun] Beijing Union Med Coll Hosp, Dept Neurol, Beijing, Peoples R China. [Ni, Jun; Auriel, Eitan; Jindal, Jenelle; Ayres, Alison; Schwab, Kristin M.; Martinez-Ramirez, Sergi; Gurol, Edip M.; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Ni, Jun; Auriel, Eitan; Jindal, Jenelle; Ayres, Alison; Schwab, Kristin M.; Martinez-Ramirez, Sergi; Gurol, Edip M.; Greenberg, Steven M.; Viswanathan, Anand] Harvard Univ, Sch Med, Boston, MA USA. RP Viswanathan, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM aviswanathan1@partners.org RI Gurol, Edip/J-2279-2014 OI Gurol, Edip/0000-0002-2169-4457 FU NIA NIH HHS [K23 AG028726, 2R01 AG26484, 5K23AG028726-05, 5R01AG026484-10, K23AG028726-05, P50 AG005134, P50AG005134-30, R01 AG026484, R01 AG047975]; NINDS NIH HHS [K23 NS083711] NR 23 TC 8 Z9 8 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PD JUN PY 2015 VL 39 IS 5-6 BP 278 EP 286 DI 10.1159/000381223 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CK1CK UT WOS:000355942800004 PM 25871492 ER PT J AU Bansal, N Shlipak, MG AF Bansal, Nisha Shlipak, Michael G. TI Should Hemoglobin A1C Be Routinely Measured in Patients with CKD? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR RISK; GLYCEMIC CONTROL; AVERAGE GLUCOSE; ASSOCIATION; OUTCOMES; ADULTS; MODEL C1 [Bansal, Nisha] Univ Washington, Kidney Res Inst, Div Nephrol, Seattle, WA 98195 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, Med, 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM Michael.Shlipak@ucsf.edu NR 12 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2015 VL 10 IS 6 BP 914 EP 916 DI 10.2215/CJN.04200415 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA CJ8XV UT WOS:000355787700002 PM 25979974 ER PT J AU Murugan, R Wen, XY Keener, C Pike, F Palevsky, PM Unruh, M Finkel, K Vijayan, A Elder, M Chen, YF Kellum, JA AF Murugan, Raghavan Wen, Xiaoyan Keener, Christopher Pike, Francis Palevsky, Paul M. Unruh, Mark Finkel, Kevin Vijayan, Anitha Elder, Michele Chen, Yi-Fan Kellum, John A. CA Biol Markers Recovery Kidney TI Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RENAL-REPLACEMENT THERAPY; CRITICALLY-ILL PATIENTS; ACUTE KIDNEY INJURY; MARKERS; SEPSIS; PNEUMONIA; MORTALITY; CYTOKINE; FAILURE AB Background and objectives Critically ill patients requiring RRT have higher circulating plasma concentrations of inflammatory and apoptosis markers that are associated with subsequent RRT dependence and death. Whether intensive dosing of RRT is associated with changes in specific mediators is unknown. Design, setting, participants, & measurements A multicenter, prospective, cohort study of 817 critically ill patients receiving RRT ancillary to the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study was conducted between November 2003 and July 2007. Plasma inflammatory (IL-6, IL-8, IL-10, IL-18, and macrophage migration inhibitory factor) and apoptosis (TNF receptor-I [TNFR-I] TNFR-II, and death receptor-5) biomarkers on days 1 and 8 were examined after initiation of intensive RRT. Whether intensive RRT, given day 1 biomarkers, is associated with RRT independence and lower mortality at day 60 was also examined. Results Overall, no differences were found in day 8 biomarker concentrations between intensive and less-intensive RRT groups. When adjusted for day 1 biomarkers and clinical variables, intensive RRT was not associated with renal recovery (adjusted odds ratio [OR], 0.80; 95% confidence interval, 0.56 to 1.14) or mortality (adjusted OR, 1.15; 95% confidence interval, 0.81 to 1.64). Use of intensive RRT, however, was associated with lower day 8 concentrations when day 1 plasma IL-6, macrophage migration inhibitory factor, and TNFR-I concentrations were high (interaction P value for all markers, <0.01). In contrast, day 8 marker concentrations were higher when day 1 levels were low (P<0.01). Elevated biomarker concentrations on day 8 among 476 participants were associated with lower renal recovery (adjusted OR range, 0.19-0.87) and higher mortality (adjusted OR range, 1.26-3.18). Conclusions Among critically ill patients receiving RRT, intensive dosing of RRT has variable association with biomarker concentration and no association with renal recovery and mortality. However, elevated concentrations of inflammatory and apoptosis markers on day 8 of RRT were associated with RRT dependence and death. C1 [Murugan, Raghavan; Wen, Xiaoyan; Keener, Christopher; Pike, Francis; Palevsky, Paul M.; Elder, Michele; Kellum, John A.] Univ Pittsburgh, Sch Med, Ctr Crit Care Nephrol, Pittsburgh, PA USA. [Murugan, Raghavan; Wen, Xiaoyan; Keener, Christopher; Pike, Francis; Palevsky, Paul M.; Unruh, Mark; Elder, Michele; Chen, Yi-Fan; Kellum, John A.] Univ Pittsburgh, Sch Med, Clin Res Invest & Syst Modeling Acute Illness Ctr, Dept Crit Care Med, Pittsburgh, PA USA. [Keener, Christopher; Pike, Francis; Chen, Yi-Fan] 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. [Unruh, Mark] Univ New Mexico, Dept Internal Med, Div Nephrol, Albuquerque, NM 87131 USA. [Finkel, Kevin] Univ Texas Med Sch Houston, Div Renal Dis & Hypertens, Houston, TX USA. [Vijayan, Anitha] Washington Univ, Div Renal Dis, St Louis, MO USA. RP Kellum, JA (reprint author), Ctr Crit Care Nephrol, Crit Care Med, Translat Sci & Bioengn, 608 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kellumja@ccm.upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK070910]; National Center For Advancing Translational Sciences of the National Institutes of Health [KL2-TR000146]; Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (CSP) [530]; NIDDK [Y1-DK-3508] FX The BioMaRK study was conducted by the BioMaRK investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grant no. R01-DK070910) and the National Center For Advancing Translational Sciences of the National Institutes of Health (award no. KL2-TR000146). The Veterans Affairs/National Institutes of Health ATN study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (CSP no. 530) and by NIDDK by an interagency agreement (no. Y1-DK-3508). NR 18 TC 5 Z9 5 U1 0 U2 3 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 JUN PY 2015 VL 10 IS 6 BP 926 EP 933 DI 10.2215/CJN.04560514 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CJ8XV UT WOS:000355787700006 PM 25862777 ER PT J AU Fried, LF Lewis, J AF Fried, Linda F. Lewis, Julia TI Albuminuria is Not an Appropriate Therapeutic Target in Patients with CKD: The Con View SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC RENAL-INSUFFICIENCY; TYPE-2 DIABETES-MELLITUS; CHRONIC KIDNEY-DISEASE; SURROGATE END-POINTS; BLOOD-PRESSURE CONTROL; CLINICAL-TRIALS; NEPHROPATHY; PROGRESSION; EFFICACY; CHOLESTEROL AB Albuminuria is a risk factor for progression of kidney disease. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers slow the progression to ESRD, an effect that is correlated with reduction in albuminuria. This has led to the hypothesis that albuminuria should be a target for therapy. This work argues that there are issues with this hypothesis. The previously reported studies were not designed to test the hypothesis that achieving a specific albuminuria target would be beneficial in and of itself irrespective the mechanism used to achieve that goal. One cannot assume that the beneficial effect observed was causally related to the effect on albuminuria or that it would extend to other interventions. Most importantly, it is not known if the approach of maximizing therapy to reduce proteinuria is safe. Recent studies have shown that combining renin-angiotensin system therapies decreases albuminuria without significant clinical benefit but with increased risk of adverse events. More studies are needed, but at this time, albuminuria has not jumped the hurdle needed to be accepted as a surrogate end point or target for treatment. Primum non nocere, first do no harm. C1 [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Fried, Linda F.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Lewis, Julia] Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol & Hypertens, Nashville, TN 37212 USA. RP Fried, LF (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Univ Dr, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov NR 47 TC 14 Z9 14 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 JUN PY 2015 VL 10 IS 6 BP 1089 EP 1093 DI 10.2215/CJN.10681014 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CJ8XV UT WOS:000355787700024 PM 25887070 ER PT J AU Fried, LF Lewis, J AF Fried, Linda F. Lewis, Julia TI Rebuttal of the Pro View: Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID DIABETIC-NEPHROPATHY; END-POINTS; TYPE-2; TRIAL; PROTEINURIA; ALISKIREN; LOSARTAN; OUTCOMES C1 [Fried, Linda F.] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Lewis, Julia] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Fried, LF (reprint author), Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Univ Dr,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov NR 13 TC 1 Z9 1 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 JUN PY 2015 VL 10 IS 6 BP 1095 EP 1098 DI 10.2215/CJN.01610215 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA CJ8XV UT WOS:000355787700025 PM 25887072 ER PT J AU Baca, CB Pieters, HC Iwaki, TJ Mathern, GW Vickrey, BG AF Baca, Christine B. Pieters, Huibrie C. Iwaki, Tomoko J. Mathern, Gary W. Vickrey, Barbara G. TI "A journey around the world": Parent narratives of the journey to pediatric resective epilepsy surgery and beyond SO EPILEPSIA LA English DT Article DE Epilepsy surgery; Pediatric; Access to care; Parent ID TEMPORAL-LOBE EPILEPSY; MEDICALLY REFRACTORY EPILEPSY; UNITED-STATES; RACIAL DISPARITIES; IMPROVED OUTCOMES; CHILDREN; HEMISPHERECTOMY; RECOMMENDATIONS; NEUROLOGISTS; ACCEPTANCE AB ObjectiveAlthough shorter time to pediatric resective epilepsy surgery is strongly associated with greater disease severity, other nonclinical diagnostic and sociodemographic factors also play a role. We aimed to examine parent-reported barriers to timely receipt of pediatric epilepsy surgery. MethodsWe conducted 37 interviews of parents of children who previously had resective epilepsy surgery at University of California Los Angeles (UCLA; 2006-2011). Interviews were audio-recorded, transcribed, and systematically coded using thematic analysis by two independent coders, and subsequently checked for agreement. Clinical data, including time to surgery (age of epilepsy onset to surgery) were abstracted from medical records. ResultsThe mean time to surgery was 5.3years (standard deviation [SD] 3.8); surgery types included 32% hemispherectomy, 43% lobar/focal, and 24% multilobar. At surgery, parents were on average 38.4years (SD 6.6) and children were on average 8.2years (SD 4.7). The more arduous and longer aspect of the journey to surgery was perceived by parents to be experienced prior to presurgical referral. The time from second antiepileptic drug failure to presurgical referral was 1year in 64% of children. Thematic analysis revealed four themes (with subthemes) along the journey to surgery and beyond: (1) recognitionsomething is wrong (unfamiliarity with epilepsy, identification of medical emergency); (2) searching and findinga circuitous journey (information seeking, finding the right doctors, multiple medications, insurance obstacles, parental stress); (3) surgery is a viable optionthe right spot (surgery as last resort, surgery as best option, hoping for candidacy); and (4) life nowwe took the steps we needed to (a new life, giving back). SignificanceMultipronged interventions targeting parent-, provider-, and system-based barriers should focus on the critical presurgical referral period; such interventions are needed to remediate delays and improve access to subspecialty care for children with medically refractory epilepsy and potentially eligible for surgery. C1 [Baca, Christine B.; Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Baca, Christine B.; Vickrey, Barbara G.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. [Pieters, Huibrie C.; Iwaki, Tomoko J.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Mathern, Gary W.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. RP Baca, CB (reprint author), Univ Calif Los Angeles, Dept Neurol, 710 Westwood Plaza,C-239, Los Angeles, CA 90095 USA. EM cbower@mednet.ucla.edu FU Epilepsy Foundation of America [20111278]; National Institute of Neurological Diseases and Stroke (NINDS) [R01 NS38992] FX This study was supported by grants from the Epilepsy Foundation of America (20111278 - PI Baca) and the National Institute of Neurological Diseases and Stroke (NINDS; R01 NS38992 PI - Mathern). We thank Frances Barry for her assistance with statistical programming. NR 40 TC 4 Z9 4 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD JUN PY 2015 VL 56 IS 6 BP 822 EP 832 DI 10.1111/epi.12988 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CK1DU UT WOS:000355946900005 PM 25894906 ER PT J AU Alvarez, V Drislane, FW Westover, MB Dworetzky, BA Lee, JW AF Alvarez, Vincent Drislane, Frank W. Westover, M. Brandon Dworetzky, Barbara A. Lee, Jong Woo TI Characteristics and role in outcome prediction of continuous EEG after status epilepticus: A prospective observational cohort SO EPILEPSIA LA English DT Article DE Neurocritical care; Terminology; Status epilepticus; Electroencephalography background activity ID CRITICALLY-ILL PATIENTS; LOGISTIC-REGRESSION; STEPWISE REGRESSION; PERIODIC DISCHARGES; SEVERITY SCORE; TERMINOLOGY; PROGNOSIS; CONSCIOUSNESS; ORGANIZATION; GUIDELINES AB ObjectiveContinuous electroencephalography (cEEG) is important for treatment guidance in status epilepticus (SE) management, but its role in clinical outcome prediction is unclear. Our aim is to determine which cEEG features give independent outcome information after correction for clinical predictor. MethodscEEG data of 120 consecutive adult patients with SE were prospectively collected in three academic medical centers using the 2012 American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. Association between cEEG features and two clinical outcome measures (mortality and complete recovery) was assessed. ResultsIn the first 24h of EEG recording, 49 patients (40.8%) showed no periodic or rhythmic pattern, 45 (37.5%) had periodic discharges, 20 (16.7%) had rhythmic delta activity, and 6 (5%) had spike-and-wave discharges. Seizures were recorded in 68.3% of patients. After adjusting for known clinical predictive factors for mortality including the STatus Epilepticus Severity Score (STESS) and the presence of a potentially fatal etiology, the only EEG features (among rhythmic and periodic patterns, seizures, and background activity) that remained significantly associated with outcome were the absence of a posterior dominant rhythm (odds ratio [OR] 9.8; p=0.033) for mortality and changes in stage II sleep pattern characteristics (OR 2.59 for each step up among these categories: absent, present and abnormal, present and normal; p=0.002) for complete recovery. SignificanceAfter adjustment for relevant clinical findings, including SE severity and etiology, cEEG background information (posterior dominant rhythm and sleep patterns) is more predictive for clinical outcome after SE than are rhythmic and periodic patterns or seizures. C1 [Alvarez, Vincent; Dworetzky, Barbara A.; Lee, Jong Woo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Alvarez, Vincent; Drislane, Frank W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Alvarez, Vincent; Westover, M. Brandon] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Alvarez, V (reprint author), Hop Valais, Serv Neurol Etage C, Ave Grand Champsec 80, CH-1950 Sion, Switzerland. EM vincent.alvarez@hopitalvs.com OI Dworetzky, Barbara/0000-0002-3364-2347 FU Swiss National Science Foundation [P2GEP3_148510]; Gottfried und Julia Bangerter-Rhyner Foundation; American Brain Foundation; FDA; Epilepsy Foundation; American Epilepsy Society; UCB, Inc; Duke Clinical Research Institute; Sunovion, Inc. FX Dr. Alvarez is funded by the Swiss National Science Foundation, grant: P2GEP3_148510 and the Gottfried und Julia Bangerter-Rhyner Foundation. Dr. M. Brandon Westover has received research funding from the American Brain Foundation. Dr. Barbara A. Dworetzky has received research funding from the FDA, the Epilepsy Foundation, and the American Epilepsy Society. She is a consultant for SleepMed., and Best Doctors. Dr. Jong W. Lee has received research funding from UCB, Inc, the Duke Clinical Research Institute, and Sunovion, Inc. Dr Drislane has no disclosures with regard to this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 35 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD JUN PY 2015 VL 56 IS 6 BP 933 EP 941 DI 10.1111/epi.12996 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CK1DU UT WOS:000355946900018 PM 25953195 ER PT J AU King-Stephens, D Mirro, E Weber, PB Laxer, KD Van Ness, PC Salanova, V Spencer, DC Heck, CN Goldman, A Jobst, B Shields, DC Bergey, GK Eisenschenk, S Worrell, GA Rossi, MA Gross, RE Cole, AJ Sperling, MR Nair, DR Gwinn, RP Park, YD Rutecki, PA Fountain, NB Wharen, RE Hirsch, LJ Miller, IO Barkley, GL Edwards, JC Geller, EB Berg, MJ Sadler, TL Sun, FT Morrell, MJ AF King-Stephens, David Mirro, Emily Weber, Peter B. Laxer, Kenneth D. Van Ness, Paul C. Salanova, Vicenta Spencer, David C. Heck, Christianne N. Goldman, Alica Jobst, Barbara Shields, Donald C. Bergey, Gregory K. Eisenschenk, Stephan Worrell, Gregory A. Rossi, Marvin A. Gross, Robert E. Cole, Andrew J. Sperling, Michael R. Nair, Dileep R. Gwinn, Ryder P. Park, Yong D. Rutecki, Paul A. Fountain, Nathan B. Wharen, Robert E. Hirsch, Lawrence J. Miller, Ian O. Barkley, Gregory L. Edwards, Jonathan C. Geller, Eric B. Berg, Michel J. Sadler, Toni L. Sun, Felice T. Morrell, Martha J. TI Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography SO EPILEPSIA LA English DT Article DE EEG monitoring; Electrocorticography; Ambulatory EEG; Intracranial EEG; Responsive stimulation; Localization ID PARTIAL SEIZURES; WITHDRAWAL; SURGERY; EEG; STIMULATION; RECURRENCE; ADULTS; TRIAL; BRAIN AB ObjectivePatients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. MethodsAmbulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. ResultsEighty-two subjects were implanted with bilateral MTL leads and followed for 4.7years on average (median 4.9years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6days (median 13days, range 0-376days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6years of recording. SignificanceAbout one third of the subjects implanted with bilateral MTL electrodes required >1month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions. C1 [King-Stephens, David; Weber, Peter B.; Laxer, Kenneth D.] Pacific Med Ctr, Pacific Epilepsy Program, San Francisco, CA 94115 USA. [Mirro, Emily; Sun, Felice T.; Morrell, Martha J.] NeuroPace Inc, Mountain View, CA 94043 USA. [Van Ness, Paul C.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Salanova, Vicenta] Indiana Univ, Dept Neurol, Indianapolis, IN 46202 USA. [Spencer, David C.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Heck, Christianne N.] Univ So Calif, Comprehens Epilepsy Program, Los Angeles, CA 90089 USA. [Goldman, Alica] Baylor Coll Med, Houston, TX 77030 USA. [Jobst, Barbara] Dartmouth Hitchcock Epilepsy Ctr, Lebanon, NH 03756 USA. [Shields, Donald C.] George Washington Univ, Washington, DC 20052 USA. [Bergey, Gregory K.] Johns Hopkins Epilepsy Ctr, Baltimore, MD 21287 USA. [Eisenschenk, Stephan] Univ Florida, Dept Neurol, Gainesville, FL 32611 USA. [Worrell, Gregory A.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. [Rossi, Marvin A.] Rush Epilepsy Ctr, Chicago, IL 60612 USA. [Gross, Robert E.] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA USA. [Cole, Andrew J.] Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. [Sperling, Michael R.] Thomas Jefferson Univ, Jefferson Comprehens Epilepsy Ctr, Philadelphia, PA 19107 USA. [Nair, Dileep R.] Cleveland Clin, Neurol Inst, Cleveland, OH 44195 USA. [Gwinn, Ryder P.] Swedish Neurosci Inst, Seattle, WA 98052 USA. [Park, Yong D.] Georgia Regents Univ, Augusta, GA 30912 USA. [Rutecki, Paul A.] Univ Wisconsin, Madison, WI 53792 USA. [Fountain, Nathan B.] Univ Virginia, Comprehens Epilepsy Ctr, Charlottesville, VA 22908 USA. [Wharen, Robert E.] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Hirsch, Lawrence J.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Miller, Ian O.] Miami Childrens Hosp, Comprehens Epilepsy Ctr, Miami, FL 33155 USA. [Barkley, Gregory L.] Henry Ford Hosp, Detroit, MI 48202 USA. [Edwards, Jonathan C.] Med Univ S Carolina, Charleston, SC 29425 USA. [Geller, Eric B.] Inst Neurol & Neurosurg St Barnabas, Livingston, NJ 07039 USA. [Berg, Michel J.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Sadler, Toni L.] Via Christi Comprehens Epilepsy Ctr, Wichita, KS 67214 USA. [Morrell, Martha J.] Stanford Comprehens Epilepsy Ctr, Stanford, CA 94305 USA. RP Morrell, MJ (reprint author), NeuroPace Inc, 455 N Bernardo Ave, Mountain View, CA 94043 USA. EM mmorrell@neuropace.com NR 20 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD JUN PY 2015 VL 56 IS 6 BP 959 EP 967 DI 10.1111/epi.13010 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CK1DU UT WOS:000355946900021 PM 25988840 ER PT J AU Juratli, TA Cahill, DP McCutcheon, IE AF Juratli, Tareq A. Cahill, Daniel P. McCutcheon, Ian E. TI Determining optimal treatment strategy for diffuse glioma: the emerging role of IDH mutations SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material DE chemotherapy; gliomas; IDH mutation; radiotherapy; surgery ID ANAPLASTIC OLIGODENDROGLIAL TUMORS; GLIOBLASTOMA-MULTIFORME; MUTANT GLIOBLASTOMA; MALIGNANT GLIOMAS; GRADE GLIOMA; TRIAL; DIFFERENTIATION; ASTROCYTOMAS; CHEMOTHERAPY; RADIOTHERAPY AB The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes mutate frequently in gliomas, and it has become increasingly apparent that IDH mutation status accounts for much of the prognostic information previously rendered by histological grading. Most glioblastomas (90-95%) are IDH wild-type and most lower-grade diffuse gliomas (80%) are IDH-mutant. We examine here how IDH mutation status interacts with treatments known to influence survival (surgery, chemotherapy and radiotherapy) in patients with gliomas, and the impact of the IDH mutations on patients' survival after such treatments. IDH mutations is associated with more complete surgical resection of enhancing disease, and with a better response to RT. In addition, there is increasing clinical evidence that, in certain contexts, IDH mutations predict chemotherapeutic sensitivity. Mutations in IDH and other genes are beginning to drive decisions on therapy for diffuse gliomas and will likely allow tailoring of treatment by molecular profile in the future. C1 [Juratli, Tareq A.] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Neurosurg, D-01307 Dresden, Germany. [Cahill, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg, Boston, MA 02114 USA. [McCutcheon, Ian E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Cahill, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg, 32 Fruit St, Boston, MA 02114 USA. EM dcahill@partners.org OI Cahill, Daniel/0000-0003-2552-6546 FU NCI NIH HHS [P50 CA165962] NR 31 TC 1 Z9 1 U1 1 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD JUN PY 2015 VL 15 IS 6 BP 603 EP 606 DI 10.1586/14737140.2015.1047351 PG 4 WC Oncology SC Oncology GA CJ8KO UT WOS:000355749300001 PM 25980633 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Clinical management of radicular pain SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE cervical disc herniation; cervical radicular pain; cervical spondylosis; discectomy; epidural steroids; fusion; lumbar disc herniation; lumbar radicular pain; thoracic radicular pain ID LOW-BACK-PAIN; LUMBAR DISC HERNIATION; CENTRAL SPINAL STENOSIS; CAUDAL EPIDURAL INJECTIONS; RESEARCH TRIAL SPORT; LONG-TERM RELIEF; 2-YEAR FOLLOW-UP; NECK PAIN; CERVICAL RADICULOPATHY; NONOPERATIVE TREATMENT AB This review provides an overview of the diagnosis and treatment strategies for the management of radicular pain. While it is not as common as axial spinal pain, radicular pain combines the advantage of leveraging appropriate diagnostic strategies and definitive treatments with well-informed outcome measures. Multiple diagnostic measures include not only history and physical examination, but also imaging. The treatment modalities include pharmacologic management, physical and rehabilitation measures, interventional techniques and surgical treatments. Here, the authors describe the prevalence and pathophysiology of radicular pain, risk factors, diagnostic strategies, treatment modalities and the evidence for these management strategies. Finally, the authors show the efficacy of conservative management, despite surgical management being the gold standard. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd Paducah, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 98 TC 5 Z9 5 U1 4 U2 22 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 EI 1744-8360 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD JUN PY 2015 VL 15 IS 6 BP 681 EP 693 DI 10.1586/14737175.2015.1048226 PG 13 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CJ8KL UT WOS:000355748900011 PM 25982996 ER PT J AU Joseph, N Clark, RM Dizon, DS Lee, MS Goodman, A Boruta, D Schorge, JO del Carmen, MG Growdon, WB AF Joseph, Naima Clark, Rachel M. Dizon, Don S. Lee, Malinda S. Goodman, Annekathryn Boruta, David, Jr. Schorge, John O. del Carmen, Marcela G. Growdon, Whitfield B. TI Delay in chemotherapy administration impacts survival in elderly patients with epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Elderly; Ovarian cancer; Chemotherapy; Dose delay ID PLATINUM-BASED CHEMOTHERAPY; RELATIVE DOSE INTENSITY; GREATER-THAN-OR-EQUAL-TO-70 YEARS; CENTER EXPERIENCE; PROGNOSTIC FACTOR; PRIMARY SURGERY; STAGE-III; AGE; WOMEN; CARBOPLATIN AB Objectives. The objective of this study was to characterize chemotherapy treatment patterns in elderly patients with epithelial ovarian cancer (EOC) and their impact on overall survival (OS). Methods. We identified patients age >= 65 years with stage II-IV EOC who underwent cytoreduction from 2003 to 2011. Relevant clinical variables were extracted and correlated with OS. Statistical analyses were performed using logistic regression, Kaplan-Meier methods, and multivariable Cox proportional hazard models. Results. One hundred and eighty-four patients were included in the analysis. The average age was 73 years with American Society of Anesthesiology Physical Status Class 2 or 3. Approximately 78% undeiwent primary debulking surgery (PDS). OS for the entire cohort was 33 years. One hundred and fifty-seven patients received adjuvant chemotherapy, of which 70% received initial platinum-based doublet therapy; 67.5% of patients were able to complete the intended six cycles of chemotherapy; of these, 34% experienced a dose reduction and 45% experienced one or more dose delays. Any dose delay was associated with a decrease in overall survival (p = 0.02) and remained significant even after controlling for age, stage, and residual disease and number of chemotherapy cycles received (p = 0.029). Conclusions. Elderly EOC patients frequently required chemotherapy dose reductions and delays in chemotherapy administration. Multivariate analysis confirmed that dose delays are an independent factor associated with decreased OS. (C) 2015 Elsevier Inc. All rights reserved. C1 [Joseph, Naima; Lee, Malinda S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02115 USA. [Clark, Rachel M.; Dizon, Don S.; Goodman, Annekathryn; Boruta, David, Jr.; Schorge, John O.; del Carmen, Marcela G.; Growdon, Whitfield B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02115 USA. RP Growdon, WB (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Gynecol Oncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM njoseph11@partners.org; rmclark@mgh.harvard.edu; ddizon@mgh.harvard.edu; mlee33@partners.org; agoodman@mgh.harvard.edu; dboruta@mgh.harvard.edu; jschorge@partners.org; mdelcarmen@mgh.harvard.edu; wgrowdon@partners.org NR 36 TC 8 Z9 8 U1 0 U2 6 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 JUN PY 2015 VL 137 IS 3 BP 401 EP 405 DI 10.1016/j.ygyno.2015.03.052 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CJ8UM UT WOS:000355779000007 PM 25839911 ER PT J AU Davis, MR Howitt, BE Quade, BJ Crum, CP Horowitz, NS Goldstein, DP Berkowitz, RS AF Davis, M. R. Howitt, B. E. Quade, B. J. Crum, C. P. Horowitz, N. S. Goldstein, D. P. Berkowitz, R. S. TI Epithelioid trophoblastic tumor: A single institution case series at the New England Trophoblastic Disease Center SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Epithelioid trophoblastic tumor; Gestational trophoblastic neoplasia ID OF-THE-LITERATURE; CHEMOTHERAPY; NEOPLASM; LUNG AB Objective. Epithelioid trophoblastic tumor (ETT) is a rare form of gestational trophoblastic neoplasm which is distinct based on its development from intermediate trophoblast cells and nodular growth pattern. The aim of this study is to describe a case series from a single institution with a review of the literature to better understand the clinical characteristics and outcomes for patients with ETT. Methods. A retrospective review was performed using the IRB approved New England Trophoblastic Disease Center (NETDC) database from 1998 to 2014. Eight patients were identified of which seven had complete records. Follow-up data was obtained from the longitudinal medical records. Results. Four (57.1%) patients presented with vaginal bleeding and two (28.6%) patients were asymptomatic at presentation. Three (42.9%) patients had extrauterine disease. All three patients with extrauterine disease who received chemotherapy had stable or progressive disease at follow-up. Only two (29%) patients who presented with non-metastatic disease and underwent hysterectomy were alive with no evidence of disease. The mean interval following antecedent pregnancy was 104 months. All patients with an interval >4 years demonstrated stable or progressive disease despite intensive chemotherapy. Two patients with non-metastatic disease who declined hysterectomy developed stable or progressive disease despite chemotherapy. Conclusions. This series highlights several, features of Elf including the potential for asymptomatic presentation of extrauterine disease. The series also demonstrates chemoresistance, even with multi-agent therapy and a poor prognosis with extrauterine disease and an interval greater than 4 years following the antecedent pregnancy suggesting that surgery remains critical in disease control. (C) 2015 Elsevier Inc. All rights reserved. C1 [Davis, M. R.; Horowitz, N. S.; Goldstein, D. P.; Berkowitz, R. S.] Harvard Univ, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Sch Med,Div Gynecol Oncol, Boston, MA 02115 USA. [Horowitz, N. S.; Goldstein, D. P.; Berkowitz, R. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Horowitz, N. S.; Goldstein, D. P.; Berkowitz, R. S.] Donald P Goldstein MD Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. [Howitt, B. E.; Quade, B. J.; Crum, C. P.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med,Div Womens & Perinatal Pathol, Boston, MA 02115 USA. RP Davis, MR (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Sch Med,Div Gynecol Oncol, Boston, MA 02115 USA. OI Davis, Michelle/0000-0002-6925-9139 NR 22 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2015 VL 137 IS 3 BP 456 EP 461 DI 10.1016/j.ygyno.2015.03.006 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CJ8UM UT WOS:000355779000016 PM 25773203 ER PT J AU Joseph, N Pilliod, R Clark, R Goodman, A Growdon, W AF Joseph, N. Pilliod, R. Clark, R. Goodman, A. Growdon, W. TI Proposed algorithm for the management of age 21 and older undergoing primary cervical cancer screening using primary HPV testing with cytology or colposcopy triage: A decision analysis SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Joseph, N.; Pilliod, R.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. [Clark, R.; Goodman, A.; Growdon, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 JUN PY 2015 VL 137 IS 3 MA 6 BP 593 EP 593 DI 10.1016/j.ygyno.2015.03.023 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CJ8UM UT WOS:000355779000042 ER PT J AU Rauh-Hain, JA Connor, S Clemmer, JB Clark, RM Hall, T Growdon, WB Goodman, AK Borutall, D Schorge, JO del Carmen, MG AF Rauh-Hain, J. A. Connor, S. Clemmer, J. B. Clark, R. M. Hall, T. Growdon, W. B. Goodman, A. K. Borutall, D. Schorge, J. O. del Carmen, M. G. TI Trends in treatment of uterine serous cancer in the medicare population SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Rauh-Hain, J. A.; Connor, S.; Clemmer, J. B.; Clark, R. M.; Hall, T.; Growdon, W. B.; Goodman, A. K.; Borutall, D.; Schorge, J. O.; del Carmen, M. G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JUN PY 2015 VL 137 IS 3 MA 13 BP 595 EP 596 DI 10.1016/j.ygyno.2015.03.030 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CJ8UM UT WOS:000355779000049 ER PT J AU Sharma, A Menche, J Huang, CC Ort, T Zhou, XB Kitsak, M Sahni, N Thibault, D Voung, L Guo, F Ghiassian, SD Gulbahce, N Baribaud, F Tocker, J Dobrin, R Barnathan, E Liu, H Panettieri, RA Tantisira, KG Qiu, WL Raby, BA Silverman, EK Vidal, M Weiss, ST Barabasi, AL AF Sharma, Amitabh Menche, Joerg Huang, C. Chris Ort, Tatiana Zhou, Xiaobo Kitsak, Maksim Sahni, Nidhi Thibault, Derek Voung, Linh Guo, Feng Ghiassian, Susan Dina Gulbahce, Natali Baribaud, Frederic Tocker, Joel Dobrin, Radu Barnathan, Elliot Liu, Hao Panettieri, Reynold A., Jr. Tantisira, Kelan G. Qiu, Weiliang Raby, Benjamin A. Silverman, Edwin K. Vidal, Marc Weiss, Scott T. Barabasi, Albert-Laszlo TI A disease module in the interactome explains disease heterogeneity, drug response and captures novel pathways and genes in asthma SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; PRIORITIZING CANDIDATE GENES; PROTEIN-INTERACTION NETWORK; LARGE-SCALE; EXPRESSION; SIGNATURE; DISCOVERY; BIOLOGY; CELLS; YEAST AB Recent advances in genetics have spurred rapid progress towards the systematic identification of genes involved in complex diseases. Still, the detailed understanding of the molecular and physiological mechanisms through which these genes affect disease phenotypes remains a major challenge. Here, we identify the asthma disease module, i.e. the local neighborhood of the interactome whose perturbation is associated with asthma, and validate it for functional and pathophysiological relevance, using both computational and experimental approaches. We find that the asthma disease module is enriched with modest GWAS P-values against the background of random variation, and with differentially expressed genes from normal and asthmatic fibroblast cells treated with an asthma-specific drug. The asthma module also contains immune response mechanisms that are shared with other immune-related disease modules. Further, using diverse omics (genomics, gene-expression, drug response) data, we identify the GAB1 signaling pathway as an important novel modulator in asthma. The wiring diagram of the uncovered asthma module suggests a relatively close link between GAB1 and glucocorticoids (GCs), which we experimentally validate, observing an increase in the level of GAB1 after GC treatment in BEAS-2B bronchial epithelial cells. The siRNA knockdown of GAB1 in the BEAS-2B cell line resulted in a decrease in the NFkB level, suggesting a novel regulatory path of the pro-inflammatory factor NFkB by GAB1 in asthma. C1 [Sharma, Amitabh; Menche, Joerg; Kitsak, Maksim; Ghiassian, Susan Dina; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Networks Res, Dept Phys, Boston, MA 02115 USA. [Sharma, Amitabh; Menche, Joerg; Kitsak, Maksim; Sahni, Nidhi; Ghiassian, Susan Dina; Vidal, Marc; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA. [Sharma, Amitabh; Menche, Joerg; Kitsak, Maksim; Sahni, Nidhi; Ghiassian, Susan Dina; Vidal, Marc; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Sharma, Amitabh; Zhou, Xiaobo; Thibault, Derek; Voung, Linh; Guo, Feng; Tantisira, Kelan G.; Qiu, Weiliang; Raby, Benjamin A.; Silverman, Edwin K.; Weiss, Scott T.; Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Menche, Joerg; Barabasi, Albert-Laszlo] Budapest Univ Technol & Econ, Dept Theoret Phys, H-H1111 Budapest, Hungary. [Huang, C. Chris; Ort, Tatiana; Baribaud, Frederic; Tocker, Joel; Dobrin, Radu; Barnathan, Elliot; Liu, Hao] Janssen Res & Dev Inc, Spring House, PA 19477 USA. [Gulbahce, Natali] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA. [Panettieri, Reynold A., Jr.] Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. [Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, H-1051 Budapest, Hungary. [Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Networks Res, Dept Phys, Boston, MA 02115 USA. EM barabasi@gmail.com RI Menche, Jorg/G-3994-2015; OI Menche, Jorg/0000-0002-1583-6404; Dobrin, Radu/0000-0002-3336-0091 FU Janssen RD; National Institutes of Health (NIH) [P50-HG004233-CEGS]; MapGen grant [1U01HL108630-01]; [5P01-HL083069-5]; [U01 HL065899]; [P01 HL105339]; [R01HL111759]; [-RC HL10154301] FX This research received funding from Janssen R&D and was supported in part by National Institutes of Health (NIH) grants P50-HG004233-CEGS, MapGen grant (1U01HL108630-01) and 5P01-HL083069-5, U01 HL065899, P01 HL105339, R01HL111759 and -RC HL10154301. NR 60 TC 19 Z9 19 U1 1 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2015 VL 24 IS 11 BP 3005 EP 3020 DI 10.1093/hmg/ddv001 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CJ7KN UT WOS:000355674000001 PM 25586491 ER PT J AU Cassidy, B Solo, V AF Cassidy, Ben Solo, Victor TI Spatially Sparse, Temporally Smooth MEG Via Vector l(0) SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Biomedical imaging; encephalography; optimization; sparsity ID M/EEG INVERSE PROBLEM; SOURCE RECONSTRUCTION; SOURCE LOCALIZATION; REGRESSION-MODELS; CORTICAL ACTIVITY; SUBSPACE PURSUIT; MAGNETIC-FIELDS; BRAIN; REGULARIZATION; SELECTION AB In this paper, we describe a new method for solving the magnetoencephalography inverse problem: temporal vector l(0)-penalized least squares (TV-L0LS). The method calculates maximally sparse current dipole magnitudes and directions via spatial l(0) regularization on a cortically-distributed source grid, while constraining the solution to be smooth with respect to time. We demonstrate the utility of this method on real and simulated data by comparison to existing methods. C1 [Cassidy, Ben; Solo, Victor] Univ New S Wales, Sch Elect Engn, Sydney, NSW 2052, Australia. [Cassidy, Ben; Solo, Victor] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Solo, Victor] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Solo, Victor] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Cassidy, B (reprint author), Univ New S Wales, Sch Elect Engn, Sydney, NSW 2052, Australia. EM b.cassidy@neura.edu.au FU Australian Postgraduate Award; NeuRA Foundation Scholarship; National Institutes of Health (NIH); National Institute of Biomedical Imaging and Bioengineering (NIBIB) [2P41EB015896] FX This work was supported in part by an Australian Postgraduate Award and a NeuRA Foundation Scholarship. This work was also supported in part by a National Institutes of Health (NIH) shared instrument grant and National Institute of Biomedical Imaging and Bioengineering (NIBIB)-supported P41 Center for Functional Neuroimaging Technologies under Grant 2P41EB015896. Views expressed are not necessarily endorsed by NIH. NR 56 TC 1 Z9 1 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUN PY 2015 VL 34 IS 6 BP 1282 EP 1293 DI 10.1109/TMI.2014.2383376 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA CJ8ML UT WOS:000355755700007 PM 25576564 ER PT J AU Brown, DE Nick, HJ McCoy, MW Moreland, SM Stepanek, AM Benik, R O'Connell, KE Pilonieta, MC Nagy, TA Detweiler, CS AF Brown, Diane E. Nick, Heidi J. McCoy, Melissa W. Moreland, Sarah M. Stepanek, Aaron M. Benik, Ross O'Connell, Karyn E. Pilonieta, Maria C. Nagy, Toni A. Detweiler, Corrella S. TI Increased Ferroportin-1 Expression and Rapid Splenic Iron Loss Occur with Anemia Caused by Salmonella enterica Serovar Typhimurium Infection in Mice SO INFECTION AND IMMUNITY LA English DT Article ID NITRIC-OXIDE SYNTHASE; MURINE TYPHOID-FEVER; HEMOPHAGOCYTIC MACROPHAGES; PERITONEAL-MACROPHAGES; INTRACELLULAR GROWTH; DEFICIENCY ANEMIA; CHRONIC DISEASE; HOMEOSTASIS; LIMITS; ACTIVATION AB The Gram-negative intracellular bacterium Salmonella enterica serovar Typhimurium causes persistent systemic inflammatory disease in immunocompetent mice. Following oral inoculation with Serovar Typhimurium, mice develop a hematopathological syndrome akin to typhoid fever with splenomegaly, microcytic anemia, extramedullary erythropoiesis, and increased hemophagocytic macrophages in the bone marrow, liver, and spleen. Additionally, there is marked loss of iron from the spleen, an unanticipated result, given the iron sequestration reported in anemia of inflammatory disease. To establish why tissue iron does not accumulate, we evaluated multiple measures of pathology for 4 weeks following oral infection in mice. We demonstrate a quantitative decrease in splenic iron following infection despite increased numbers of splenic phagocytes. Infected mice have increased duodenal expression of the iron exporter ferroportin-1, consistent with increased uptake of dietary iron. Liver and splenic macrophages also express high levels of ferroportin-1. These observations indicate that splenic and hepatic macrophages export iron during Serovar Typhimurium infection, in contrast to macrophage iron sequestration observed in anemia of inflammatory disease. Tissue macrophage export of iron occurs concurrent with high serum concentrations of interferon gamma (IFN-gamma) and interleukin 12 (IL-12). In individual mice, high concentrations of both proinflammatory (tumor necrosis factor alpha [TNF-alpha]) and anti-inflammatory (IL-10) cytokines in serum correlate with increased tissue bacterial loads throughout 4 weeks of infection. These in vivo observations are consistent with previous cell culture studies and suggest that the relocation of iron from tissue macrophages during infection may contribute to anemia and also to host survival of acute Serovar Typhimurium infection. C1 [Brown, Diane E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brown, Diane E.] Harvard Univ, Sch Med, Boston, MA USA. [Brown, Diane E.; Stepanek, Aaron M.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Nick, Heidi J.; McCoy, Melissa W.; Moreland, Sarah M.; Pilonieta, Maria C.; Nagy, Toni A.; Detweiler, Corrella S.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Benik, Ross] Premier Labs, Boulder, CO USA. [O'Connell, Karyn E.] Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. RP Brown, DE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM dbrown31@mgh.harvard.edu; detweile@colorado.edu FU NIH [AI095395, AI072492]; Massachusetts General Hospital Center for Comparative Medicine FX This work was supported by NIH grants AI095395 and AI072492 (C.S.D.) and the Massachusetts General Hospital Center for Comparative Medicine (D.E.B.). NR 56 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2015 VL 83 IS 6 BP 2290 EP 2299 DI 10.1128/IAI.02863-14 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CK5DS UT WOS:000356243000009 PM 25824831 ER PT J AU Maust, DT Chen, SH Benson, A Mavandadi, S Streim, JE DiFilippo, S Snedden, TM Oslin, DW AF Maust, Donovan T. Chen, Shirley H. Benson, Amy Mavandadi, Shahrzad Streim, Joel E. DiFilippo, Suzanne Snedden, Thomas M. Oslin, David W. TI Older adults recently started on psychotropic medication: where are the symptoms? SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE psychotropic medication; primary care; older adults ID LATE-LIFE DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; ANXIETY DISORDERS; RISK; MANAGEMENT; PEOPLE; BENZODIAZEPINE; POPULATION; IMPAIRMENT AB Objective: The objective of this study is to understand the characteristics of older adults on newly prescribed psychotropic medication with minimal psychiatric symptoms. Methods: Naturalistic cohort study of non-institutionalized older adults in Pennsylvania participating in the Pharmaceutical Assistance Contract for the Elderly. Persons newly prescribed antidepressant or anxiolytic monotherapy or combination therapy were contacted for clinical assessment by a telephone-based behavioral health service. The initial assessment included standardized mental health screening instruments and scales including the Blessed Orientation-Memory-Concentration test, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Medical Outcomes Survey (SF-12). In addition, patients were asked for their understanding of the prescription indication. Results: Of the 254 participants who met minimal symptom criteria (Patient Health Questionnaire 9<5 and Generalized AnxietyDisorder-7<5), women comprised slightly more of the anxiolytic compared with antidepressant monotherapy group (88.9% vs. 76.7%, p = 0.04). The most common self-reported reason for prescription of an antidepressant or anxiolytic was depression or anxiety, respectively, despite near-absence of these symptoms on clinical assessment. Comparing monotherapy to combination therapy groups, those with combination therapy were more likely to report a history of depression (12.6% vs. 1.8%, p< 0.001) and also report depression as the reason for the prescription (40.2% vs. 21.0%, p< 0.01). Conclusions: In this sample of older adults on new psychotropic medication with minimal psychiatric symptoms, there are few patient characteristics that distinguish those on antidepressant versus anxiolytic monotherapy or those on monotherapy versus combination therapy. While quality of care in late-life mental health has focused on improving detection and treatment, there should be further attention to low-symptom patients potentially receiving inappropriate pharmacotherapy. Copyright (C) 2014 John Wiley & Sons, Ltd. C1 [Maust, Donovan T.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Maust, Donovan T.] VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. [Chen, Shirley H.; Mavandadi, Shahrzad; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chen, Shirley H.; Mavandadi, Shahrzad; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David W.] VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Philadelphia, PA USA. [Benson, Amy; Mavandadi, Shahrzad; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Snedden, Thomas M.] Penn Dept Aging, PACE Program, Harrisburg, PA USA. RP Maust, DT (reprint author), Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. EM maustd@umich.edu FU PACE Program of the Pennsylvania Department of Aging FX This work was funded by the PACE Program of the Pennsylvania Department of Aging. Mr Snedden directs the PACE Program. The authors have no further disclosures to report. NR 36 TC 1 Z9 1 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUN PY 2015 VL 30 IS 6 BP 580 EP 586 DI 10.1002/gps.4187 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CK1RT UT WOS:000355985600005 PM 25116369 ER PT J AU Vasterling, JJ Taft, CT Proctor, SP Macdonald, HZ Lawrence, A Kalill, K Kaiser, AP Lee, LO King, DW King, LA Fairbank, JA AF Vasterling, Jennifer J. Taft, Casey T. Proctor, Susan P. Macdonald, Helen Z. Lawrence, Amy Kalill, Kathleen Kaiser, Anica P. Lee, Lewina O. King, Daniel W. King, Lynda A. Fairbank, John A. TI Establishing a methodology to examine the effects of war-zone PTSD on the family: the family foundations study SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article DE war-zone veterans; family; PTSD; longitudinal; risk factors ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY SERVICE MEMBERS; MALE VIETNAM VETERANS; NEUROCOGNITION DEPLOYMENT HEALTH; INTIMATE PARTNER VIOLENCE; ALCOHOL-USE DISORDERS; YOUNG-CHILDREN; MENTAL-HEALTH; US MILITARY; HEAD-INJURY AB Military deployment may adversely affect not only returning veterans, but their families, as well. As a result, researchers have increasingly focused on identifying risk and protective factors for successful family adaptation to war-zone deployment, re-integration of the returning veteran, and the longer-term psychosocial consequences of deployment experienced by some veterans and families. Post-traumatic stress disorder (PTSD) among returning veterans may pose particular challenges to military and military veteran families; however, questions remain regarding the impact of the course of veteran PTSD and other potential moderating factors on family adaptation to military deployment. The Family Foundations Study builds upon an established longitudinal cohort of Army soldiers (i.e. the Neurocognition Deployment Health Study) to help address remaining knowledge gaps. This report describes the conceptual framework and key gaps in knowledge that guided the study design, methodological challenges and special considerations in conducting military family research, and how these gaps, challenges, and special considerations are addressed by the study. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Vasterling, Jennifer J.; Taft, Casey T.; Kaiser, Anica P.; Lee, Lewina O.; King, Daniel W.; King, Lynda A.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA 02130 USA. [Vasterling, Jennifer J.; Taft, Casey T.; Lawrence, Amy; Kalill, Kathleen; Kaiser, Anica P.; Lee, Lewina O.; King, Daniel W.; King, Lynda A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Proctor, Susan P.] US Army Res Inst Environm Med, Boston, MA USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Macdonald, Helen Z.] Univ Cambridge Emmanuel Coll, Boston, MA USA. [Lawrence, Amy; Kalill, Kathleen] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Fairbank, John A.] Duke Univ, Durham VA Med Ctr, VA Mid Atlantic VISN 6, MIRECC, Durham, NC USA. RP Vasterling, JJ (reprint author), VA Boston Healthcare Syst, Psychol 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM jennifer.vasterling@va.gov FU National Institute for Mental Health [1R01MH094422-02]; VA National Center for PTSD FX The Family Foundations Study is supported by the National Institute for Mental Health (1R01MH094422-02). A related pilot phase was supported by the VA National Center for PTSD. Interface with VA CSP #566 has been greatly facilitated by the VA Cooperative Studies Program Central Office and the Clinical Epidemiological Research Center at VA Connecticut Healthcare System. The authors also appreciate the assistance of Ms Molly Franz in initiating the study, the assistance of Ms Rebecca Wilken in both the on-going conduct of the study and manuscript preparation, and the contributions of Dr Michael Suvak to a previous version of the quantitative methodology. NR 86 TC 1 Z9 1 U1 8 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1049-8931 EI 1557-0657 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PD JUN PY 2015 VL 24 IS 2 BP 143 EP 155 DI 10.1002/mpr.1464 PG 13 WC Psychiatry SC Psychiatry GA CK5ZP UT WOS:000356307600004 PM 26077194 ER PT J AU Foo, JP Aronis, KN Chamberland, JP Mantzoros, CS AF Foo, J-P Aronis, K. N. Chamberland, J. P. Mantzoros, C. S. TI Lack of Day/Night variation in fibroblast growth factor 21 levels in young healthy men SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID FREE FATTY-ACIDS; METABOLIC REGULATOR; ENERGY-EXPENDITURE; CIRCADIAN-RHYTHM; FGF21; WOMEN; LIPOLYSIS; INSULIN; HUMANS; NOREPINEPHRINE AB BACKGROUND: Fibroblast growth factor (FGF) 21 is an endocrine factor with an emerging role as a metabolic regulator. We previously reported the presence of a significant day/night variation of FGF-21 in energy-replete, healthy female subjects. However the day/night patterns of secretion in male subjects remain to be fully elucidated. To elucidate day/night pattern of FGF-21 levels in male subjects in the energy-replete state, its relationship to FFA and to investigate whether a sexual dimorphism exists in FGF-21 physiology. METHODS: Eight healthy lean male subjects were studied for up to 5 days while on an isocaloric diet. Blood samples were obtained for measurement of FGF-21 and free fatty acids (FFA) hourly from 0800 AM on day 4 till 0800AM on day 5. RESULTS: FGF-21 did not exhibit any statistically significant day/night variation pattern of circulating FGF-21 levels during the isocaloric fed state in male subjects. FGF-21 levels in male subjects are closely cross-correlated with FFA levels, similar to female subjects. CONCLUSIONS: A sexual dimorphism exists in FGF-21 physiology; that as opposed to female subjects, no significant day/night variation exists in FGF-21 rhythm in male subjects in the energy-replete state. Circulating pattern of FGF-21, similar to the female subjects, was highly cross-correlated to the FFA levels in the male subjects, signifying that the sexual dimorphism in FGF-21 physiology may be related to the differing lipid metabolism in both the genders. C1 [Foo, J-P; Aronis, K. N.; Chamberland, J. P.; Mantzoros, C. S.] Harvard Univ, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02130 USA. [Aronis, K. N.; Chamberland, J. P.; Mantzoros, C. S.] Harvard Univ, Sect Endocrinol, Boston VA Healthcare Syst, Sch Med, Boston, MA 02130 USA. [Aronis, K. N.] Boston Univ, Dept Med, Boston Med Ctr, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, 150 S Huntington Ave, Boston, MA 02130 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 FU National Institutes of Health National Center for Research Resources [M01-RR-01032] FX This study was supported by the National Institutes of Health National Center for Research Resources grant M01-RR-01032 (Harvard Clinical and Translational Science Center). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Clinical trial registration: NCT00140231. NR 28 TC 1 Z9 1 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD JUN PY 2015 VL 39 IS 6 BP 945 EP 948 DI 10.1038/ijo.2014.215 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CK2KO UT WOS:000356039500011 PM 25540981 ER PT J AU Almeida, RP Schultz, SA Austin, BP Boots, EA Dowling, NM Gleason, CE Bendlin, BB Sager, MA Hermann, BP Zetterberg, H Carlsson, CM Johnson, SC Asthana, S Okonkwo, OC AF Almeida, Rodrigo P. Schultz, Stephanie A. Austin, Benjamin P. Boots, Elizabeth A. Dowling, N. Maritza Gleason, Carey E. Bendlin, Barbara B. Sager, Mark A. Hermann, Bruce P. Zetterberg, Henrik Carlsson, Cynthia M. Johnson, Sterling C. Asthana, Sanjay Okonkwo, Ozioma C. TI Effect of Cognitive Reserve on Age-Related Changes in Cerebrospinal Fluid Biomarkers of Alzheimer Disease SO JAMA NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PITTSBURGH COMPOUND-B; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; PHYSICAL-ACTIVITY; FDG-PET; EDUCATION; DEMENTIA; BRAIN AB IMPORTANCE Although advancing age is the strongest risk factor for the development of symptomatic Alzheimer disease (AD), recent studies have shown that there are individual differences in susceptibility to age-related alterations in the biomarkers of AD pathophysiology. OBJECTIVE To investigate whether cognitive reserve (CR) modifies the adverse influence of age on key cerebrospinal fluid (CSF) biomarkers of AD. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional cohort of 268 individuals (211 in a cognitively normal group and 57 in a cognitively impaired group) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center participated in this study. They underwent lumbar puncture for collection of CSF samples, from which A beta 42, total tau (t-tau), and phosphorylated tau (p-tau) were immunoassayed. In addition, we computed t-tau/A beta 42 and p-tau/A beta 42 ratios. Cognitive reserve was indexed by years of education, with 16 or more years taken to confer high reserve. Covariate-adjusted regression analyses were used to test whether the effect of age on CSF biomarkers was modified by CR. The study dates were March 5, 2010, to February 13, 2013. MAIN OUTCOMES AND MEASURES Cerebrospinal fluid levels of A beta 42, t-tau, p-tau, t-tau/A beta 42, and p-tau/A beta 42. RESULTS There were significant age x CR interactions for CSF t-tau (beta [SE] = -6.72 [2.84], P = .02), p-tau (beta [SE] = -0.71 [0.27], P = .01), t-tau/A beta 42 (beta [SE] = -0.02 [0.01], P = .02), and p-tau/A beta 42 (beta [SE] = -0.002 [0.001], P = .004). With advancing age, individuals with high CR exhibited attenuated adverse alterations in these CSF biomarkers compared with individuals with low CR. This attenuation of age effects by CR tended to be more pronounced in the cognitively impaired group compared with the cognitively normal group. There was evidence of a dose-response relationship such that the effect of age on the biomarkers was progressively attenuated given additional years of schooling. CONCLUSIONS AND RELEVANCE In a sample composed of a cognitively normal group and a cognitively impaired group, higher CR was associated with a diminution of age-related alterations in CSF biomarkers of AD. This suggests one pathway through which CR might favorably alter lifetime risk for symptomatic AD. C1 [Almeida, Rodrigo P.; Schultz, Stephanie A.; Austin, Benjamin P.; Boots, Elizabeth A.; Gleason, Carey E.; Bendlin, Barbara B.; Carlsson, Cynthia M.; Johnson, Sterling C.; Asthana, Sanjay; Okonkwo, Ozioma C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Almeida, Rodrigo P.; Schultz, Stephanie A.; Boots, Elizabeth A.; Bendlin, Barbara B.; Sager, Mark A.; Hermann, Bruce P.; Johnson, Sterling C.; Asthana, Sanjay; Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53792 USA. [Almeida, Rodrigo P.; Schultz, Stephanie A.; Austin, Benjamin P.; Boots, Elizabeth A.; Dowling, N. Maritza; Gleason, Carey E.; Bendlin, Barbara B.; Sager, Mark A.; Hermann, Bruce P.; Carlsson, Cynthia M.; Johnson, Sterling C.; Asthana, Sanjay; Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53792 USA. [Dowling, N. Maritza] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53792 USA. [Dowling, N. Maritza; Hermann, Bruce P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53792 USA. [Zetterberg, Henrik] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Molndal, Sweden. [Zetterberg, Henrik] Univ London, Inst Neurol, London, England. RP Okonkwo, OC (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Alzheimers Dis Res Ctr, Madison, WI 53792 USA. EM ozioma@medicine.wisc.edu OI Schultz, Stephanie/0000-0001-8460-4415 FU National Institute on Aging [K23 AG045957, R01 AG031790, R01 AG021155, R01 AG027161, P50 AG033514]; Clinical and Translational Science Award [UL1RR025011]; Wisconsin Alumni Research Foundation; Helen Bader Foundation; Northwestern Mutual Foundation; Extendicare Foundation; US Department of Veterans Affairs; Coordination for the Improvement of Higher Education Personnel (CAPES) Foundation FX This work was supported by grants K23 AG045957 (Dr Okonkwo), R01 AG031790 (Dr Carlsson), R01 AG021155 and R01 AG027161 (Dr Johnson), and P50 AG033514 (Dr Asthana) from the National Institute on Aging and by Clinical and Translational Science Award UL1RR025011 to the University of Wisconsin, Madison. Portions of this research were supported by the Wisconsin Alumni Research Foundation, Helen Bader Foundation, Northwestern Mutual Foundation, and Extendicare Foundation, as well as by the US Department of Veterans Affairs, including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison. Mr Almeida's yearlong study abroad at the University of Wisconsin, Madison, was funded by a scholarship from the Coordination for the Improvement of Higher Education Personnel (CAPES) Foundation. NR 43 TC 13 Z9 13 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2015 VL 72 IS 6 BP 699 EP 706 DI 10.1001/jamaneurol.2015.0098 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CK1BC UT WOS:000355939400015 PM 25893879 ER PT J AU Fox, MD Alterman, RL AF Fox, Michael D. Alterman, Ron L. TI Brain Stimulation for Torsion Dystonia SO JAMA NEUROLOGY LA English DT Review ID SURGICAL-TREATMENT; SEGMENTAL DYSTONIA; CERVICAL DYSTONIA; ADVERSE EVENTS; DBS; MANAGEMENT; TRIAL AB IMPORTANCE Dystonia is a heterogeneous neurologic disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly used. OBJECTIVES To review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation and to discuss recent advances relevant to patient selection, surgical approach, programming, and mechanism of action. EVIDENCE REVIEW PubMed was searched for publications on the clinical effect of brain stimulation in dystonia up through December 31, 2014. Recent meta-analyses, consensus statements, and evidence-based guidelines were incorporated. Emphasis was placed on deep brain stimulation (DBS) and randomized clinical trials; however, other stimulation modalities and trial designs were included. For each intervention the mean change in dystonia severity, number of patients studied, and evidence of efficacy based on American Academy of Neurology criteria were determined. FINDINGS Strong (level B) evidence supports the use of DBS for the treatment of primary generalized or segmental dystonia, especially when due to mutation in the DYT1 gene, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer's cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques, including epidural cortical stimulation and noninvasive brain stimulation, have been investigated, but generally report smaller effect sizes in fewer patients. CONCLUSIONS AND RELEVANCE Patients with dystonia that is not adequately controlled with standard medical therapy should be referred for consideration of DBS, especially patients with generalized, segmental, or cervical dystonia. Other less-invasive stimulation modalities require further research before being considered a therapeutic alternative. C1 [Fox, Michael D.] Harvard Univ, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Fox, Michael D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02215 USA. [Fox, Michael D.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02215 USA. [Alterman, Ron L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Neurosurg,Dept Surg, Boston, MA 02215 USA. RP Fox, MD (reprint author), Harvard Univ, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Kirstein Ste 448, Boston, MA 02215 USA. EM foxmdphd@gmail.com FU National Institutes of Health [K23NSO83741]; AAN/American Brain Foundation; Sidney R. Baer Foundation FX The present work was supported in part by grant K23NSO83741 from the National Institutes of Health, by AAN/American Brain Foundation, and by the Sidney R. Baer Foundation. NR 27 TC 11 Z9 11 U1 3 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2015 VL 72 IS 6 BP 713 EP 719 DI 10.1001/jamaneurol.2015.51 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CK1BC UT WOS:000355939400017 PM 25894231 ER PT J AU Nagiel, A Sadda, SR Sarraf, D AF Nagiel, Aaron Sadda, SriniVas R. Sarraf, David TI A Promising Future for Optical Coherence Tomography Angiography SO JAMA OPHTHALMOLOGY LA English DT Editorial Material C1 [Nagiel, Aaron; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA. [Sadda, SriniVas R.] Univ Calif Los Angeles, David Geffen Sch Med, Doheny Eye Inst, Los Angeles, CA 90095 USA. [Sarraf, David] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu OI Nagiel, Aaron/0000-0001-7275-6980 NR 7 TC 26 Z9 27 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JUN PY 2015 VL 133 IS 6 BP 629 EP 630 DI 10.1001/jamaophthalmol.2015.0668 PG 2 WC Ophthalmology SC Ophthalmology GA CK2MI UT WOS:000356044400009 PM 25856444 ER PT J AU Chen, TC Schein, OD Miller, JW AF Chen, Teresa C. Schein, Oliver D. Miller, Joan W. TI Sentinel Events, Serious Reportable Events, and Root Cause Analysis SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID SURGERY C1 [Chen, Teresa C.; Miller, Joan W.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Schein, Oliver D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu NR 7 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JUN PY 2015 VL 133 IS 6 BP 631 EP 632 DI 10.1001/jamaophthalmol.2015.0672 PG 2 WC Ophthalmology SC Ophthalmology GA CK2MI UT WOS:000356044400010 PM 25742139 ER PT J AU Mathieu, AL Verronese, E Rice, GI Fouyssac, F Bertrand, Y Picard, C Chansel, M Walter, JE Notarangelo, LD Butte, MJ Nadeau, KC Csomos, K Chen, DJ Chen, K Delgado, A Riga, C Bardin, C Schuetz, C Moshous, D Reumaux, H Plenat, F Phan, A Zabot, MT Balme, B Viel, S Bienvenu, J Cochat, P van der Burg, M Caux, C Kemp, EH Rouvet, I Malcus, C Meritet, JF Lim, A Crow, YJ Fabien, N Menetrier-Caux, C De Villartay, JP Walzer, T Belot, A AF Mathieu, Anne-Laure Verronese, Estelle Rice, Gillian I. Fouyssac, Fanny Bertrand, Yves Picard, Capucine Chansel, Marie Walter, Jolan E. Notarangelo, Luigi D. Butte, Manish J. Nadeau, Kari Christine Csomos, Krisztian Chen, David J. Chen, Karin Delgado, Ana Riga, Chantal Bardin, Christine Schuetz, Catharina Moshous, Despina Reumaux, Heloise Plenat, Francois Phan, Alice Zabot, Marie-Therese Balme, Brigitte Viel, Sebastien Bienvenu, Jacques Cochat, Pierre van der Burg, Mirjam Caux, Christophe Kemp, E. Helen Rouvet, Isabelle Malcus, Christophe Meritet, Jean-Francois Lim, Annick Crow, Yanick J. Fabien, Nicole Menetrier-Caux, Christine De Villartay, Jean-Pierre Walzer, Thierry Belot, Alexandre TI PRKDC mutations associated with immunodeficiency, granuloma, and autoimmune regulator-dependent autoimmunity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Autoimmune regulator; tolerance; DNA-dependent protein kinase catalytic subunit; PRKDC; autoimmunity; VDJ recombination; severe combined immunodeficiency; recombination-activating gene ID HYPEREOSINOPHILIA OMENNS SYNDROME; CALCIUM-SENSING RECEPTOR; T-CELLS; DISEASE; AUTOANTIBODIES; DEFICIENCY; TOLERANCE; RESPONSES; DEFECTS; THYMUS AB Background: PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-dependent protein kinase [DNA-PK]) crucial for DNA double-strand break repair and V(D)J recombination. In mice DNA-PK also interacts with the transcription factor autoimmune regulator (AIRE) to promote central T-cell tolerance. Objective: We sought to understand the causes of an inflammatory disease with granuloma and autoimmunity associated with decreasing T- and B-cell counts over time that had been diagnosed in 2 unrelated patients. Methods: Genetic, molecular, and functional analyses were performed to characterize an inflammatory disease evocative of a combined immunodeficiency. Results: We identified PRKDC mutations in both patients. These patients exhibited a defect in DNA double-strand break repair and V(D)J recombination. Whole-blood mRNA analysis revealed a strong interferon signature. On activation, memory T cells displayed a skewed cytokine response typical of T(H)2 and T(H)1 but not T(H)17. Moreover, mutated DNA-PKcs did not promote AIRE-dependent transcription of peripheral tissue antigens in vitro. The latter defect correlated in vivo with production of anti-calcium-sensing receptor autoantibodies, which are typically found in AIRE-deficient patients. In addition, 9 months after bone marrow transplantation, patient 1 had Hashimoto thyroiditis, suggesting that organ-specific autoimmunity might be linked to nonhematopoietic cells, such as AIRE-expressing thymic epithelial cells. Conclusion: Deficiency of DNA-PKcs, a key AIRE partner, can present as an inflammatory disease with organ-specific autoimmunity, suggesting a role for DNA-PKcs in regulating autoimmune responses and maintaining AIRE-dependent tolerance in human subjects. C1 [Mathieu, Anne-Laure; Viel, Sebastien; Bienvenu, Jacques; Walzer, Thierry; Belot, Alexandre] Univ Lyon, Int Ctr Infectiol Res, CIRI, Lyon, France. [Mathieu, Anne-Laure; Viel, Sebastien; Bienvenu, Jacques; Walzer, Thierry; Belot, Alexandre] INSERM, U1111, F-69008 Lyon, France. [Mathieu, Anne-Laure; Viel, Sebastien; Bienvenu, Jacques; Walzer, Thierry; Belot, Alexandre] Ecole Normale Super Lyon, F-69364 Lyon, France. [Mathieu, Anne-Laure; Rice, Gillian I.; Viel, Sebastien; Bienvenu, Jacques; Walzer, Thierry; Belot, Alexandre] CNRS, UMR5308, Lyon, France. [Verronese, Estelle; Delgado, Ana; Riga, Chantal; Bardin, Christine; Caux, Christophe; Menetrier-Caux, Christine] Univ Lyon, Plateforme Innovat Immunomonitoring & Immunothera, Ctr Rech Cancerol Lyon, INSERM,U1052,Ctr Leon Berard, Lyon, France. [Crow, Yanick J.] Manchester Acad Hlth Ctr, Fac Med & Human Sci, Inst Human Dev, Manchester Ctr Genom Med, Manchester, Lancs, England. [Fouyssac, Fanny] CHU NANCY, Children Hosp, Dept Oncol, Vandoeuvre Les Nancy, France. [Bertrand, Yves] Univ Lyon 1, Hosp Civils Lyon, Inst Hematol & Oncol Pediat, F-69365 Lyon, France. [Picard, Capucine] Paris Descartes Univ, Necker Hosp,AP HP, Necker Branch,INSERM,U1163,Sorbonne Paris Cite,Im, Study Ctr Primary Immunodeficiencies,Lab Human Ge, Paris, France. [Moshous, Despina; De Villartay, Jean-Pierre] Univ Paris 05, Lab Dynam Genome & Syst Immunitaire, Sorbonne Paris Cite, INSERM,UMR 1163,Imagine Inst, Paris, France. [Walter, Jolan E.; Csomos, Krisztian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Allergy & Immunol, Boston, MA USA. [Walter, Jolan E.; Csomos, Krisztian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Chansel, Marie; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Chansel, Marie; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Boston, MA USA. [Butte, Manish J.; Nadeau, Kari Christine] Stanford Univ, Dept Pediat, Div Immunol Allergy & Rheumatol, Stanford, CA 94305 USA. [Chen, David J.] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Div Mol Radiat Biol, Dallas, TX 75390 USA. [Chen, Karin] Univ Utah, Sch Med, Dept Pediat, Div Allergy Immunol & Rheumatol, Salt Lake City, UT USA. [Schuetz, Catharina] Univ Med Ctr Ulm, Dept Pediat & Adolescent Med, Ulm, Germany. [Reumaux, Heloise] Jeanne de Flandre Hosp, Pediat Rheumatol & Emergency Unit, Lille, France. [Plenat, Francois] CHU Nancy, Hematooncol Pediat, Dept Pathol, Vandoeuvre Les Nancy, France. [Balme, Brigitte] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Dept Pathol, Lyon, France. [Zabot, Marie-Therese; Rouvet, Isabelle] Hosp Civils Lyon, Biotechnol Dept, Lyon, France. [Viel, Sebastien; Bienvenu, Jacques; Fabien, Nicole] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Dept Immunobiol, Lyon, France. [Phan, Alice; Cochat, Pierre; Belot, Alexandre] Hosp Civils Lyon, Pediat Rheumatol Nephrol & Dermatol Dept, Lyon, France. [Phan, Alice; Cochat, Pierre; Belot, Alexandre] Hosp Civils Lyon, EPICIME, Lyon, France. [Phan, Alice; Cochat, Pierre; Belot, Alexandre] Univ Lyon 1, F-69365 Lyon, France. [van der Burg, Mirjam] Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Kemp, E. Helen] Univ Sheffield, Dept Human Metab, Sheffield S10 2TN, S Yorkshire, England. [Malcus, Christophe] Hosp Civils Lyon, Hop Edouard Herriot, Cell Immunol Dept, Lyon, France. [Meritet, Jean-Francois] Hop Cochin, AP HP, Virol Unit, F-75674 Paris, France. [Lim, Annick] Inst Pasteur, Dept Immunol, Immunoscope Grp, F-75724 Paris, France. RP Belot, A (reprint author), Hosp Civils Lyon, Hop Femme Mere Enfant, Serv Nephrol, Rhumatol,Dermatol Pediat, 57 Bd Pinel, F-69677 Bron, France. EM alexandre.belot@chu.lyon.fr RI Notarangelo, Luigi/F-9718-2016; Viel, Sebastien/A-7258-2016; Walzer, Thierry/L-9418-2014; Caux, Christophe/G-2851-2013; Moshous, Despina/B-7507-2017; Kemp, Elizabeth Helen/D-1665-2011; Rice, Gillian/G-3128-2015 OI Crow, Yanick/0000-0001-7211-7564; Butte, Manish/0000-0002-4490-5595; Notarangelo, Luigi/0000-0002-8335-0262; Viel, Sebastien/0000-0002-5085-443X; Kemp, Elizabeth Helen/0000-0002-0313-8916; Rice, Gillian/0000-0002-4223-0571 FU Hospices Civils de Lyon; Societe Francaise de Rhumatologie; INSERM; ANR [ANR-14-CE14-0026-03]; National Institutes of Health [CA162804, CPRIT RP110465]; LYRIC grant [INCa_4664]; European Research Council [ERC-Stg 281025]; Institut National de la Sante et de la Recherche Medicale (INSERM); Centre National de la Recherche Scientifique (CNRS); Universite Claude Bernard Lyon 1; ENS de Lyon FX Supported by Hospices Civils de Lyon, Societe Francaise de Rhumatologie, INSERM and ANR (ANR-14-CE14-0026-03) (to A.B.), as well as National Institutes of Health grant CA162804 (to D.J.C.), CPRIT RP110465 (to D.J.C.), and LYRIC grant INCa_4664 (to C.C.). T.W.'s laboratory is supported by European Research Council (ERC-Stg 281025), Institut National de la Sante et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Universite Claude Bernard Lyon 1, ENS de Lyon. Y.J.C. acknowledges the European Research Council (GA 309449). NR 42 TC 17 Z9 17 U1 3 U2 17 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2015 VL 135 IS 6 BP 1578 EP U294 DI 10.1016/j.jaci.2015.01.040 PG 16 WC Allergy; Immunology SC Allergy; Immunology GA CK0ZC UT WOS:000355933400021 PM 25842288 ER PT J AU Ruben, MA Hall, JA Curtin, EM Blanch-Hartigan, D Ship, AN AF Ruben, Mollie A. Hall, Judith A. Curtin, Elizabeth M. Blanch-Hartigan, Danielle Ship, Amy N. TI Discussion increases efficacy when training accurate perception of patients' affect SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID CLINICIAN; SATISFACTION; RECOGNITION; SKILLS AB Patients benefit when their healthcare providers accurately recognize their affect. The efficacy of three short-term training components, practice, practice with feedback, and discussion with practice and feedback, to improve accuracy for judging patients' affect was experimentally assessed. Undergraduate participants were randomly assigned in pairs to one of the training conditions or an untrained control condition and the effect of training was measured using the Test of Accurate Perception of Patients' Affect (TAPPA). Participants were significantly more accurate on the TAPPA in the discussion with feedback and practice condition compared with the control condition. There was a significant linear trend in accuracy across training elements. Results suggest that a 40-min discussion with feedback and practice training can significantly improve interpersonal accuracy. C1 [Ruben, Mollie A.] US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Hall, Judith A.] Northeastern Univ, Psychol Dept, Boston, MA USA. [Curtin, Elizabeth M.] Arbour Counseling Serv, Allston, MA USA. [Blanch-Hartigan, Danielle] Bentley Univ, Nat & Appl Sci, Bentley, WA, Australia. [Ship, Amy N.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. [Ship, Amy N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ruben, MA (reprint author), US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, 150 South Huntington Ave,Bldg 9, Boston, MA 02130 USA. EM Mollie.Ruben@va.gov FU Agency for Healthcare Research and Quality FX Funded by a grant from the Agency for Healthcare Research and Quality. NR 30 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9029 EI 1559-1816 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD JUN PY 2015 VL 45 IS 6 BP 355 EP 362 DI 10.1111/jasp.12301 PG 8 WC Psychology, Social SC Psychology GA CJ8FR UT WOS:000355736100005 ER PT J AU Fisher, MB Henning, EA Soegaard, N Bostrom, M Esterhai, JL Mauck, RL AF Fisher, Matthew B. Henning, Elizabeth A. Soeegaard, Nicole Bostrom, Marc Esterhai, John L. Mauck, Robert L. TI Engineering meniscus structure and function via multi-layered mesenchymal stem cell-seeded nanofibrous scaffolds SO JOURNAL OF BIOMECHANICS LA English DT Article DE Tissue engineering; Meniscus; Nanofibrous scaffold; Electrospinning; Mechanical properties ID MEDIAL MENISCUS; POLYURETHANE SCAFFOLD; PARTIAL MENISCECTOMY; ANNULUS FIBROSUS; KNEE MENISCUS; JOINT; REGENERATION; MECHANICS; MODEL; REPLACEMENT AB Despite complex macroscopic and microscopic structural features of native tissue, including the circumferentially and radially aligned collagen bundles essential for mechanical function. To mimic this structural hierarchy, this study developed multi-lamellar mesenchymal stem cell (MSC)-seeded nanofibrous constructs. Bovine MSCs were seeded onto nanofibrous scaffolds comprised of poly(e-caprolactone) with fibers aligned in a single direction (0 degrees or 90 degrees to the scaffold long axis) or circumferentially aligned (C). Multi-layer groups (0 degrees/0 degrees/0 degrees, 90 degrees/90 degrees/90 degrees, 0 degrees/90 degrees/0 degrees, 90 degrees/0 degrees/90 degrees, and C/C/C) were created and cultured for a total of 6 weeks under conditions favoring fibrocartilaginous tissue formation. Tensile testing showed that 0 degrees and C single layer constructs had stiffness values several fold higher than 90 degrees constructs. For multi-layer groups, the stiffness of 0 degrees/0 degrees/0 degrees constructs was higher than all other groups, while 90 degrees/90 degrees/90 degrees constructs had the lowest values. Data for collagen content showed a general positive interactive effect for multi-layers relative to single layer constructs, while a positive interaction for stiffness was found only for the C/C/C group. Collagen content and cell infiltration occurred independent of scaffold alignment, and newly formed collagenous matrix followed the scaffold fiber direction. Structural hierarchies within multi-lamellar constructs dictated biomechanical properties, and only the C/C/C constructs with non-orthogonal alignment within layers featured positive mechanical reinforcement as a consequence of the layered construction. These multi-layer constructs may serve as functional substitutes for the meniscus as well as test beds to understand the complex mechanical principles that enable meniscus function. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Fisher, Matthew B.; Henning, Elizabeth A.; Soeegaard, Nicole; Bostrom, Marc; Esterhai, John L.; Mauck, Robert L.] Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Fisher, Matthew B.; Henning, Elizabeth A.; Esterhai, John L.; Mauck, Robert L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. [Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Fisher, Matthew B.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA. [Fisher, Matthew B.] N Carolina State Univ, Raleigh, NC 27695 USA. RP Mauck, RL (reprint author), Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, 424 Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu RI Fisher, Matthew/M-5809-2016 OI Fisher, Matthew/0000-0002-3212-0870 FU National Institutes of Health [R01 AR056624]; Department of Veterans' Affairs [I01 RX000174]; NIH Post-Doctoral National Research Service Award [F32 AR062971]; NIH sponsored Penn Center for Musculoskeletal Disorders [P30 AR050950] FX This work was supported by the National Institutes of Health (R01 AR056624) and the Department of Veterans' Affairs (I01 RX000174). Additional support was provided by an NIH Post-Doctoral National Research Service Award (F32 AR062971) and the NIH sponsored Penn Center for Musculoskeletal Disorders (P30 AR050950). Study sponsors had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. NR 44 TC 8 Z9 8 U1 7 U2 31 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 EI 1873-2380 J9 J BIOMECH JI J. Biomech. PD JUN 1 PY 2015 VL 48 IS 8 SI SI BP 1412 EP 1419 DI 10.1016/j.jbiomech.2015.02.036 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA CK3MK UT WOS:000356120000012 PM 25817333 ER PT J AU Maurer, MS Adamson, PB Costanzo, MR Eigler, N Gilbert, J Gold, MR Klapholz, M Saxon, LA Singh, JP Troughton, R Abraham, WT AF Maurer, Mathew S. Adamson, Philip B. Costanzo, Maria Rosa Eigler, Neal Gilbert, Joanne Gold, Michael R. Klapholz, Marc Saxon, Leslie A. Singh, Jagmeet P. Troughton, Richard Abraham, William T. TI Rationale and Design of the Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy Study (LAPTOP-HF) SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; hemodynamic monitoring; left atrial pressure; physician-directed; patient self-management ID PULMONARY-ARTERY PRESSURE; FOCUSED UPDATE; COMPASS-HF; MANAGEMENT; GUIDELINES; DEVICE; TRIAL; OUTCOMES; SENSOR AB Background: Daily measurements of left atrial pressure (LAP) may be useful for guiding adjustments in medical therapy that prevent clinical decompensation in patients with severe heart failure (BF). Study Design: LAPTOP-HF is a prospective, multicenter, randomized, controlled clinical trial in ambulatory patients with advanced heart failure in which the safety and clinical effectiveness of a physician-directed patient self-management therapeutic strategy based on LAP measured twice daily by means of an implantable sensor will be compared with a control group receiving optimal medical therapy. The trial will enroll up to 730 patients with New York Heart Association functional class III symptoms and either a hospitalization for HF during the previous 12 months or an elevated B-type natriuretic peptide level, regardless of ejection fraction, at up to 75 investigational centers. Randomization to the treatment group or control group will be at a 1:1 ratio in 3 strata based on the ejection fraction (EF > or <= 35%) and the presence of a de novo CRT device indication. Summary: LAPTOP-HF will provide essential information about the role of implantable LAP monitoring in conjunction with a new HF treatment paradigm across the spectrum of HF patients. C1 [Maurer, Mathew S.] Columbia Univ, New York Presbyterian Hosp, Allen Hosp, Med Ctr, New York, NY 10034 USA. [Adamson, Philip B.] Oklahoma Heart Hosp, Heart Failure Inst, Oklahoma City, OK USA. [Adamson, Philip B.] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK USA. [Adamson, Philip B.; Gilbert, Joanne] St Jude Med, Sylmar, CA USA. [Costanzo, Maria Rosa] Edward Heart Hosp, Midwest Heart Fdn, Naperville, IL USA. [Eigler, Neal] St Jude Med, Global Clin Affairs, Sylmar, CA USA. [Gold, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Klapholz, Marc] Rutgers State Univ, New Jersey Med Sch, Div Cardiovasc Dis, Newark, NJ 07102 USA. [Saxon, Leslie A.] Univ So Calif, Keck Sch Med, Div Cardiovasc Dis, Los Angeles, CA 90033 USA. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Cardiol Div,Electrophysiol Lab,Cardiac Arrhythmia, Boston, MA USA. [Troughton, Richard] Christchurch Sch Med & Hlth Sci, Dept Med, Christchurch, New Zealand. [Abraham, William T.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA. RP Maurer, MS (reprint author), Columbia Univ, New York Presbyterian Hosp, Allen Hosp, Med Ctr, 5141 Broadway,3 Field West,Room 035, New York, NY 10034 USA. EM msm10@cumc.columbia.edu FU St Jude Medical; LAPTOP-HF Steering Committee; Roche Diagnostics FX This trial is sponsored by St Jude Medical. Drs Mathew S. Maurer, Phil Adamson, Marc Klapholz, Leslie Saxon, Jagmeet P. Singh, and William T. Abraham are on the LAPTOP-HF Steering Committee and receive financial compensation for this activity. Dr Michael R. Gold is a consultant and does clinical trials for St Jude Medical, Boston Scientific, and Medtronic and is on the LAPTOP-HF Steering Committee. Dr Richard Troughton is on the LAPTOP Steering Committee and receives grant funding from St Jude Medical and Roche Diagnostics. Dr Maria Rosa Costanzo is a paid member of the LAPTOP-HF Steering Committee: Dr Neal Bigler is a paid consultant to St Jude Medical. Joanne Gilbert is the study manager and an employee of the sponsor, St Jude Medical. NR 24 TC 10 Z9 10 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD JUN PY 2015 VL 21 IS 6 BP 479 EP 488 DI 10.1016/j.cardfail.2015.04.012 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK3GP UT WOS:000356104900008 PM 25921522 ER PT J AU Fang, JC Ewald, GA Allen, LA Butler, J Canary, CAW Colvin-Adams, M Dickinson, MG Levy, P Stough, WG Sweitzer, NK Teerlink, JR Whellan, DJ Albert, NM Krishnamani, R Rich, MW Walsh, MN Bonnell, MR Carson, PE Chan, MC Dries, DL Hernandez, AF Hershberger, RE Katz, SD Moore, S Rodgers, JE Rogers, JG Vest, AR Givertz, MM AF Fang, James C. Ewald, Gregory A. Allen, Larry A. Butler, Javed Canary, Cheryl A. Westlake Colvin-Adams, Monica Dickinson, Michael G. Levy, Phillip Stough, Wendy Gattis Sweitzer, Nancy K. Teerlink, John R. Whellan, David J. Albert, Nancy M. Krishnamani, Rajan Rich, Michael W. Walsh, Mary N. Bonnell, Mark R. Carson, Peter E. Chan, Michael C. Dries, Daniel L. Hernandez, Adrian F. Hershberger, Ray E. Katz, Stuart D. Moore, Stephanie Rodgers, Jo E. Rogers, Joseph G. Vest, Amanda R. Givertz, Michael M. TI Advanced (Stage D) Heart Failure: A Statement From the Heart Failure Society of America Guidelines Committee SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; advanced; stage D ID VENTRICULAR ASSIST DEVICE; CARDIAC RESYNCHRONIZATION THERAPY; MECHANICAL CIRCULATORY SUPPORT; ARTERY CATHETERIZATION EFFECTIVENESS; ASSOCIATION TASK-FORCE; 6-MINUTE WALK TEST; II RISK SCORE; DESTINATION THERAPY; PULMONARY-HYPERTENSION; INTERNATIONAL-SOCIETY AB We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure. C1 [Fang, James C.] Univ Utah, Dept Med, Div Cardiovasc Med, Salt Lake City, UT 84112 USA. [Ewald, Gregory A.; Rich, Michael W.] Washington Univ, Sch Med, St Louis, MO USA. [Allen, Larry A.] Univ Colorado, Sch Med, Aurora, CO USA. [Butler, Javed] SUNY Stony Brook, Sch Med, Stony Brook Heart Inst, Stony Brook, NY 11794 USA. [Canary, Cheryl A. Westlake] Azusa Pacific Univ, Sch Nursing, Azusa, CA USA. [Colvin-Adams, Monica] Univ Michigan, Ann Arbor, MI 48109 USA. [Dickinson, Michael G.] Spectrum Hlth, Grand Rapids, MI USA. [Levy, Phillip] Wayne State Univ, Detroit, MI USA. [Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Dept Clin Res, Buies Creek, NC 27506 USA. [Sweitzer, Nancy K.] Univ Arizona, Sarver Heart Ctr, Tucson, AZ USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Whellan, David J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. [Albert, Nancy M.] Cleveland Clin, Nursing Inst, Cleveland, OH 44106 USA. [Albert, Nancy M.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Krishnamani, Rajan] Adv Cardiovasc Inst, Middletown, OH USA. [Walsh, Mary N.] Care Grp, Indianapolis, IN USA. [Bonnell, Mark R.] Univ Toledo, Toledo, OH 43606 USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Carson, Peter E.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Chan, Michael C.] Univ Alberta, Edmonton, AB, Canada. [Dries, Daniel L.] Temple Univ Hosp & Med Sch, Temple Heart & Vasc Inst, Philadelphia, PA 19140 USA. [Hernandez, Adrian F.; Rogers, Joseph G.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Hershberger, Ray E.] Ohio State Univ, Columbus, OH 43210 USA. [Katz, Stuart D.] NYU, Sch Med, Leon H Charney Div Cardiol, New York, NY USA. [Moore, Stephanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rodgers, Jo E.] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA. [Vest, Amanda R.] Tufts Med Ctr, Boston, MA USA. [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. RP Givertz, MM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mgivertz@partners.org RI Stough, Wendy/R-4287-2016; Hernandez, Adrian F./A-7818-2016; OI Stough, Wendy/0000-0001-8290-1205; Hernandez, Adrian F./0000-0003-3387-9616; Stuart, Katz/0000-0003-2340-2021 FU Thoratec; Biocontrol; Novartis; Shape Systems; St. Jude Medical; Otsuka; National Institutes of Health; National Heart, Lung, and Blood Institute; Patient-Centered Outcome Research Institute; Acorda; Amgen; Cadio3 Bioscienc; Janssen; Mast Therapeutics; Medtronic; St Jude; Trevena; Forest; Merck; ResMed; Pozon; Dalantin; AstraZeneca; Boston Scientific; Bristol-Myers Squibb; GlaxoSmithKline; Portola Pharmaceuticals FX Gregory A. Ewald: Honoraria/Speakers Bureau (Thoratec, Heart Ware); Research Grants/Fellowship Support (Thoratec, Biocontrol, Novartis, Shape Systems, St. Jude Medical).; Larry A. Allen: Consultant/Advisory Board (Novartis, Johnson & Johnson, Janssen); Research Grants/Fellowship Support (Otsuka, National Institutes of Health, National Heart, Lung, and Blood Institute, Patient-Centered Outcome Research Institute).; Nancy K. Sweitzer: Research Grants/Fellowship Support (Novartis, Acorda).; John Teerlink: Consultant/Advisory Board (Amgen, Luitpold, Madeleine Pharma, Mast Therapeutics); Research Grants/Fellowship Support (Amgen, Cadio3 Bioscience, Janssen, Mast Therapeutics, Medtronic, Novartis, St Jude, Trevena).; David J. Whellan: Consultant/Advisory Board (Clinalogix); Research Grants/Fellowship Support (Medtronic, Forest, Merck, ResMed, Pozon).; Daniel L. Dries: Research Grants/Fellowship Support (Dalantin).; Adrian F. Hernandez: Honoraria/Speakers Bureau (Amgen, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Pluristem, Sensible, MyoKardia); Consultant/Advisory Board (Amgen, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Pluristem, Sensible, MyoKardia); Research Grants/Fellowship Support (Amgen, AstraZeneca, Boston Scientific, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Medtronic, Portola Pharmaceuticals). NR 143 TC 28 Z9 28 U1 5 U2 10 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD JUN PY 2015 VL 21 IS 6 BP 519 EP 534 DI 10.1016/j.cardfail.2015.04.013 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK3GP UT WOS:000356104900011 PM 25953697 ER PT J AU Meyerhardt, JA Tepper, JE Venook, AP AF Meyerhardt, Jeffrey A. Tepper, Joel E. Venook, Alan P. TI Special Series: Advances in GI Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID COMPREHENSIVE MOLECULAR CHARACTERIZATION; METASTATIC PANCREATIC-CANCER; ADVANCED GASTRIC-CANCER; RANDOMIZED PHASE-III; LEUKEMIA GROUP-B; COLORECTAL-CANCER; 1ST-LINE THERAPY; ESOPHAGEAL CANCERS; RECTAL-CANCER; ONCOLOGY C1 [Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tepper, Joel E.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Venook, Alan P.] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jmeyerhardt@partners.org NR 35 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2015 VL 33 IS 16 BP 1717 EP + DI 10.1200/JCO.2015.60.8661 PG 5 WC Oncology SC Oncology GA CK2SK UT WOS:000356062200001 PM 25918284 ER PT J AU Van Blarigan, EL Meyerhardt, JA AF Van Blarigan, Erin L. Meyerhardt, Jeffrey A. TI Role of Physical Activity and Diet After Colorectal Cancer Diagnosis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID RANDOMIZED-CONTROLLED-TRIAL; III COLON-CANCER; LIFE-STYLE INTERVENTION; QUALITY-OF-LIFE; VITAMIN-D; NUTRITION COHORT; EXERCISE PROGRAM; PROSTATE-CANCER; DAIRY-PRODUCTS; BREAST-CANCER AB This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. (C) 2015 by American Society of Clinical Oncology C1 [Van Blarigan, Erin L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Van Blarigan, EL (reprint author), UCSF Box 0560,550 16th St,2nd Floor, San Francisco, CA 94158 USA. EM erin.vanblarigan@ucsf.edu FU National Institutes of Health [R01CA149222] FX Supported by Grant No. R01CA149222 from the National Institutes of Health. NR 61 TC 18 Z9 18 U1 6 U2 34 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2015 VL 33 IS 16 BP 1825 EP + DI 10.1200/JCO.2014.59.7799 PG 11 WC Oncology SC Oncology GA CK2SK UT WOS:000356062200013 PM 25918293 ER PT J AU Kreimer, S Belov, AM Ghiran, I Murthy, SK Frank, DA Ivanov, AR AF Kreimer, Simion Belov, Arseniy M. Ghiran, Ionita Murthy, Shashi K. Frank, David A. Ivanov, Alexander R. TI Mass-Spectrometry-Based Molecular Characterization of Extracellular Vesicles: Lipidomics and Proteomics SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE extracellular vesicle; EV; exosome; microvesicle; microparticle; molecular profiling; mass spectrometry; proteomics; lipidomics; post-translational modifications ID PROTEIN IDENTIFICATION TECHNOLOGY; CELL-DERIVED EXOSOMES; BLUE NATIVE ELECTROPHORESIS; HUMAN BLOOD-PLASMA; URINARY EXOSOMES; MEMBRANE-VESICLES; OVARIAN-CANCER; QUANTITATIVE PROTEOMICS; UBIQUITINATED PROTEINS; MULTIVESICULAR BODIES AB This review discusses extracellular vesicles (EVs), which are submicron-scale, anuclear, phospholipid bilayer membrane enclosed vesicles that contain lipids, metabolites, proteins, and RNA (micro and messenger). They are shed from many, if not all, cell types and are present in biological fluids and conditioned cell culture media. The term EV, as coined by the International Society of Extracellular Vesicles (ISEV), encompasses exosomes (30-100 nm in diameter), microparticles (100-1000 nm), apoptotic blebs, and other EV subsets. EVs have been implicated in cell cell communication, coagulation, inflammation, immune response modulation, and disease progression. Multiple studies report that EV secretion from disease-affected cells contributes to disease progression, e.g., tumor niche formation and cancer metastasis. EVs are attractive sources of biomarkers due to their biological relevance and relatively noninvasive accessibility from a range of physiological fluids. This review is focused on the molecular profiling of the protein and lipid constituents of EVs, with emphasis on mass-spectrometry-based "omic" analytical techniques. The challenges in the purification and molecular characterization of EVs, including contamination of isolates and limitations in sample quantities, are discussed along with possible solutions. Finally, the review discusses the limited but growing investigation of post-translational modifications of EV proteins and potential strategies for future in-depth molecular characterization of EVs. C1 [Kreimer, Simion; Belov, Arseniy M.; Murthy, Shashi K.; Ivanov, Alexander R.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. [Kreimer, Simion; Belov, Arseniy M.; Ivanov, Alexander R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Murthy, Shashi K.] Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. [Ghiran, Ionita] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Frank, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ivanov, AR (reprint author), Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. EM a.ivanov@neu.edu FU Dana-Farber Cancer Institute/Northeastern University Joint Program in Cancer Drug Development Grant [331062] FX This work was supported in part by a Dana-Farber Cancer Institute/Northeastern University Joint Program in Cancer Drug Development Grant no. 331062. This is contribution no. 1053 from the Barnett Institute. NR 182 TC 15 Z9 15 U1 12 U2 89 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD JUN PY 2015 VL 14 IS 6 BP 2367 EP 2384 DI 10.1021/pr501279t PG 18 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CK1IW UT WOS:000355962000001 PM 25927954 ER PT J AU Gbormittah, FO Bones, J Hincapie, M Tousi, F Hancock, WS Iliopoulos, O AF Gbormittah, Francisca O. Bones, Jonathan Hincapie, Marina Tousi, Fateme Hancock, William S. Iliopoulos, Othon TI Clusterin Glycopeptide Variant Characterization Reveals Significant Site-Specific Glycan Changes in the Plasma of Clear Cell Renal Cell Carcinoma SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Clear cell renal cell carcinoma; clusterin; site-specific analysis; glycoforms; collision-induced dissociation; N-glycan ID PROSTATE-SPECIFIC ANTIGEN; PANCREATIC-CANCER; MASS-SPECTROMETRY; HEPATOCELLULAR-CARCINOMA; ALPHA-FETOPROTEIN; SEMINAL PLASMA; GLYCOPROTEIN MICROARRAYS; GLYCOSYLATION PATTERNS; SELECTIVE DETECTION; LECTIN-BINDING AB Cancer-related alterations in protein glycosylation may serve as diagnostic or prognostic biomarkers or may be used for monitoring disease progression. Clusterin is a medium abundance, yet heavily glycosylated, glycoprotein that is upregulated in clear cell renal cell carcinoma (ccRCC) tumors. We recently reported that the N-glycan profile of clusterin is altered in the plasma of ccRCC patients. Here, we characterized the occupancy and the degree of heterogeneity of individual N-glycosylation sites of clusterin in the plasma of patients diagnosed with localized ccRCC, before and after curative nephrectomy (n = 40). To this end, we used tandem mass spectrometry of immunoaffinity-enriched plasma samples to analyze the individual glycosylation sites in clusterin. We determined the levels of targeted clusterin glycoforms containing either a biantennary digalactosylated disialylated (A2G2S2) glycan or a core fucosylated biantennary digalactosylated disialylated (FA2G2S2) glycan at N-glycosite N374. We showed that the presence of these two clusterin glycoforms differed significantly in the plasma of patients prior to and after curative nephrectomy for localized ccRCC. Removal of ccRCC led to a significant increase in the levels of both FA2G2S2 and A2G2S2 glycans in plasma clusterin. These changes were further confirmed by lectin blotting of plasma clusterin. It is envisioned that these identified glycan alterations may provide an additional level of therapeutic or biomarker sensitivity than levels currently achievable by monitoring expression differences alone. C1 [Gbormittah, Francisca O.; Tousi, Fateme; Hancock, William S.] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. [Gbormittah, Francisca O.; Tousi, Fateme; Hancock, William S.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Bones, Jonathan] NIBRT Natl Inst Bioproc Res & Training, Blackrock, Co Dublin, Ireland. [Hincapie, Marina] Genzyme Corp, Framingham, MA 01701 USA. [Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA. [Iliopoulos, Othon] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Hancock, WS (reprint author), Northeastern Univ, Barnett Inst, 360 Huntington Ave, Boston, MA 02115 USA. EM wi.hancock@neu.edu; oiliopoulos@partners.org FU National Institutes of Health/National Cancer Institute (NIH/NCI) [RO1 CA122591] FX This work was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) grant no. RO1 CA122591 (to O.I. and W.S.H.). We thank Dr. Shiaw-Lin Wu for helpful advice in the design of the mass spectrometric measurements. NR 65 TC 5 Z9 5 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD JUN PY 2015 VL 14 IS 6 BP 2425 EP 2436 DI 10.1021/pr501104j PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CK1IW UT WOS:000355962000005 PM 25855029 ER PT J AU Minzenberg, MJ Lesh, T Niendam, T Yoon, JH Cheng, YA Rhoades, R Carter, CS AF Minzenberg, Michael J. Lesh, Tyler Niendam, Tara Yoon, Jong H. Cheng, Yaoan Rhoades, Remy Carter, Cameron S. TI Conflict-related anterior cingulate functional connectivity is associated with past suicidal ideation and behavior in recent-onset schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Conflict-monitoring; Suicidal ideation; Suicidal behavior; Anterior cingulate; Functional connectivity ID MAJOR DEPRESSIVE DISORDER; PREFRONTAL CORTEX DYSFUNCTION; POSITRON-EMISSION-TOMOGRAPHY; 1ST EPISODE PSYCHOSIS; COGNITIVE CONTROL; BIPOLAR DISORDER; WORST-POINT; BRAIN; RISK; TASK AB Suicide is highly prevalent in schizophrenia (SZ), yet it remains unclear how suicide risk factors such as past suicidal ideation or behavior relate to brain function. Circuits modulated by the prefrontal cortex (PFC) are altered in SZ, including in dorsal anterior cingulate cortex (dACC) during conflict-monitoring (an important component of cognitive control), and dACC changes are observed in post-mortem studies of heterogeneous suicide victims. We tested whether conflict-related dACC functional connectivity is associated with past suicidal ideation and behavior in SZ. 32 patients with recent-onset of DSM-IV-TR-deflned SZ were evaluated with the Columbia Suicide Severity Rating Scale and functional MRI during cognitive control (AX-CPT) task performance. Group-level regression models relating past history of suicidal ideation or behavior to dACC-seeded functional connectivity during conflict-monitoring controlled for severity of depression, psychosis and impulsivity. Past suicidal ideation was associated with relatively higher functional connectivity of the dACC with the precuneus during conflict-monitoring. Intensity of worst-point past suicidal ideation was associated with relatively higher dACC functional connectivity in medial parietal lobe and striato-thalamic nuclei. In contrast, among those with past suicidal ideation (n = 17), past suicidal behavior was associated with lower conflict-related dACC connectivity with multiple lateral and medial PFC regions, parietal and temporal cortical regions. This study provides unique evidence that recent-onset schizophrenia patients with past suicidal ideation or behavior show altered dACC-based circuit function during conflict-monitoring. Suicidal ideation and suicidal behavior have divergent patterns of associated dACC functional connectivity, suggesting a differing pattern of conflict-related brain dysfunction with these two distinct features of suicide phenomenology. Published by Elsevier Ltd. C1 [Minzenberg, Michael J.; Cheng, Yaoan] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Lesh, Tyler; Niendam, Tara; Carter, Cameron S.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. [Yoon, Jong H.; Rhoades, Remy] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Carter, Cameron S.] Stanford Sch Med, Dept Psychiat, Palo Alto, CA USA. RP Minzenberg, MJ (reprint author), San Francisco VA Med Ctr, Outpatient Mental Hlth, 116C,4150 Clement St, San Francisco, CA 94121 USA. EM Michael.minzenberg@ucsf.edu RI Niendam, Tara/K-8475-2015; OI Niendam, Tara/0000-0003-2285-5002; Cheng, Yaoan/0000-0001-5858-6161 FU American Foundation for Suicide Prevention Young Investigator Award; Doris Duke Charitable Foundation [2009045, MH059883] FX This work was supported by an American Foundation for Suicide Prevention Young Investigator Award, and the Doris Duke Charitable Foundation Grant # 2009045, both to MJM, and MH059883 to CSC. NR 58 TC 5 Z9 5 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2015 VL 65 BP 95 EP 101 DI 10.1016/j.jpsychires.2015.04.002 PG 7 WC Psychiatry SC Psychiatry GA CK3NR UT WOS:000356123300013 PM 25891474 ER PT J AU Piel, J Finkle, MJ Giske, M Leong, GB AF Piel, Jennifer Finkle, Michael J. Giske, Megan Leong, Gregory B. TI Determining a Criminal Defendant's Competency to Proceed With an Extradition Hearing SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID TRIAL AB When a criminal defendant flees from one state (often referred to as the requesting state) to another (often referred to as the asylum state), the requesting state can demand that the asylum state return the defendant through a process called extradition. Only a handful of states have considered a fugitive's right to be competent to proceed with an extradition hearing. Those states fall into three categories. Some states apply the same standard as in criminal trial competency cases. Others apply a more limited competency standard. Two have found that a fugitive has no right to be competent to proceed in an extradition hearing. The particular legal test adopted affects the nature and scope of the competency evaluation conducted by the psychiatrist or psychologist in the extradition hearing. In addition, we are not aware of any state that has considered what happens to the fugitive if he is ultimately found not competent to proceed. Legislation, either state by state or through amendments to the Uniform Criminal Extradition Act, can provide the legal and psychiatric communities with guidance in assessing competency initially and in taking appropriate steps if the fugitive is ultimately found not competent. C1 [Piel, Jennifer] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Piel, Jennifer] Univ Washington, Seattle, WA 98195 USA. [Finkle, Michael J.] King Cty Dist Court, King County, WA USA. [Finkle, Michael J.] Seattle Univ, Sch Law, Law, Seattle, WA 98122 USA. [Giske, Megan] King Cty Dept Publ Def, Northwest Defenders Div, Seattle, WA USA. [Leong, Gregory B.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. RP Piel, J (reprint author), 1660 South Columbian Way,MS-116, Seattle, WA 98108 USA. EM jennifer.piel@va.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 EI 1943-3662 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PD JUN 1 PY 2015 VL 43 IS 2 BP 201 EP 209 PG 9 WC Law; Psychiatry SC Government & Law; Psychiatry GA CK4FB UT WOS:000356175700011 PM 26071510 ER PT J AU Bancroft, LW Kransdorf, MI Adler, R Appel, M Beaman, FD Bernard, SA Bruno, MA Dempsey, ME Fries, IB Khoury, V Khurana, B Mosher, TJ Roberts, CC Tuite, MJ Ward, RJ Zoga, AC Weissman, BN AF Bancroft, Laura W. Kransdorf, Mark I. Adler, Ronald Appel, Marc Beaman, Francesca D. Bernard, Stephanie A. Bruno, Michael A. Dempsey, Molly E. Fries, Ian B. Khoury, Viviane Khurana, Bharti Mosher, Timothy J. Roberts, Catherine C. Tuite, Michael J. Ward, Robert J. Zoga, Adam C. Weissman, Barbara N. TI ACR Appropriateness Criteria Acute Trauma to the Foot SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria; acute trauma; foot trauma; Ottawa Rules; adult; child ID OTTAWA ANKLE RULES; CLINICAL-PREDICTION RULES; TISSUE FOREIGN-BODIES; LISFRANC LIGAMENT; SOFT-TISSUE; PROSPECTIVE VALIDATION; ANATOMIC CORRELATION; SURGICAL CORRELATION; COMPUTED-TOMOGRAPHY; DIAGNOSTIC-ACCURACY AB This ACR Appropriateness Criteria article offers imaging triage guidance for several variants of patients presenting with acute foot trauma. Patients meeting inclusion criteria for the Ottawa Rules should undergo a 3-view radiographic series. Diabetic patients with peripheral neuropathy should undergo radiography, even though they do not meet the Ottawa Rules inclusion criteria. Patients with suspected midfoot and/or Lisfranc injury should undergo 3-view radiographs with weight bearing on at least the anterior posterior view. Patients with suspected Lisfranc injury and normal radiographs should be considered for MRI and CT on a case-by-case basis. MRI or ultrasound could confirm cases of suspected acute tendon rupture. Radiography is the initial imaging modality for suspected plantar plate injury after metatarsal phalangeal joint injury. Weight-bearing anterior posterior, lateral, and sesamoid axial views may detect proximal migration of the hallux sesamoids. Ultrasound or MRI can directly evaluate the capsuloligamentous complex, specifically the plantar plate. Radiography can detect radiopaque penetrating foreign bodies, and ultrasound can be helpful in detecting those that are nonradiopaque. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures, by the panel. In instances in which evidence is lacking or is not definitive, expert opinion may be used to recommend imaging and treatment. C1 [Bancroft, Laura W.] Radiol Specialists Florida, Maitland, FL 32751 USA. [Kransdorf, Mark I.; Roberts, Catherine C.] Mayo Clin, Phoenix, AZ USA. [Adler, Ronald] NYU, Ctr Musculoskeletal Care, New York, NY USA. [Appel, Marc] James J Peters VA Med Ctr, Bronx, NY USA. [Appel, Marc; Fries, Ian B.] Amer Acad Orthopaed Surg, Rosemont, IL USA. [Beaman, Francesca D.] Univ Kentucky, Lexington, KY USA. [Bernard, Stephanie A.; Bruno, Michael A.; Mosher, Timothy J.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Dempsey, Molly E.] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA. [Khoury, Viviane] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Khurana, Bharti; Weissman, Barbara N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tuite, Michael J.] Univ Wisconsin Hosp, Madison, WI USA. [Ward, Robert J.] Tufts Med Ctr, Boston, MA USA. [Zoga, Adam C.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Bancroft, LW (reprint author), Radiol Specialists Florida, 900 Winderley Pl Ste 1100, Maitland, FL 32751 USA. EM laura.bancroft@flhosp.org RI Mosher, Timothy/J-5146-2015; OI Mosher, Timothy/0000-0001-8573-3614; Bancroft, Laura/0000-0002-3997-5759 FU Medical Metrics; Kensey Nash Corporation FX Timothy J. Mosher, MD, is a paid consultant for Medical Metrics, a paid consultant for Kensey Nash Corporation, and a stockholder with Johnson and Johnson. NR 52 TC 1 Z9 1 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2015 VL 12 IS 6 BP 575 EP 581 DI 10.1016/j.jacr.2015.02.018 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1IM UT WOS:000355961000011 PM 25935824 ER PT J AU Boland, GW Weilburg, J Duszak, R AF Boland, Giles W. Weilburg, Jeffrey Duszak, Richard, Jr. TI Imaging Appropriateness and Implementation of Clinical Decision Support SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Boland, Giles W.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Weilburg, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Sch Med, Dept Radiol, Atlanta, GA USA. RP Boland, GW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 4 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2015 VL 12 IS 6 BP 601 EP 603 DI 10.1016/j.jacr.2015.03.014 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1IM UT WOS:000355961000016 PM 26047400 ER PT J AU Margolis, NE Mackey, RA Sarwar, A Fintelmann, FJ AF Margolis, Nathaniel E. Mackey, Robert A. Sarwar, Ammar Fintelmann, Florian J. TI 15 Practical Ways to Add Value in Daily Practice: An Imaging 3.0 Primer for Trainees SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Margolis, Nathaniel E.] NYU, Dept Radiol, Sch Med, New York, NY 10016 USA. [Mackey, Robert A.] Georgia Regents Univ, Dept Radiol, Augusta, GA USA. [Sarwar, Ammar] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Fintelmann, Florian J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Margolis, NE (reprint author), NYU, Dept Radiol, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA. EM natemargolismd@gmail.com NR 5 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2015 VL 12 IS 6 BP 638 EP 640 DI 10.1016/j.jacr.2015.03.002 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1IM UT WOS:000355961000025 PM 26047405 ER PT J AU Morey, JM Haney, NM Schoppe, K Hawkins, CM AF Morey, Jose M. Haney, Nora M. Schoppe, Kurt Hawkins, C. Matthew TI Adding Value as Young Radiologists: Challenges and Opportunities, Part 2 SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID SOCIAL MEDIA; IMPACT C1 [Morey, Jose M.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Morey, Jose M.] US Dept Vet Affairs, Hampton, VA USA. [Haney, Nora M.] Tulane Univ, Sch Med, New Orleans, LA 70130 USA. [Schoppe, Kurt] Radiol Associates North Texas, Arlington, TX USA. [Hawkins, C. Matthew] Emory Univ, Sch Med, Atlanta, GA USA. RP Haney, NM (reprint author), Tulane Univ, Sch Med, 929 Washington Ave, New Orleans, LA 70130 USA. EM nhaney@tulane.edu NR 24 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2015 VL 12 IS 6 BP 641 EP 644 DI 10.1016/j.jacr.2015.02.004 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1IM UT WOS:000355961000026 PM 25935823 ER PT J AU Stahlman, S Javanbakht, M Cochran, S Hamilton, AB Shoptaw, S Gorbach, PM AF Stahlman, Shauna Javanbakht, Marjan Cochran, Susan Hamilton, Alison B. Shoptaw, Steven Gorbach, Pamina M. TI Mental Health and Substance Use Factors Associated With Unwanted Sexual Contact Among US Active Duty Service Women SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; GENDER-DIFFERENCES; RECENT VICTIMS; MILITARY; VETERANS; ASSAULT; TRAUMA; RAPE; HARASSMENT; DRINKING AB Many U.S. military women are exposed to unwanted sexual contact during military service, which can have important implications for mental health. Using data from the 2008 Department of Defense Survey of Health Related Behaviors, we employed multiple logistic regression methods to examine whether unwanted sexual contact was associated with stress, screening positive for mental disorders, or substance use, among active duty service women. The sample included 7,415 female military personnel, of whom 13.4% reported unwanted sexual contact (including any touching of genitals) since entering the military. After adjusting for potentially confounding variables, factors independently associated with unwanted sexual contact included military-related stress (adjusted odds ratio [AOR] = 2.44), family/personal life-related stress (AOR = 1.78), and gender-related stress (AOR = 1.98) in the past 12 months. In addition, screening positive for depression, anxiety, posttraumatic stress disorder, or psychological distress, and suicidal ideation or attempt were associated with unwanted sexual contact (AOR = 1.57-2.11). For drug/alcohol use, only misuse of tranquilizers/muscle relaxers (past 12 months) was associated with report of unwanted sexual contact (AOR = 1.35). Given the prevalence of unwanted sexual contact and corresponding adverse health outcomes in this sample of active duty women, strategies to create military structural/cultural changes and reduce gender-related stress and sexism are needed. Resumen `Muchas mujeres militares estan expuestas a contacto sexual no deseado durante el servicio militar, lo cual puede tener implicancias importantes para la salud mental. Utilizando informacion de la Encuesta del Departamento de Defensa sobre Conductas relacionadas con la salud del 2008, utilizamos multiples metodos de regresion logistica para examinar si el contacto sexual no deseado se asocio con estres, tamizaje positivo para trastornos mentales, o uso de sustancias entre mujeres en servicio activo. La muestra incluyo 7.415 militares femeninas, de las cuales el 13,4% reporto contacto sexual no deseado (incluyendo cualquier contacto de genitales) desde su entrada como militar. Despues del ajuste de variables potencialmente confundidoras, los factores asociados independientemente con contacto sexual no deseado incluyeron estres relacionado a la actividad militar (AOR:2.44), estres relacionado a la vida personal/familiar (AOR: 1.78), y estres relacionado a genero (AOR:1.98) en los ultimos 12 meses. Ademas, el tamizaje positivo para depresion, ansiedad, TEPT, distress psicologico, e ideacion o intento suicida fueron asociados con contacto sexual no deseado (AOR:1.57-2.11). En relacion al uso de drogas/alcohol, solo el mal uso de tranquilizantes/relajantes musculares (ultimos 12 meses) estuvo asociado con el reporte de contacto sexual no deseado (AOR: 1.35). Dada la prevalencia de contacto sexual no deseado y las correspondientes consecuencias adversas en la salud en la muestra de mujeres en servicio activo, son necesarias estrategias para crear cambios en la estructura/cultura militar y reducir el estres relacionado al genero y machismo. Traditional and Simplified Chinese Abstracts by AsianSTSS ?? : ??????????????????????????? ??: ?????????????????????,?????????????????????2008?????????????????,??????????????????????????????????????????????????7415????,13.4%?????????????(?????????)?????????????,???????????????????12?????????(???????[AOR] = 2.44)?????????????(AOR = 1.78)????????(AOR = 1.98)???,???????????????????????????????????????????(AOR = 1.57 ? 2.11)??????????,????12??????????????????????????(AOR = 1.35)????????????????????????????????,?????????????????,??????????????? ?? : ??????????????????????????? ??: ????????????????????,?????????????????????2008?????????????????,??????????????????????????????????????????????????7415????,13.4%?????????????(?????????)?????????????,???????????????????12?????????(???????[AOR] = 2.44)?????????????(AOR = 1.78)????????(AOR = 1.98)???,???????????????????????????????????????????(AOR = 1.57 ? 2.11)??????????,????12??????????????????????????(AOR = 1.35)????????????????????????????????,?????????????????,??????????????? C1 [Stahlman, Shauna; Javanbakht, Marjan; Cochran, Susan; Gorbach, Pamina M.] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Hamilton, Alison B.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Hamilton, Alison B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Shoptaw, Steven] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90095 USA. RP Stahlman, S (reprint author), Univ Calif Los Angeles, Dept Epidemiol, Box 951772, Los Angeles, CA 90095 USA. EM sstahlman@ucla.edu OI Stahlman, Shauna/0000-0003-2861-7734 FU UCLA; NIMH [P30 MH58107] FX This research was supported by funds from the UCLA Dr. Ursula Mandel Scholarship (Stahlman), the 2013-2014 Fellowship in Epidemiology (Stahlman), and NIMH research grant P30 MH58107 (Shoptaw and Gorbach). The views expressed in this article are those of the authors and do not reflect the official policy or position of the U.S. Department of Defense, U.S. Department of Veterans Affairs, or the U.S. government. The funding organizations had no role in the design and conduct of the study; collection, analysis, or preparation of the data; or preparation, review, or approval of the manuscript. Shauna Stahlman 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. NR 44 TC 1 Z9 1 U1 5 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2015 VL 28 IS 3 BP 167 EP 173 DI 10.1002/jts.22009 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CK2XZ UT WOS:000356080100001 PM 25976935 ER PT J AU Paul, LA Felton, JW Adams, ZW Welsh, K Miller, S Ruggiero, KJ AF Paul, Lisa A. Felton, Julia W. Adams, Zachary W. Welsh, Kyleen Miller, Stephanie Ruggiero, Kenneth J. TI Mental Health Among Adolescents Exposed to a Tornado: The Influence of Social Support and Its Interactions With Sociodemographic Characteristics and Disaster Exposure SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC STRESS SYMPTOMS; HURRICANE KATRINA; RISK-FACTORS; LIFE EVENTS; DEPRESSION; CHILDREN; PREVALENCE; PTSD; PSYCHOPATHOLOGY; DISTRESS AB Approximately 25% of youths experience a natural disaster and many experience disaster-related distress, including symptoms of posttraumatic stress disorder (PTSD) and depression. This study contributes to the literature by examining PTSD and depressive symptoms among 2,000 adolescents (50.9% female, 70.5% White) assessed after exposure to tornadoes in 2011. The authors hypothesized that greater tornado exposure, female sex, and younger age would be associated with distress, and that social support would interact with these associations. Analyses showed that PTSD symptoms were associated with lower levels of social support ( = -.28, p < .001), greater tornado exposure ( = .14, p < .001), lower household income ( = -.06, p = .013, female sex ( = -.10, p < .001), and older age ( = .07, p = .002), with a 3-way interaction between tornado exposure, sex, and social support ( = -.06, p = .017). For boys, the influence of tornado exposure on PTSD symptoms increased as social support decreased. Regardless of level of tornado exposure, low social support was related to PTSD symptoms for girls; depressive symptom results were similar. These findings were generally consistent with the literature and provide guidance for intervention development focused on strengthening social support at the individual, family, and community levels. Resumen Aproximadamente un 25% de los jovenes experimentan desastres naturales y muchos sufren estres relacionado con los desastres, incluyendo sintomas de Trastorno por Estres Postraumatico (TEPT) y Depresion. Este estudio contribuye a la literatura investigando sintomas de Trastorno por Estres Postraumatico y Depresion en 2.000 adolescentes (50,9% mujeres; 70,5% de raza blanca), evaluados, despues de un tornado en el 2011. Los autores plantearon la hipotesis que la exposicion a un gran tornado, en personas jovenes y de sexo femenino podrian tener asociacion con estres y que el apoyo social podria interactuar con estas asociaciones. El analisis mostro que escaso apoyo social (B = - .28, p < .001), exposicion a un gran tornado (B = - .14, p< .001), bajos ingresos familiares (B = -.06, p< .013) sexo femenino (B = -.10, P<.001) y edades mayores (B = .07, p< .002) predijeron sintomas de TEPT con una interaccion de 3 vias, la exposicion al tornado, sexo y apoyo social (B = -.06, p< .017). En varones, la influencia de la exposicion a un tornado aumenta los sintomas de TEPT cuando el apoyo social es menor. En ninas, independientemente del nivel de exposicion a un tornado, el escaso apoyo social estuvo relacionado con sintomas de TEPT. Estos resultados fueron similares para los sintomas depresivos. Estos hallazgos son consistentes con la literatura y provee un referente de desarrollo de intervencion focalizado en fortalecer el apoyo social tanto a nivel individual, familiar y comunitario. Traditional and Simplified Chinese Abstracts by AsianSTSS ?? : ???????????????????????????????????? ??: ?25%?????????????,????????????,????????(PTSD)????????????2000????(50.9% ??, 70.5% ??)?2011????????????PTSD?????,????????????????????????????????????,?????????????????????PTSD???????????( = -.28, p < .001)????????( = .14, p < .001)???????( = -.06, p = .013)??????( = -.10, p < .001)?????( = .07, p = .002)???,?????????????????????????( = -.06, p = .017)?????,????????,??????PTSD???????????????????,??????????PTSD????;??????????????????????,????????????????????????????????? ?? : ?????????????????????????????????? ??: ?25%????????????,???????????,????????(PTSD)????????????2000????(50.9% ??, 70.5% ??)?2011???????????PTSD?????,???????????????????????????????????,?????????????????????PTSD???????????( = -.28, p < .001)???????( = .14, p < .001)???????( = -.06, p = .013)??????( = -.10, p < .001)?????( = .07, p = .002)???,????????????????????????( = -.06, p = .017)?????,????????,?????PTSD???????????????????,??????????PTSD????;??????????????????????,????????????????????????????????? C1 [Paul, Lisa A.] Univ Illinois, Dept Psychol, De Kalb, IL USA. [Felton, Julia W.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Adams, Zachary W.; Miller, Stephanie; Ruggiero, Kenneth J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Welsh, Kyleen; Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Ruggiero, KJ (reprint author), Med Univ S Carolina, 67 President St,MSC 861, Charleston, SC 29425 USA. EM ruggierk@musc.edu FU National Institute of Mental Health [R01-MH081056]; [T32-MH018869] FX The National Institute of Mental Health (Grant R01-MH081056 to KJR) supported this study as well as the team of collaborators (T32-MH018869 sponsoring LAP and ZWA). We thank the many families affected by the spring 2011 tornado outbreak for participating in this study. NR 42 TC 0 Z9 0 U1 5 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2015 VL 28 IS 3 BP 232 EP 239 DI 10.1002/jts.22012 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CK2XZ UT WOS:000356080100009 PM 26031997 ER PT J AU Schumm, JA Monson, CM O'Farrell, TJ Gustin, NG Chard, KM AF Schumm, Jeremiah A. Monson, Candice M. O'Farrell, Timothy J. Gustin, Nancy G. Chard, Kathleen M. TI Couple Treatment for Alcohol Use Disorder and Posttraumatic Stress Disorder: Pilot Results From US Military Veterans and Their Partners SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ADMINISTERED PTSD SCALE; IRAQ WAR; THERAPY; CLINICIAN; SYMPTOMS AB We studied 13 U.S. male military veterans and their female partners who consented to participate in an uncontrolled trial of couple treatment for alcohol use disorder and posttraumatic stress disorder (CTAP). CTAP is a 15-session, manualized therapy, integrating behavioral couples therapy for alcohol use disorder (AUD) with cognitive-behavioral conjoint therapy for posttraumatic stress disorder (PTSD). Due to ineligibility (n = 1) and attrition (n = 3), 9 couples completed the study, and 7 completed 12 or more sessions. There were 8 veterans who showed clinically reliable pre- to posttreatment reduction of PTSD outcomes. There were also significant group-level reductions in clinician-, veteran-, and partner-rated PTSD symptoms (d = 0.94 to 1.71). Most veterans showed clinically reliable reductions in percentage days of heavy drinking. Group-level reduction in veterans' percentage days of heavy drinking was significant (d = 1.01). There were 4 veterans and 3 partners with clinically reliable reductions in depression, and group-level change was significant for veterans (d = 0.93) and partners (d = 1.06). On relationship satisfaction, 3 veterans and 4 partners had reliable improvements, and 2 veterans and 1 partner had reliable deterioration. Group-level findings were nonsignificant for veteran relationship satisfaction (d = 0.26) and for partners (d = 0.52). These findings indicate that CTAP may be a promising intervention for individuals with comorbid PTSD and AUD who have relationship partners. Resumen Estudiamos a 13 veteranos militares varones y sus parejas mujeres quienes consintieron en participar en un ensayo no controlado de Tratamiento de Pareja para el Trastorno por Uso de Alcohol y Trastorno por Estres Postraumatico (CTAP, sigla en ingles para Couple Treatment for Alcohol Use Disorder and Postraumatic Stress Disorder). La CTAP es una terapia de 15 sesiones en formato manual que integra terapia conductual de parejas para el trastorno por uso de alcohol (TUA) con terapia conjunta cognitivo-conductual para el trastorno por estres postraumatico (TEPT). Debido a la inelegibilidad (n = 1) y retiro del consentimiento (n = 3), 9 parejas completaron el estudio y 7 completaron 12 o mas sesiones. Hubo 8 veteranos que mostraron una reduccion clinicamente confiable de los resultados de TEPT entre el pre y post-tratamiento. Hubo tambien reducciones significativas a nivel de grupo en los sintomas TEPT calificados por los clinicos, los veteranos y las parejas (d = 0.94 a 1.71). La mayoria de los veteranos mostro reducciones clinicamente confiables en el porcentaje de dias de abuso de alcohol. La reduccion a nivel de grupo en el porcentaje de dias de abuso de alcohol en veteranos fue significativa (d = 1.01). Hubo 4 veteranos y 3 companeras con reduccion clinicamente confiable en depresion y el cambio a nivel de grupo fue significativo para los veteranos (d = 0.93) y las companeras (d = 1.06). En la satisfaccion de la relacion, 3 veteranos y 4 companeras tuvieron mejorias confiables y 2 veteranos y 1 companera tuvieron real deterioro. Los hallazgos a nivel de grupo no fueron significativos para la satisfaccion de pareja en los veteranos (d = 0.26) ni para sus parejas (d = 0.52). Estos hallazgos indican que la CTAP puede ser una intervencion prometedora para los individuos con comorbilidad TEPT y Trastorno por uso de alcohol y que tienen relacion de pareja. Traditional and Simplified Chinese Abstracts by AsianSTSS ?? : ???????????????????????????????????? ??: ????????????????????????????????(CTAP),??13??????????????????????CTAP????15???????,??????????(AUD)????????????????(PTSD)???????????????(n = 1)????(n = 3)???,9???????,7????12?????????8???????????PTSD??????????????????????????????????PTSD???????(d = 0.94 ? 1.71)???????????????????????,???????????????????????????????(d = 1.01)?4??????3????????????????????,????????????(d = 0.93)???(d = 1.06)???????????,3??????4?????????,2??????1????????????????????????????(d = 0.26)?????????(d = 0.52)???????????,CTAP???? PTSD?AUD???????,?????????????? ?? : ???????????????????????????????????? ??: ????????????????????????????????(CTAP),??13??????????????????????CTAP????15???????,??????????(AUD)????????????????(PTSD)???????????????(n = 1)????(n = 3)???,9???????,7????12?????????8???????????PTSD??????????????????????????????????PTSD???????(d = 0.94 ? 1.71)???????????????????????,???????????????????????????????(d = 1.01)?4??????3????????????????????,????????????(d = 0.93)???(d = 1.06)???????????,3??????4?????????,2??????1????????????????????????????(d = 0.26)?????????(d = 0.52)???????????,CTAP???? PTSD?AUD???????,?????????????? C1 [Schumm, Jeremiah A.; Gustin, Nancy G.; Chard, Kathleen M.] Cincinnati VA Med Ctr, Trauma Recovery Ctr, Cincinnati, OH USA. [Schumm, Jeremiah A.; Chard, Kathleen M.] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [Monson, Candice M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [O'Farrell, Timothy J.] VA Boston Healthcare Syst, Families & Addict Program, Brockton, MA USA. [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02401 USA. RP Schumm, JA (reprint author), VA Med Ctr, 1000 South Ft Thomas Ave, Ft Thomas, KY 41075 USA. EM Jeremiah.Schumm@va.gov FU Department of Veterans Affairs [CDA-2-019-09S] FX This study was supported by Department of Veterans Affairs grant CDA-2-019-09S (Jeremiah A. Schumm). Manuscript content does not necessarily reflect the views of the United States Government or the Department of Veterans Affairs. Thank you to Lindsey Linz for study coordination assistance, Kristen Walter and Benjamin Dickstein for serving as study assessors, Shauna Murray for serving as study therapist, and the couples who volunteered to participate. NR 25 TC 4 Z9 4 U1 9 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2015 VL 28 IS 3 BP 247 EP 252 DI 10.1002/jts.22007 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CK2XZ UT WOS:000356080100011 PM 25965768 ER PT J AU Ghaneie, A Grajo, JR Derr, C Kumm, TR AF Ghaneie, Ashkan Grajo, Joseph R. Derr, Charlotte Kumm, Todd R. TI Unusual Ectopic Pregnancies Sonographic Findings and Implications for Management SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Review DE ectopic pregnancy; obstetric ultrasound; pregnancy; transvaginal sonography ID CESAREAN SCAR PREGNANCY; PRIMARY OVARIAN PREGNANCY; ABDOMINAL PREGNANCY; INTERSTITIAL PREGNANCY; CERVICAL PREGNANCY; METHOTREXATE TREATMENT; MEDICAL-MANAGEMENT; SECTION SCAR; DIAGNOSIS; ULTRASOUND AB Ectopic pregnancy is a considerable source of morbidity and mortality for women of childbearing age. Improved detection and increased risk factors have led to a dramatic rise in the incidence of ectopic pregnancy in recent years. Early diagnosis is critical for the health of the patient as well as the success rate offuture pregnancies. Besides laparoscopy, sonography is the mainstay for evaluating ectopic pregnancy. It is important to understand the sonographic features of ectopic pregnancies, including unusual cases that occur outside the fallopian tube. C1 [Ghaneie, Ashkan; Kumm, Todd R.] Univ S Florida, Dept Radiol, Tampa, FL USA. [Derr, Charlotte] Univ S Florida, Dept Emergency Med, Tampa, FL USA. [Grajo, Joseph R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Grajo, JR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, 55 Fruit St,White 270, Boston, MA 02114 USA. EM joegrajo@gmail.com NR 76 TC 3 Z9 3 U1 1 U2 7 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUN PY 2015 VL 34 IS 6 BP 951 EP 962 DI 10.7863/ultra.34.6.951 PG 12 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA CJ8QI UT WOS:000355768200002 PM 26014313 ER PT J AU Avila, JO Noble, VE AF Avila, Jacob O. Noble, Vicki E. TI The Irregular Diaphragmatic Pleural Interface A Novel Sonographic Sign Facilitating the Diagnosis of Pneumonia SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE infection; pneumonia; point-of-care ultrasound; pulmonary; thoracic ID COMMUNITY-ACQUIRED PNEUMONIA; CHEST-X-RAY; RESPIRATORY-DISTRESS-SYNDROME; LUNG ULTRASOUND; COMPUTED-TOMOGRAPHY; FOLLOW-UP; EMERGENCY-DEPARTMENT; THORACIC ULTRASOUND; RADIATION-EXPOSURE; BEDSIDE ULTRASOUND AB Pneumonia, a disease that has been reported to be the sixth leading cause of death in the United States, has worsening mortality with delays in diagnosis. As the history and physical examination are excessively inaccurate in the diagnosis of pneumonia, we often rely on chest radiography to rule in or out disease. However, it is found to lack sufficient accuracy when computed tomography is used as the reference standard. Sonography has emerged as a viable alternative to chest radiography in the diagnosis of pneumonia. Here, we describe a novel sonographic sign that can be used to assist in the diagnosis of pneumonia. C1 [Avila, Jacob O.] Univ Tennessee, Coll Med, Dept Emergency Med, Chattanooga, TN 37403 USA. [Noble, Vicki E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,Div Emergency Ultrasound, Boston, MA USA. RP Avila, JO (reprint author), Univ Tennessee, Coll Med, Dept Emergency Med, 975 East Third St, Chattanooga, TN 37403 USA. EM j.owen.avila@gmail.com NR 54 TC 0 Z9 0 U1 0 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUN PY 2015 VL 34 IS 6 BP 1147 EP 1157 DI 10.7863/ultra.34.6.1147 PG 11 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA CJ8QI UT WOS:000355768200025 PM 26014336 ER PT J AU Drechsler, C Kalim, S Wenger, JB Suntharalingam, P Hod, T Thadhani, RI Karumanchi, SA Wanner, C Berg, AH AF Drechsler, Christiane Kalim, Sahir Wenger, Julia B. Suntharalingam, Pirianthini Hod, Tammy Thadhani, Ravi I. Karumanchi, S. Ananth Wanner, Christoph Berg, Anders H. TI Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE cardiovascular disease; congestive heart failure; hemodialysis; urea; uremia; uremic toxins ID KIDNEY-DISEASE; NOCTURNAL HEMODIALYSIS; ENDOTHELIAL-CELLS; DIALYSIS PATIENTS; DEATH; ATHEROSCLEROSIS; UREMIA; RISK; ATHEROGENESIS; ROSUVASTATIN AB Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb. C1 [Drechsler, Christiane; Wanner, Christoph] Univ Hosp Wurzburg, Div Nephrol, Dept Internal Med, Wurzburg, Germany. [Drechsler, Christiane; Wanner, Christoph] Univ Hosp Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany. [Kalim, Sahir; Wenger, Julia B.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Kalim, Sahir; Wenger, Julia B.; Hod, Tammy; Thadhani, Ravi I.; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. [Suntharalingam, Pirianthini; Berg, Anders H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Hod, Tammy; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Hod, Tammy; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Dept Med, Boston, MA 02215 USA. [Hod, Tammy; Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Berg, AH (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave,YA309, Boston, MA 02215 USA. EM ahberg@bidmc.harvard.edu FU NIH [KO8 HL121801]; Howard Hughes Medical Institute [K24 DK094872]; German Federal Ministry for Education and Research [BMBF01EO1004]; University Hospital Wuerzberg 'Gundausstattung' grant programme FX This work was supported by the NIH KO8 HL121801 (to AHB), Howard Hughes Medical Institute (to SAK), K24 DK094872 (to Rh), grants from the German Federal Ministry for Education and Research (BMBF01EO1004) and the University Hospital Wuerzberg 'Gundausstattung' grant programme (to CD and CW). NR 34 TC 13 Z9 14 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2015 VL 87 IS 6 BP 1201 EP 1208 DI 10.1038/ki.2014.429 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CK1IL UT WOS:000355960900015 PM 25671766 ER PT J AU McCarty, TP Baddley, JW Walsh, TJ Alexander, BD Kontoyiannis, DP Perl, TM Walker, R Patterson, TF Schuster, MG Lyon, GM Wingard, JR Andes, DR Park, BJ Brandt, ME Pappas, PG AF McCarty, Todd P. Baddley, John W. Walsh, Thomas J. Alexander, Barbara D. Kontoyiannis, Dimitrios P. Perl, Trish M. Walker, Randall Patterson, Thomas F. Schuster, Mindy G. Lyon, G. Marshall Wingard, John R. Andes, David R. Park, Benjamin J. Brandt, Mary E. Pappas, Peter G. CA TRANSNET Investigators TI Phaeohyphomycosis in transplant recipients: Results from the Transplant Associated Infection Surveillance Network (TRANSNET) SO MEDICAL MYCOLOGY LA English DT Article DE phaeohyphomycosis; dematiaceous mold; Alternaria; Exserohilum ID VITRO ANTIFUNGAL SUSCEPTIBILITY; INVASIVE FUNGAL-INFECTIONS; METHYLPREDNISOLONE INJECTIONS; CEREBRAL PHEOHYPHOMYCOSIS; VORICONAZOLE; DIAGNOSIS AB Transplant recipients are at a high risk for developing invasive fungal infections. The agents of phaeohyphomycosis are environmental molds found worldwide, and they cause a broad spectrum of disease including skin and subcutaneous lesions, pneumonia, central nervous system disease, fungemia, and disseminated disease. Using data from the Transplant Associated Infection Surveillance Network (TRANSNET), we evaluated patients with proven and probable phaeohyphomycosis. Centers collected data on demographics, co-morbid conditions, clinical features, treatment, and three-month mortality. Fifty-six patients with phaeohyphomycosis were identified from 15 centers, comprising 26 stem cell transplant (SCT) and 30 solid organ transplant (SOT) recipients. Median time to diagnosis post-transplant was 358 days (SCT 100 days; SOT 685 days; P = <.001). The most frequent pathogen was Alternaria species (32%). Disseminated disease was found in 55.4%. Cutaneous infection was more common in SOT (53.3% vs 23.1%; P = .021), while pulmonary disease was more common in SCT (57.7 vs. 26.7; P = .019). Voriconazole (44.6%) and amphotericin B preparations (37.5%) were the most common antifungal therapies. Overall mortality was 25% and was higher in SCT than in SOT (42% vs 10%; P = <.001). A wide variety of organisms encompass phaeohyphomycosis contributing to varying types of infection in transplant recipients. Site of infection, time to disease, and mortality varies significantly between SCT and SOT recipients. Lipid formulations of amphotericin B and voriconazole were the most common antifungals used to treat this disorder. C1 [McCarty, Todd P.; Baddley, John W.; Pappas, Peter G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Walsh, Thomas J.] Weill Cornell Med Ctr, New York Presbyterian Hosp, Dept Med, New York, NY USA. [Walsh, Thomas J.] Weill Cornell Med Ctr, New York Presbyterian Hosp, Dept Pediat, New York, NY USA. [Walsh, Thomas J.] Weill Cornell Med Ctr, New York Presbyterian Hosp, Dept Microbiol & Immunol, New York, NY USA. [Alexander, Barbara D.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. [Perl, Trish M.] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA. [Perl, Trish M.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Perl, Trish M.] Johns Hopkins Univ Hosp, Dept Epidemiol, Baltimore, MD 21287 USA. [Walker, Randall] Mayo Clin, Dept Med, Rochester, MN USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Schuster, Mindy G.] Univ Penn, Med Ctr, Dept Med, Philadelphia, PA 19104 USA. [Lyon, G. Marshall] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Wingard, John R.] Univ Florida, Dept Med, Gainesville, FL USA. [Andes, David R.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Park, Benjamin J.; Brandt, Mary E.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP McCarty, TP (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. EM tmccarty@uabmc.edu FU Centers for Disease Control and Prevention [5U01CI000286-05]; Merck Co., Inc.; Astellas US, Inc.; Pfizer, Inc.; Enzon Pharmaceuticals, Inc.; Vicuron Pharmaceuticals FX Funding was provided by the Centers for Disease Control and Prevention (Grant 5U01CI000286-05) and grants from Merck & Co., Inc.; Astellas US, Inc.; Pfizer, Inc.; Enzon Pharmaceuticals, Inc.; and Vicuron Pharmaceuticals. NR 22 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1369-3786 EI 1460-2709 J9 MED MYCOL JI Med. Mycol. PD JUN PY 2015 VL 53 IS 5 BP 440 EP 446 DI 10.1093/mmy/myv018 PG 7 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA CK5GA UT WOS:000356249800002 PM 25908651 ER PT J AU Best, MW Wu, JJ Pauli, SA Kane, MA Pierzchalski, K Session, DR Woods, DC Shang, WR Taylor, RN Sidell, N AF Best, Monica W. Wu, Juanjuan Pauli, Samuel A. Kane, Maureen A. Pierzchalski, Keely Session, Donna R. Woods, Dori C. Shang, Weirong Taylor, Robert N. Sidell, Neil TI A role for retinoids in human oocyte fertilization: regulation of connexin 43 by retinoic acid in cumulus granulosa cells SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE all-trans retinoic acid; connexin 43; cumulus granulosa cells; oocyte competency ID JUNCTIONAL INTERCELLULAR COMMUNICATION; FOLLICLE-STIMULATING-HORMONE; ENDOMETRIAL STROMAL CELLS; RECEPTOR GENE-EXPRESSION; MOUSE OVARIAN-FOLLICLES; BOVINE LUTEAL CELLS; IN-VITRO MATURATION; LUTEINIZING-HORMONE; GAP-JUNCTIONS; BINDING-PROTEIN AB Retinoids are essential for ovarian steroid production and oocyte maturation in mammals. Oocyte competency is known to positively correlate with efficient gap junction intercellular communication (GJIC) among granulosa cells in the cumulus-oocyte complex. Connexin 43 (Cx43) is the main subunit of gap junction channels in human cumulus granulosa cells (CGC) and is regulated by all-trans retinoic acid (ATRA) in other hormone responsive cell types. The objectives of this study were to quantify retinoid levels in human CGC obtained during IVF oocyte retrievals, to investigate the potential relationship between CGC ATRA levels and successful oocyte fertilization, and to determine the effects of ATRA on Cx43 protein expression in CGC. Results showed that CGC cultures actively metabolize retinol to produce ATRA. Grouped according to fertilization rate tertiles, mean ATRA levels were 2-fold higher in pooled CGC from women in the highest versus the lowest tertile (P < 0.05). ATRA induced a rapid dephosphorylation of Cx43 in CGC and granulosa cell line (KGN) cultures resulting in a > 2-fold increase in the expression of the functional non-phosphorylated (P0) species (P < 0.02). Similar enhancement of P0 by ATRA was shown in CGC and KGN cultures co-treated with LH or hCG which, by themselves, enhanced the protein levels of Cx43 without altering its phosphorylation profile. Correspondingly, the combination of ATRA+hCG treatment of KGN caused a significant increase in GJIC compared with single agent treatments (P < 0.025) and a doubling of GJIC from that seen in untreated cells (P < 0.01). These findings indicate that CGC are a primary site of retinoid uptake and ATRA biosynthesis. Regulation of Cx43 by ATRA may serve an important role in folliculogenesis, development of oocyte competency, and successful fertilization by increasing GJIC in CGC. C1 [Best, Monica W.; Wu, Juanjuan; Pauli, Samuel A.; Session, Donna R.; Shang, Weirong; Sidell, Neil] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA 30322 USA. [Kane, Maureen A.; Pierzchalski, Keely] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Woods, Dori C.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Vincent Ctr Reprod Biol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Taylor, Robert N.] Wake Forest Sch Med, Dept Obstet & Gynecol, Winston Salem, NC USA. RP Sidell, N (reprint author), Emory Univ, Sch Med, Dept Gynecol & Obstet, 1639 Pierce Dr,WMB4303, Atlanta, GA 30322 USA. EM nsidell@emory.edu OI Pierzchalski, Keely/0000-0002-2456-0382 FU Eunice Kennedy Shriver/National Institute of Child Health [RO1HD55379, UO1HD66439, U54HD55787, R01HD077260]; National Institute of Allergy and Infectious Diseases [HHSN272202000046C]; University of Maryland School of Pharmacy Mass Spectrometry Center [SOP1841-IQB2014] FX This work was supported by Eunice Kennedy Shriver/National Institute of Child Health grants RO1HD55379 (N.S.), UO1HD66439 (N.S., R.N.T.), U54HD55787 (R.N.T.), R01HD077260 (MAK), the National Institute of Allergy and Infectious Diseases contract HHSN272202000046C (MAK) and the University of Maryland School of Pharmacy Mass Spectrometry Center #SOP1841-IQB2014 (MAK). NR 46 TC 2 Z9 2 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 EI 1460-2407 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD JUN PY 2015 VL 21 IS 6 BP 527 EP 534 DI 10.1093/molehr/gav017 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA CK5JV UT WOS:000356261000004 PM 25877907 ER PT J AU Yang, NJ Liu, DV Sklaviadis, D Gui, DY Vander Heiden, MG Wittrup, KD AF Yang, Nicole J. Liu, David V. Sklaviadis, Demetra Gui, Dan Y. Vander Heiden, Matthew G. Wittrup, K. Dane TI Antibody-Mediated Neutralization of Perfringolysin 0 for Intracellular Protein Delivery SO MOLECULAR PHARMACEUTICS LA English DT Article DE perfringolysin O; cholesterol-dependent cytolysin; intracellular delivery; protein delivery; endosomal release; neutralizing antibody ID CHOLESTEROL-DEPENDENT CYTOLYSIN; GROWTH-FACTOR RECEPTOR; YEAST SURFACE DISPLAY; LISTERIOLYSIN-O; STREPTOLYSIN-O; IN-VIVO; CYTOSOLIC DELIVERY; BINDING-PROTEINS; LIVING CELLS; TOXIN AB Perfringolysin O (PFO) is a member of the cholesterol-dependent cytolysin (CDC) family of bacterial pore-forming proteins, which are highly efficient in delivering exogenous proteins to the cytoplasm. However, the indiscriminate and potent cytotoxicity of PFO limits its practical use as an intracellular delivery system. In this study, we describe the design and engineering of a bispecific, neutralizing antibody against PFO, which targets reversibly attenuated PFO to endocytic compartments via receptor-mediated internalization. This PFO-based system efficiently mediated the endosomal release of a co-targeted gelonin construct with high specificity and minimal toxicity in vitro. Consequently, the therapeutic window of PFO was improved by more than 5 orders of magnitude. Our results demonstrating that the activity of pore-forming proteins can be controlled by antibody-mediated neutralization present a novel strategy for utilizing these potent membrane-lytic agents as a safe and effective intracellular delivery vehicle. C1 [Yang, Nicole J.; Liu, David V.; Wittrup, K. Dane] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Sklaviadis, Demetra; Wittrup, K. Dane] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Gui, Dan Y.; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yang, Nicole J.; Liu, David V.; Gui, Dan Y.; Vander Heiden, Matthew G.; Wittrup, K. Dane] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Wittrup, KD (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM wittrup@mit.edu FU National Institutes of Health [CA101830]; MIT/NIGMS Biotechnology Training Program FX This work was funded by the National Institutes of Health Grant CA101830. N.J.Y. was supported by the MIT/NIGMS Biotechnology Training Program. The Koch Institute Flow Cytometry core and the MIT Biophysical Instrumentation facilities provided equipment and technical assistance with fluorescence-activated cell sorting and analytical ultracentrifugation, respectively. All schematics were prepared using Servier Medical Art. NR 49 TC 2 Z9 2 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUN PY 2015 VL 12 IS 6 BP 1992 EP 2000 DI 10.1021/mp500797n PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CJ6XG UT WOS:000355637900029 PM 25881713 ER PT J AU Naumova, AV Modo, M Moore, A Frank, JA Murry, CE AF Naumova, Anna V. Modo, Michel Moore, Anna Frank, Joseph A. Murry, Charles E. TI Cardiac regeneration validated Reply SO NATURE BIOTECHNOLOGY LA English DT Letter C1 [Naumova, Anna V.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Naumova, Anna V.; Murry, Charles E.] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98195 USA. [Naumova, Anna V.; Murry, Charles E.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA. [Modo, Michel] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Modo, Michel] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA USA. [Modo, Michel] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Modo, Michel] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. [Moore, Anna] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Frank, Joseph A.] NIH, Radiol & Imaging Sci, Clin, Bethesda, MD 20892 USA. [Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Murry, Charles E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Murry, Charles E.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Murry, Charles E.] Univ Washington, Dept Med Cardiol, Seattle, WA 98195 USA. RP Naumova, AV (reprint author), Univ Washington, Dept Radiol, Seattle, WA 98195 USA. EM murry@uw.edu NR 5 TC 1 Z9 1 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2015 VL 33 IS 6 BP 587 EP 587 DI 10.1038/nbt.3257 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CK2DE UT WOS:000356019700010 PM 26057970 ER PT J AU Kotini, AG Chang, CJ Boussaad, I Delrow, JJ Dolezal, EK Nagulapally, AB Perna, F Fishbein, GA Klimek, VM Hawkins, RD Huangfu, D Murry, CE Graubert, T Nimer, SD Papapetrou, EP AF Kotini, Andriana G. Chang, Chan-Jung Boussaad, Ibrahim Delrow, Jeffrey J. Dolezal, Emily K. Nagulapally, Abhinav B. Perna, Fabiana Fishbein, Gregory A. Klimek, Virginia M. Hawkins, R. David Huangfu, Danwei Murry, Charles E. Graubert, Timothy Nimer, Stephen D. Papapetrou, Eirini P. TI Functional analysis of a chromosomal deletion associated with myelodysplastic syndromes using isogenic human induced pluripotent stem cells SO NATURE BIOTECHNOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; METHYLTRANSFERASE GENE EZH2; TUMOR-SUPPRESSOR; POINT MUTATIONS; MALIGNANCIES; GENERATION; DISORDERS; GENOME; CANCER; IMPACT AB Chromosomal deletions associated with human diseases, such as cancer, are common, but synteny issues complicate modeling of these deletions in mice. We use cellular reprogramming and genome engineering to functionally dissect the loss of chromosome 7q (del(7q)), a somatic cytogenetic abnormality present in myelodysplastic syndromes (MDS). We derive del(7q)- and isogenic karyotypically normal induced pluripotent stem cells (iPSCs) from hematopoietic cells of MDS patients and show that the del(7q) iPSCs recapitulate disease-associated phenotypes, including impaired hematopoietic differentiation. These disease phenotypes are rescued by spontaneous dosage correction and can be reproduced in karyotypically normal cells by engineering hemizygosity of defined chr7q segments in a 20-Mb region. We use a phenotype-rescue screen to identify candidate haploinsufficient genes that might mediate the del(7q)-hematopoietic defect. Our approach highlights the utility of human iPSCs both for functional mapping of disease-associated large-scale chromosomal deletions and for discovery of haploinsufficient genes. C1 [Kotini, Andriana G.; Chang, Chan-Jung; Papapetrou, Eirini P.] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. [Kotini, Andriana G.; Chang, Chan-Jung; Papapetrou, Eirini P.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Kotini, Andriana G.; Chang, Chan-Jung] Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, New York, NY 10029 USA. [Boussaad, Ibrahim; Papapetrou, Eirini P.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. [Boussaad, Ibrahim; Nagulapally, Abhinav B.; Hawkins, R. David; Murry, Charles E.; Papapetrou, Eirini P.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA. [Delrow, Jeffrey J.] Fred Hutchinson Canc Res Ctr, Genom Resource, Seattle, WA 98104 USA. [Dolezal, Emily K.; Nimer, Stephen D.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Nagulapally, Abhinav B.; Hawkins, R. David] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Perna, Fabiana] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10021 USA. [Fishbein, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Klimek, Virginia M.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Huangfu, Danwei] Sloan Kettering Inst, Dev Biol Program, New York, NY USA. [Murry, Charles E.; Papapetrou, Eirini P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Murry, Charles E.] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98195 USA. [Murry, Charles E.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Murry, Charles E.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. [Graubert, Timothy] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Papapetrou, Eirini P.] Icahn Sch Med Mt Sinai, Dept Med, Div Hematol & Med Oncol, New York, NY 10029 USA. RP Papapetrou, EP (reprint author), Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. EM eirini.papapetrou@mssm.edu OI Perna, Fabiana/0000-0002-3744-8672; Huangfu, Danwei/0000-0002-1145-6199; Graubert, Timothy/0000-0002-7710-1171; Fishbein, Gregory/0000-0002-3632-5654; KOTINI, ANDRIANA/0000-0001-9148-6015 FU National Institutes of Health (NIH) [R00 DK087923, R01 HL121570, P30 CA15704]; University of Washington Royalty Research Fund; American Society of Hematology; Sidney Kimmel Foundation for Cancer Research; Aplastic Anemia & MDS International Foundation; Ellison Medical Foundation; Damon Runyon Cancer Research Foundation; John H. Tietze Stem Cell Scientist Award FX This work was supported by the National Institutes of Health (NIH) grants R00 DK087923 (E.P.P.), R01 HL121570 (E.P.P.), P30 CA15704 and by awards from the University of Washington Royalty Research Fund (E.P.P.), the American Society of Hematology (E.P.P.), the Sidney Kimmel Foundation for Cancer Research (E.P.P.), the Aplastic Anemia & MDS International Foundation (E.P.P.), the Ellison Medical Foundation (E.P.P.), the Damon Runyon Cancer Research Foundation (E.P.P.) and a John H. Tietze Stem Cell Scientist Award (E.P.P.). We thank D. Russell and L. Li for sharing their expertise in AAV-mediated gene targeting and T. Papayannopoulou for sharing her expertise in assessment of May-Giemsa slides and for useful discussions. We thank C. Husser, C. Sather and R. Basom for excellent technical assistance and J. Overbey for statistical advice. NR 50 TC 28 Z9 31 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2015 VL 33 IS 6 BP 646 EP + DI 10.1038/nbt.3178 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CK2DE UT WOS:000356019700025 PM 25798938 ER PT J AU Lee, EQ Reardon, DA Schiff, D Drappatz, J Muzikansky, A Grimm, SA Norden, AD Nayak, L Beroukhim, R Rinne, ML Chi, AS Batchelor, TT Hempfling, K McCluskey, C Smith, KH Gaffey, SC Wrigley, B Ligon, KL Raizer, JJ Wen, PY AF Lee, Eudocia Q. Reardon, David A. Schiff, David Drappatz, Jan Muzikansky, Alona Grimm, Sean A. Norden, Andrew D. Nayak, Lakshmi Beroukhim, Rameen Rinne, Mikael L. Chi, Andrew S. Batchelor, Tracy T. Hempfling, Kelly McCluskey, Christine Smith, Katrina H. Gaffey, Sarah C. Wrigley, Brendan Ligon, Keith L. Raizer, Jeffrey J. Wen, Patrick Y. TI Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma SO NEURO-ONCOLOGY LA English DT Article DE anaplastic glioma; antiangiogenesis; bevacizumab; glioblastoma; panobinostat ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; TYROSINE KINASE INHIBITOR; SINGLE-AGENT BEVACIZUMAB; MALIGNANT GLIOMAS; PLUS IRINOTECAN; IN-VITRO; GROWTH; ANGIOGENESIS; TRIAL AB Background. Panobinostat is a histone deacetylase inhibitor with antineoplastic and antiangiogenic effects in glioma that may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat combined with bevacizumab in patients with recurrent high-grade glioma (HGG). Methods. Patients with recurrent HGG were treated with oral panobinostat 30 mg 3 times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was a 6-month progression-fee survival (PFS6) rate for participants with recurrent glioblastoma (GBM). Patients with recurrent anaplastic glioma (AG) were evaluated as an exploratory arm of the study. Results. At interim analysis, the GBM arm did not meet criteria for continued accrual, and the GBM arm was closed. A total of 24 patients with GBM were accrued prior to closure. The PFS6 rate was 30.4% (95%, CI 12.4%-50.7%), median PFS was 5 months (range, 3-9 months), and median overall survival (OS) was 9 months (range, 6-19 months). Accrual in the AG arm continued to completion, and a total of 15 patients were enrolled. The PFS6 rate was 46.7% (range, 21%-73%), median PFS was 7 months (range, 2-10 months), and median OS was 17 months (range, 5 months-27 months). Conclusions. This phase II study of panobinostat and bevacizumab in participants with recurrent GBM did not meet criteria for continued accrual, and the GBM cohort of the study was closed. Although it was reasonably well tolerated, the addition of panobinostat to bevacizumab did not significantly improve PFS6 compared with historical controls of bevacizumab monotherapy in either cohort. C1 [Lee, Eudocia Q.; Reardon, David A.; Norden, Andrew D.; Nayak, Lakshmi; Beroukhim, Rameen; Rinne, Mikael L.; Hempfling, Kelly; McCluskey, Christine; Smith, Katrina H.; Gaffey, Sarah C.; Wrigley, Brendan; Ligon, Keith L.; Wen, Patrick Y.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Schiff, David] Univ Virginia, Charlottesville, VA USA. [Drappatz, Jan] Univ Pittsburgh, Pittsburgh, PA USA. [Muzikansky, Alona; Chi, Andrew S.; Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Grimm, Sean A.] Cent DuPage Hosp, Warrenville, IL USA. [Raizer, Jeffrey J.] Northwestern Univ, Chicago, IL 60611 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,Dana 2122, Boston, MA 02215 USA. EM patrick_wen@dfci.harvard.edu FU Novartis; Genentech FX This work is supported by Novartis and Genentech. NR 27 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2015 VL 17 IS 6 BP 862 EP 867 DI 10.1093/neuonc/nou350 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CK5LF UT WOS:000356265100011 PM 25572329 ER PT J AU La Roche, MJ Fuentes, MA Hinton, D AF La Roche, Martin J. Fuentes, Milton A. Hinton, Devon TI A Cultural Examination of the DSM-5: Research and Clinical Implications for Cultural Minorities SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE DSM-5; diagnosis; culture; assessment ID PSYCHIATRY; RETHINKING AB The fifth edition of the Diagnostic and Statistical Manual (DSM-5) was recently released and it contains significant cultural revisions in comparison to the DSM-IV. In this article, the research, assessment, and psychotherapeutic implications of these changes for cultural minorities are examined. The DSM-5' s cultural revisions are categorized into 2 types: modifications that are an extension of previous revisions and changes that resulted from the DSM-5' s overall restructuring. A cultural framework is used to analyze these revisions. In addition, throughout this article suggestions for the development of a more culturally sensitive and inclusive DSM are discussed. To conclude some of the main research and clinical implications of DSM-5' s cultural revisions are underscored. C1 [La Roche, Martin J.] Harvard Univ, Sch Med, Psychol, Boston, MA 02138 USA. [La Roche, Martin J.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA. [Fuentes, Milton A.] Montclair State Univ, Dept Psychol, Montclair, NJ USA. [Hinton, Devon] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Hinton, Devon] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP La Roche, MJ (reprint author), Harvard Univ, Sch Med, 49 Hancock St,Suite 104, Cambridge, MA 02139 USA. EM Martin.Laroche@Childrens.Harvard.edu NR 29 TC 0 Z9 0 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD JUN PY 2015 VL 46 IS 3 BP 183 EP 189 DI 10.1037/a0039278 PG 7 WC Psychology, Multidisciplinary SC Psychology GA CK1CA UT WOS:000355941800006 ER PT J AU Sieverdes, JC Nemeth, LS Magwood, GS Baliga, PK Chavin, KD Ruggiero, KJ Treiber, FA AF Sieverdes, John C. Nemeth, Lynne S. Magwood, Gayenell S. Baliga, Prabhakar K. Chavin, Kenneth D. Ruggiero, Ken J. Treiber, Frank A. TI African American kidney transplant patients' perspectives on challenges in the living donation process SO PROGRESS IN TRANSPLANTATION LA English DT Article ID STAGE RENAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE; RACIAL DISPARITIES; ORGAN DONATION; UNITED-STATES; LONG-TERM; DONOR; BARRIERS; CANDIDATES AB Context-The increasing shortage of deceased donor kidneys suitable for African Americans highlights the critical need to increase living donations among African Americans. Little research has addressed African American transplant recipients' perspectives on challenges and barriers related to the living donation process. Objective-To understand the perspectives of African American recipients. of deceased and living donor kidney transplants on challenges, barriers, and educational needs related to pursuing such transplants. Participants and Design-A mixed-method design involved 27 African American kidney recipients (13 male) in 4 focus groups (2 per recipient type: 16 African American deceased donor and 11 living donor recipients) and questionnaires. Focus group transcripts were evaluated with NVivo 10.0 (QSR, International) by using inductive and deductive qualitative methods along with crystallization to develop themes, of underlying bathers to the living donor kidney transplant process and were compared with the questionnaires. Results-Four main themes were identified from groups: concerns, knowledge and learning, expectations of support, and communication. Many concerns for the donor were identified (eg, process too difficult, financial burden, effect on relationships). A general lack of knowledge about the donor process and lack of behavioral skills on how to approach others was noted. The latter was especially evident among deceased donor recipients. Findings from the questionnaires On myths and perceptions supported the lack of knowledge in a variety of domains, including donors' surgical outcomes risks, costs of surgery, and impact on future health. Participants thought that an educational program led by an African American recipient of a living donor kidney transplant, including practice in approaching others, would increase the likelihood of transplant-eligible patients pursuing living donor kidney transplant. (C) 2015 NATCO, The Organization far Transplant Professionals C1 [Sieverdes, John C.; Nemeth, Lynne S.; Magwood, Gayenell S.; Baliga, Prabhakar K.; Chavin, Kenneth D.; Ruggiero, Ken J.; Treiber, Frank A.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ruggiero, Ken J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Treiber, FA (reprint author), Med Univ S Carolina, Coll Nursing, 1002 Harbor View Off Tower,19 Hagood Ave, Charleston, SC 29425 USA. EM treiberf@musc.edu OI Nemeth, Lynne/0000-0001-8691-1400 FU National Institutes of Health (NIH) [DK 098777]; South Carolina Clinical and Translational Research Institute; Medical University of South Carolina, Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) [UL1RR029882] FX This publication was supported with funding from National Institutes of Health (NIH) grant DK 098777 and the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina, Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS), grant UL1RR029882. The content does not represent the official views of the NIH or the NCATS. NR 45 TC 2 Z9 2 U1 0 U2 4 PU NATCO-THE ORGANIZATION FOR TRANSPLANT PROFESSIONALS SN 1526-9248 EI 2164-6708 J9 PROG TRANSPLANT JI Prog. Transplant. PD JUN PY 2015 VL 25 IS 2 BP 164 EP 175 DI 10.7182/pit2015852 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA CK3GS UT WOS:000356105200011 PM 26107278 ER PT J AU Ip, IK Raja, AS Seltzer, SE Gawande, AA Joynt, KE Khorasani, R AF Ip, Ivan K. Raja, Ali S. Seltzer, Steven E. Gawande, Atul A. Joynt, Karen E. Khorasani, Ramin TI Use of Public Data to Target Variation in Providers' Use of CT and MR Imaging among Medicare Beneficiaries SO RADIOLOGY LA English DT Article ID EXTREMITY AMPUTATION RATES; CLINICAL DECISION-SUPPORT; COMPUTED-TOMOGRAPHY; REGIONAL INTENSITY; RADIATION-EXPOSURE; VASCULAR CARE; BACK-PAIN; RADIOLOGY; IMPACT; CANCER AB Purpose: To examine geographic variation in providers' use of diagnostic imaging to identify potential targets for quality improvement initiatives after adjusting for imaging referral across hospital referral regions (HRRs). Materials and Methods: Using two Centers for Medicare and Medicaid Services datasets, the authors included all claims for beneficiaries enrolled in the Medicare fee-for-service program. Diagnostic imaging procedures were selected on the basis of common procedure coding system codes, excluding interventional procedures. The authors assessed providers' use of imaging for each HRR after creating an imaging referral index (IRI) to adjust for imaging referral rates across HRRs. Relative risk statistics were used to assess geographic variation. The authors calculated two imaging measures for computed tomography (CT) and magnetic resonance (MR) imaging: IRI-adjusted utilization intensity (number of examinations per 1000 beneficiaries) and total payments (in dollars, after deducting deductibles and coinsurances) in each HRR. High-impact regions were defined as those in the highest deciles for both imaging intensity and payment. Results: For 34 million Medicare beneficiaries, 124 million unique diagnostic imaging services (totaling $5.6 billion) were performed in 2012. The average adjusted CT utilization intensity ranged from 330.4 studies per 1000 beneficiaries in the lowest decile to 684.0 in the highest decile (relative risk, 2.1); adjusted MR imaging utilization intensity varied from 105.7 studies per 1000 beneficiaries to 256.3 (relative risk, 2.4). The most common CT and MR imaging procedures were head CT and lumbar spine MR imaging. Conclusion: With use of public data, the authors identified a wide variation in imaging use across the United States. Potential targets for future imaging quality improvement initiatives include head CT and lumbar spine MR imaging. (C)RSNA, 2015 C1 [Ip, Ivan K.; Raja, Ali S.; Khorasani, Ramin] Brigham & Womens Hosp, Ctr Evidence Based Imaging, Boston, MA 02120 USA. [Ip, Ivan K.; Raja, Ali S.; Seltzer, Steven E.; Khorasani, Ramin] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02120 USA. [Ip, Ivan K.; Joynt, Karen E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02120 USA. [Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02120 USA. [Raja, Ali S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02120 USA. [Gawande, Atul A.; Joynt, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Joynt, Karen E.] VA Boston Healthcare Syst, Boston, MA USA. RP Ip, IK (reprint author), Brigham & Womens Hosp, Ctr Evidence Based Imaging, 20 Kent St,2nd Floor, Boston, MA 02120 USA. EM iip@partners.org FU GE Healthcare; Siemens FX I.K.I. disclosed no relevant relationships. A.S.R. disclosed no relevant relationships. S.E.S. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution has grants/grants pending from GE Healthcare and Siemens. Other relationships: disclosed no relevant relationships. A.A.G. disclosed no relevant relationships. K.E.J. disclosed no relevant relationships. R.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a paid consultant for Medicalis. Other relationships: is named on a U.S. patent held by the institution licensed to Medicalis and, as a result, the institution has equity and royalty interest in Medicalis and some of its products. NR 33 TC 4 Z9 4 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2015 VL 275 IS 3 BP 718 EP 724 DI 10.1148/radiol.15141964 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SZ UT WOS:000355988900012 PM 25658040 ER PT J AU Farrar, CT Buhrman, JS Liu, GS Kleijn, A Lamfers, MLM McMahon, MT Gilad, AA Fulci, G AF Farrar, Christian T. Buhrman, Jason S. Liu, Guanshu Kleijn, Anne Lamfers, Martine L. M. McMahon, Michael T. Gilad, Assaf A. Fulci, Giulia TI Establishing the Lysine-rich Protein CEST Reporter Gene as a CEST MR Imaging Detector for Oncolytic Virotherapy SO RADIOLOGY LA English DT Article ID CONTRAST AGENTS; BRAIN-TUMORS; PET TRACERS; RAT-BRAIN; EXCHANGE; EXPRESSION; THERAPY; GLIOMA; WATER; FIELD AB Purpose: To (a) evaluate whether the lysine-rich protein (LRP) magnetic resonance (MR) imaging reporter gene can be engineered into G47 Delta, a herpes simplex-derived oncolytic virus that is currently being tested in clinical trials, without disrupting its therapeutic effectiveness and (b) establish the ability of chemical exchange saturation transfer (CEST) MR imaging to demonstrate G47 Delta-LRP. Materials and Methods: The institutional subcommittee for research animal care approved all in vivo procedures. Oncolytic herpes simplex virus G47 Delta, which carried the LRP gene, was constructed and tested for its capacity to replicate in cancer cells and express LRP in vitro. The LRP gene was detected through CEST imaging of lysates derived from cells infected with G47 Delta-LRP or the control G47 Delta-empty virus. G47 Delta-LRP was then tested for its therapeutic effectiveness and detection with CEST MR imaging in vivo. Images of rat gliomas were acquired before and 8-10 hours after injection of G47 Delta-LRP (n = 7) or G47 Delta-empty virus (n = 6). Group comparisons were analyzed with a paired t test. Results: No significant differences were observed in viral replication or therapeutic effectiveness between G47 Delta-LRP and G47 Delta-empty virus. An increase in CEST image contrast was observed in cell lysates (mean +/- standard deviation, 0.52% +/- 0.06; P = .01) and in tumors (1.1% +/- 0.3, P = .02) after infection with G47 Delta-LRP but not G47 Delta-empty viruses. No histopathologic differences were observed between tumors infected with G47 Delta-LRP and G47 Delta-empty virus. Conclusion: This study has demonstrated the ability of CEST MR imaging to show G47 Delta-LRP at acute stages of viral infection. The introduction of the LRP transgene had no effect on the viral replication or therapeutic effectiveness. This can aid in development of the LRP gene as a reporter for the real-time detection of viral spread. (C)RSNA, 2015 C1 [Farrar, Christian T.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Buhrman, Jason S.; Kleijn, Anne; Fulci, Giulia] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Boston, MA 02114 USA. [Buhrman, Jason S.; Kleijn, Anne; Fulci, Giulia] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Liu, Guanshu; McMahon, Michael T.; Gilad, Assaf A.] Kennedy Krieger Inst, Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA. [Liu, Guanshu; McMahon, Michael T.; Gilad, Assaf A.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Kleijn, Anne; Lamfers, Martine L. M.] Erasmus MC, Josephine Nefkens Inst, Dept Neurosurg, Rotterdam, Netherlands. [Gilad, Assaf A.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Cellular Imaging Sect, Baltimore, MD USA. [Gilad, Assaf A.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Vasc Biol Program, Baltimore, MD USA. RP Fulci, G (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, 185 Cambridge St,Simches CRPZN-3800, Boston, MA 02114 USA. EM gfulci@partners.org RI Lamfers, Martine/C-6246-2016; McMahon, Michael/B-5942-2008 OI Lamfers, Martine/0000-0001-7745-9029; McMahon, Michael/0000-0002-8917-7640 FU National Institutes of Health [R21 CA135526] FX This research was supported by the National Institutes of Health (grant R21 CA135526). NR 29 TC 6 Z9 7 U1 0 U2 10 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2015 VL 275 IS 3 BP 746 EP 754 DI 10.1148/radiol.14140251 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SZ UT WOS:000355988900015 PM 25686366 ER PT J AU Masterson, S Wright, P O'Donnell, C Vellinga, A Murphy, AW Hennelly, D Sinnott, B Egan, J O'Reilly, M Keaney, J Bury, G Deasy, C AF Masterson, S. Wright, P. O'Donnell, C. Vellinga, A. Murphy, A. W. Hennelly, D. Sinnott, B. Egan, J. O'Reilly, M. Keaney, J. Bury, G. Deasy, C. CA OHCAR Steering Grp TI Urban and rural differences in out-of-hospital cardiac arrest in Ireland SO RESUSCITATION LA English DT Article DE Pre-hospital resuscitation; Geographic variation; Community response ID AUTOMATED EXTERNAL DEFIBRILLATORS; PUBLIC-ACCESS DEFIBRILLATION; SURVIVAL; RESUSCITATION; OUTCOMES; POLICE; SYSTEM; POPULATION; EXPERIENCE; LOCATIONS AB Background: More than a third of Ireland's population lives in a rural area, defined as the population residing in all areas outside clusters of 1500 or more inhabitants. This presents a challenge for the provision of effective pre-hospital resuscitation services. In 2012, Ireland became one of three European countries with nationwide Out-of-Hospital Cardiac Arrest (OHCA) register coverage. An OHCA register provides an ability to monitor quality and equity of access to life-saving services in Irish communities. Aim: To use the first year of national OHCAR data to assess differences in the occurrence, incidence and outcomes of OHCA where resuscitation is attempted and the incident is attended by statutory Emergency Medical Services between rural and urban settings. Methods: The geographical coordinates of incident locations were identified and co-ordinates were then classified as 'urban' or 'rural' according to the Irish Central Statistics Office (CSO) definition. Results: 1798 OHCA incidents were recorded which were attended by statutory Emergency Medical Services (EMS) and where resuscitation was attempted. There was a higher percentage of male patients in rural settings (71% vs. 65%; p = 0.009) but the incidence of male patients did not differ significantly between urban and rural settings (26 vs. 25 males/100,000 population/year p = 0.353). A higher proportion of rural patients received bystander cardiopulmonary resuscitation (B-CPR) 70% vs. 55% (p <= 0.001), and had defibrillation attempted before statutory EMS arrival (7% vs. 4% (p = 0.019), respectively). Urban patients were more likely to receive a statutory EMS response in 8 min or less (33% vs. 9%; p <= 0.001). Urban patients were also more likely to be discharged alive from hospital (6% vs. 3%; p = 0.006) (incidence 2.5 vs. 1.1/100,000 population/year; p <= 0.001). Multivariable analysis of survival showed that the main variable of interest i.e. urban vs. rural setting was also independently associated with discharge from hospital alive (OR 3.23 (95% CI 1.43-7.31)). Conclusion: There are significant disparities in the incidence of resuscitation attempts in urban and rural areas. There are challenges in the provision of services and subsequent outcomes from OHCA that occur outside of urban areas requiring novel and innovative solutions. An integrated community response system is necessary to improve metrics around OHCA response and outcomes in rural areas. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Masterson, S.; Wright, P.] Hlth Serv Execut, Dept Publ Hlth Med, Donegal, Ireland. [Masterson, S.; Vellinga, A.; Murphy, A. W.] Natl Univ Ireland, Discipine Gen Practice, Galway, Ireland. [O'Donnell, C.; Hennelly, D.; Deasy, C.] Hlth Serv Execut, Natl Ambulance Serv, Naas, Kildare, Ireland. [Sinnott, B.] Irish Heart Fdn, Dublin, Ireland. [Egan, J.] Prehosp Emergency Care Council, Naas, Kildare, Ireland. [Keaney, J.] Massachusets Gen Hosp, Boston, MA USA. [Bury, G.] Univ Coll Dublin, Ctr Emergency Med Sci, Dublin 4, Ireland. [Deasy, C.] Cork Univ Hosp, Cork, Ireland. [O'Reilly, M.] Dublin Fire Brigade, Dublin, Ireland. RP Deasy, C (reprint author), Cork Univ Hosp, Dept Emergency Med, Cork, Ireland. EM conor.deasy@hse.ie RI Vellinga, Akke/H-2130-2011; OI Vellinga, Akke/0000-0002-6583-4300; Bury, Gerard/0000-0002-4441-6724 FU National Ambulance Service; Pre-hospital Emergency Care Council FX The authors wish to acknowledge the pre-hospital practitioners and hospital staff whose cooperation with OHCAR data collection has made this study possible. OHCAR is jointly funded by the National Ambulance Service and the Pre-hospital Emergency Care Council. NR 44 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD JUN PY 2015 VL 91 BP 42 EP 47 DI 10.1016/j.resuscitation.2015.03.012 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA CK0ZV UT WOS:000355935500016 PM 25818707 ER PT J AU Chen, ZY Ma, F Huang, HL He, CY AF Chen, Zhi-Ying Ma, Fei Huang, Hailiang He, Cheng-Yi TI Synthetic immunity to break down the bottleneck of cancer immunotherapy SO SCIENCE BULLETIN LA English DT Review DE Cancer immunotherapy; Synthetic immunity; Non-viral vector; Engineered antibody; Bispecific antibody; Retargeting T cell ID MODIFIED T-CELLS; IN-VIVO; TUMOR MICROENVIRONMENT; DENDRITIC CELLS; INTRATUMOR HETEROGENEITY; CLONAL EVOLUTION; LUNG-CANCER; ANTIBODY; THERAPY; MINICIRCLE AB As a result of recent breakthroughs in cancer immunotherapies, unprecedented and durable remission, and even cure, has been reported in some patients. Importantly, this progress has been achieved, not by the induction of immunity, but by the delivery of immunity in the form of engineered antibodies (eAbs) or effector T cells. However, these single-target technologies have failed to result in a therapeutic effect in some patients, and evidence suggests that further advances depend on an effective strategy for coping with cancer heterogeneity and dynamics. A synthetic immunity (SI) strategy is proposed to achieve this goal. The fundamental basis of SI involves the generation of a panel of eAbs and antibody-retargeted CTLs designed to destroy all cell lineages of a cancer with high specificity. This goal can be achieved only when the composition of the eAbs is determined using a systematic approach, i.e., selecting the antigens targeted by the eAbs based on an epitope-tree illustrating the clonal antigen architecture of the cancer. Integration of technologies that increase the epitope breadth, eAb affinity and T cell activity will further enhance the efficacy of SI. Using DNA vectors to express the eAbs will be a safe, effective and affordable solution. C1 [Chen, Zhi-Ying; Ma, Fei; He, Cheng-Yi] Chinese Acad Sci, Shenzhen Inst Adv Technol, Lab Gene & Cell Therapy, Shenzhen, Peoples R China. [Huang, Hailiang] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Huang, Hailiang] MIT, Broad Inst, Cambridge, MA 02139 USA. [Huang, Hailiang] Harvard Univ, Cambridge, MA 02138 USA. RP Chen, ZY (reprint author), Chinese Acad Sci, Shenzhen Inst Adv Technol, Lab Gene & Cell Therapy, Shenzhen, Peoples R China. EM zy.chen1@siat.ac.cn OI Huang, Hailiang/0000-0003-1461-5762 FU government funds of Shenzhen, China [SFG 2012.566, SKC 2012.237] FX This work was supported by the government funds of Shenzhen, China (SFG 2012.566 and SKC 2012.237). NR 82 TC 2 Z9 2 U1 1 U2 11 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 2095-9273 EI 2095-9281 J9 SCI BULL JI Sci. Bull. PD JUN PY 2015 VL 60 IS 11 BP 977 EP 985 DI 10.1007/s11434-015-0794-z PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ9LN UT WOS:000355823900001 ER PT J AU Sankari, A Martin, JL Badr, M AF Sankari, A. Martin, J. L. Badr, M. TI A retrospective review of sleep-disordered breathing, hypertenstion and cardiovascular diseases in spinal cord injury patients SO SPINAL CORD LA English DT Letter ID BLOOD-PRESSURE C1 [Sankari, A.; Badr, M.] John D Dingell VA Med Ctr, Dept Med, Detroit, MI 48201 USA. [Sankari, A.; Badr, M.] Wayne State Univ, Sch Med, Detroit, MI USA. [Martin, J. L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA USA. [Martin, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Sankari, A (reprint author), John D Dingell VA Med Ctr, Dept Med, Detroit, MI 48201 USA. EM abdulghani.sankari@va.gov FU CSRD VA [I01 CX001040, IK2 CX000547] NR 3 TC 1 Z9 1 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 EI 1476-5624 J9 SPINAL CORD JI Spinal Cord PD JUN PY 2015 VL 53 IS 6 BP 496 EP 497 DI 10.1038/sc.2015.16 PG 2 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CK1DP UT WOS:000355946300017 PM 25665540 ER PT J AU Fortenbaugh, FC VanVleet, TM Silver, MA Robertson, LC AF Fortenbaugh, Francesca C. VanVleet, Thomas M. Silver, Michael A. Robertson, Lynn C. TI Spatial distortions in localization and midline estimation in hemianopia and normal vision SO VISION RESEARCH LA English DT Article DE Hemianopia; Hemianopic Line Bisection Error; Pseudoneglect; Bisection; Space perception; Peripheral localization ID VISUAL-FIELD DEFECTS; VIEWING PERCEPTUAL ASYMMETRIES; IN-LINE BISECTION; STRIATE CORTEX; INDIVIDUAL VARIABILITY; ATTENTIONAL BIASES; NORMAL OBSERVERS; SIZE PERCEPTION; FILLING-IN; TEST SCORE AB Studies have shown that individuals with hemianopia tend to bisect a line toward their blind, contralesional visual field, termed the hemianopic line bisection error (HLBE). One theory proposes that the HLBE is a perceptual distortion resulting from expansion of the central region of visual space. If true, perceptual expansions of the central regions in the intact hemifield should also be present and observable across different tasks. We tested this hypothesis using a peripheral localization task to assess localization and midpoint estimation along the horizontal axis of the visual field. In this task, participants judged the location of a target dot presented inside a Goldmann perimeter relative to their perceived visual field boundary. In Experiment 1, we tested neurologically healthy participants on the peripheral localization task as well as a novel midpoint assessment task in which participants reported their perceived midpoint along the horizontal axis of their left and right visual fields. The results revealed consistency in individual biases across the two tasks. We then used the peripheral localization task to test whether two patients with hemianopia showed a selective expansion of central visual space. For these patients, three axes were tested: the spared temporal horizontal axis and the upper and lower vertical axes. The results support the notion that the HLBE is due to expansion of perceived space along the spared temporal axis. Together, the results of both experiments validate the use of these novel paradigms for exploring perceptual asymmetries in both healthy individuals and patients with visual field loss. Published by Elsevier Ltd. C1 [Fortenbaugh, Francesca C.; VanVleet, Thomas M.; Robertson, Lynn C.] US Dept Vet Affairs, Martinez, CA USA. [Fortenbaugh, Francesca C.; Robertson, Lynn C.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [VanVleet, Thomas M.] Brain Plast Inc, San Francisco, CA USA. [Silver, Michael A.] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA. [Silver, Michael A.; Robertson, Lynn C.] Univ Calif Berkeley, Vis Sci Grad Grp, Berkeley, CA 94720 USA. [Silver, Michael A.; Robertson, Lynn C.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. RP Robertson, LC (reprint author), Univ Calif Berkeley, Dept Psychol, 4143 Tolman Hall 5050, Berkeley, CA 94720 USA. EM lynnrob@berkeley.edu FU Veterans Administration; National Institutes of Health [R01-EY016975]; Chancellor's Faculty Partnership Fund from the University of California Berkeley; NEI [EY003176]; Veterans Administration in the VA Clinical Sciences Research Service, Department of Veterans Affairs Medical Center, Martinez, CA FX The authors would especially like to thank the patients for participating in the current study. This research was partially supported by the Veterans Administration as well as National Institutes of Health Grant R01-EY016975 (L.C.R.), the Chancellor's Faculty Partnership Fund from the University of California Berkeley (M.A.S. and L.C.R.), and NEI Core grant EY003176 (L.C.R. and M.A.S). L.C.R. has a Senior Research Career Scientist award from the Veterans Administration in the VA Clinical Sciences Research Service, Department of Veterans Affairs Medical Center, Martinez, CA. The contents within do not represent the views of the Department of Veterans Affairs of the United States government. NR 66 TC 3 Z9 3 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 EI 1878-5646 J9 VISION RES JI Vision Res. PD JUN PY 2015 VL 111 BP 1 EP 12 DI 10.1016/j.visres.2015.03.022 PN A PG 12 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA CK2FW UT WOS:000356027200001 PM 25872177 ER PT J AU Carvalho, LS Vandenberghe, LH AF Carvalho, Livia S. Vandenberghe, Luk H. TI Promising and delivering gene therapies for vision loss SO VISION RESEARCH LA English DT Article DE Retina; Gene therapy; AAV; Lentiviral vector; LCA; Clinical trial ID LEBER CONGENITAL AMAUROSIS; ADENOASSOCIATED VIRAL VECTORS; CILIARY NEUROTROPHIC FACTOR; RETINAL-PIGMENT EPITHELIUM; NULL MUTATION DOG; RETINITIS-PIGMENTOSA; LONG-TERM; VIRUS VECTORS; SUBRETINAL INJECTION; MACULAR DEGENERATION AB The maturity in our understanding of the genetics and the pathogenesis of disease in degenerative retinal disorders has intersected in past years with a novel treatment paradigm in which a genetic intervention may lead to sustained therapeutic benefit, and in some cases even restoration of vision. Here, we review this prospect of retinal gene therapy, discuss the enabling technologies that have led to first-in-human demonstrations of efficacy and safety, and the road that led to this exciting point in time. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Carvalho, Livia S.; Vandenberghe, Luk H.] Harvard Univ, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. RP Vandenberghe, LH (reprint author), Harvard Univ, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Med Sch, 20 Staniford St, Boston, MA 02114 USA. EM luk_vandenberghe@meei.harvard.edu OI Carvalho, Livia/0000-0002-3909-5778 FU NIH [1DP1OD008267-01]; Curing Kids Fund; Foundation for Retina Research; Foundation Fighting Blindness; Research to Prevent Blindness FX Research was supported by NIH grant 1DP1OD008267-01, The Curing Kids Fund, Foundation for Retina Research, Foundation Fighting Blindness (Individual Investigator Award and Center Grant), Research to Prevent Blindness and Institutional Funds. LHV is an inventors on patents related to AAV gene therapy. LHV has served as a consultant and is inventor on technologies licensed to biotechnology and pharmaceutical industry. LHV is co-founder and consultant to GenSight Biologics. NR 112 TC 8 Z9 10 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 EI 1878-5646 J9 VISION RES JI Vision Res. PD JUN PY 2015 VL 111 SI SI BP 124 EP 133 DI 10.1016/j.visres.2014.07.013 PN B PG 10 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA CK1IO UT WOS:000355961200002 PM 25094052 ER PT J AU Parekh, PK Ozburn, AR McClung, CA AF Parekh, Puja K. Ozburn, Angela R. McClung, Colleen A. TI Circadian clock genes: Effects on dopamine, reward and addiction SO ALCOHOL LA English DT Article DE Circadian; Dopamine; Alcohol; Addiction ID ALCOHOL-SEEKING BEHAVIOR; MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; SUPRACHIASMATIC NUCLEUS; ACTIVITY RHYTHMS; ETHANOL WITHDRAWAL; COCAINE REWARD; TYROSINE-HYDROXYLASE; SYNAPTIC PLASTICITY; LOCOMOTOR-ACTIVITY AB Addiction is a widespread public health issue with social and economic ramifications. Substance abuse disorders are often accompanied by disruptions in circadian rhythms including sleep/wake cycles, which can exacerbate symptoms of addiction and dependence. Additionally, genetic disturbance of circadian molecular mechanisms can predispose some individuals to substance abuse disorders. In this review, we will discuss how circadian genes can regulate midbrain dopaminergic activity and subsequently, drug intake and reward. We will also suggest future directions for research on circadian genes and drugs of abuse. (C) 2015 Elsevier Inc. All rights reserved. C1 [Parekh, Puja K.; Ozburn, Angela R.; McClung, Colleen A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15219 USA. [Ozburn, Angela R.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Ozburn, Angela R.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP McClung, CA (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, 450 Technology Dr,Suite 223, Pittsburgh, PA 15219 USA. EM mcclungca@upmc.edu FU NIDA [DA023988]; NIMH [MH082876]; NIAAA [AA020452]; NARSAD FX Studies from our group were supported by NIDA (DA023988 to CAM), NIMH (MH082876 to CAM), NIAAA (AA020452 to ARO), and NARSAD Young Investigator Award (to ARO). The authors declare no conflict of interest. NR 112 TC 12 Z9 12 U1 2 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 EI 1873-6823 J9 ALCOHOL JI Alcohol PD JUN PY 2015 VL 49 IS 4 SI SI BP 341 EP 349 DI 10.1016/j.alcohol.2014.09.034 PG 9 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA CJ8YC UT WOS:000355788400005 PM 25641765 ER PT J AU Cherrier, MM Anderson, K Shofer, J Millard, S Matsumoto, AM AF Cherrier, M. M. Anderson, K. Shofer, J. Millard, S. Matsumoto, A. M. TI Testosterone Treatment of Men With Mild Cognitive Impairment and Low Testosterone Levels SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE mild cognitive impairment; testosterone treatment; verbal memory; cognition; quality of life; low serum testosterone ID HEALTHY OLDER MEN; ALZHEIMERS-DISEASE; BIOAVAILABLE TESTOSTERONE; ELDERLY-MEN; SERUM TESTOSTERONE; CLINICAL-TRIALS; ALTERNATE FORMS; VERBAL MEMORY; RISK; PERFORMANCE AB Introduction: This study investigated the effects of testosterone (T) treatment on cognition, mood, and quality of life in men with mild cognitive impairment (MCI) and low serum T levels. Methods: A total of 351 community-dwelling men were screened, and 37 men evidenced both MCI and low T of whom 27 agreed for further screening. Twenty-two met all the study inclusion/exclusion criteria and enrolled in a 6-month randomized, double-blind, placebo-controlled study. Results: Total T levels significantly increased in the T treatment group. No significant changes were observed in measures of cognition, mood, or quality of life other than improvement in 1 objective measure of verbal memory (P < .05) and decreased depression symptoms (P < .02) in the treatment group. Conclusions: Testosterone treatment may modestly improve verbal memory and depression symptoms in men with both MCI and low T. C1 [Cherrier, M. M.; Anderson, K.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Shofer, J.; Millard, S.; Matsumoto, A. M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Matsumoto, A. M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Cherrier, MM (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Box 356560, Seattle, WA 98195 USA. EM cherrier@uw.edu FU NIA [AG027156]; VA Puget Sound Health Care System, Seattle, WA; University of Washington, Seattle, WA; Abbott Laboratories FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Supported in part by NIA # AG027156. This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, WA as well as the University of Washington, Seattle, WA. The study was also supported by Abbott Laboratories who provided study medication, but did not participate in study design, analyzing data or preparing the manuscript. We would also like to acknowledge the administrative support of Christina Bradic and Ashley Holder. NR 48 TC 7 Z9 7 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 EI 1938-2731 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD JUN PY 2015 VL 30 IS 4 BP 421 EP 430 DI 10.1177/1533317514556874 PG 10 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA CJ6RK UT WOS:000355620900014 PM 25392187 ER PT J AU Cavender, MA Joynt, KE Parzynski, CS Resnic, FS Rumsfeld, JS Moscucci, M Masoudi, FA Curtis, JP Peterson, ED Gurm, HS AF Cavender, Matthew A. Joynt, Karen E. Parzynski, Craig S. Resnic, Frederick S. Rumsfeld, John S. Moscucci, Mauro Masoudi, Frederick A. Curtis, Jeptha P. Peterson, Eric D. Gurm, Hitinder S. TI State Mandated Public Reporting and Outcomes of Percutaneous Coronary Intervention in the United States SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR DATA REGISTRY; ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; AMERICAN-COLLEGE; CARDIOLOGY; ASSOCIATION; PERFORMANCE; IMPROVEMENT; MORTALITY; SURGERY AB Public reporting has been proposed as a strategy to improve health care quality. Percutaneous coronary interventions (PCIs) performed in the United States from July 1, 2009, to June 30, 2011, included in the CathPCI Registry were identified (n = 1,340,213). Patient characteristics and predicted and observed in-hospital mortality were compared between patients treated with PCI in states with mandated public reporting (Massachusetts, New York, Pennsylvania) and states without mandated public reporting. Most PCIs occurred in states without mandatory public reporting (88%, n = 1,184,544). Relative to patients treated in nonpublic reporting states, those who underwent PCI in public reporting states had similar predicted in-hospital mortality (1.39% vs 1.37%, p = 0.17) but lower observed in-hospital mortality (1.19% vs 1.41%, adjusted odds ratio [ORadj] 0.80; 95% confidence interval [CI] 0.74, 0.88; p <0.001). In patients for whom outcomes were available at 180 days, the differences in mortality persisted (4.6% vs 5.4%, ORadj 0.85, 95% CI 0.79 to 0.92, p <0.001), whereas there was no difference in myocardial infarction (ORadj 0.97,95% CI 0.89 to 1.07) or revascularization (ORadj 1.05, 95% CI 0.92 to 1.20). Hospital readmissions were increased at 180 days in patients who underwent PCI in public reporting states (ORadj 1.08, 95% CI 1.03 to 1.12, p = 0.001). In conclusion, patients who underwent PCI in states with mandated public reporting of outcomes had similar, predicted risks but significantly lower observed risks of death during hospitalization and in the 6 months after PCI. These findings support considering public reporting as a potential strategy for improving outcomes of patients who underwent PCI although further studies are warranted to delineate the reasons for these differences. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cavender, Matthew A.; Joynt, Karen E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Joynt, Karen E.] Harvard Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Parzynski, Craig S.; Curtis, Jeptha P.] Yale Univ, Sch Med, Yale Ctr Outcomes Res & Evaluat, New Haven, CT USA. [Resnic, Frederick S.] Lahey Clin Fdn, Burlington, MA USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Moscucci, Mauro] Univ Miami, Sch Med, Miami, FL USA. [Masoudi, Frederick A.] Univ Colorado, Aurora, CO USA. [Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Gurm, Hitinder S.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Cavender, MA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. EM mcavender@partners.org OI Gurm, Hitinder/0000-0002-1646-0218 FU American College of Cardiology Foundation's National Cardiovascular Data Registry; National Heart, Lung, and Blood Institute in Bethesda, Maryland [U01 HL105270-03]; Oklahoma Foundation for Medical Quality; ACC-NCDR; CMS; NCDR CathPCI Registry; National Institutes of Health; AHRQ FX This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry and by grant U01 HL105270-03 (Center for Cardiovascular Outcomes Research at Yale University) from the National Heart, Lung, and Blood Institute in Bethesda, Maryland. The views expressed in this manuscript represent those of the authors and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. Drs Cavender, Joynt, Resnic, Parzynski, and Moscucci report no conflicts of interest. Dr. Rumsfeld reports the following relationship: NCDR (Chief Science Officer). Dr. Masoudi reports the following relationships: NCDR (Senior Medical Officer), Oklahoma Foundation for Medical Quality (contract). Dr. Curtis reports the following relationships: ACC-NCDR (salary support, significant) and CMS (salary support, significant). Dr. Peterson reports the following relationship: NCDR CathPCI Registry (Research grant, principal investigator for data co-ordinating center). Dr. Gurm reports the following relationships: National Institutes of Health and AHRQ (research support). NR 23 TC 5 Z9 5 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2015 VL 115 IS 11 BP 1494 EP 1501 DI 10.1016/j.amjcard.2015.02.050 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CJ6ZL UT WOS:000355643600004 PM 25891991 ER PT J AU Garvey, WT AF Garvey, W. Timothy TI The conundrum of whole foods versus macronutrient composition in assessing effects on insulin sensitivity SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID HIGH-CARBOHYDRATE DIET; RESISTANCE; FAT; OBESITY; GLUCOSE; RISK C1 [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Webb 616,1675 Univ Boulevard, Birmingham, AL 35294 USA. EM garveyt@uab.edu FU NIDDK NIH HHS [DK-083562, P60-DK079626, P30 DK079626, DK-038765] NR 12 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2015 VL 101 IS 6 BP 1109 EP 1110 DI 10.3945/ajcn.115.112292 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CJ6YU UT WOS:000355641900002 PM 25971718 ER PT J AU Assaggaf, MA Kantarci, A Sume, SS Trackman, PC AF Assaggaf, Mohammad A. Kantarci, Alpdogan Sume, Siddika S. Trackman, Philip C. TI Prevention of Phenytoin-Induced Gingival Overgrowth by Lovastatin in Mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TISSUE GROWTH-FACTOR; TO-MESENCHYMAL TRANSITION; TUMOR PROGRESSION; GENE-EXPRESSION; LYSYL OXIDASE; TRANSFORMING GROWTH-FACTOR-BETA-1; BREAST CARCINOMAS; CELL-ADHESION; IN-VIVO; CYCLOSPORINE AB Drug-induced gingival overgrowth is caused by the antiseizure medication phenytoin, calcium channel blockers, and ciclosporin. Characteristics of these drug-induced gingival overgrowth lesions differ. We evaluate the ability of a mouse model to mimic human phenytoin-induced gingival overgrowth and assess the ability of a drug to prevent its development. Lovastatin was chosen based on previous analyses of tissue-specific regulation of CCN2 production in human gingival fibroblasts and the known roles of CCN2 in promoting fibrosis and epithelial to mesenchymal transition. Data indicate that anterior gingival tissue overgrowth occurred in phenytoin-treated mice based on gross tissue observations and histomorphometry of tissue sections. Molecular markers of epithelial plasticity and fibrosis were regulated by phenytoin in gingival epithelial tissues and in connective tissues similar to that seen in humans. Lovastatin attenuated epithelial gingival tissue growth in phenytoin-treated mice and altered the expressions of markers for epithelial to mesenchymal transition. Data indicate that phenytoin-induced gingival overgrowth in mice mimics molecular aspects of human gingival overgrowth and that Lovastatin normalizes the tissue morphology and the expression of the molecular markers studied. Data are consistent with characterization of phenytoin-induced human gingival overgrowth in vivo and in vitro characteristics of cultured human gingival epithelial and connective tissue cells. Findings suggest that statins may serve to prevent or attenuate phenytoin-induced human gingival overgrowth, although specific human studies are required. C1 [Assaggaf, Mohammad A.; Sume, Siddika S.; Trackman, Philip C.] Boston Univ, Dept Mol & Cell Biol, Henry M Goldman Sch Dent Med, Boston, MA 02118 USA. [Kantarci, Alpdogan] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. RP Trackman, PC (reprint author), Boston Univ, Dept Mol & Cell Biol, Henry M Goldman Sch Dent Med, 700 Albany St,W-201, Boston, MA 02118 USA. EM trackman@bu.edu FU NTH/National Institute of Dental and Craniofacial Research grant [R01DE011004]; Faculty of Dentistry, King Abdulaziz University, Ministry of Higher Education, Saudi Arabia FX Supported by NTH/National Institute of Dental and Craniofacial Research grant R01DE011004 (P.C.T.) and by a scholarship from the Faculty of Dentistry, King Abdulaziz University, Ministry of Higher Education, Saudi Arabia (M.A.A.). NR 48 TC 2 Z9 2 U1 0 U2 4 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 JUN PY 2015 VL 185 IS 6 BP 1588 EP 1599 DI 10.1016/j.ajpath.2015.02.004 PG 12 WC Pathology SC Pathology GA CJ2YL UT WOS:000355350500010 PM 25843680 ER PT J AU Ostacher, MJ Perlis, RH Geddes, J AF Ostacher, Michael J. Perlis, Roy H. Geddes, John TI Monotherapy Antidepressant Treatment is Not Associated With Mania in Bipolar I Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Ostacher, Michael J.] VA Palo Alto Hlth Care Syst, Dept Psychiat, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Univ Oxford, Dept Psychiat, Wameford Hosp, Oxford, England. RP Ostacher, MJ (reprint author), VA Palo Alto Hlth Care Syst, Dept Psychiat, Palo Alto, CA 94304 USA. OI Ostacher, Michael/0000-0003-0353-7535 NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2015 VL 172 IS 6 BP 586 EP 586 DI 10.1176/appi.ajp.2015.14111443 PG 1 WC Psychiatry SC Psychiatry GA CJ6ZD UT WOS:000355642800015 PM 26029807 ER PT J AU McCoy, KJM AF McCoy, Karin J. M. TI Clinical Neuropsychology: A Pocket Handbook for Assessment, 3rd edition SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Book Review C1 [McCoy, Karin J. M.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP McCoy, KJM (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM Karin.McCoy@va.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD JUN PY 2015 VL 30 IS 4 BP 356 EP 357 DI 10.1093/arclin/acv023 PG 2 WC Psychology, Clinical; Psychology SC Psychology GA CJ6VF UT WOS:000355632300007 PM 25948292 ER PT J AU Ramos, EM Gillis, T Mysore, JS Lee, JM Alonso, I Gusella, JF Smoller, JW Sklar, P MacDonald, ME Perlis, RH AF Ramos, Eliana Marisa Gillis, Tammy Mysore, Jayalakshmi S. Lee, Jong-Min Alonso, Isabel Gusella, James F. Smoller, Jordan W. Sklar, Pamela MacDonald, Marcy E. Perlis, Roy H. TI Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; depression; Huntington's disease; neurodegenerative disease; polyglutamine expansion; trinucleotide repeat ID ASSOCIATION; CHROMOSOMES; EXPANSION; EVOLUTION AB ObjectivesHuntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTTCAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. MethodsWe assessed the distribution of HTTCAG repeat alleles in a cohort of individuals with bipolar disorder. HTTCAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. ResultsWe found that HTTCAG repeat alleles > 35units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. ConclusionsThese findings do not support an association between bipolar disorder and Huntington's disease. C1 [Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S.; Lee, Jong-Min; Gusella, James F.; Smoller, Jordan W.; MacDonald, Marcy E.; Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ramos, Eliana Marisa; Alonso, Isabel] Univ Porto, IBMC Inst Mol & Cell Biol, UnIGENe, P-4100 Oporto, Portugal. [Sklar, Pamela] Mt Sinai Sch Med, Div Psychiat Gen, Dept Psychiat, New York, NY USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Bldg 185 Cambridge St, Boston, MA 02114 USA. EM rperlis@mgh.harvard.edu RI Alonso, Isabel/I-4307-2013 OI Alonso, Isabel/0000-0001-8549-6903 FU Fundacao para a Ciencia e a Tecnologia [SFRH/BD/44335/2008]; National Institutes of Health NINDS Huntington's Disease Center without Walls [NS16367, NS32765]; CHDI Foundation, Inc.; National Institute of Mental Health [R01MH086026] FX The authors wish to thank Drs. Seung Kwak, Jamshid Arajomond, and Ignacio Munoz-Sanjuan of the CHDI Foundation, Inc. EMR is the recipient of a scholarship from Fundacao para a Ciencia e a Tecnologia (SFRH/BD/44335/2008). Support is provided from grants from the National Institutes of Health NINDS NS16367 Huntington's Disease Center without Walls (JFG, MEM), NS32765 (MEM), and the CHDI Foundation, Inc. (JFG, MEM). RHP is supported by R01MH086026 from the National Institute of Mental Health. NR 17 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 IS 4 BP 403 EP 408 DI 10.1111/bdi.12289 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ9PV UT WOS:000355835600006 PM 25726852 ER PT J AU Ionescu, DF Luckenbaugh, DA Niciu, MJ Richards, EM Zarate, CA AF Ionescu, Dawn F. Luckenbaugh, David A. Niciu, Mark J. Richards, Erica M. Zarate, Carlos A., Jr. TI A single infusion of ketamine improves depression scores in patients with anxious bipolar depression SO BIPOLAR DISORDERS LA English DT Article DE anxious depression; bipolar disorder; ketamine; N-methyl-d-aspartate antagonist; predictors of response ID D-ASPARTATE ANTAGONIST; ADD-ON TRIAL; COMORBID ANXIETY; DOUBLE-BLIND; I DEPRESSION; DISORDER; SCALE; MONOTHERAPY; LURASIDONE; STATES AB ObjectivePatents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressed patients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine's ability to decrease symptoms of depression. MethodsThirty-six patients with anxious (n=21) and non-anxious (n=15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5mg/kg) over 40min. Post-hoc analyses compared changes in the Montgomery-angstrom sberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressed patients with bipolar disorder through 14days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus a HDRS Anxiety/Somatization Factor score of 7. ResultsA linear mixed model revealed a significant effect of anxiety group on the MADRS (p=0.04) and HDRS (p=0.04). Significant drug effects (all p<0.001) suggested that both anxious and non-anxious groups had an antidepressant response to ketamine. The drug-by-anxiety interactions were not significant (all p>0.28). ConclusionsBoth anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest a need for further investigations into ketamine's novel role in the treatment of anxious bipolar depression. C1 [Ionescu, Dawn F.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Ionescu, Dawn F.] Harvard Univ, Sch Med, Boston, MA USA. [Luckenbaugh, David A.; Niciu, Mark J.; Richards, Erica M.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ionescu, DF (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,Floor 6, Boston, MA 02114 USA. EM dionescu@mgh.harvard.edu RI Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015 OI Niciu, Mark/0000-0002-5612-3021; FU Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH); NARSAD Independent Investigator; Brain & Behavior Mood Disorders Research Award FX Funding for this work was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH), by a NARSAD Independent Investigator to CAZ, and by the Brain & Behavior Mood Disorders Research Award to CAZ. NR 26 TC 5 Z9 5 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 IS 4 BP 438 EP 443 DI 10.1111/bdi.12277 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ9PV UT WOS:000355835600010 PM 25400146 ER PT J AU Mohty, M Malard, F Abecassis, M Aerts, E Alaskar, AS Aljurf, M Arat, M Bader, P Baron, F Bazarbachi, A Blaise, D Ciceri, F Corbacioglu, S Dalle, JH Duarte, RF Fukuda, T Huynh, A Masszi, T Michallet, M Nagler, A NiChonghaile, M Pagluica, T Peters, C Petersen, FB Richardson, PG Ruutu, T Savani, BN Wallhult, E Yakoub-Agha, I Carreras, E AF Mohty, M. Malard, F. Abecassis, M. Aerts, E. Alaskar, A. S. Aljurf, M. Arat, M. Bader, P. Baron, F. Bazarbachi, A. Blaise, D. Ciceri, F. Corbacioglu, S. Dalle, J-H Duarte, R. F. Fukuda, T. Huynh, A. Masszi, T. Michallet, M. Nagler, A. NiChonghaile, M. Pagluica, T. Peters, C. Petersen, F. B. Richardson, P. G. Ruutu, T. Savani, B. N. Wallhult, E. Yakoub-Agha, I. Carreras, E. TI Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT) SO BONE MARROW TRANSPLANTATION LA English DT Article ID STEM-CELL TRANSPLANTATION; HEPATIC VENOOCCLUSIVE-DISEASE; ALLOGENEIC HEMATOPOIETIC SCT; ACUTE MYELOID-LEUKEMIA; HIGH-RISK POPULATION; URSODEOXYCHOLIC ACID; INTRAVENOUS BUSULFAN; CONDITIONING REGIMEN; ENDOTHELIAL-CELLS; RANDOMIZED-TRIAL AB Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/ VOD prevention and treatment in adults and children. C1 [Mohty, M.; Malard, F.] Hop St Antoine, Dept Hematol, F-75571 Paris 12, France. [Mohty, M.; Malard, F.] Univ Paris 06, Paris, France. [Abecassis, M.] Inst Portugues Oncol Francisco Gentil, Lisbon, Portugal. [Aerts, E.] Univ Zurich Hosp, Dept Haematol, CH-8091 Zurich, Switzerland. [Alaskar, A. S.] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Dept Oncol, King Abdulaziz Med City,Minist Natl Guard Hlth Af, Riyadh, Saudi Arabia. [Aljurf, M.] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Arat, M.] Sisli Florence Nightingale Hosp, HSCT Unit, Istanbul, Turkey. [Bader, P.] Goethe Univ Frankfurt, Univ Hosp, Dept Children & Adolescents, Div Stem Cell Transplantat & Immunol, D-60054 Frankfurt, Germany. [Baron, F.] Univ Liege, Dept Hematol, Liege, Belgium. [Bazarbachi, A.] Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon. [Blaise, D.] Inst J Paoli I Calmettes, Dept Hematol, Blood & Marrow Transplantat Program, F-13009 Marseille, France. [Ciceri, F.] IRCCS, San Raffaele Sci Inst, Hematol & Bone Marrow Transplantat Unit, Milan, Italy. [Corbacioglu, S.] Univ Regensburg, Dept Hematol Oncol & Stem Cell Transplant, D-93053 Regensburg, Germany. [Dalle, J-H] Univ Paris 07, Hosp Robert Debre, Dept Hematol & Immunol, Paris, France. [Duarte, R. F.] Hosp Duran & Reynals, Inst Catala Oncol, Dept Haematol, Barcelona, Spain. [Fukuda, T.] Natl Canc Ctr, HSCT Div, Tokyo, Japan. [Huynh, A.] Inst Univ Canc Toulouse Oncopole, Dept Hematol, Toulouse, France. [Masszi, T.] Semmelweis Univ, Dept Hematol & Stem Cell Transplantat, St Istvan & St Laszlo Hosp, Budapest Dept Internal Med 3, H-1085 Budapest, Hungary. [Michallet, M.] Univ Lyon 1, EST, Hosp Civils Lyon, Hematol Dept,Grp Hosp Sud, Pierre Benite, France. [Nagler, A.] Chaim Sheba Med Ctr, Hematol & Bone Marrow Transplantat, IL-52621 Tel Hashomer, Israel. [NiChonghaile, M.] Univ Dublin Trinity Coll, Natl Stem Cell Transplant Unit Adults, Dept Haematol, St Jamess Hosp, Dublin 2, Ireland. [NiChonghaile, M.] Univ Dublin Trinity Coll, Acad Dept Haematol, Dublin 2, Ireland. [Pagluica, T.] Kings Coll Hosp London, Dept Haematol, London, England. [Peters, C.] St Anna Childrens Hosp, Dept Pediat, Vienna, Austria. [Petersen, F. B.] LDS Hosp, Salt Lake City, UT USA. [Richardson, P. G.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancy, Boston, MA 02115 USA. [Ruutu, T.] Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland. [Savani, B. N.] Vanderbilt Univ, Dept Med, Hematol & Stem Cell Transplantat Sect, Div Hematol Oncol, Nashville, TN USA. [Savani, B. N.] Vet Affairs Med Ctr, Nashville, TN 37212 USA. [Wallhult, E.] Sahlgrens Univ Hosp, Dept Internal Med, Sect Haematol & Coagulat, Gothenburg, Sweden. [Yakoub-Agha, I.] CHU Lille, Bone Marrow Transplantat Unit, F-59037 Lille, France. [Carreras, E.] Josep Carreras Leukaemia Res Inst, Barcelona, Spain. [Carreras, E.] Hosp Clin Barcelona, Dept Haematol, Barcelona, Spain. [Carreras, E.] Josep Carreras Fdn, Spanish Bone Marrow Donor Program, Barcelona, Spain. RP Mohty, M (reprint author), Hop St Antoine, Dept Hematol, 184 Rue Faubourg St Antoine, F-75571 Paris 12, France. EM mohamad.mohty@inserm.fr OI /0000-0002-0648-3256 FU 'Association for Training, Education and Research in Hematology, Immunology and Transplantation' (ATERHIT, Nantes, France) FX MM thanks Professor JV Melo (Adelaide, Australia) for critical reading of the manuscript. FM was supported by educational grants from the 'Association for Training, Education and Research in Hematology, Immunology and Transplantation' (ATERHIT, Nantes, France). NR 68 TC 28 Z9 30 U1 0 U2 8 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 JUN PY 2015 VL 50 IS 6 BP 781 EP 789 DI 10.1038/bmt.2015.52 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CJ6HO UT WOS:000355594900005 PM 25798682 ER PT J AU Renteria, AS Sanchorawala, V Niehaus, ED Sun, F Semigran, MJ Seldin, DC AF Renteria, A. S. Sanchorawala, V. Niehaus, E. D. Sun, F. Semigran, M. J. Seldin, D. C. TI Serum free light chain trends between orthotopic heart transplantation and auto-SCT in patients with AL amyloidosis SO BONE MARROW TRANSPLANTATION LA English DT Letter ID STEM-CELL TRANSPLANTATION; HIGH-DOSE MELPHALAN; CARDIAC AMYLOIDOSIS C1 [Renteria, A. S.; Sanchorawala, V.; Seldin, D. C.] Boston Univ, Sch Med, Amyloidosis Ctr, Boston, MA 02215 USA. [Renteria, A. S.; Sanchorawala, V.; Seldin, D. C.] Boston Med Ctr, Boston, MA 02215 USA. [Niehaus, E. D.; Semigran, M. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Heart Failure & Cardiac Transplant Program, Boston, MA USA. [Sun, F.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Renteria, AS (reprint author), Boston Univ, Sch Med, Amyloidosis Ctr, Boston, MA 02215 USA. EM david.seldin@bmc.org NR 10 TC 0 Z9 0 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 JUN PY 2015 VL 50 IS 6 BP 868 EP 869 DI 10.1038/bmt.2015.9 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CJ6HO UT WOS:000355594900020 PM 25751645 ER PT J AU Ruddy, KJ Guo, H Barry, W Dang, CT Yardley, DA Moy, B Marcom, PK Albain, KS Rugo, HS Ellis, MJ Shapira, I Wolff, AC Carey, LA Overmoyer, BA Hudis, C Krop, IE Burstein, HJ Winer, EP Partridge, AH Tolaney, SM AF Ruddy, Kathryn J. Guo, Hao Barry, William Dang, Chau T. Yardley, Denise A. Moy, Beverly Marcom, P. Kelly Albain, Kathy S. Rugo, Hope S. Ellis, Matthew J. Shapira, Iuliana Wolff, Antonio C. Carey, Lisa A. Overmoyer, Beth A. Hudis, Clifford Krop, Ian E. Burstein, Harold J. Winer, Eric P. Partridge, Ann H. Tolaney, Sara M. TI Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT trial) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Chemotherapy; Fertility; Premenopausal ID EARLY BREAST-CANCER; LONG-TERM AMENORRHEA; PREMENOPAUSAL WOMEN; TIME-COURSE; TAXANE; ANTHRACYCLINE; SUPPRESSION; MENOPAUSE; GOSERELIN; MODALITY AB Chemotherapy-related amenorrhea (CRA) is associated with infertility and menopausal symptoms. Learning how frequently paclitaxel and trastuzumab cause amenorrhea is important. Most other adjuvant breast cancer therapies induce CRA in approximately 50 % of all premenopausal recipients [1]. 410 patients enrolled on the APT Trial, a single-arm phase 2 adjuvant study of 12 weeks of paclitaxel and trastuzumab followed by nine months of trastuzumab monotherapy. Eligible patients had a parts per thousand currency sign3 cm node-negative HER2 + breast cancers. Premenopausal enrollees were asked to complete menstrual surveys every 3-12 months for 72 months. Women who responded to at least one survey at least 15 months after chemotherapy initiation (and who did not undergo hysterectomy and/or bilateral oophorectomy or receive ovarian suppressing medications prior to 15 months) were included in this analysis. A participant was defined as having amenorrhea in follow-up if her self-reported last menstrual period at last follow-up was greater than 12 months prior to the survey. Among the 64 women in the evaluable population (median age at study entry 44 years, range 27-52 years), the median time between chemotherapy initiation and last menstrual survey was 51 months (range 16-79). 18 of 64 women (28 %, 95 % CI 18-41 %) were amenorrheic at that time point. Amenorrhea rates among premenopausal women treated with adjuvant paclitaxel and trastuzumab for early stage breast cancer appear lower than those seen historically with standard alkylator-based breast cancer regimens. Future studies are needed to understand the impact of this regimen on related issues of fertility and menopausal symptoms. C1 [Ruddy, Kathryn J.] Mayo Clin, Rochester, MN 55905 USA. [Guo, Hao; Barry, William; Overmoyer, Beth A.; Krop, Ian E.; Burstein, Harold J.; Winer, Eric P.; Partridge, Ann H.; Tolaney, Sara M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dang, Chau T.; Hudis, Clifford] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Yardley, Denise A.] Sarah Cannon Res Inst, Nashville, TN USA. [Yardley, Denise A.] Tennessee Oncol PLLC, Nashville, TN USA. [Moy, Beverly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marcom, P. Kelly] Duke Univ, Med Ctr, Durham, NC USA. [Albain, Kathy S.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Rugo, Hope S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ellis, Matthew J.] Washington Univ, St Louis, MO USA. [Shapira, Iuliana] Hofstra North Shore LIJ Med Sch, Hempstead, NY USA. [Wolff, Antonio C.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Carey, Lisa A.] Univ N Carolina, Chapel Hill, NC USA. RP Ruddy, KJ (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM ruddy.kathryn@mayo.edu RI Guo, Hao/E-8921-2015; OI Guo, Hao/0000-0003-1658-0989; Wolff, Antonio/0000-0003-3734-1063 FU Genentech; CTSA from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) [UL1TR000135, KL2TR000136-09] FX This trial was supported by Genentech. This publication was made possible by CTSA Grant Numbers UL1TR000135 and KL2TR000136-09 (KJR) from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. Precis: Paclitaxel-trastuzumab is likely less gonadotoxic than standard chemotherapy for breast cancer. This regimen may be appealing for women who wish to preserve ovarian function. NR 24 TC 5 Z9 5 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2015 VL 151 IS 3 BP 589 EP 596 DI 10.1007/s10549-015-3426-z PG 8 WC Oncology SC Oncology GA CJ7FB UT WOS:000355658700010 PM 25981899 ER PT J AU Vaz-Luis, I Lin, NU Keating, NL Barry, WT Lii, HC Winer, EP Freedman, RA AF Vaz-Luis, Ines Lin, Nancy U. Keating, Nancy L. Barry, William T. Lii, Huichuan Winer, Eric P. Freedman, Rachel A. TI Racial differences in outcomes for patients with metastatic breast cancer by disease subtype SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Metastatic breast cancer; Racial disparities; Disease subtype; Trastuzumab ID SEER-MEDICARE DATA; CLINICAL-OUTCOMES; TREATMENT PATTERNS; COMORBIDITY INDEX; SYSTEMIC THERAPY; UNITED-STATES; WHITE WOMEN; SURVIVAL; CHEMOTHERAPY; TRENDS AB Treatment advances have differed by breast cancer subtype. We examined the impact of race on survival of women with metastatic breast cancer by disease subgroup. Using surveillance, epidemiology, and end results -Medicare data, we included white and black patients aged a parts per thousand yen66 with de novo metastatic breast cancer diagnosed between 1998 and 2009. Using trastuzumab as a proxy for human epidermal growth factor receptor 2 (HER2)-positive status, we defined three disease subgroups: (1) HER2-positive (received trastuzumab), (2) HER2-negative/unknown (never received trastuzumab)/hormone receptor (HR)-positive, and (3) HER2-negative/unknown/HR-negative. Multivariate Cox proportional models assessed the impact of race on overall survival (OS) and breast cancer-specific survival by subgroup. We also examined trastuzumab treatment patterns. Among 4364 women (86 % white, 14 % black), 9 % had HER2-positive, 72 % had HER2-negative/unknown/HR-positive, and 18 % had HER2-negative/unknown/HR-negative tumors. Patients with HER2-positive disease experienced longer median OS compared with others: 2.4 versus 1.8 years for women with HER2-negative/unknown/HR-positive and 0.5 years for women with HER2-negative/unknown/HR-negative disease (P < 0.001). Racial differences in OS were only observed among patients with HER2-positive tumors: median OS: 1.4 versus 2.7 years for black and white women, adjusted hazard ratio 1.45; 95 % Confidence interval 1.01-2.08. Results for breast cancer-specific survival were similar. We also observed racial differences in trastuzumab utilization, with longer median time to trastuzumab initiation and lower likelihood of continuation over time for black (vs. white) patients. Among women with de novo metastatic breast cancer, racial differences in survival were only apparent for those with inferred HER2-positive tumors. Further study of how treatment patterns affect outcomes is warranted. C1 [Vaz-Luis, Ines; Lin, Nancy U.; Winer, Eric P.; Freedman, Rachel A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lii, Huichuan] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org FU National Cancer Institute's Surveillance, Epidemiology and End Results Program [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02]; CJL Foundation; Susan G. Komen for the Cure; Fundacao para a Ciencia e Tecnologia [HMSP-ICS/0004/2011]; Dana-Farber Cancer Institute Friends Award FX This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Sect. 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. The study was supported by the CJL Foundation (to W T Barry), Susan G. Komen for the Cure (to E P Winer and N L Keating), Fundacao para a Ciencia e Tecnologia (HMSP-ICS/0004/2011, Career Development Award) (to I Vaz-Luis) and a Dana-Farber Cancer Institute Friends Award (to R Freedman). NR 44 TC 8 Z9 8 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2015 VL 151 IS 3 BP 697 EP 707 DI 10.1007/s10549-015-3432-1 PG 11 WC Oncology SC Oncology GA CJ7FB UT WOS:000355658700021 PM 26022349 ER PT J AU Varga, C Xie, WL Laubach, J Ghobrial, IM O'Donnell, EK Weinstock, M Paba-Prada, C Warren, D Maglio, ME Schlossman, R Munshi, NC Raje, N Weller, E Anderson, KC Mitsiades, CS Richardson, PG AF Varga, Cindy Xie, Wanling Laubach, Jacob Ghobrial, Irene M. O'Donnell, Elizabeth K. Weinstock, Matthew Paba-Prada, Claudia Warren, Diane Maglio, Michelle E. Schlossman, Robert Munshi, Nikhil C. Raje, Noopur Weller, Edie Anderson, Kenneth C. Mitsiades, Constantine S. Richardson, Paul G. TI Development of extramedullary myeloma in the era of novel agents: no evidence of increased risk with lenalidomide-bortezomib combinations SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; extraosseous plasmacytoma; extramedullary disease; bortezomib; lenalidomide ID MULTIPLE-MYELOMA; STAGING SYSTEM; DISEASE; FEATURES; THERAPY; PLASMACYTOMA; MECHANISMS; PROGNOSIS; SURVIVAL; IMPACT AB Proteasome inhibitors (PI) and immunomodulatory agents (IMIDs) have improved the overall survival (OS) of patients with multiple myeloma (MM), but concerns have been raised about increased incidence of extramedullary disease (EMD) after the combined use of PIs and IMIDs for upfront therapy. We evaluated whether the addition of lenalidomide to bortezomib-based front-line regimens precipitated earlier development of EMD. We reviewed the charts of 117 MM patients (median follow-up from diagnosis 61years; range 01-102years) enrolled in eight clinical trials of first-line treatment with bortezomib-based regimens, with or without lenalidomide. We assessed development of EMD as extraosseous (distant from bone) or osseous (originating from bone) plasmacytomas. The primary endpoint was time from diagnosis until development of EMD, based on imaging, biopsy and/or physical examination. Any form of EMD at progression was observed in 40 (342%) patients, including 21 (18%) osseous, 8 (7%) extraosseous and 11 (9%) both osseous and extraosseous. Median OS was 09years (range 01-48years) after extraosseous EMD development. Sensitivity analyses with follow-up times truncated at 5years detected no statistically significant difference in rates of any EMD form between the two groups (P>02 for each comparison). Therefore, we observed no evidence that bortezomib-lenalidomide-based front-line therapy precipitates earlier EMD. C1 [Varga, Cindy; Xie, Wanling; Laubach, Jacob; Ghobrial, Irene M.; Weinstock, Matthew; Paba-Prada, Claudia; Warren, Diane; Maglio, Michelle E.; Schlossman, Robert; Munshi, Nikhil C.; Weller, Edie; Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. [O'Donnell, Elizabeth K.; Raje, Noopur; Mitsiades, Constantine S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM constantine_mitsiades@dfci.harvard.edu; paul_richardson@dfci.harvard.edu FU National Institutes of Health [R01 CA127435, R01 CA179483]; Shawna Ashlee Corman Investigatorship in Multiple Myeloma Research; de Gunzburg Myeloma Research Fund; Cobb Family Myeloma Research Fund; Chambers Family Advanced Myeloma Research Fund; Leukemia and Lymphoma Society; Multiple Myeloma Research Foundation; RJ Corman Multiple Myeloma Research Fund FX The study was supported by Grant Nos R01 CA127435 (C.S.M., K.C.A), R01 CA179483 (C.S.M.) from the National Institutes of Health, by the Shawna Ashlee Corman Investigatorship in Multiple Myeloma Research, the de Gunzburg Myeloma Research Fund, the Cobb Family Myeloma Research Fund, the Chambers Family Advanced Myeloma Research Fund, the Leukemia and Lymphoma Society Translational Research Program and Quest for Cure Program, the Multiple Myeloma Research Foundation and the RJ Corman Multiple Myeloma Research Fund. The authors would like to thank Jeffrey Sorrell for administrative assistance in support of the preparation of this manuscript. NR 24 TC 8 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2015 VL 169 IS 6 BP 843 EP 850 DI 10.1111/bjh.13382 PG 8 WC Hematology SC Hematology GA CJ7EN UT WOS:000355657300012 PM 26032514 ER PT J AU Weinstock, M Aljawai, Y Morgan, EA Laubach, J Gannon, M Roccaro, AM Varga, C Mitsiades, CS Paba-Prada, C Schlossman, R Munshi, N Anderson, KC Richardson, PP Weller, E Ghobrial, IM AF Weinstock, Mathew Aljawai, Yosra Morgan, Elizabeth A. Laubach, Jacob Gannon, Muriel Roccaro, Aldo M. Varga, Cindy Mitsiades, Constantine S. Paba-Prada, Claudia Schlossman, Robert Munshi, Nikhil Anderson, Kenneth C. Richardson, Paul P. Weller, Edie Ghobrial, Irene M. TI Incidence and clinical features of extramedullary multiple myeloma in patients who underwent stem cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; extramedullary; novel agents; stem cell transplantation; CD44 ID PRESENTING FEATURES; PLUS DEXAMETHASONE; DISEASE; BORTEZOMIB; EXPRESSION; PROGNOSIS; SURVIVAL; THERAPY; TRIAL; CD44 AB Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow, is an uncommon manifestation of multiple myeloma. Six hundred and sixty-three consecutive patients with multiple myeloma who underwent stem cell transplantation between January 2005 and December 2011 were assessed for the presence of EMD. A cohort of 55 patients with biopsy-proven EMD was identified, comprising 83% of the total study population. EMD was present at the time of diagnosis in 145% of cases and at the time of relapse in 76% of patients. The most common EMD presentations at relapse were liver involvement and pleural effusions. EMD specimens had high expression of CD44 (92%) and moderate expression of CXCR4. The median overall survival from time of myeloma diagnosis was 41years (95% CI: 31, 51) and the median overall survival from time of EMD diagnosis was 13years (95% CI: 08, 23). This report demonstrates that the incidence of EMD has not increased with the introduction of novel agents and stem cell transplantation. The most common EMD presentations in the relapsed setting were liver and pleural fluid. The presence of CD44 and CXCR4 expression may represent new markers of EMD that warrant further investigation. C1 [Weinstock, Mathew; Aljawai, Yosra; Laubach, Jacob; Gannon, Muriel; Roccaro, Aldo M.; Varga, Cindy; Mitsiades, Constantine S.; Paba-Prada, Claudia; Schlossman, Robert; Munshi, Nikhil; Anderson, Kenneth C.; Richardson, Paul P.; Weller, Edie; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Weinstock, Mathew] Harvard Univ, Sch Med, Beth Israel Deaconess, Boston, MA USA. [Morgan, Elizabeth A.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu OI Roccaro, Aldo/0000-0002-1872-5128; Morgan, Elizabeth/0000-0001-5880-9337 FU Leukemia and Lymphoma Society; NIH/NCI [R01CA181683] FX This work was supported by Leukemia and Lymphoma Society and NIH/NCI R01CA181683. NR 20 TC 11 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2015 VL 169 IS 6 BP 851 EP 858 DI 10.1111/bjh.13383 PG 8 WC Hematology SC Hematology GA CJ7EN UT WOS:000355657300013 PM 25833301 ER PT J AU Wecht, JM Cirnigliaro, CM Azarelo, F Bauman, WA Kirshblum, SC AF Wecht, Jill M. Cirnigliaro, Christopher M. Azarelo, Frank Bauman, William A. Kirshblum, Steven C. TI Orthostatic responses to anticholinesterase inhibition in spinal cord injury SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Pyridostigmine; Hypotension; Blood pressure; Heart rate; Tetraplegia ID LOW BLOOD-PRESSURE; CONTINGENT NEGATIVE-VARIATION; ACETYLCHOLINESTERASE INHIBITION; DEPRESSIVE SYMPTOMS; COGNITIVE PERFORMANCE; HYPOTENSION; POPULATION; ASSOCIATION; TETRAPLEGIA; COMMUNITY AB Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of norepinephrine, thereby increasing systemic blood pressure (BP). The primary objective of this investigation was to determine the hemodynamic effect of pyridostigmine bromide (PYRIDO: 60 mg), an Ach inhibitor (AchI), compared to no-drug (NO-D) during head-up tilt (HUT) in individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effects of PYRIDO compared to NO-D on symptoms of orthostatic intolerance (OI) and adverse event reporting (AE). Ten individuals with SCI (C4-C7) were studied on two occasions: visit (1) NO-D and visit (2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15A degrees, 25A degrees, 35A degrees for 5 min at each angle and 45 min at 45A degrees. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP and DBP), as well as monitored and symptoms of OI and AE were monitored and recorded. Supine hemodynamics did not differ between the trials. The significant fall in SBP during the NO-D trial was diminished with PYRIDO, and five subjects had an increased DBP during HUT with PYRIDO compared to the NO-D trial. Individuals that responded to PYRIDO with an increase in orthostatic BP had significantly lower resting HR than non-responders (p < 0.01), which suggests increased levels of pre-synaptic Ach. Subjective symptoms of OI and AE reporting did not differ between the two trials. These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI. C1 [Wecht, Jill M.; Cirnigliaro, Christopher M.; Azarelo, Frank; Bauman, William A.] James J Peters VAMC, Natl Ctr Excellence, Bronx, NY 10468 USA. [Wecht, Jill M.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Wecht, Jill M.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Wecht, Jill M.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Bauman, William A.] James J Peters VAMC, Med Serv, Bronx, NY 10468 USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Rutgers New Jersey Med Sch, Newark, NJ USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Rm 7A-13,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM jm.wecht@va.gov FU Veterans Affairs Rehabilitation Research and Development Service [B9212C] FX This research was supported by the Veterans Affairs Rehabilitation Research and Development Service (Grant # B9212C). NR 39 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0959-9851 EI 1619-1560 J9 CLIN AUTON RES JI Clin. Auton. Res. PD JUN PY 2015 VL 25 IS 3 BP 179 EP 187 DI 10.1007/s10286-015-0272-3 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CK1CF UT WOS:000355942300006 PM 25916633 ER PT J AU Pasparakis, E Koiliari, E Zouraraki, C Tsapakis, EM Roussos, P Giakoumaki, SG Bitsios, P AF Pasparakis, E. Koiliari, E. Zouraraki, C. Tsapakis, E. -M. Roussos, P. Giakoumaki, S. G. Bitsios, P. TI The effects of the CACNA1C rs1006737 A/G on affective startle modulation in healthy males SO EUROPEAN PSYCHIATRY LA English DT Article DE Psychosis; Bipolar affective disorder; Genetics; IAPS pictures; Emotional processing ID MAJOR DEPRESSIVE DISORDER; GENOME-WIDE ASSOCIATION; BORDERLINE PERSONALITY-DISORDER; BIPOLAR DISORDER; GENETIC-VARIATION; EMOTIONAL MEMORY; SCHIZOPHRENIA; REFLEX; ANXIETY; REACTIVITY AB Background: The CACNA1C rs1006737 risk A allele has been associated with affective psychoses and functional studies indicate that it is associated with increased hippocampal/amygdala activity during emotional face-processing. Here we studied the impact of the risk A allele on affective startle modulation. Methods: Hundred and ninety-four healthy males stratified for their CACNA1C rs1006737 genotype (GG:111, GA:67, AA:16) were presented with 18 pleasant, 18 unpleasant and 18 neutral pictures with acoustic probes (104 dB) occurring during 12 pictures in each affective category. Baseline startle was assessed during blank screens. State mood was self-rated on arrival, pre- and post-test and the emotional valence and arousal of affective pictures at post-test. Results: Relative to the other genotypes, risk A allele homozygotes presented with higher anxiety/negative affect at pre-test, reduced and exaggerated physiological responses to the pleasant and negative pictures respectively, negative affect with reduced arousal at post-test and rated the affective pictures as less arousing and inconsistently to their physiological responses (all P < 0.05). Sustained contextual negative mood predicted reduced baseline and affective startle reactivity in the AA group. Conclusions: Healthy homozygous males for the risk A allele appear to have marked contextual sensitivity, affective reactivity akin to anxiety and depression and inefficient emotional appraisal. Our findings provide phenotypic detail of the CACNA1C AA genotype in non-symptomatic individuals, which suggest primary effects in emotional circuitry, consistent with previously documented alterations in hippocampal/amygdala processing. (C) 2015 Elsevier Masson SAS. All rights reserved. C1 [Pasparakis, E.; Koiliari, E.; Tsapakis, E. -M.; Roussos, P.; Bitsios, P.] Univ Crete, Fac Med, Dept Psychiat & Behav Sci, Iraklion 71003, Crete, Greece. [Zouraraki, C.; Giakoumaki, S. G.] Univ Crete, Dept Psychol, Rethimnon, Crete, Greece. [Tsapakis, E. -M.] Aghios Charalambos Mental Hlth Clin, Iraklion, Crete, Greece. [Roussos, P.] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, Dept Psychiat,Friedman Brain Inst, New York, NY 10029 USA. [Roussos, P.] MIRECC, James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Bitsios, P (reprint author), Univ Crete, Fac Med, Dept Psychiat & Behav Sci, Iraklion 71003, Crete, Greece. EM pbitsios@med.uoc.gr RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU University of Crete Research Funds Account [E.L.K.E. 1348]; "Manasaki" scholarship FX This project was supported by the University of Crete Research Funds Account (E.L.K.E. 1348). E.K. was supported by a "Manasaki" scholarship. We thank the participants for their help with the study. NR 75 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PD JUN PY 2015 VL 30 IS 4 BP 492 EP 498 DI 10.1016/j.eurpsy.2015.03.004 PG 7 WC Psychiatry SC Psychiatry GA CJ7LB UT WOS:000355675400009 PM 25841664 ER PT J AU Suh, J Moncaster, JA Wang, LR Hafeez, I Herz, J Tanzi, RE Goldstein, LE Guenette, SY AF Suh, Jaehong Moncaster, Juliet A. Wang, Lirong Hafeez, Imran Herz, Joachim Tanzi, Rudolph E. Goldstein, Lee E. Guenette, Suzanne Y. TI FE65 and FE65L1 amyloid precursor protein-binding protein compound null mice display adult-onset cataract and muscle weakness SO FASEB JOURNAL LA English DT Article DE APP; congenital muscular dystrophy; extracellular matrix; laminin; lens ID APP FAMILY-MEMBERS; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; EXTRACELLULAR-MATRIX; MYOTONIC-DYSTROPHY; BRAIN-DEVELOPMENT; SKELETAL-MUSCLE; MAMMALIAN FE65; DEFICIENT MICE; BETA AB FE65 and FE65L1 are cytoplasmic adaptor proteins that bind a variety of proteins, including the amyloid precursor protein, and that mediate the assembly of multimolecular complexes. We previously reported that FE65/FE65L1 double knockout (DKO) mice display disorganized laminin in meningeal fibroblasts and a cobblestone lissencephaly-like phenotype in the developing cortex. Here, we examined whether loss of FE65 and FE65L1 causes ocular and muscular deficits, 2 phenotypes that frequently accompany cobblestone lissencephaly. Eyes of FE65/FE65L1 DKO mice develop normally, but lens degeneration becomes apparent in young adult-mice. Abnormal lens epithelial cell migration, widespread small vacuole formation, and increased laminin expression underneath lens capsules suggest impaired interaction between epithelial cells and capsular extracellular matrix in DKO lenses. Cortical cataracts develop in FE65L1 knockout (KO) mice aged 16 months or more but are absent in wild-type or FE65 KO mice. FE65 family KO mice show attenuated grip strength, and the nuclei of DKO muscle cells frequently locate in the middle of muscle fibers. These findings reveal that FE65 and FE65L1 are essential for the maintenance of lens transparency, and their loss produce phenotypes in brain, eye, and muscle that are comparable to the clinical features of congenital muscular dystrophies in humans. C1 [Suh, Jaehong; Wang, Lirong; Hafeez, Imran; Tanzi, Rudolph E.; Guenette, Suzanne Y.] Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Genet & Aging Res Unit,Dept Neurol,Med Sch, Boston, MA 02129 USA. [Moncaster, Juliet A.; Goldstein, Lee E.] Boston Univ, Sch Med, Mol Aging & Dev Lab, Boston, MA 02118 USA. [Herz, Joachim] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA. RP Suh, J (reprint author), Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Genet & Aging Res Unit,Dept Neurol,Med Sch, 114 16th St, Boston, MA 02129 USA. EM suh.jaehong@mgh.harvard.edu; suzanne.guenette@gmail.com OI Moncaster, Juliet/0000-0002-7849-4325 FU U.S. National Institutes of Health; Korea Research Foundation FX The authors thank D. Romano for her technical assistance in muscle pathology experiments. The authors also thank M. Lawlor (Boston Children Hospital) for his advice on muscle tissue preparation and C. Vanderburg (Massachusetts General Hospital) for his scientific expertise and advice on the muscle study. This work was supported by grants from the U.S. National Institutes of Health (to S.Y.G. and R.E.T.) and by a fellowship from the Korea Research Foundation (to J.S.). NR 63 TC 2 Z9 2 U1 0 U2 3 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 JUN PY 2015 VL 29 IS 6 BP 2628 EP 2639 DI 10.1096/fj.14-261453 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CJ0ZF UT WOS:000355209500038 PM 25757569 ER PT J AU Fargali, S Garcia, AL Sadahiro, M Jiang, C Janssen, WG Lin, WJ Cogliani, V Elste, A Mortillo, S Cero, C Veitenheimer, B Graiani, G Pasinetti, GM Mahata, SK Osborn, JW Huntley, GW Phillips, GR Benson, DL Bartolomucci, A Salton, SR AF Fargali, Samira Garcia, Angelo L. Sadahiro, Masato Jiang, Cheng Janssen, William G. Lin, Wei-Jye Cogliani, Valeria Elste, Alice Mortillo, Steven Cero, Cheryl Veitenheimer, Britta Graiani, Gallia Pasinetti, Giulio M. Mahata, Sushil K. Osborn, John W. Huntley, George W. Phillips, Greg R. Benson, Deanna L. Bartolomucci, Alessandro Salton, Stephen R. TI The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure (vol 28, pg 2120, 2014) SO FASEB JOURNAL LA English DT Correction C1 [Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res & Clin Ctr, Bronx, NY USA. Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurosci, New York, NY 10029 USA. Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurol, New York, NY 10029 USA. FU NIGMS NIH HHS [T32 GM008471] NR 1 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JUN PY 2015 VL 29 IS 6 BP 2679 EP 2679 DI 10.1096/fj.13-239509ERR PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CJ0ZF UT WOS:000355209500042 PM 26032479 ER PT J AU Butrick, M Kelly, S Peshkin, BN Luta, G Nusbaum, R Hooker, GW Graves, K Feeley, L Isaacs, C Valdimarsdottir, HB Jandorf, L DeMarco, T Wood, M McKinnon, W Garber, J McCormick, SR Schwartz, MD AF Butrick, Morgan Kelly, Scott Peshkin, Beth N. Luta, George Nusbaum, Rachel Hooker, Gillian W. Graves, Kristi Feeley, Lisa Isaacs, Claudine Valdimarsdottir, Heiddis B. Jandorf, Lina DeMarco, Tiffani Wood, Marie McKinnon, Wendy Garber, Judy McCormick, Shelley R. Schwartz, Marc D. TI Disparities in uptake of BRCA1/2 genetic testing in a randomized trial of telephone counseling SO GENETICS IN MEDICINE LA English DT Article DE cancer; genetic counseling; genetic testing; psychosocial predictors; telephone counseling ID BREAST-CANCER SUSCEPTIBILITY; HEREDITARY BREAST; OVARIAN-CANCER; RACIAL-DIFFERENCES; HIGH-RISK; WOMEN; COMMUNICATION; VALIDATION; QUALITY; PATIENT AB Purpose: As genetic counseling and testing become more fully integrated into clinical care, alternative delivery models are increasingly prominent. This study examines predictors of genetic testing for hereditary breast/ovarian cancer among high-risk women in a randomized trial of in-person versus telephone-based genetic counseling. Methods: Methods include multivariable logistic regression and interaction analyses. Results: Of the 669 participants, 600 completed counseling and 523 received test results. As previously reported, participants randomized to telephone counseling were significantly less likely to be tested. In intention-to-treat analyses, completion of counseling and testing was associated with: race/ethnicity (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.20-3.20), perceived stress (OR = 0.89, 95% CI: 0.81-0.98), knowledge (OR = 1.12, 95% CI: 1.02-1.23), and randomization group (OR = 1.48, 95% CI: 1.01-2.16). Further, race/ ethnicity moderated the association between randomization group and testing; minority women receiving telephone counseling were least likely to complete testing. Conclusion: Evidence for logistical and communication-based explanations for this interaction is presented. The overall increased access made possible with telephone genetic counseling should be considered in light of the possibility that this may also lead to lower rates of testing among high-risk minority women. Additional care should be taken to assess and address potential barriers when services are delivered by telephone. C1 [Butrick, Morgan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Kelly, Scott; Peshkin, Beth N.; Nusbaum, Rachel; Graves, Kristi; Feeley, Lisa; Isaacs, Claudine; DeMarco, Tiffani; Schwartz, Marc D.] Georgetown Univ, Dept Oncol, Canc Prevent & Control Program, Washington, DC 20057 USA. [Kelly, Scott; Peshkin, Beth N.; Nusbaum, Rachel; Graves, Kristi; Feeley, Lisa; Isaacs, Claudine; DeMarco, Tiffani; Schwartz, Marc D.] Georgetown Univ, Fisher Ctr Familial Canc Res, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Luta, George] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC USA. [Hooker, Gillian W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Valdimarsdottir, Heiddis B.; Jandorf, Lina] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. [Wood, Marie; McKinnon, Wendy] Univ Vermont, Coll Med, Vermont Canc Ctr, Familial Canc Program, Burlington, VT USA. [Garber, Judy; McCormick, Shelley R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genet & Prevent, Boston, MA 02115 USA. RP Schwartz, MD (reprint author), Georgetown Univ, Dept Oncol, Canc Prevent & Control Program, Washington, DC 20057 USA. EM schwartm@georgetown.edu RI Kelly, Scott/D-3195-2013; OI Kelly, Scott/0000-0002-0375-1040; Luta, George/0000-0001-9013-2207; Luta, George/0000-0002-4035-7632 FU National Cancer Institute [R01 CA108933, P30 CA051008]; Jess and Mildred Fisher Center for Familial Cancer Research FX Grant support was received from the National Cancer Institute (grants R01 CA108933 and P30 CA051008) and the Jess and Mildred Fisher Center for Familial Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 40 TC 9 Z9 9 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JUN PY 2015 VL 17 IS 6 BP 467 EP 475 DI 10.1038/gim.2014.125 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CJ5WS UT WOS:000355564200006 PM 25232856 ER PT J AU Ju, YS Tubio, JMC Mifsud, W Fu, BY Davies, HR Ramakrishna, M Li, YL Yates, L Gundem, G Tarpey, PS Behjati, S Papaemmanuil, E Martin, S Fullam, A Gerstung, M Nangalia, J Green, AR Caldas, C Borg, A Tutt, A Lee, MTM van't Veer, LJ Tan, BKT Aparicio, S Span, PN Martens, JWM Knappskog, S Vincent-Salomon, A Borresen-Dale, AL Eyfjord, JE Flanagan, AM Foster, C Neal, DE Cooper, C Eeles, R Lakhani, SR Desmedt, C Thomas, G Richardson, AL Purdie, CA Thompson, AM McDermott, U Yang, FT Nik-Zainal, S Campbell, PJ Stratton, MR AF Ju, Young Seok Tubio, Jose M. C. Mifsud, William Fu, Beiyuan Davies, Helen R. Ramakrishna, Manasa Li, Yilong Yates, Lucy Gundem, Gunes Tarpey, Patrick S. Behjati, Sam Papaemmanuil, Elli Martin, Sancha Fullam, Anthony Gerstung, Moritz Nangalia, Jyoti Green, Anthony R. Caldas, Carlos Borg, Ake Tutt, Andrew Lee, Ming Ta Michael van't Veer, Laura J. Tan, Benita K. T. Aparicio, Samuel Span, Paul N. Martens, John W. M. Knappskog, Stian Vincent-Salomon, Anne Borresen-Dale, Anne-Lise Eyfjoerd, Jorunn Erla Flanagan, Adrienne M. Foster, Christopher Neal, David E. Cooper, Colin Eeles, Rosalind Lakhani, Sunil R. Desmedt, Christine Thomas, Gilles Richardson, Andrea L. Purdie, Colin A. Thompson, Alastair M. McDermott, Ultan Yang, Fengtang Nik-Zainal, Serena Campbell, Peter J. Stratton, Michael R. CA ICGC Prostate Cancer Working Grp ICGC Bone Canc Working Grp ICGC Breast Canc Working Grp TI Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells SO GENOME RESEARCH LA English DT Article ID HUMAN GENETIC-DISEASE; FOREIGN DNA; SEQUENCES; CHROMOSOMES; MECHANISMS; EVOLUTION; REARRANGEMENTS; INSERTIONS; LANDSCAPE; AUTOPHAGY AB Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells. C1 [Ju, Young Seok; Tubio, Jose M. C.; Mifsud, William; Davies, Helen R.; Ramakrishna, Manasa; Li, Yilong; Yates, Lucy; Gundem, Gunes; Tarpey, Patrick S.; Behjati, Sam; Papaemmanuil, Elli; Martin, Sancha; Fullam, Anthony; Gerstung, Moritz; Nangalia, Jyoti; McDermott, Ultan; Nik-Zainal, Serena; Campbell, Peter J.; Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England. [Fu, Beiyuan; Yang, Fengtang] Wellcome Trust Sanger Inst, Cytogenet Facil, Cambridge CB10 1SA, England. [Nangalia, Jyoti; Green, Anthony R.; Caldas, Carlos] Cambridge Univ Hosp, NHS Fdn Trust, Cambridge CB2 0QQ, England. [Nangalia, Jyoti; Green, Anthony R.] Univ Cambridge, Dept Haematol, Cambridge CB2 0XY, England. [Caldas, Carlos] Univ Cambridge, CRUK Cambridge Inst, Cambridge CB2 0RE, England. [Borg, Ake] BioCare, Strateg Canc Res Program, SE-22381 Lund, Sweden. [Borg, Ake] CREATE Hlth, Strateg Ctr Translat Canc Res, SE-22100 Lund, Sweden. [Borg, Ake] Lund Univ, Ctr Canc, Dept Pathol & Oncol, SE-22185 Lund, Sweden. [Tutt, Andrew] Kings Coll London, Guys Hosp, Res Oncol, Breakthrough Breast Canc Res Unit, London SE1 9RT, England. [Lee, Ming Ta Michael] RIKEN, Ctr Integrat Med Sci, Lab Int Alliance Genom Res, Yokohama, Kanagawa 2300045, Japan. [Lee, Ming Ta Michael] Acad Sinica, Inst Biomed Sci, Natl Ctr Genome Med, Taipei 115, Taiwan. [van't Veer, Laura J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Lab Med, San Francisco, CA 94158 USA. [van't Veer, Laura J.] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [Tan, Benita K. T.] Singapore Gen Hosp, Dept Gen Surg, Singapore 169608, Singapore. [Aparicio, Samuel] British Columbia Canc Agcy, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada. [Span, Paul N.] Radboud Univ Nijmegen, Dept Radiat Oncol, Med Ctr, NL-6525 HP Nijmegen, Netherlands. [Span, Paul N.] Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, NL-6525 HP Nijmegen, Netherlands. [Martens, John W. M.] Erasmus Univ, Med Ctr, Dept Med Oncol, Erasmus MC Canc Inst, NL-3015 CE Rotterdam, Netherlands. [Knappskog, Stian] Univ Bergen, Dept Clin Sci, Sect Oncol, N-5020 Bergen, Norway. [Knappskog, Stian] Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway. [Vincent-Salomon, Anne] INSERM, Inst Curie, U934, F-75248 Paris 05, France. [Vincent-Salomon, Anne] Dept Tumor Biol, F-75248 Paris 05, France. [Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway. [Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0450 Oslo, Norway. [Eyfjoerd, Jorunn Erla] Univ Iceland, Canc Res Lab, IS-101 Reykjavik, Iceland. [Flanagan, Adrienne M.] Royal Natl Orthopaed Hosp, Stanmore HA7 4LP, Middx, England. [Flanagan, Adrienne M.] UCL, UCL Canc Inst, London WC1E 6DD, England. [Foster, Christopher] Univ Liverpool, London WC1E 6JA, England. [Foster, Christopher] HCA Pathol Labs, London WC1E 6JA, England. [Neal, David E.] Canc Res UK Cambridge Res Inst, Urol Res Lab, Cambridge CB2 0RE, England. [Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Dept Surg Oncol, Cambridge CB2 0QQ, England. [Cooper, Colin] Sutton, Inst Canc Res, London SM2 5NG, England. [Cooper, Colin] Univ E Anglia, Dept Biol Sci, Norwich NR4 7TJ, Norfolk, England. [Cooper, Colin] Univ E Anglia, Sch Med, Norwich NR4 7TJ, Norfolk, England. [Eeles, Rosalind] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London SW3 6JJ, England. [Lakhani, Sunil R.] Univ Queensland, Sch Med, Brisbane, Qld 4006, Australia. [Lakhani, Sunil R.] Royal Brisbane & Womens Hosp, Pathol Queensland, Brisbane, Qld 4029, Australia. [Lakhani, Sunil R.] Univ Queensland, UQ Ctr Clin Res, Brisbane, Qld 4029, Australia. [Desmedt, Christine] Univ Libre Bruxelles, Breast Canc Translat Res Lab, Inst Jules Bordet, B-1000 Brussels, Belgium. [Thomas, Gilles] Univ Lyon 1, Inst Natl Canc INCa Synergie, F-69008 Lyon, France. [Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Richardson, Andrea L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Purdie, Colin A.] Ninewells Hosp, Dept Pathol, Dundee DD1 9SY, Scotland. [Purdie, Colin A.] Sch Med, Dundee DD1 9SY, Scotland. [Thompson, Alastair M.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. RP Stratton, MR (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England. EM mrs@sanger.ac.uk RI Tubio, Jose/H-5076-2015; Ju, Young Seok/E-1324-2012; Span, Paul/G-4710-2012; Simpson, Peter/F-1225-2010; Mifsud, William/B-7274-2008; OI Tubio, Jose/0000-0003-3540-2459; Ju, Young Seok/0000-0002-5514-4189; Span, Paul/0000-0002-1930-6638; Simpson, Peter/0000-0002-4816-8289; Fullam, Anthony/0000-0002-0884-8124; Mithen, Richard/0000-0001-7307-4324; Mifsud, William/0000-0002-9805-6461; chin, suet-feung/0000-0001-5697-1082; Gerstung, Moritz/0000-0001-6709-963X; Purdie, Colin/0000-0002-1258-4010; Eeles, Rosalind/0000-0002-3698-6241; Knappskog, Stian/0000-0002-4153-1655; McDermott, Ultan/0000-0001-9032-4700; Wedge, David/0000-0002-7572-3196; Desmedt, Christine/0000-0002-5223-5579; Martin, Sancha/0000-0001-6213-5259; Massie, Charlie/0000-0003-2314-4843; Ehinger, Anna/0000-0001-9225-7396; Berney, Daniel/0000-0001-5474-8696 FU Wellcome Trust; European Molecular Biology Organization long-term fellowship [LTF 1203_2012]; Marie Curie Fellowship FP7-PEOPLE-IEF [328264]; National Institute for Health Research (NIHR) UCLH Biomedical Research Centre; European Union (BASIS); Cancer Research UK; Dallaglio Foundation [C5047/A14835]; National Institute for Health Research; Royal Marsden NHS Foundation Trust; National Cancer Research Prostate Cancer Mechanisms of Progression and Treatment (PROMPT) collaborative in Cambridge [G0500966/75466]; Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award; Breakthrough Breast Cancer Research [ICGC 08/09, KCL] FX We thank Thomas Bleazard at the Faculty of Medical and Human Sciences, University of Manchester for discussion and assistance with manuscript preparation. We also thank The Cancer Genome Atlas (TCGA) Project Team and their specimen donors for providing sequencing data used in this study. This work was supported by the Wellcome Trust. Y.S.J is supported by a European Molecular Biology Organization long-term fellowship (LTF 1203_2012). J.M. C.T. is supported by Marie Curie Fellowship FP7-PEOPLE-2012-IEF (project number 328264). P.J.C. is a Wellcome Trust Senior Clinical Fellow. Support was provided to A.M.F. by the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre. The ICGC Breast Cancer Consortium was supported by a grant from the European Union (BASIS) and the Wellcome Trust. The ICGC Prostate Cancer Consortium was funded by Cancer Research UK with a grant from the Dallaglio Foundation (grant number C5047/A14835). R.E. is supported by National Institute for Health Research support to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. We also thank the National Cancer Research Prostate Cancer Mechanisms of Progression and Treatment (PROMPT) collaborative (grant code G0500966/75466) which has funded tissue and urine collections in Cambridge. The authors also acknowledge financial support from the Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's and St. Thomas' NHS Foundation Trust and Breakthrough Breast Cancer Research (ICGC 08/09 and KCL) (A.T.). NR 48 TC 9 Z9 10 U1 3 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD JUN PY 2015 VL 25 IS 6 BP 814 EP 824 DI 10.1101/gr.190470.115 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CJ5XF UT WOS:000355565900004 PM 25963125 ER PT J AU Cordeira, LS Pednekar, MS Nagler, EM Gautam, J Wallace, L Stoddard, AM Gupta, PC Sorensen, GC AF Cordeira, L. Shulman Pednekar, M. S. Nagler, E. M. Gautam, J. Wallace, L. Stoddard, A. M. Gupta, P. C. Sorensen, G. C. TI Experiences recruiting Indian worksites for an integrated health protection and health promotion randomized control trial in Maharashtra, India SO HEALTH EDUCATION RESEARCH LA English DT Article ID BEHAVIOR-CHANGE; INTERVENTION RESEARCH; SMOKING-CESSATION; CANCER PREVENTION; UNITED-STATES; WORKING-CLASS; DIRECTIONS; WORKPLACES; PROGRAMS AB This article provides an overview of the recruitment strategies utilized in the Mumbai Worksites Tobacco Control Study, a cluster randomized trial testing the effectiveness of an integrated tobacco control and occupational safety and health program in Indian manufacturing worksites. From June 2012 to June 2013, 20 companies were recruited. Companies were identified using association lists, referrals, internet searches and visits to industrial areas. Four hundred eighty companies were contacted to validate information, introduce the study and seek an in-person meeting with a company representative. Eighty-three company representatives agreed to meet. Of those 83 companies, 55 agreed to a formal 'pitch meeting' with key decision makers at the company. Seventy-seven recruitment 'pitches' were given, including multiple meetings in the same companies. If the company was interested, we obtained a letter of participation and employee roster. Based on this experience, recommendations are made that can help inform future researchers and practitioners wishing to recruit Indian worksites. When compared with recruitment of US manufacturing worksites, recruitment of Indian worksites lacked current industrial lists of companies to serve as a sampling frame, and required more in-person visits, incentives for control companies and more assurances around confidentiality to allow occupational safety and health experts into their worksite. C1 [Cordeira, L. Shulman; Nagler, E. M.; Wallace, L.; Sorensen, G. C.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Pednekar, M. S.; Gupta, P. C.] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai 400614, India. [Nagler, E. M.; Sorensen, G. C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Stoddard, A. M.] New England Res Inst, Watertown, MA 02472 USA. RP Cordeira, LS (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM laura.shulmanMPH@gmail.com FU National Cancer Institute [R01 CA140304] FX National Cancer Institute - R01 CA140304 - Mumbai Worksite Tobacco Control Study. NR 23 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 EI 1465-3648 J9 HEALTH EDUC RES JI Health Educ. Res. PD JUN PY 2015 VL 30 IS 3 BP 412 EP 421 DI 10.1093/her/cyv010 PG 10 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA CJ7IS UT WOS:000355669000005 PM 25796269 ER PT J AU Lam, A Hoang, JD Singleton, A Han, X Bleier, BS AF Lam, Allen Hoang, John D. Singleton, Amy Han, Xue Bleier, Benjamin S. TI Itraconazole and clarithromycin inhibit P-glycoprotein activity in primary human sinonasal epithelial cells SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic sinusitis with nasal polyps; immunomodulator; nasal epithelium; P-glycoprotein; Th2 inflammation; itraconazole; clarithromycin ID ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; CHRONIC RHINOSINUSITIS; NASAL POLYPOSIS; CHRONIC SINUSITIS; AMPHOTERICIN-B; ANTIFUNGAL TREATMENT; LONG-TERM; ANTIBIOTICS; MACROLIDES; INFLAMMATION AB BackgroundItraconazole and clarithromycin are clinically effective in the treatment of chronic rhinosinusitis (CRS) through incompletely understood anti-inflammatory properties. P-glycoprotein (P-gp) is overexpressed in CRS and inhibition results in decreased inflammatory cytokine secretion. Both itraconazole and clarithromycin have also been shown to have P-gp inhibitory properties in other tissues, suggesting a novel explanation for their immunomodulatory effects in CRS. The purpose of this study is to therefore confirm whether these drugs are capable of inhibiting P-gp specifically in sinonasal epithelial cells. MethodsThis was an institutional review board (IRB)-approved study in which primary sinonasal epithelial cells were cultured in 96-well plates. A Calcein AM assay was used to quantify P-gp inhibition as determined by an increase in intracellular fluorescence. A dose-response curve was generated for itraconazole and clarithromycin (maximal concentration 100M) and compared to that of Zosuquidar, a highly specific known P-gp inhibitor. Results were compared using a Student t test with a significance defined as p < 0.05. ResultsBoth itraconazole and clarithromycin demonstrated a dose-response curve for P-gp inhibition similar to that of Zosuquidar. The respective maximal inhibitory concentrations of Zosuquidar, itraconazole, and clarithromycin prior to induction of cytotoxicity were 0.31, 3.13, and 1.56M, respectively, as demonstrated by a statistically significant increase in total intracellular fluorescence (p < 0.05 in all groups). ConclusionBoth itraconazole and clarithromycin are capable of inhibiting sinonasal epithelial cell associated P-gp. The anti-inflammatory effects of these agents in CRS may be attributable, in part, to their heretofore unrecognized P-gp modulatory properties. (C) 2015 ARS-AAOA, LLC C1 [Lam, Allen; Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Hoang, John D.; Singleton, Amy; Han, Xue] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Bleier, BS (reprint author), 243 Charles St, Boston, MA 02114 USA. EM benjamin_bleier@meei.harvard.edu NR 34 TC 4 Z9 5 U1 1 U2 2 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 JUN PY 2015 VL 5 IS 6 BP 477 EP 480 DI 10.1002/alr.21454 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA CJ9YQ UT WOS:000355860600003 PM 25907295 ER PT J AU Chan, CKY Oldenburg, B Viswanath, K AF Chan, Carina K. Y. Oldenburg, Brian Viswanath, Kasisomayajula TI Advancing the Science of Dissemination and Implementation in Behavioral Medicine: Evidence and Progress SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article ID DIABETES PREVENTION; INTERVENTIONS; WASTE AB The enormous time lag between the discovery of new knowledge and its implementation poses a significant challenge to improving public health because of the very slow uptake into policy and practice. The field of dissemination and implementation research in behavioral medicine is receiving increased attention because of the keen interest in accelerating knowledge transfer from relevant research to improve the health and wellbeing of populations in many different settings, contexts, and countries around the world. This is particularly important in high-risk populations, resource-poor and developing regions of the world where the difference in health systems, languages, and cultures very significantly influences the translation of evidence into policy and practice. Moreover, demonstrating the broader societal and economic value of behavioral interventions in settings where they are implemented can further support the sustainability, uptake, and implementation of these findings in other settings and contexts. This special issue presents a series of empirical studies, reviews, and case studies that address dissemination, implementation, and translation issues in both developed and developing countries. Specifically, the learnings from the application of many and varied theories and research methodologies are very relevant for bridging the current division between research findings and their translation and uptake into policy and practice. C1 [Chan, Carina K. Y.] Australian Catholic Univ, Sch Psychol, Banyo, Qld 4014, Australia. [Chan, Carina K. Y.] Monash Univ, Bandar Sunway, Malaysia. [Oldenburg, Brian] Univ Melbourne, Melbourne, Vic, Australia. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chan, CKY (reprint author), Australian Catholic Univ, Sch Psychol, 1100 Nudgee Rd, Banyo, Qld 4014, Australia. EM carina.chan@acu.edu.au OI Oldenburg, Brian/0000-0002-7712-5413 NR 38 TC 0 Z9 0 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 EI 1532-7558 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD JUN PY 2015 VL 22 IS 3 SI SI BP 277 EP 282 DI 10.1007/s12529-015-9490-2 PG 6 WC Psychology, Clinical SC Psychology GA CJ2UR UT WOS:000355340700001 PM 26001382 ER PT J AU Mueller, S Wang, DH Pan, RQ Holt, DJ Liu, HS AF Mueller, Sophia Wang, Danhong Pan, Ruiqi Holt, Daphne J. Liu, Hesheng TI Abnormalities in Hemispheric Specialization of Caudate Nucleus Connectivity in Schizophrenia SO JAMA PSYCHIATRY LA English DT Article ID INTRINSIC FUNCTIONAL CONNECTIVITY; POSITRON-EMISSION-TOMOGRAPHY; PLANUM TEMPORALE ASYMMETRY; LANGUAGE LATERALIZATION; CEREBRAL ASYMMETRY; BRAIN ASYMMETRY; HUMAN STRIATUM; DOPAMINE FUNCTION; HEAD MOTION; HANDEDNESS AB IMPORTANCE Hemispheric specialization of the human brain is a marker of successful neurodevelopment. Altered brain asymmetry that has been repeatedly reported in schizophrenia may represent consequences of disrupted neurodevelopment in the disorder. However, a complete picture of functional specialization in the schizophrenic brain and its connectional substrates is yet to be unveiled. OBJECTIVES To quantify intrinsic hemispheric specialization at cortical and subcortical levels and to reveal potential disease effects in schizophrenia. DESIGN, SETTING, AND PARTICIPANTS Resting-state functional connectivity magnetic resonance imaging has been previously used to quantitatively measure hemispheric specialization in healthy individuals in a reliable manner. We quantified the intrinsic hemispheric specialization at the whole brain level in 31 patients with schizophrenia and 37 demographically matched healthy controls from November 28, 2007, through June 29, 2010, using resting-state functional magnetic resonance imaging. RESULTS The caudate nucleus and cortical regions with connections to the caudate nucleus had markedly abnormal hemispheric specialization in schizophrenia. Compared with healthy controls, patients exhibited weaker specialization in the left, but the opposite pattern in the right, caudate nucleus (P < .001). Patients with schizophrenia also had a disruption of the interhemispheric coordination among the cortical regions with connections to the caudate nucleus. A linear classifier based on the specialization of the caudate nucleus distinguished patients from controls with a classification accuracy of 74% (with a sensitivity of 68% and a specificity of 78%). CONCLUSIONS AND RELEVANCE These data suggest that hemispheric specialization could serve as a potential imaging biomarker of schizophrenia that, compared with task-based functional magnetic resonance imaging measures, is less prone to the confounding effects of variation in task compliance, cognitive ability, and command of language. C1 [Mueller, Sophia; Wang, Danhong; Pan, Ruiqi; Holt, Daphne J.; Liu, Hesheng] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mueller, Sophia] Univ Munich, Inst Clin Radiol, Munich, Germany. [Holt, Daphne J.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Liu, HS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Ste 2301, Charlestown, MA 02129 USA. EM hesheng@nmr.mgh.harvard.edu FU National Institutes of Health [1K25NS069805, K23MH076054, R01MH095904]; National Alliance for Research on Schizophrenia and Depression Young Investigator Grant; German Research Foundation [MU 3222/2-1] FX This study was supported by grants 1K25NS069805 (Dr Liu), K23MH076054 (Dr Holt), and R01MH095904 (Dr Holt) from the National Institutes of Health, a National Alliance for Research on Schizophrenia and Depression Young Investigator Grant (Dr Liu), and grant MU 3222/2-1 from the German Research Foundation (Dr Mueller). NR 82 TC 6 Z9 6 U1 3 U2 14 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 JUN PY 2015 VL 72 IS 6 BP 552 EP 560 DI 10.1001/jamapsychiatry.2014.3176 PG 9 WC Psychiatry SC Psychiatry GA CJ9FH UT WOS:000355807400005 PM 25830688 ER PT J AU Luthra, S Ramady, O Monge, M Fitzsimons, MG Kaleta, TR Sundt, TM AF Luthra, Suvitesh Ramady, Omar Monge, Mary Fitzsimons, Michael G. Kaleta, Terry R. Sundt, Thoralf M. TI "Knife to Skin" Time Is a Poor Marker of Operating Room Utilization and Efficiency in Cardiac Surgery SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID LIST EFFICIENCY; ANESTHESIA; IMPACT; PERFORMANCE; MANAGEMENT; DESCRIBE; FORMULA; SUITE; START; TERM AB BackgroundMarkers of operation room (OR) efficiency in cardiac surgery are focused on knife to skin and start time tardiness. These do not evaluate the middle and later parts of the cardiac surgical pathway. The purpose of this analysis was to evaluate knife to skin time as an efficiency marker in cardiac surgery. MethodsWe looked at knife to skin time, procedure time, and transfer times in the cardiac operational pathway for their correlation with predefined indices of operational efficiency (Index of Operation Efficiency - InOE, Surgical Index of Operational Efficiency - sInOE). A regression analysis was performed to test the goodness of fit of the regression curves estimated for InOE relative to the times on the operational pathway. ResultsThe mean knife to skin time was 90.613minutes (23% of total OR time). The mean procedure time was 282 +/- 123minutes (71% of total OR time). Utilization efficiencies were highest for aortic valve replacement and coronary artery bypass grafting and least for complex aortic procedures. There were no significant procedure-specific or team-specific differences for standard procedures. Procedure times correlated the strongest with InOE (r=-0.98, p<0.01). Compared to procedure times, knife to skin is not as strong an indicator of efficiency. A statistically significant linear dependence on InOE was observed with procedure times only. ConclusionsProcedure times are a better marker of OR efficiency than knife to skin in cardiac cases. Strategies to increase OR utilization and efficiency should address procedure times in addition to knife to skin times. C1 [Luthra, Suvitesh; Ramady, Omar; Monge, Mary; Kaleta, Terry R.; Sundt, Thoralf M.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. [Fitzsimons, Michael G.] Massachusetts Gen Hosp, Div Cardiac Anesthesia, Boston, MA 02114 USA. RP Luthra, S (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Corrigan Minehan Heart Ctr, 55 Fruit St, Boston, MA 02114 USA. EM sluthra@mgh.harvard.edu NR 25 TC 0 Z9 0 U1 0 U2 2 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 JUN PY 2015 VL 30 IS 6 BP 477 EP 487 DI 10.1111/jocs.12528 PG 11 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA CJ7DL UT WOS:000355654300001 PM 25868385 ER PT J AU Blasi, F Whalen, MJ Ayata, C AF Blasi, Francesco Whalen, Michael J. Ayata, Cenk TI Lasting pure-motor deficits after focal posterior internal capsule white-matter infarcts in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE endothelin-1; internal capsule; motor deficits; stroke; white matter ID LACUNAR INFARCTION; EXPERIMENTAL-MODEL; STROKE; ENDOTHELIN-1; LESIONS; LOCATION; RECOVERY; BRAIN; CORTEX; LIMB AB Small white-matter infarcts of the internal capsule are clinically prevalent but underrepresented among currently available animal models of ischemic stroke. In particular, the assessment of long-term outcome, a primary end point in clinical practice, has been challenging due to mild deficits and the rapid and often complete recovery in most experimental models. We, therefore, sought to develop a focal white-matter infarction model that can mimic the lasting neurologic deficits commonly observed in stroke patients. The potent vasoconstrictor endothelin-1 (n=24) or vehicle (n=9) was stereotactically injected into the internal capsule at one of three antero-posterior levels (1, 2, or 3 mm posterior to bregma) in male Sprague-Dawley rats. Endothelin-injected animals showed highly focal (similar to 1 mm(3)) and reproducible ischemic infarcts, with severe axonal and myelin loss accompanied by cellular infiltration when examined 2 and 4 weeks after injection. Only those rats injected with endothelin-1 at the most posterior location developed robust and pure-motor deficits in adhesive removal, cylinder and foot-fault tests that persisted at 1 month, without detectable sensory impairments. In summary, we present an internal capsule stroke model optimized to produce lasting pure-motor deficits in rats that may be suitable to study neurologic recovery and rehabilitation after white-matter injury. C1 [Blasi, Francesco; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA USA. [Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. [Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Intens Care Unit,Dept Neurol, Boston, MA USA. RP Ayata, C (reprint author), Massachusetts Gen Hosp, Neurovasc Res Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Blasi, Francesco/G-1055-2015 OI Blasi, Francesco/0000-0002-6616-8418 FU National Institutes of Health [NS061505, NS055104]; Fondation Leducq; Andrew David Heitman Foundation; Ellison Foundation FX This study was supported by the National Institutes of Health (NS061505 and NS055104), Fondation Leducq, Neuroendovascular Research Fund from the Andrew David Heitman Foundation, and The Ellison Foundation. NR 40 TC 5 Z9 5 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2015 VL 35 IS 6 BP 977 EP 984 DI 10.1038/jcbfm.2015.7 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CJ6AO UT WOS:000355575600012 PM 25649992 ER PT J AU Suh, JY Shim, WH Cho, G Fan, X Kwon, SJ Kim, JK Dai, G Wang, XY Kim, YR AF Suh, J. Y. Shim, Woo H. Cho, Gyunggoo Fan, Xiang Kwon, Seon J. Kim, Jeong K. Dai, George Wang, Xiaoying Kim, Young R. TI Reduced microvascular volume and hemispherically deficient vasoreactivity to hypercapnia in acute ischemia: MRI study using permanent middle cerebral artery occlusion rat model SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE acute stroke; animal models; cerebal hemodynamics; MRI; brain imaging ID PERFUSION COMPUTED-TOMOGRAPHY; ACUTE STROKE PATIENTS; CORTICAL BLOOD-FLOW; CEREBROVASCULAR REACTIVITY; SPREADING DEPRESSION; CO2 REACTIVITY; FUNCTIONAL MRI; CARBON-DIOXIDE; BRAIN; CONTRAST AB Vasoreactivity to hypercapnia has been used for assessing cerebrovascular tone and control altered by ischemic stroke. Despite the high prognostic potential, traits of hypercapnia-induced hemodynamic changes have not been fully characterized in relation with baseline vascular states and brain tissue damage. To monitor cerebrovascular responses, T2- and T2*-weighted magnetic resonance imaging (MRI) images were acquired alternatively using spin- and gradient-echo echo plannar imaging (GESE EPI) sequence with 5% CO2 gas inhalation in normal (n =5) and acute stroke rats (n=10). Dynamic relative changes in cerebrovascular volume (CBV), microvascular volume (MW), and vascular size index (VSI) were assessed from regions of interest (ROIs) delineated by the percent decrease of apparent diffusion coefficient (ADC). The baseline CBV was not affected by middle cerebral artery occlusion (MCAO) whereas the baseline MW in ischemic areas was significantly lower than that in the rest of the brain and correlated with ADC. Vasoreactivity to hypercapnic challenge was considerably attenuated in the entire ipsilesional hemisphere including normal ADC regions, in which unsolicited, spreading depression-associated increases of CBV and MW were observed. The lesion-dependent inhomogeneity in baseline MW indicates the effective perfusion reserve for accurately delineating the true ischemic damage while the cascade of neuronal depolarization is probably responsible for the hemispherically lateralized changes in overall neurovascular physiology. C1 [Suh, J. Y.; Shim, Woo H.; Kwon, Seon J.; Kim, Jeong K.; Dai, George; Kim, Young R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. [Suh, J. Y.; Cho, Gyunggoo] Korea Basic Sci Inst, Div Magnet Resonance Res, Cheongwon, Chungbuk, South Korea. [Shim, Woo H.; Kim, Jeong K.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol,Res Inst Radiol, Seoul, South Korea. [Fan, Xiang; Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol & Neurol, Charlestown, MA 02129 USA. [Kwon, Seon J.] Kangs Med Ctr, Dept Neurol, Pochon, South Korea. [Kim, Young R.] Ulsan Natl Inst Sci & Technol, Sch Nanobiosci & Chem Engn, Ulsan, South Korea. RP Kim, YR (reprint author), Harvard Univ, Sch Med, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. EM spmn@nmr.mgh.harvard.edu FU National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2010-0025731, 2011-0028826]; Korea Basic Science Institute [E33600] FX This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0025731 and 2011-0028826) and by a grant from Korea Basic Science Institute (E33600). NR 40 TC 1 Z9 1 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2015 VL 35 IS 6 BP 1033 EP 1043 DI 10.1038/jcbfm.2015.22 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CJ6AO UT WOS:000355575600018 PM 25690471 ER PT J AU Chaparro, RE Izutsu, M Sasaki, T Sheng, HX Zheng, Y Sadeghian, H Qin, T von Bornstadt, D Herisson, F Duan, B Li, JS Jiang, K Pearlstein, M Pearlstein, RD Smith, DE Goldberg, ID Ayata, C Warner, DS AF Chaparro, Rafael E. Izutsu, Miwa Sasaki, Toshihiro Sheng, Huaxin Zheng, Yi Sadeghian, Homa Qin, Tao von Bornstadt, Daniel Herisson, Fanny Duan, Bin Li, Jing-Song Jiang, Kai Pearlstein, Molly Pearlstein, Robert D. Smith, David. E. Goldberg, Itzhak D. Ayata, Cenk Warner, David S. TI Sustained functional improvement by hepatocyte growth factor-like small molecule BB3 after focal cerebral ischemia in rats and mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain; hepatocyte growth factor; ischemia; preclinical; stroke ID ARTERY OCCLUSION; EPITHELIAL-CELLS; THERAPEUTIC STRATEGY; C-MET; BRAIN; STROKE; INJURY; MODEL; GENE; HGF AB Hepatocyte growth factor (HGF), efficacious in preclinical models of acute central nervous system injury, is burdened by administration of full-length proteins. A multiinstitutional consortium investigated the efficacy of BB3, a small molecule with HGF-like activity that crosses the blood brain barrier in rodent focal ischemic stroke using Stroke Therapy Academic Industry Roundtable (STAIR) and Good Laboratory Practice guidelines. In rats, BB3, begun 6 hours after temporary middle cerebral artery occlusion (tMCAO) reperfusion, or permanent middle cerebral artery occlusion (pMCAO) onset, and continued for 14 days consistently improved long-term neurologic function independent of sex, age, or laboratory. BB3 had little effect on cerebral infarct size and no effect on blood pressure. BB3 increased HGF receptor c-Met phosphorylation and synaptophysin expression in penumbral tissue consistent with a neurorestorative mechanism from HGF-like activity. In mouse tMCAO, BB3 starting 10 minutes after reperfusion and continued for 14 days improved neurologic function that persisted for 8 weeks in some, but not all measures. Study in animals with comorbidities and those exposed to common stroke drugs are the next steps to complete preclinical assessment. These data, generated in independent, masked, and rigorously controlled settings, are the first to suggest that the HGF pathway can potentially be harnessed by BB3 for neurologic benefit after ischemic stroke. C1 [Chaparro, Rafael E.; Izutsu, Miwa; Sasaki, Toshihiro; Sheng, Huaxin; Pearlstein, Molly; Warner, David S.] Duke Univ, Med Ctr, Dept Anesthesiol, Multidisciplinary Neuroprotect Labs, Durham, NC 27710 USA. [Zheng, Yi; Sadeghian, Homa; Qin, Tao; von Bornstadt, Daniel; Herisson, Fanny; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA USA. [Duan, Bin; Li, Jing-Song; Jiang, Kai; Smith, David. E.; Goldberg, Itzhak D.] Ang Biomed Corp, Uniondale, NY USA. [Pearlstein, Robert D.; Warner, David S.] Duke Univ, Med Ctr, Dept Surg, Multidisciplinary Neuroprotect Labs, Durham, NC 27710 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit,Dept Neur, Charlestown, MA USA. [Warner, David S.] Duke Univ, Med Ctr, Dept Neurobiol, Multidisciplinary Neuroprotect Labs, Durham, NC 27710 USA. RP Warner, DS (reprint author), Duke Univ, Med Ctr, Dept Anesthesiol, Box 3094, Durham, NC 27710 USA. EM david.warner@duke.edu FU NIH/NINDS [2R44NS045373, 5R44NS045373] FX This study was supported by NIH/NINDS 2R44NS045373 and 5R44NS045373. NR 40 TC 5 Z9 5 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2015 VL 35 IS 6 BP 1044 EP 1053 DI 10.1038/jcbfm.2015.23 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CJ6AO UT WOS:000355575600019 PM 25712497 ER PT J AU Canver, MC Bauer, DE Orkin, SH AF Canver, Matthew C. Bauer, Daniel E. Orkin, Stuart H. TI Embryonic stem cells as sources of donor-independent platelets SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID MEGAKARYOCYTES; GATA1; HEMATOPOIESIS; CHALLENGES; BIOLOGY; ANEMIA AB The creation of a donor-independent source of platelets has been challenging; however, recent advances show growing promise for alternative platelet sources. Pluripotent stem cells have the capacity to differentiate into mature megalcaryocytes with the ability to produce functional platelets. In this issue of JCI, Noh et al. provide a proof-of-principle demonstration that embryonic stem cells can be used to produce platelets on a clinical scale by controlling the level of the transcription factor GATA1. This study emphasizes the importance of precise regulation of gene expression for regenerative medicine applications. C1 [Canver, Matthew C.; Bauer, Daniel E.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA USA. [Bauer, Daniel E.; Orkin, Stuart H.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Bauer, Daniel E.; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Stuart_Orkin@dfci.harvard.edu FU Howard Hughes Medical Institute NR 27 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2015 VL 125 IS 6 BP 2261 EP 2263 DI 10.1172/JCI82348 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CJ5ZX UT WOS:000355573900012 PM 25961451 ER PT J AU Basak, A Hancarova, M Ulirsch, JC Balci, TB Trkova, M Pelisek, M Vickova, M Muzikova, K Cermak, J Trka, J Dyment, DA Orkin, SH Daly, MJ Sedlacek, Z Sankaran, VG AF Basak, Anindita Hancarova, Miroslava Ulirsch, Jacob C. Balci, Tugce B. Trkova, Marie Pelisek, Michal Vickova, Marketa Muzikova, Katerina Cermak, Jaroslav Trka, Jan Dyment, David A. Orkin, Stuart H. Daly, Mark J. Sedlacek, Zdenelc Sankaran, Vijay G. TI BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MICRODELETION SYNDROME; AUTISM; EXPRESSION; DISORDER AB A transition from fetal hemoglobin (HbF) to adult hemoglobin (HbA) normally occurs within a few months after birth. Increased production of HbF after this period of infancy ameliorates clinical symptoms of the major disorders of adult beta-hemoglobin: beta-thalassemia and sickle cell disease. The transcription factor BCL11A silences HbF and has been an attractive therapeutic target for increasing HbF levels; however, it is not clear to what extent BCL11A inhibits HbF production or mediates other developmental functions in humans. Here, we identified and characterized 3 patients with rare microdeletions of 2p15-p16.1 who presented with an autism spectrum disorder and developmental delay. Moreover, these patients all exhibited substantial persistence of HbF but otherwise retained apparently normal hematologic and immunologic function. Of the genes within 2p15-p16.1, only BCL11A was commonly deleted in all of the patients. Evaluation of gene expression data sets from developing and adult human brains revealed that BCL11A expression patterns are similar to other genes associated with neurodevelopmental disorders. Additionally, common SNPs within the second intron of BCL11A are strongly associated with schizophrenia. Together, the study of these rare patients and orthogonal genetic data demonstrates that BCL11A plays a central role in silencing HbF in humans and implicates BCL11A as an important factor for neurodevelopment. C1 [Basak, Anindita; Ulirsch, Jacob C.; Orkin, Stuart H.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res,Div Hematol Ontol, Boston, MA USA. [Basak, Anindita; Ulirsch, Jacob C.; Orkin, Stuart H.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Basak, Anindita; Ulirsch, Jacob C.; Daly, Mark J.; Sankaran, Vijay G.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Hancarova, Miroslava; Vickova, Marketa; Muzikova, Katerina; Trka, Jan; Sedlacek, Zdenelc] Charles Univ Prague, Fac Med 2, Prague, Czech Republic. [Hancarova, Miroslava; Vickova, Marketa; Muzikova, Katerina; Trka, Jan; Sedlacek, Zdenelc] Univ Hosp Motol, Prague, Czech Republic. [Balci, Tugce B.; Dyment, David A.] Univ Ottawa, Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON, Canada. [Trkova, Marie] Gennet, Prague, Czech Republic. [Pelisek, Michal] Reg Hosp Strakanice, Strakonice, Czech Republic. [Cermak, Jaroslav] Inst Hematol & Blood Transfus, CR-12820 Prague, Czech Republic. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Sedlacek, Zdenelc] Harvard Univ, Sch Med, Boston, MA USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, 3 Blackfan Circle,CLS 03001, Boston, MA 02115 USA. EM zdenek.sedlacek@lfmotol.cuni.cz; sankaran@broadinsti-tute.org OI Balci, Tugce/0000-0002-5409-8387 FU NIH [U01 HL117720, R21 HL120791, R01 DK103794]; Czech Ministry of Health [NT/14200, 00064203] FX This work was supported by grants from the NIH (U01 HL117720, R21 HL120791, and R01 DK103794) (to V.G. Sankaran) and from the Czech Ministry of Health (NT/14200 and 00064203) (to Z. Sedlacek). A. Basak is a Translational Research Development Scholar at Boston Children's Hospital. NR 24 TC 22 Z9 22 U1 0 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 JUN PY 2015 VL 125 IS 6 BP 2363 EP 2368 DI 10.1172/JCI81163 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CJ5ZX UT WOS:000355573900023 PM 25938782 ER PT J AU Noh, JY Gandre-Babbe, S Wang, Y Hayes, V Yao, Y Gadue, P Sullivan, SK Chou, ST Machlus, KR Italiano, JE Kyba, M Finkelstein, D Ulirsch, JC Sankaran, VG French, DL Poncz, M Weiss, MJ AF Noh, Ji-Yoon Gandre-Babbe, Shilpa Wang, Yuhuan Hayes, Vincent Yao, Yu Gadue, Paul Sullivan, Spencer K. Chou, Stella T. Machlus, Kellie R. Italiano, Joseph E., Jr. Kyba, Michael Finkelstein, David Ulirsch, Jacob C. Sankaran, Vijay G. French, Deborah L. Poncz, Mortimer Weiss, Mitchell J. TI Inducible Gata1 suppression expands megakaryocyte-erythroid progenitors from embryonic stem cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; GENE-EXPRESSION; IN-VIVO; DEFINITIVE HEMATOPOIESIS; RETICULATED PLATELETS; FUNCTIONAL PLATELETS; MEGAKARYOPOIESIS; MATURATION; GENERATION; MUTATION AB Transfusion of donor-derived platelets is commonly used for thrombocytopenia, which results from a variety of clinical conditions and relies on a constant donor supply due to the limited shelf life of these cells. Embryonic stem (ES) and induced pluripotent stem (iPS) cells represent a potential source of megakaryocytes and platelets for transfusion therapies; however, the majority of current ES/iPS cell differentiation protocols are limited by low yields of hematopoietic progeny. In both mice and humans, mutations in the gene-encoding transcription factor GATA1 cause an accumulation of proliferating, developmentally arrested megakaryocytes, suggesting that GATA1 suppression in ES and iPS cell-derived hematopoietic progenitors may enhance megakaryocyte production. Here, we engineered ES cells from WT mice to express a doxycycline-regulated (dox-regulated) shRNA that targets Gata1 transcripts for degradation. Differentiation of these cells in the presence of dox and thrombopoietin (TPO) resulted in an exponential (at least 10(13)-fold) expansion of immature hematopoietic progenitors. Dox withdrawal in combination with multilineage cytokines restored GATA1 expression, resulting in differentiation into erythroblasts and megakaryocytes. Following transfusion into recipient animals, these dox-deprived mature megakaryocytes generated functional platelets. Our findings provide a readily reproducible strategy to exponentially expand ES cell-derived megakaryocyte-erythroid progenitors that have the capacity to differentiate into functional platelet-producing megakaryocytes. C1 [Noh, Ji-Yoon; Gandre-Babbe, Shilpa; Wang, Yuhuan; Hayes, Vincent; Yao, Yu; Sullivan, Spencer K.; Chou, Stella T.; Poncz, Mortimer] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. [Gadue, Paul; French, Deborah L.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Machlus, Kellie R.; Italiano, Joseph E., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. [Machlus, Kellie R.; Italiano, Joseph E., Jr.] Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA USA. [Kyba, Michael] Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN USA. [Kyba, Michael] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Finkelstein, David] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA. [Ulirsch, Jacob C.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Cambridge, MA 02138 USA. [Ulirsch, Jacob C.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Cambridge, MA 02138 USA. [Ulirsch, Jacob C.; Sankaran, Vijay G.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Weiss, Mitchell J.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. RP Weiss, MJ (reprint author), St Jude Childrens Res Hosp, 262 Danny Thomas Pl,MS 355, Memphis, TN 38105 USA. EM mitch.weiss@stjude.org OI Machlus, Kellie/0000-0002-2155-1050; Kyba, Michael/0000-0002-5579-7534 FU NIH [P30DK090969, U01 HL099656, U01HL100407, K12HL0806406]; National Hemophilia Foundation Judith Graham Pool fellowship FX This work was supported by NIH grants P30DK090969 (to M.J. Weiss and M. Poncz), U01 HL099656 (to M. Poncz, D.J. French, and M.J. Weiss), U01HL100407 (to M. Kyba), and K12HL0806406 (to S.K. Sullivan) and a National Hemophilia Foundation Judith Graham Pool fellowship (to J.Y. Nob). We thank Timothy J. Stalker, Vikram Paralkar, and Elizabeth Traxler for intellectual and technical support. NR 37 TC 9 Z9 10 U1 0 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2015 VL 125 IS 6 BP 2369 EP 2374 DI 10.1172/JCI77670 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CJ5ZX UT WOS:000355573900024 PM 25961454 ER PT J AU Binder, W Maldonado, NG Brown, DFM Miller, ES AF Binder, William Maldonado, Nicholas G. Brown, David F. M. Miller, Emily S. TI A GARDENER WITH A FEVER FOR 2 WEEKS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID HUMAN BABESIOSIS; UNITED-STATES; BORNE DISEASES; HUMAN HEALTH; TRANSMISSION C1 [Binder, William] Brown Univ, Rhode Isl Hosp, Miriam Hosp, Dept Emergency Med,Alpert Sch Med, Providence, RI 02903 USA. [Maldonado, Nicholas G.] Univ Florida, Coll Med, Hlth Shands Hosp, Dept Emergency Med, Gainesville, FL USA. [Brown, David F. M.; Miller, Emily S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Miller, ES (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD JUN PY 2015 VL 48 IS 6 BP 720 EP 723 PG 4 WC Emergency Medicine SC Emergency Medicine GA CJ2UU UT WOS:000355341000022 PM 25858338 ER PT J AU Kline, JA Kabrhel, C AF Kline, Jeffrey A. Kabrhel, Christopher TI EMERGENCY EVALUATION FOR PULMONARY EMBOLISM, PART 1: CLINICAL FACTORS THAT INCREASE RISK SO JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE pulmonary embolism; medicolegal; defensive medicine; decision making; venous thromboembolism; pregnancy; diagnosis ID DEEP-VEIN THROMBOSIS; UNPROVOKED VENOUS THROMBOEMBOLISM; FACTOR-V-LEIDEN; PATIENT-LEVEL METAANALYSIS; REVISED GENEVA SCORE; REAL-WORLD REGISTRY; COMPUTED-TOMOGRAPHY; DEPARTMENT PATIENTS; D-DIMER; PREDICTION RULES AB Background: Pulmonary embolism (PE) can be fatal, but profligate testing for PE can harm patients. Objectives: With consideration of potential medicolegal implications, this two-part review provides current evidence about the care of patients with suspected and diagnosed PE in the emergency department (ED) setting. Discussion: In part 1, we review published evidence to describe the epidemiology, risk factors, and clinical presentation of PE in the ED setting. Older age, surgery requiring endotracheal intubation within the past 30 days, new use of oral contraceptives, and prior unprovoked venous thromboembolism in nonanticoagulated patients are clear risk factors for PE in ED patients. Recent history of unexplained dyspnea, pleuritic chest pain, and hemoptysis increase probability, but the effect of syncope is less clear. Treated and inactive cancer, smoking, obesity, and pregnancy have not been found to increase the probability of PE in symptomatic ED patients. Unexplained dyspnea, tachycardia, and a low pulse oximetry reading increase probability of PE. Finding of wheezing on lung auscultation reduces the probability of PE, and findings that suggest deep venous thrombosis increase the probability of PE. Conclusions: Understanding of risk factors, historical data, and physical findings that have been found to increase or decrease the probability of PE in symptomatic ED patients can help create rational guidelines for the diagnostic approach to PE. (C) 2015 Elsevier Inc. C1 [Kline, Jeffrey A.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Kline, Jeffrey A.] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA. [Kabrhel, Christopher] Massachusetts Gen Hosp, Ctr Vasc Emergencies, Dept Emergency Med, Boston, MA 02114 USA. [Kabrhel, Christopher] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. RP Kline, JA (reprint author), Indiana Univ Sch Med, Dept Emergency Med, 720 Eskanazi Ave, Indianapolis, IN 46202 USA. OI Kabrhel, Christopher/0000-0002-8699-7176 NR 104 TC 6 Z9 6 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD JUN PY 2015 VL 48 IS 6 BP 771 EP 780 DI 10.1016/j.jemermed.2014.12.040 PG 10 WC Emergency Medicine SC Emergency Medicine GA CJ2UU UT WOS:000355341000032 PM 25863772 ER PT J AU Cooper, CM Fenves, AZ AF Cooper, Cynthia M. Fenves, Andrew Z. TI Before you call renal: Acute kidney injury for hospitalists SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID ACUTE INTERSTITIAL NEPHRITIS; GLOMERULAR-FILTRATION-RATE; URINARY BIOMARKERS; SERUM CREATININE; CHRONIC DIALYSIS; CRITICALLY-ILL; FAILURE; RISK; DISEASE; DIAGNOSIS AB Acute kidney injury is a clinical problem of growing incidence in hospitalized patients. It increases the risk of poor outcomes, length of stay and the cost of hospitalization. Successful management of acute kidney injury requires early recognition and diagnosis through detailed medical history, careful physical exam, judicious use of laboratory and radiologic tests and timely renal consultation. Subsequent management is tailored to the likely mechanism of injury with emphasis on limiting both further injury and systemic consequences. A common sense approach to acute kidney injury is essential for hospitalists aiming to limit further injury, prevent acute complications and lessen the risk of chronic morbidity. Journal of Hospital Medicine 2015;10:403-408. (c) 2015 Society of Hospital Medicine C1 [Cooper, Cynthia M.; Fenves, Andrew Z.] Harvard Univ, Massachusetts Gen Hosp, Inpatient Clinician Educ Serv, Hosp Med Unit,Dept Med,Med Sch, Boston, MA USA. RP Cooper, CM (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM ccooper1@partners.org NR 42 TC 1 Z9 1 U1 1 U2 4 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 JUN PY 2015 VL 10 IS 6 BP 403 EP 408 DI 10.1002/jhm.2325 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CJ8GU UT WOS:000355739000010 PM 25628039 ER PT J AU Vu, JP Larauche, M Flores, M Luong, L Norris, J Oh, S Liang, LJ Waschek, J Pisegna, JR Germano, PM AF Vu, John P. Larauche, Muriel Flores, Martin Luong, Leon Norris, Joshua Oh, Suwan Liang, Li-Jung Waschek, James Pisegna, Joseph R. Germano, Patrizia M. TI Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP) SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Vasoactive intestinal peptide; Feeding; Body composition; Appetite; Metabolism; Hormones ID CYCLASE-ACTIVATING POLYPEPTIDE; RAT GASTRIC FUNDUS; ADENYLATE-CYCLASE; FOOD-INTAKE; GENE-EXPRESSION; DEFICIENT MICE; PEPTIDE VIP; NULL MICE; PITUITARY; LEPTIN AB Vasoactive intestinal peptide (VIP) is a 28-amino acid neuropeptide that belongs to the secretin-glucagon super-family of peptides and has 68 % homology with PACAP. VIP is abundantly expressed in the central and peripheral nervous system and in the gastrointestinal tract, where it exercises several physiological functions. Previously, it has been reported that VIP regulates feeding behavior centrally in different species of vertebrates such as goldfishes, chicken and rodents. Additional studies are necessary to analyze the role of endogenous VIP on the regulation of appetite/satiety, feeding behavior, metabolic hormones, body mass composition and energy balance. The aim of the study was to elucidate the physiological pathways by which VIP regulates appetite/satiety, feeding behavior, metabolic hormones, and body mass composition. VIP deficient (VIP -/-) and age-matched wild-type (WT) littermates were weekly monitored from 5 to 22 weeks of age using a whole body composition EchoMRI analyzer. Food intake and feeding behavior were analyzed using the BioDAQ automated monitoring system. Plasma levels of metabolic hormones including active-ghrelin, GLP-1, leptin, PYY, pancreatic polypeptide (PP), adiponectin, and insulin were measured in fasting as well as in postprandial conditions. The genetic lack of VIP led to a significant reduction of body weight and fat mass and to an increase of lean mass as the mice aged. Additionally, VIP-/- mice had a disrupted pattern of circadian feeding behavior resulting in an abolished regular nocturnal/diurnal feeding. These changes were associated with an altered secretion of adiponectin, GLP-1, leptin, PYY and insulin in VIP-/- mice. Our data demonstrates that endogenous VIP is involved in the control of appetite/satiety, feeding behavior, body mass composition and in the secretion of six different key regulatory metabolic hormones. VIP plays a key role in the regulation of body phenotype by significantly enhancing body weight and fat mass accumulation. Therefore, VIP signaling is critical for the modulation of appetite/satiety and body mass phenotype and is a potential target for future treatment of obesity. C1 [Vu, John P.; Larauche, Muriel; Luong, Leon; Norris, Joshua; Oh, Suwan; Pisegna, Joseph R.; Germano, Patrizia M.] Univ Calif Los Angeles, Dept Med, Digest Dis Res Ctr, CURE, Los Angeles, CA 90024 USA. [Vu, John P.; Larauche, Muriel; Luong, Leon; Norris, Joshua; Oh, Suwan; Pisegna, Joseph R.; Germano, Patrizia M.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Flores, Martin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Liang, Li-Jung] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Waschek, James] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. RP Germano, PM (reprint author), Univ Calif Los Angeles, Dept Med, Digest Dis Res Ctr, CURE, Los Angeles, CA 90024 USA. EM pgermano@ucla.edu OI Larauche, Muriel/0000-0003-3320-3675 FU Department of Veterans Affairs RRD Merit Review; NIH [K01 DK088937]; Animal Core Services performed through CURE: Digestive Disease Research Center - NIH [P30DK41301] FX This work received grant support from: Department of Veterans Affairs RR&D Merit Review (JRP); Department of Veterans Affairs RR&D Merit Review (PMG); NIH K01 DK088937 (ML); and Animal Core Services performed through CURE: Digestive Disease Research Center supported by NIH grant P30DK41301. NR 62 TC 3 Z9 4 U1 4 U2 22 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JUN PY 2015 VL 56 IS 2 BP 377 EP 387 DI 10.1007/s12031-015-0556-z PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CJ8LW UT WOS:000355753800014 PM 25904310 ER PT J AU Borgquist, R Singh, JP AF Borgquist, Rasmus Singh, Jagmeet P. TI An Electrophysiologist Perspective on Risk Stratification in Heart Failure: Can Better Understanding of the Condition of the Cardiac Sympathetic Nervous System Help? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE cardiology (clinical); autonomic defibrillator; sudden death ID IMPLANTABLE-CARDIOVERTER-DEFIBRILLATOR; T-WAVE ALTERNANS; VENTRICULAR EJECTION FRACTION; CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; DILATED CARDIOMYOPATHY; RATE-VARIABILITY; PROGNOSTIC VALUE; UNITED-STATES; SUDDEN-DEATH AB Heart failure is often complicated by arrhythmias that can adversely affect the quality of life and increase the risk for sudden cardiac death. Current risk stratification strategies for sudden cardiac death in the heart failure patient are not ideal, with much potential for further refinement. Overactivation of the sympathetic nervous system has been shown to be associated with worsening heart failure as well as arrhythmic events. Recent advances in our understanding of the autonomic nervous system and new methods for quantification of the pathologic activation of the sympathetic nerves have triggered increasing interest in this field. This viewpoint focuses on the need for and challenges of risk stratification of sudden death in the heart failure patient and discusses the potential value of measuring sympathetic nervous system activity to better stratify risk and to select patients with heart failure for implantable cardioverter defibrillator therapy. C1 [Borgquist, Rasmus; Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA USA. [Borgquist, Rasmus] Lund Univ, Skane Univ Hosp, Arrhythmia Clin, Lund, Sweden. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@mgh.harvard.edu NR 67 TC 2 Z9 2 U1 0 U2 1 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 JUN PY 2015 VL 56 SU 4 BP 59S EP 64S DI 10.2967/jnumed.114.148452 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ6ZH UT WOS:000355643200011 PM 26033906 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 Experimental Comparison of Parametric Versus Nonparametric Analyses of Data From the Cold Pressor Test SO JOURNAL OF PAIN LA English DT Article DE Non parametric analysis; Wilcoxon Mann-Whitney test; t-test; cold pressor test; tolerance ID NEUROPATHIC PAIN; SENSITIVITY; MANAGEMENT; IMPACT; TASK AB Parametric statistical methods are common in human pain research. They require normally distributed data, but this assumption is rarely tested. The current study analyzes the appropriateness of parametric testing for outcomes from the cold pressor test (CPT), a common human experimental pain test. We systematically reviewed published CPT studies to quantify how often researchers test for normality and how often they use parametric versus nonparametric tests. We then measured the normality of CPT data from 7 independent small to medium cohorts and 1 study of >10,000 subjects. We then examined the ability of 2 common mathematical transformations to normalize our skewed data sets. Lastly, we performed Monte Carlo simulations on a representative data set to compare the statistical power of the parametric t-test versus the nonparametric Wilcoxon Mann-Whitney test. We found that only 39% of published CPT studies (47/122) mentioned checking data distribution, yet 72% (88/122) used parametric statistics. Furthermore, among our 8 data sets, CPT outcomes were virtually always nonnormally distributed, and mathematical transformations were largely ineffective in normalizing them. The simulations demonstrated that the nonparametric Wilcoxon Mann-Whitney test had greater statistical power than the parametric t-test for all scenarios tested: For small effect sizes, the Wilcoxon Mann-Whitney test had up to 300% more power. Perspective: These results demonstrate that parametric analyses of CPT data are routine but incorrect and that they likely increase the chances of failing to detect significant between-group differences. They suggest that non parametric analyses become standard for CPT studies and that assumptions of normality be routinely tested for other types of pain outcomes as well. (C) 2015 by the American Pain Society C1 [Treister, Roi; Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, 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, 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. RP Treister, R (reprint author), Massachusetts Gen Hosp, 275 Charles St,Warren Bldg 310, Boston, MA 02114 USA. EM treister.roi@gmail.com FU Public Health Service [NINDS K24-NS059892] FX Supported in part by the Public Health Service (NINDS K24-NS059892). NR 34 TC 3 Z9 3 U1 0 U2 4 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 JUN PY 2015 VL 16 IS 6 BP 537 EP 548 DI 10.1016/j.jpain.2015.03.001 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ8XP UT WOS:000355787100005 PM 25801300 ER PT J AU Nyer, MB Cassiello-Robbins, C Nock, MK Petrie, SR Holt, DJ Fisher, LB Jaeger, A Pedrelli, P Baer, L Farabaugh, A AF Nyer, Maren B. Cassiello-Robbins, Clair Nock, Matthew K. Petrie, Samuel R. Holt, Daphne J. Fisher, Lauren B. Jaeger, Adrienne Pedrelli, Paola Baer, Lee Farabaugh, Amy TI A Case Series of Individual Six-Week Cognitive Behavioral Therapy With Individually Tailored Manual-Based Treatment Delivery for Depressed College Students With or Without Suicidal Ideation SO JOURNAL OF RATIONAL-EMOTIVE AND COGNITIVE-BEHAVIOR THERAPY LA English DT Article DE Depression; Suicidality; Shot-term treatment; Cognitive-behavioral therapy (CBT); Undergraduate ID STAR-ASTERISK-D; HIGH-RISK; 2ND-STEP TREATMENTS; PREVENT SUICIDE; SYMPTOMS; INTERVENTIONS; QUESTIONNAIRE; METAANALYSIS; POPULATION; STRATEGIES AB Despite their prevalence, depression and suicidal ideation (SI) are relatively unaddressed problems in the college student population. There are limited individual treatment studies targeting this population. Nine students (M = 19.33 years of age; SD +/- .87) with depressive symptoms and/or SI were enrolled in 6-weeks of individual cognitive behavioral therapy (CBT) with a individually tailored manual-based treatment delivery. Measures were given before and after treatment. Primary results, presented as a case series, suggested decreases in depression across students and an overall downward trend in SI. As a secondary analysis, paired samples t tests showed significant decreases in both depression and SI. In summary, short-term, individually tailored manual-based CBT may be beneficial for reducing depressive symptoms and SI among college students. More research is needed to determine the best clinical interventions and targeted treatments for this vulnerable population. C1 [Nyer, Maren B.; Cassiello-Robbins, Clair; Petrie, Samuel R.; Holt, Daphne J.; Fisher, Lauren B.; Jaeger, Adrienne; Pedrelli, Paola; Baer, Lee; Farabaugh, Amy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, DCRP,Dept Psychiat, Boston, MA 02114 USA. [Nock, Matthew K.] Harvard Univ, Cambridge, MA 02138 USA. RP Nyer, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, DCRP,Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM mnyer@partners.org NR 47 TC 0 Z9 0 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9085 EI 1573-6563 J9 J RATION-EMOT COGN-B JI J. Ration.-Emot. Cogn.-Behav. Ther. PD JUN PY 2015 VL 33 IS 2 BP 134 EP 147 DI 10.1007/s10942-015-0206-y PG 14 WC Psychology, Clinical SC Psychology GA CJ7EK UT WOS:000355657000002 ER PT J AU Baker, JF Cannon, GW Ibrahim, S Haroldsen, C Caplan, L Mikuls, TR AF Baker, Joshua F. Cannon, Grant W. Ibrahim, Said Haroldsen, Candace Caplan, Liron Mikuls, Ted R. TI Predictors of Longterm Changes in Body Mass Index in Rheumatoid Arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RHEUMATOID ARTHRITIS; BODY MASS INDEX; CACHEXIA; INFLAMMATION ID DISEASE-ACTIVITY; WEIGHT CHANGE; CIGARETTE-SMOKING; US VETERANS; NECROSIS-FACTOR; RISK-FACTORS; MORTALITY; CACHEXIA; ASSOCIATION; SEVERITY AB Objective. Low body mass index (BMI) is a risk factor for poor longterm outcomes in rheumatoid arthritis (RA). The purpose of this study was to identify factors associated with longterm changes in BMI. Methods. Subjects with RA from the Veterans Affairs (VA) Rheumatoid Arthritis (VARA) Registry (n = 1474) were studied. Information on inflammatory markers, presence of erosions, and smoking status were extracted from the VARA database. BMI was extracted from VA electronic medical records within 14 days of each visit date. VA pharmacy records were queried to identify prescriptions for specific RA therapies within 1 month of the visit date. We used robust generalized estimating equations marginal regression models to calculate independent associations between clinical variables and BMI over time. Similar models determined predictors of change in weight and risk of weight loss over the subsequent study observation period. Results. Increasing age, active smoking, and the presence of erosions at baseline were associated with lower BMI. Weight decreased over time among older adults. Factors associated with greater reductions in BMI over time and a greater risk of weight loss were higher inflammatory markers, smoking, older age, higher BMI, and less subsequent improvement in inflammation. Methotrexate use was associated with a lower risk of weight loss. The use of prednisone or anti-tumor necrosis factor therapies was not associated with change in BMI or the risk of weight loss independent of other factors. Conclusion. Greater age, greater inflammatory activity, and active smoking are associated with greater weight loss in RA over time. C1 [Baker, Joshua F.] Philadelphia Vet Affairs VA Med Ctr, Div Rheumatol, Camden, NJ USA. [Ibrahim, Said] Philadelphia Vet Affairs VA Med Ctr, Ctr Hlth Equ Res & Promot, Camden, NJ USA. [Baker, Joshua F.] Univ Penn, Div Rheumatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Baker, Joshua F.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Cannon, Grant W.; Haroldsen, Candace] Salt Lake City VA Med Ctr, Salt Lake City, UT USA. [Cannon, Grant W.; Haroldsen, Candace] Univ Utah, Salt Lake City, UT USA. [Caplan, Liron] Denver VA Med Ctr, Dept Med, Denver, CO USA. [Mikuls, Ted R.] Nebraska Western Iowa VA Med Ctr, Dept Med, Omaha, NE USA. RP Baker, JF (reprint author), Hosp Univ Penn, Div Rheumatol, Dept Med, 8 Penn Tower Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu FU Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center; Veterans Affairs Health Services Research and Development Program of the Veterans Health Administration; VA Clinical Science Research and Development Career Development Award [IK2 CX000955]; VA Health Service Research and Development Career Development Award [07-221]; VA Merit Award FX The Veterans Affairs Rheumatoid Arthritis (VARA) registry is supported by the Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center and by the Veterans Affairs Health Services Research and Development Program of the Veterans Health Administration. Dr. Baker is funded by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Dr. Caplan is supported by the VA Health Service Research and Development Career Development Award (07-221). Dr. Mikuls is funded by a VA Merit Award. NR 44 TC 3 Z9 3 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 2015 VL 42 IS 6 BP 920 EP 927 DI 10.3899/jrheum.141363 PG 8 WC Rheumatology SC Rheumatology GA CJ5QO UT WOS:000355543300004 PM 25834210 ER PT J AU Sauser, K Bravata, DM Hayward, RA Levine, DA AF Sauser, Kori Bravata, Dawn M. Hayward, Rodney A. Levine, Deborah A. TI A National Evaluation of Door-to-Imaging Times among Acute Ischemic Stroke Patients within the Veterans Health Administration SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Stroke; brain imaging; veterans; emergency care ID RT-PA STROKE; QUALITY; CARE AB Background: Rapid brain imaging for ischemic stroke is important for patient outcomes. We sought to determine the proportion of ischemic stroke patients receiving brain imaging within the guideline-recommended 24 hours, and predictors of faster imaging among patients with acute symptoms. Methods: Retrospective analysis of Veterans Health Administration (VHA) Office of Performance Measurement Stroke Special Project data. Of 3000 ischemic stroke patients, secondary samples included 649 presenting within 6 hours of onset, and 217 potentially tissue plasminogen activator (tPA)-eligible patients (onset-to-arrival time,3 hours, National Institutes of Health Stroke Scale >2). Two linear regression models examined the association between door-to-imaging time and predictors among secondary samples, accounting for clustering within hospital. Results: Of the 3000 ischemic stroke patients, 97.1% had brain imaging within 24 hours. Among patients presenting within 6 hours of onset, median door-to-imaging time was 59 minutes (interquartile range [IQR], 33-109). Predictors of faster door-to-imaging time included elevated arrival blood pressure and stroke center presentation. Among the potentially tPA-eligible patients, median door-to-imaging time was 52 minutes (IQR, 31-105); no significant predictors were identified. Conclusions: Nearly all ischemic stroke patients at VHA hospitals have door-to-imaging time within 24 hours. There remains room for improvement for timely brain imaging among patients with acute symptom onset. C1 [Sauser, Kori] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Bravata, Dawn M.] Ctr Hlth Informat & Commun, VHA HSR&D Stroke Qual Enhancement Res Initiat Pro, Indianapolis, IN USA. [Bravata, Dawn M.] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. [Bravata, Dawn M.] Indiana Univ, Sch Med, Dept Internal Med, Indianapolis, IN 46204 USA. [Hayward, Rodney A.; Levine, Deborah A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Hayward, Rodney A.; Levine, Deborah A.] Ann Arbor Vet Affairs Hosp, Ctr Clin Management Res, Ann Arbor, MI USA. [Levine, Deborah A.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. RP Sauser, K (reprint author), Zero Emerson St,Suite 3B, Boston, MA 02114 USA. EM ksauser@partners.org OI Sauser-Zachrison, Kori/0000-0001-8160-3257 FU NIA NIH HHS [K23 AG040278] NR 8 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD JUN PY 2015 VL 24 IS 6 BP 1329 EP 1332 DI 10.1016/j.jstrokecerebrovasdis.2015.02.007 PG 4 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CJ2TT UT WOS:000355338200044 PM 25881775 ER PT J AU Weir, MR Burgess, ED Cooper, JE Fenves, AZ Goldsmith, D McKay, D Mehrotra, A Mitsnefes, MM Sica, DA Taler, SJ AF Weir, Matthew R. Burgess, Ellen D. Cooper, James E. Fenves, Andrew Z. Goldsmith, David McKay, Dianne Mehrotra, Anita Mitsnefes, Mark M. Sica, Domenic A. Taler, Sandra J. TI Assessment and Management of Hypertension in Transplant Patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID AMBULATORY BLOOD-PRESSURE; RENAL-ALLOGRAFT SURVIVAL; LEFT-VENTRICULAR HYPERTROPHY; CONVERTING-ENZYME-INHIBITOR; END-POINT REDUCTION; TERM-FOLLOW-UP; KIDNEY-TRANSPLANTATION; ARTERIAL-HYPERTENSION; POSTTRANSPLANTATION HYPERTENSION; RECEPTOR ANTAGONIST AB Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients. C1 [Weir, Matthew R.] Univ Maryland, Div Nephrol, Dept Med, Sch Med, Baltimore, MD 21201 USA. [Burgess, Ellen D.] Univ Calgary, Dept Med, Div Renal Med, Calgary, AB, Canada. [Cooper, James E.] Univ Colorado, Dept Med, Div Renal Dis & Hypertens, Denver, CO USA. [Fenves, Andrew Z.] Harvard Univ, Sch Med, Dept Med, Div Nephrol, Boston, MA USA. [Fenves, Andrew Z.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldsmith, David] St Thomas & Guys Hosp, Div Cardiorenal Med, London, England. [McKay, Dianne] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Mehrotra, Anita] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY USA. [Mitsnefes, Mark M.] Univ Cincinnati, Dept Pediat, Div Nephrol, Cincinnati, OH USA. [Sica, Domenic A.] Virginia Commonwealth Univ, Dept Med, Div Nephrol, Richmond, VA 23298 USA. [Taler, Sandra J.] Mayo Clin, Div Nephrol & Hypertens, Dept Med, Rochester, MN USA. RP Weir, MR (reprint author), Univ Maryland, Div Nephrol, Dept Med, Sch Med, 22 S Greene St, Baltimore, MD 21201 USA. EM mweir@medicine.umaryland.edu FU NCATS NIH HHS [UL1 TR000077, UL1 TR001425] NR 118 TC 16 Z9 17 U1 2 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2015 VL 26 IS 6 BP 1248 EP 1260 DI 10.1681/ASN.2014080834 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA CJ3LS UT WOS:000355386100006 PM 25653099 ER PT J AU Nowling, TK Mather, AR Thiyagarajan, T Hernandez-Corbacho, MJ Powers, TW Jones, EE Snider, AJ Oates, JC Drake, RR Siskind, LJ AF Nowling, Tamara K. Mather, Andrew R. Thiyagarajan, Thirumagal Hernandez-Corbacho, Maria Jose Powers, Thomas W. Jones, E. Ellen Snider, Ashley J. Oates, Jim C. Drake, Richard R. Siskind, Leah J. TI Renal Glycosphingolipid Metabolism Is Dysfunctional in Lupus Nephritis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; LIPID-METABOLISM; MRL/LPR MICE; BIOACTIVE SPHINGOLIPIDS; QUANTITATIVE-ANALYSIS; DISEASE-ACTIVITY; NERVOUS-SYSTEM; ERYTHEMATOSUS; GANGLIOSIDES; MANIFESTATIONS AB Nearly one half of patients with lupus develop glomerulonephritis (GN), which often leads to renal failure. Although nephritis is diagnosed by the presence of proteinuria, the pathology of nephritis can fall into one of five classes defined by different forms of tissue injury, and the mechanisms involved in pathogenesis are not completely understood. Glycosphingolipids are abundant in the kidney, have roles in many cellular functions, and were shown to be involved in other renal diseases. Here, we show dysfunctional glycosphingolipid metabolism in patients with lupus nephritis and MRL/Ipr lupus mice. Specifically, we found that glucosylceramide (GlcCer) and lactosylceramide (LacCer) levels are significantly higher in the kidneys of nephritic MRL/Ipr lupus mice than the kidneys of non-nephritic lupus mice or healthy controls. This elevation may be, in part, caused by altered transcriptional regulation and/or activity of LacCer synthase (GalT5) and neuraminidase 1, enzymes that mediate glycosphingolipid metabolism. We show increased neuraminidase 1 activity early during the progression of nephritis (before significant elevation of GlcCer and LacCer in the kidney). Elevated levels of urinary LacCer were detected before proteinuria in lupus mice. Notably, LacCer levels were higher in the urine and kidneys of patients with lupus and nephritis than patients with lupus without nephritis or healthy controls. Together, these results show early and significant dysfunction of the glycosphingolipid metabolic pathway in the kidneys of lupus mice and patients with lupus nephritis and suggest that molecules in this pathway may serve as early markers in lupus nephritis. C1 [Nowling, Tamara K.; Oates, Jim C.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Nowling, Tamara K.; Thiyagarajan, Thirumagal; Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Mather, Andrew R.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Powers, Thomas W.; Jones, E. Ellen; Drake, Richard R.] Med Univ S Carolina, Dept Cell & Mol Pharmacol, Charleston, SC 29425 USA. [Hernandez-Corbacho, Maria Jose; Snider, Ashley J.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Snider, Ashley J.] Northport Vet Affairs Med Ctr, Res Serv, Northport, NY USA. [Siskind, Leah J.] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Siskind, Leah J.] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. RP Nowling, TK (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St,CSB 912 MSC 637, Charleston, SC 29425 USA. EM Nowling@musc.edu; leah.siskind@louisville.edu FU National Institutes of Health National Institute of Arthritis & Musculoskeletal Skin Diseases [P60-AR062755]; South Carolina Clinical and Translational Research (SCTR) Institute; National Institutes of Health [UL1-RR029882, UL1-TR000062]; Veteran's Administration [BX000115, CX000218]; National Institutes of Health NIAMS [R01-AR45476-11]; Alliance for Lupus Research; National Institutes of Health National Cancer Institute [R01-CA135087]; Department of Defense [W81XWH-10-1-0136]; National Institutes of Health National Center for Research Resources [P20-RR17677]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK093462]; Cancer Center Support Grant [P30CA138313] FX Support for these studies was provided by National Institutes of Health National Institute of Arthritis & Musculoskeletal & Skin Diseases Grant P60-AR062755 Multidisciplinary Clinical Research Center Pilot Project (to T.K.N.) and Patient Resource Core (to J.C.O.), South Carolina Clinical and Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, through National Institutes of Health Grant Numbers UL1-RR029882 and UL1-TR000062, Veteran's Administration Merit Review Grants BX000115 (to T.K.N.) and CX000218 (to J.C.O.), National Institutes of Health NIAMS Grant R01-AR45476-11 (to J.C.O.), the Alliance for Lupus Research (to J.C.O.), National Institutes of Health National Cancer Institute Grant R01-CA135087 (to R.R.D.), Department of Defense Grant W81XWH-10-1-0136 (to R.R.D.), National Institutes of Health National Center for Research Resources Grant P20-RR17677 Center of Biomedical Research Excellence in Lipidomics and Pathobiology Pilot Project (to L.J.S.), National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK093462 (to L.J.S.), and the Lipidomics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina supported by Cancer Center Support Grant P30CA138313. NR 41 TC 3 Z9 3 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2015 VL 26 IS 6 BP 1402 EP 1413 DI 10.1681/ASN.2014050508 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA CJ3LS UT WOS:000355386100018 PM 25270066 ER PT J AU Deutsch, B Reddy, R Mayerich, D Bhargava, R Carney, PS AF Deutsch, Bradley Reddy, Rohith Mayerich, David Bhargava, Rohit Carney, P. Scott TI Compositional prior information in computed infrared spectroscopic imaging SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID OPTICAL-COHERENCE TOMOGRAPHY; FOURIER-TRANSFORM REFRACTOMETRY; AUTOCORRELATION ARTIFACTS; BACKSCATTERING; RESOLUTION; SYSTEMS; TISSUE AB Compositional prior information is used to bridge a gap in the theory between optical coherence tomography (OCT), which provides high-resolution structural images by neglecting spectral variation, and imaging spectroscopy, which provides only spectral information without significant regard to structure. A constraint is proposed in which it is assumed that a sample is composed of N distinct materials with known spectra, allowing the structural and spectral composition of the sample to be determined with a number of measurements on the order of N. We present a forward model for a sample with heterogeneities along the optical axis and show through simulation that the N-species constraint allows unambiguous inversion of Fourier transform interferometric data within the spatial frequency passband of the optical system. We then explore the stability and limitations of this model and extend it to a general 3D heterogeneous sample. (C) 2015 Optical Society of America C1 [Deutsch, Bradley; Reddy, Rohith; Mayerich, David; Bhargava, Rohit; Carney, P. Scott] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Reddy, Rohith] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Reddy, Rohith] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bhargava, Rohit; Carney, P. Scott] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Bhargava, Rohit] Univ Illinois, Dept Mech Sci & Engn, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. [Bhargava, Rohit] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. RP Carney, PS (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. EM carney@illinois.edu OI Bhargava, Rohit/0000-0001-7360-994X FU Beckman Postdoctoral Fellowship FX Beckman Postdoctoral Fellowship. NR 32 TC 1 Z9 1 U1 3 U2 12 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 EI 1520-8532 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD JUN PY 2015 VL 32 IS 6 BP 1126 EP 1131 DI 10.1364/JOSAA.32.001126 PG 6 WC Optics SC Optics GA CJ6VM UT WOS:000355633300015 PM 26367047 ER PT J AU Pascoe, S Locantore, N Dransfield, MT Barnes, NC Pavord, ID AF Pascoe, Steven Locantore, Nicholas Dransfield, Mark T. Barnes, Neil C. Pavord, Ian D. TI Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials SO LANCET RESPIRATORY MEDICINE LA English DT Article ID COMPUTED-TOMOGRAPHY ASSESSMENT; PLACEBO-CONTROLLED TRIAL; SHORT-TERM RESPONSE; SPUTUM-EOSINOPHILIA; COPD EXACERBATIONS; DOUBLE-BLIND; CORTICOSTEROID TREATMENT; BUDESONIDE/FORMOTEROL; PREDNISOLONE; INFLAMMATION AB Background The short-term benefits of inhaled corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are greater in patients with evidence of eosinophilic airway inflammation. We investigated whether blood eosinophil count is a useful biomarker of the long-term effect of the inhaled corticosteroid fluticasone furoate on exacerbation frequency. Methods We did a post-hoc analysis of data from two replicate, randomised, double-blind trials of 12 months' duration (Sept 25, 2009 to Oct 21, 2011 and Oct 17, 2011) in which once a day vilanterol 25 mu g was compared with 25 mu g vilanterol plus 50 mu g, 100 mu g, or 200 mu g fluticasone furoate in patients with moderate-to-severe COPD and a history of one or more exacerbation in the previous year. We compared exacerbation rates according to two baseline eosinophil cell count strata (<2% and >= 2%), and according to four baseline percentage groupings. We also assessed lung function and incidence of pneumonia per strata in treatment groups. Findings We included 3177 patients in the analyses, with 2083 patients (66%) having an eosinophil count of 2% or higher at study entry. Across all doses of inhaled corticosteroids, fluticasone furoate and vilanterol reduced exacerbations by 29% compared with vilanterol alone (mean 0.91 vs 1.28 exacerbations per patient per year; p<0.0001) in patients with eosinophil counts of 2% or higher, and by 10% (0.79 vs 0.89; p=0.2827) in patients with eosinophil counts lower than 2%. Reductions in exacerbations with fluticasone furoate and vilanterol, compared with vilanterol alone, were 24% in patients with baseline eosinophil counts of >= 2-<4%, 32% for those with counts of 4-<6%, and 42% for those with eosinophil counts of >= 6%. In patients treated with vilanterol alone, exacerbation rates increased progressively with increasing eosinophil count percentage category. Improvement in trough forced expiratory volume in 1 s (FEV1) and the increased risk of pneumonia with fluticasone furoate and vilanterol compared with vilanterol alone were not associated with eosinophil count. Interpretation Blood eosinophil count is a promising biomarker of response to inhaled corticosteroids in patients with COPD. Blood eosinophil count could potentially be used to stratify patients for different exacerbation rate reduction strategies. C1 [Pascoe, Steven; Locantore, Nicholas] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. [Dransfield, Mark T.] Univ Alabama Birmingham, Lung Hlth Ctr, Birmingham, AL USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Barnes, Neil C.] GlaxoSmithKline, Uxbridge, Middx, England. [Barnes, Neil C.] Barts & London Queen Marys Sch Med & Dent, William Harvey Inst, London, England. [Pavord, Ian D.] Univ Oxford, Nuffield Dept Clin Med, Resp Med Unit, Oxford OX1 2JD, England. RP Pascoe, S (reprint author), GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. EM steven.j.pascoe@gsk.com OI Pavord, Ian/0000-0002-4288-5973 FU GlaxoSmithKline [201595] FX GlaxoSmithKline (study ID 201595). NR 27 TC 114 Z9 117 U1 5 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD JUN PY 2015 VL 3 IS 6 BP 435 EP 442 DI 10.1016/S2213-2600(15)00106-X PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CJ5UY UT WOS:000355558500020 PM 25878028 ER PT J AU Wang, LD Rao, TN Rowe, RG Nguyen, PT Sullivan, JL Pearson, DS Doulatov, S Wu, L Lindsley, RC Zhu, H DeAngelo, DJ Daley, GQ Wagers, AJ AF Wang, L. D. Rao, T. N. Rowe, R. G. Nguyen, P. T. Sullivan, J. L. Pearson, D. S. Doulatov, S. Wu, L. Lindsley, R. C. Zhu, H. DeAngelo, D. J. Daley, G. Q. Wagers, A. J. TI The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy SO LEUKEMIA LA English DT Article ID ADVANCED SYSTEMIC MASTOCYTOSIS; PROMOTES TRANSFORMATION; TRANSCRIPTION FACTOR; STEM-CELLS; EX-VIVO; PROGENITORS; LEUKEMIA; ANGIOGENESIS; EXPRESSION; LYMPHOMA AB Mast cells (MCs) are critical components of the innate immune system and important for host defense, allergy, autoimmunity, tissue regeneration and tumor progression. Dysregulated MC development leads to systemic mastocytosis (SM), a clinically variable but often devastating family of hematologic disorders. Here we report that induced expression of Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal hematopoietic program, caused MC accumulation in adult mice in target organs such as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid commitment in LIN28B-expressing hematopoietic progenitors, with increased levels of LIN28B in common myeloid and basophil-MC progenitors altering gene expression patterns to favor cell fate choices that enhanced MC specification. In addition, LIN28B-induced MCs appeared phenotypically and functionally immature, and in vitro assays suggested a slowing of MC terminal differentiation in the context of LIN28B upregulation. Finally, interrogation of human MC leukemia samples revealed upregulation of LIN28B in abnormal MCs from patients with SM. This work identifies Lin28 as a novel regulator of innate immune function and a new protein of interest in MC disease. C1 [Wang, L. D.; Rao, T. N.; Nguyen, P. T.; Sullivan, J. L.; Wagers, A. J.] Joslin Diabet Ctr, Dept Pathol, Boston, MA 02215 USA. [Wang, L. D.; Rao, T. N.; Rowe, R. G.; Nguyen, P. T.; Sullivan, J. L.; Pearson, D. S.; Doulatov, S.; Daley, G. Q.; Wagers, A. J.] Harvard Stem Cell Inst, Cambridge, MA USA. [Wang, L. D.; Rao, T. N.; Nguyen, P. T.; Sullivan, J. L.; Daley, G. Q.; Wagers, A. J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Wang, L. D.; Rowe, R. G.; Pearson, D. S.; Doulatov, S.; Daley, G. Q.] Dana Farber Boston Childrens Ctr Canc & Blood Dis, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA USA. [Wang, L. D.; Rowe, R. G.; Pearson, D. S.; Doulatov, S.; Daley, G. Q.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Rowe, R. G.; Pearson, D. S.; Doulatov, S.; Daley, G. Q.] Manton Ctr Orphan Dis Res, Boston, MA USA. [Rowe, R. G.; Pearson, D. S.; Doulatov, S.; Daley, G. Q.; Wagers, A. J.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Pearson, D. S.; Daley, G. Q.] Harvard Univ, Med Scientist Training Program, Sch Med, Boston, MA USA. [Wu, L.; Zhu, H.] Univ Texas SW Med Ctr Dallas, Childrens Res Inst, Dept Pediat & Internal Med, Dallas, TX 75390 USA. [Wu, L.] Sun Yat Sen Univ, Affiliated Hosp 1, Organ Transplant Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Lindsley, R. C.; DeAngelo, D. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lindsley, R. C.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, G. Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wagers, AJ (reprint author), Joslin Diabet Ctr, Dept Pathol, 1 Joslin Pl, Boston, MA 02215 USA. EM Amy_wagers@harvard.edu RI Zhu, Hao/L-5114-2013 OI Zhu, Hao/0000-0002-8417-9698 FU Damon Runyon-Sohn Foundation Cancer Research Fellowship [DRSG 02-12]; St. Baldrick's Foundation-PALS Scholar Award [243625]; Helen Hay Whitney Cancer Fellowship; Burroughs-Wellcome Fund Career Award; NIH [R01-HL088582, P30DK036836, R01-GM107536, K08-CA157727]; Ellison Medical Foundation FX We thank Cem Akin, Alberto Orfao, Ann Dvorak, David Weinstock, Susan Buchanan, Girijesh Buruzula, Joyce LaVecchio, Atsuya Wakabayashi, Jacobo Ramirez, Elsa Lindhe, Louise Trakimas and Maria Ericsson of the HMS electron microscopy core facility, and the DF/HCC Specialized Histopathology facility for their assistance. This work was supported by a Damon Runyon-Sohn Foundation Cancer Research Fellowship (DRSG 02-12) and a St. Baldrick's Foundation-PALS Scholar Award (243625; LDW), a Helen Hay Whitney Cancer Fellowship (SD), a Burroughs-Wellcome Fund Career Award (HZ), and grants from the NIH (R01-HL088582 and P30DK036836; AJW), (R01-GM107536; GQD), (K08-CA157727; HZ) and the Ellison Medical Foundation (GQD). NR 60 TC 8 Z9 8 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JUN PY 2015 VL 29 IS 6 BP 1320 EP 1330 DI 10.1038/leu.2015.19 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA CJ6PE UT WOS:000355615000010 PM 25655194 ER PT J AU Ray, A Das, DS Song, Y Richardson, P Munshi, NC Chauhan, D Anderson, KC AF Ray, A. Das, D. S. Song, Y. Richardson, P. Munshi, N. C. Chauhan, D. Anderson, K. C. TI Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cell interactions with T cells, natural killer cells and multiple myeloma cells SO LEUKEMIA LA English DT Letter ID THERAPEUTIC TARGET; IMMUNOTHERAPY; EXPRESSION; RESPONSES; BLOCKADE; MOLECULE; PD-L1 C1 [Ray, A.; Das, D. S.; Song, Y.; Richardson, P.; Munshi, N. C.; Chauhan, D.; Anderson, K. C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02138 USA. [Ray, A.; Das, D. S.; Song, Y.; Richardson, P.; Munshi, N. C.; Chauhan, D.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Ray, A (reprint author), Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02138 USA. EM Dharminder_Chauhan@dfci.harvard.edu; Kenneth_Anderson@dfci.harvard.edu FU NCI NIH HHS [R01 CA050947, P01-CA078378]; PHS HHS [P50100707] NR 15 TC 28 Z9 28 U1 2 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JUN PY 2015 VL 29 IS 6 BP 1441 EP 1444 DI 10.1038/leu.2015.11 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA CJ6PE UT WOS:000355615000026 PM 25634684 ER PT J AU Sorets, TR Mateen, FJ AF Sorets, Tali R. Mateen, Farrah J. TI Mandatory CPR Training in US High Schools SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID HOSPITAL CARDIAC-ARREST; SURVIVAL C1 [Sorets, Tali R.] Buckingham Browne & Nichols Sch, Cambridge, MA USA. [Sorets, Tali R.; Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 165 Cambridge St 627, Boston, MA 02114 USA. EM fmateen@partners.org NR 11 TC 1 Z9 1 U1 1 U2 2 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 JUN PY 2015 VL 90 IS 6 BP 710 EP 712 DI 10.1016/j.mayocp.2015.04.004 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CJ5UV UT WOS:000355557900006 PM 26046405 ER PT J AU Berna, C Kulich, RJ Rathmell, JP AF Berna, Chantal Kulich, Ronald J. Rathmell, James P. TI Tapering Long-term Opioid Therapy in Chronic Noncancer Pain: Evidence and Recommendations for Everyday Practice SO MAYO CLINIC PROCEEDINGS LA English DT Article ID LOW-BACK-PAIN; CHRONIC NONMALIGNANT PAIN; TREATMENT OUTCOMES; REHABILITATION PROGRAM; PSYCHIATRIC-DISORDERS; COMPREHENSIVE PAIN; OPIATE WITHDRAWAL; MULTIDISCIPLINARY REHABILITATION; MEDICATION MANAGEMENT; ANALGESIC MEDICATION AB Increasing concern about the risks and limited evidence supporting the therapeutic benefit of long-termopioid therapy for chronic noncancer pain are leading prescribers to consider discontinuing the use of opioids. In addition to overt addiction or diversion, the presence of adverse effects, diminishing analgesia, reduced function and quality of life, or the absence of progress toward functional goals can justify an attempt at weaning patients from long-term opioid therapy. However, discontinuing opioid therapy is often hindered by patients' psychiatric comorbidities and poor coping skills, as well as the lack of formal guidelines for the prescribers. The aim of this article is to review the existing literature and formulate recommendations for practitioners aiming to discontinue long-termopioid therapy. Specifically, this review aims to answer the following questions: What is an optimal opioid tapering regimen? How can the risks involved in a taper be managed? What are the alternatives to an opioid taper? A PubMed literature search was conducted using the keywords chronic pain combined with opioid withdrawal, taper, wean and detoxification. Six hundred ninety-five documents were identified and screened; 117 were deemed directly relevant and are included. On the base of this literature review, this article proposes evidence-based recommendations and expert-based suggestions for clinical practice. Furthermore, areas of lack of evidence are identified, providing opportunities for further research. (C) 2015 Mayo Foundation for Medical Education and Research C1 [Berna, Chantal; Kulich, Ronald J.; Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Berna, Chantal; Kulich, Ronald J.; Rathmell, James P.] Harvard Univ, Sch Med, Boston, MA USA. [Kulich, Ronald J.] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. RP Rathmell, JP (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Frances St, Boston, MA 02115 USA. EM jrathmell@partners.org FU Purdue Pharma; Swiss National Science Foundation [P3SMP3_151710] FX Dr Berna received salary support in part through an unrestricted educational grant from Purdue Pharma and in part from an Advanced Postdoc Mobility grant of the Swiss National Science Foundation (P3SMP3_151710). Purdue Pharma had no input or influence into the conception, design, or preparation of this manuscript. NR 115 TC 13 Z9 13 U1 7 U2 14 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 JUN PY 2015 VL 90 IS 6 BP 828 EP 842 DI 10.1016/j.mayocp.2015.04.003 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA CJ5UV UT WOS:000355557900020 PM 26046416 ER PT J AU Kyle, RA Steensma, DP Shampo, MA AF Kyle, Robert A. Steensma, David P. Shampo, Marc A. TI Howard Walter Florey-Production of Penicillin SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Kyle, Robert A.; Shampo, Marc A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. RP Kyle, RA (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 4 U2 14 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 JUN PY 2015 VL 90 IS 6 BP E63 EP E64 DI 10.1016/j.mayocp.2014.12.028 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CJ5UV UT WOS:000355557900002 PM 26046419 ER PT J AU Proctor, SP Nieto, K Heaton, KJ Dillon, CC Schlegel, RE Russell, ML Vincent, AS AF Proctor, Susan P. Nieto, Kenneth Heaton, Kristin J. Dillon, Caitlin C. Schlegel, Robert E. Russell, Michael L. Vincent, Andrea S. TI Neurocognitive Performance and Prior Injury Among US Department of Defense Military Personnel SO MILITARY MEDICINE LA English DT Article ID TRAUMATIC BRAIN-INJURY; NEUROPSYCHOLOGICAL ASSESSMENT METRICS; ASSOCIATION POSITION STATEMENT; SPORT-RELATED CONCUSSION; COGNITIVE IMPAIRMENT; SCREENING TOOL; REACTION-TIME; SAMPLE; ANAM; IRAQ AB This study examined the neurocognitive performance of U.S. military personnel completing the Automated Neuropsychological Assessment Metrics (version 4) TBI Military (ANAM4 TBI-MIL) battery as part of the Department of Defense Neurocognitive Functional Assessment Program. Descriptive analyses utilizing the ANAM4TBI Military Performance Database were performed. We examined ANAM Composite Score (ACS) differences between five injury subgroups (no injury, brain injury with current symptoms, brain injury without current symptoms, nonbrain injury with current symptoms, and nonbrain injury without current symptoms) using general linear mixed modeling. Almost 11% (70,472/641,285) reported brain injury in the 4 years before assessment. The ACS differed significantly by injury group (p < 0.0001). In comparison to the no injury group, those reporting brain injury with current symptoms (d = -0.44) and nonbrain injury with current symptoms (d = -0.24) demonstrated significantly reduced ACS scores (p < 0.0001) indicative of reduced neurocognitive proficiency. In this population-based study of U.S. military personnel, neurocognitive performance was significantly associated with reported injury within the past 4 years among those experiencing current symptoms. Occupational programs focusing on prospective brain health of injured population groups are warranted. C1 [Proctor, Susan P.; Nieto, Kenneth; Heaton, Kristin J.; Dillon, Caitlin C.] US Army, Environm Med Res Inst, Mil Performance Div, Natick, MA 01760 USA. [Proctor, Susan P.; Heaton, Kristin J.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA. [Schlegel, Robert E.; Russell, Michael L.] US Army, Off Surg Gen, Neurocognit Assessment Branch, Ft Sam Houston, TX 78234 USA. [Russell, Michael L.] Dept Vet Affairs Ctr Excellence Res Returning War, Waco, TX 76711 USA. [Vincent, Andrea S.] Univ Oklahoma, Cognit Sci Res Ctr, Norman, OK 73072 USA. RP Proctor, SP (reprint author), US Army, Environm Med Res Inst, Mil Performance Div, Kansas St,Bldg 42, Natick, MA 01760 USA. FU U.S. Army Medical Research and Materiel Command [W81XWH-08-1-0021] FX We thank the staff at the U.S. Army Office of the Surgeon General, Neurocognitive Assessment Branch, as well as the DoD Defense Manpower Data Center for their support in this project. Funding for this project has been provided by the U.S. Army Medical Research and Materiel Command to the U.S. Army Research Institute of Environmental Medicine and through award #W81XWH-08-1-0021 (PI: SP Proctor) to the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. NR 39 TC 0 Z9 0 U1 2 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD JUN PY 2015 VL 180 IS 6 BP 660 EP 669 DI 10.7205/MILMED-D-14-00298 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CJ5WM UT WOS:000355563400015 PM 26032381 ER PT J AU Maier, VK Feeney, CM Taylor, JE Creech, AL Qiao, JW Szanto, A Das, PP Chevrier, N Cifuentes-Rojas, C Orkin, SH Carr, SA Jaffe, JD Mertins, P Lee, JT AF Maier, Verena K. Feeney, Caitlin M. Taylor, Jordan E. Creech, Amanda L. Qiao, Jana W. Szanto, Attila Das, Partha P. Chevrier, Nicholas Cifuentes-Rojas, Catherine Orkin, Stuart H. Carr, Steven A. Jaffe, Jacob D. Mertins, Philipp Lee, Jeannie T. TI Functional Proteomic Analysis of Repressive Histone Methyltransferase Complexes Reveals ZNF518B as a G9A Regulator SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID EMBRYONIC STEM-CELLS; QUANTITATIVE MASS-SPECTROMETRY; PROTEIN COMPLEXES; TRANSCRIPTIONAL REGULATION; INTERACTION NETWORKS; MOUSE DEVELOPMENT; DNA METHYLATION; GENE-EXPRESSION; LYSINE 27; EZH2 AB Cell-type specific gene silencing by histone H3 lysine 27 and lysine 9 methyltransferase complexes PRC2 and G9A-GLP is crucial both during development and to maintain cell identity. Although studying their interaction partners has yielded valuable insight into their functions, how these factors are regulated on a network level remains incompletely understood. Here, we present a new approach that combines quantitative interaction proteomics with global chromatin profiling to functionally characterize repressive chromatin modifying protein complexes in embryonic stem cells. We define binding stoichiometries of 9 new and 12 known interaction partners of PRC2 and 10 known and 29 new interaction partners of G9A-GLP, respectively. We demonstrate that PRC2 and G9A-GLP interact physically and share several interaction partners, including the zinc finger proteins ZNF518A and ZNF518B. Using global chromatin profiling by targeted mass spectrometry, we discover that even sub-stoichiometric binding partners such as ZNF518B can positively regulate global H3K9me2 levels. Biochemical analysis reveals that ZNF518B directly interacts with EZH2 and G9A. Our systematic analysis suggests that ZNF518B may mediate the structural association between PRC2 and G9A-GLP histone methyltransferases and additionally regulates the activity of G9A-GLP. C1 [Maier, Verena K.; Szanto, Attila; Cifuentes-Rojas, Catherine; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Dept Mol Biol,Massachusetts Gen Hosp, Boston, MA 02143 USA. [Feeney, Caitlin M.; Taylor, Jordan E.; Creech, Amanda L.; Qiao, Jana W.; Carr, Steven A.; Jaffe, Jacob D.] Broad Inst, Prote Platform, Cambridge, MA 02142 USA. [Das, Partha P.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pediat Oncol,Dana Farber Canc Inst,Harvard S, Boston, MA 02115 USA. [Das, Partha P.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Chevrier, Nicholas] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. RP Maier, VK (reprint author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM pmertins@broadinstitute.org; lee@molbio.mgh.harvard.edu FU National Institutes of Health [R01-DA36895]; Rett Syndrome Research Trust; International Rett Syndrome Foundation; German Research Foundation FX This work was supported by grants from the National Institutes of Health (R01-DA36895), Rett Syndrome Research Trust, and International Rett Syndrome Foundation to J.T.L. J.T.L. is also in Investigator of the Howard Hughes Medical Institute. V.K.M. was supported by a fellowship of the German Research Foundation. NR 78 TC 10 Z9 10 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JUN PY 2015 VL 14 IS 6 BP 1435 EP 1446 DI 10.1074/mcp.M114.044586 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CJ5SX UT WOS:000355550400001 PM 25680957 ER PT J AU Wang, DJ Ho, L Faith, J Ono, K Janle, EM Lachcik, PJ Cooper, BR Jannasch, AH D'Arcy, BR Williams, BA Ferruzzi, MG Levine, S Zhao, W Dubner, L Pasinetti, GM AF Wang, Dongjie Ho, Lap Faith, Jeremiah Ono, Kenjiro Janle, Elsa M. Lachcik, Pamela J. Cooper, Bruce R. Jannasch, Amber H. D'Arcy, Bruce R. Williams, Barbara A. Ferruzzi, Mario G. Levine, Samara Zhao, Wei Dubner, Lauren Pasinetti, Giulio M. TI Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease -amyloid oligomerization SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE -Amyloid; Bioavailability; Grape seed polyphenol extract; Phenolic metabolites; Proanthocyanidins ID GRAPE SEED EXTRACT; BETA-PROTEIN; IN-VITRO; URINARY-EXCRETION; MOUSE MODEL; PROANTHOCYANIDIN METABOLITES; COLONIC METABOLISM; CHLOROGENIC ACID; BLOOD-PRESSURE; RING-FISSION AB ScopeGrape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer's disease (AD) and other age-related neurodegenerative disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE-derived phenolic acid in the brain. Methods and resultsWe orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of two of the phenolic acids in the brain: 3-hydroxybenzoic acid and 3-(3-hydroxyphenyl)propionic acid, resulting in the brain accumulations of the two phenolic acids at micromolar concentrations. We also provided evidence that 3-hydroxybenzoic acid and 3-(3 '-hydroxyphenyl)propionic acid potently interfere with the assembly of -amyloid peptides into neurotoxic -amyloid aggregates that play key roles in AD pathogenesis. ConclusionOur observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions. C1 [Wang, Dongjie; Williams, Barbara A.] Univ Queensland, ARC Ctr Excellence Plant Cell Walls, Ctr Nutr & Food Sci, Brisbane, Qld, Australia. [Ho, Lap; Levine, Samara; Zhao, Wei; Dubner, Lauren; Pasinetti, Giulio M.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Faith, Jeremiah] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Ono, Kenjiro] Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol & Aging, Kanazawa, Ishikawa, Japan. [Janle, Elsa M.; Lachcik, Pamela J.; Ferruzzi, Mario G.] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Cooper, Bruce R.; Jannasch, Amber H.] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47907 USA. [D'Arcy, Bruce R.] Univ Queensland, Sch Agr & Food Sci, Brisbane, Qld, Australia. [Ferruzzi, Mario G.] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Pasinetti, Giulio M.] James J Peter Vet Affairs Med Ctr, Geriatr Res & Clin Ctr, Bronx, NY USA. RP Pasinetti, GM (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU NIH/NCCAM [P01AT004511-01]; Endeavour International Postgraduate Research Scholarship (IPRS) - Australia government; Graduate School International Travel Award (GSITA) from The University of Queensland; Career Scientist Award in the Research and Development unit FX The GSPE sample used in this study was generously provided by Polyphenolics (Madera, CA). Funding was provided by NIH/NCCAM grant P01AT004511-01 (to GMP) and by the Endeavour International Postgraduate Research Scholarship (IPRS), awarded by Australia government, and the Graduate School International Travel Award (GSITA) from The University of Queensland. This material is the result of work supported in part with resources and the use of facilities at the James J. Peters Veterans Affairs Medical Center, Bronx, NY. In addition, Dr. Pasinetti holds a Career Scientist Award in the Research and Development unit and is the Director of the Basic and Biomedical Research and Training Program, GRECC, James J. Peters Veterans Affairs Medical Center. We also acknowledge that the contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. GMP and LH disclose financial interest as inventors of a patent for use of GSPE for the treatment of neurodegenerative diseases (Patent number, US 8,747,924 B2). NR 74 TC 17 Z9 18 U1 4 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 EI 1613-4133 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUN PY 2015 VL 59 IS 6 BP 1025 EP 1040 DI 10.1002/mnfr.201400544 PG 16 WC Food Science & Technology SC Food Science & Technology GA CJ8JD UT WOS:000355745400002 PM 25689033 ER PT J AU Wang, D Ho, L Faith, J Ono, K Janle, EM Lachcik, PJ Cooper, BR Jannasch, AH D'Arcy, BR Williams, BA Ferruzzi, MG Levine, S Zhao, W Dubner, L Pasinetti, GM AF Wang, D. Ho, L. Faith, J. Ono, K. Janle, E. M. Lachcik, P. J. Cooper, B. R. Jannasch, A. H. D'Arcy, B. R. Williams, B. A. Ferruzzi, M. G. Levine, S. Zhao, W. Dubner, L. Pasinetti, G. M. TI Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease beta-amyloid oligomerization (vol 59, pg 1025, 2015) SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Correction C1 [Pasinetti, G. M.] James J Peters Vet Affairs Med Ctr, GRECC, Basic & Biomed Res & Training Program, Bronx, NY USA. NR 1 TC 0 Z9 0 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 EI 1613-4133 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUN PY 2015 VL 59 IS 6 BP 1222 EP 1222 DI 10.1002/mnfr.201570064 PG 1 WC Food Science & Technology SC Food Science & Technology GA CJ8JD UT WOS:000355745400020 ER PT J AU Pandit, L Asgari, N Apiwattanakul, M Palace, J Paul, F Leite, MI Kleiter, I Chitnis, T AF Pandit, L. Asgari, N. Apiwattanakul, M. Palace, J. Paul, F. Leite, M., I Kleiter, I Chitnis, T. CA GJCF Int Clinical Consortium TI Demographic and clinical features of neuromyelitis optica: A review SO MULTIPLE SCLEROSIS JOURNAL LA English DT Review DE NMO; epidemiology; demographics; incidence; prevalence ID EXTENSIVE TRANSVERSE MYELITIS; MULTIPLE-SCLEROSIS; PROGNOSTIC-FACTORS; AQUAPORIN-4 AUTOIMMUNITY; UNITED-KINGDOM; MULTICENTER; POPULATION; SPECTRUM; NMO; DISORDERS AB The comparative clinical and demographic features of neuromyelitis optica (NMO) are not well known. In this review we analyzed peer-reviewed publications for incidence and prevalence, clinical phenotypes, and demographic features of NMO. Population-based studies from Europe, South East and Southern Asia, the Caribbean, and Cuba suggest that the incidence and prevalence of NMO ranges from 0.05-0.4 and 0.52-4.4 per 100,000, respectively. Mean age at onset (32.6-45.7) and median time to first relapse (8-12 months) was similar. Most studies reported an excess of disease in women and a relapsing course, particularly in anti-aquaporin 4 antibody (anti AQP4-IgG)-positive patients. Ethnicity may have a bearing on disease phenotype and clinical outcome. Despite limitations inherent to the review process, themes noted in clinical and demographic features of NMO among different populations promote a more global understanding of NMO and strategies to address it. C1 [Pandit, L.] Nitte Univ, KS Hegde Med Acad, Mangalore 575018, Karnataka, India. [Asgari, N.] Univ Southern Denmark, Inst Mol Med, Neurobiol, Odense, Denmark. [Asgari, N.] Vejle Hosp, Dept Neurol, Vejle, Denmark. [Apiwattanakul, M.] Prasat Neurol Inst, Bangkok, Thailand. [Palace, J.; Leite, M., I] Oxford Univ Hosp, Dept Clin Neurol, Oxford, England. [Paul, F.] Charite, Neuro Cure Clin Res Ctr, D-13353 Berlin, Germany. [Paul, F.] Charite, Clin & Expt Multiple Sclerosis Res Ctr, Dept Neurol, D-13353 Berlin, Germany. [Kleiter, I] Ruhr Univ Bochum, Dept Neurol, St Josef Hosp, Bochum, Germany. [Chitnis, T.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Chitnis, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pandit, L (reprint author), Nitte Univ, KS Hegde Med Acad, Neurol, Mangalore 575018, Karnataka, India. EM panditmng@gmail.com OI paul, friedemann/0000-0002-6378-0070 NR 38 TC 26 Z9 27 U1 3 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD JUN PY 2015 VL 21 IS 7 BP 845 EP 853 DI 10.1177/1352458515572406 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ3WH UT WOS:000355414500002 PM 25921037 ER PT J AU Thress, KS Paweletz, CP Felip, E Cho, BC Stetsonl, D Dougherty, B Lai, ZW Markovets, A Vivancos, A Kuang, Y Ercan, D Matthews, SE Cantarini, M Barrett, JC Janne, PA Oxnard, GR AF Thress, Kenneth S. Paweletz, Cloud P. Felip, Enriqueta Cho, Byoung Chul Stetsonl, Daniel Dougherty, Brian Lai, Zhongwu Markovets, Aleksandra Vivancos, Ana Kuang, Yanan Ercan, Dalia Matthews, Sarah E. Cantarini, Mireille Barrett, J. Carl Jaenne, Pasi A. Oxnard, Geoffrey R. TI Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M SO NATURE MEDICINE LA English DT Article ID FACTOR RECEPTOR EGFR; KINASE INHIBITORS; MUTANT AB Here we studied cell-free plasma DNA (cfDNA) collected from subjects with advanced lung cancer whose tumors had developed resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291. We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291. We then performed droplet digital PCR on serial cfDNA specimens collected from 15 AZD9291-treated subjects. All were positive for the T790M mutation before treatment, but upon developing AZD9291 resistance three molecular subtypes emerged: six cases acquired the C797S mutation, five cases maintained the T790M mutation but did not acquire the C797S mutation and four cases lost the T790M mutation despite the presence of the underlying EGFR activating mutation. Our findings provide insight into the diversity of mechanisms through which tumors acquire resistance to AZD9291 and highlight the need for therapies that are able to overcome resistance mediated by the EGFR C797S mutation. C1 [Thress, Kenneth S.; Stetsonl, Daniel; Dougherty, Brian; Lai, Zhongwu; Markovets, Aleksandra; Barrett, J. Carl] AstraZeneca, Waltham, MA USA. [Paweletz, Cloud P.; Kuang, Yanan; Ercan, Dalia; Matthews, Sarah E.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Paweletz, Cloud P.; Kuang, Yanan; Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Felip, Enriqueta; Vivancos, Ana] Vall dHebron Inst Oncol, Barcelona, Spain. [Felip, Enriqueta] Vall dHebron Univ Hosp, Barcelona, Spain. [Cho, Byoung Chul] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. [Cantarini, Mireille] AstraZeneca, Macclesfield, Cheshire, England. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM geoffrey_oxnard@DFCI.Harvard.edu FU National Cancer Institute of the National Institutes of Health [R01CA135257, R01CA114465, P01CA154303]; AstraZeneca; Conquer Cancer Foundation of ASCO; Stading-Younger Cancer Research Foundation; Department of Medical Oncology at Dana-Farber Cancer Institute FX This study was supported in part by the National Cancer Institute of the National Institutes of Health (R01CA135257 (P.A.J.), R01CA114465 (P.A.J.) and P01CA154303 (P.A.J.)), AstraZeneca, the Conquer Cancer Foundation of ASCO (G.R.O.), the Stading-Younger Cancer Research Foundation (G.R.O.), and the Department of Medical Oncology at Dana-Farber Cancer Institute. We would like to thank the numerous lung cancer patients and clinical investigators that contributed to this scientific effort. NR 14 TC 178 Z9 192 U1 12 U2 66 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUN PY 2015 VL 21 IS 6 BP 560 EP 562 DI 10.1038/nm.3854 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CJ8UF UT WOS:000355778300011 PM 25939061 ER PT J AU Zhu, D Wang, ZQ Zhao, JJ Calimeri, T Meng, J Hideshima, T Fulciniti, M Kang, Y Ficarro, SB Tai, YT Hunter, Z McMilin, D Tong, HX Mitsiades, CS Wu, CJ Treon, SP Dorfman, DM Pinkus, G Munshi, NC Tassone, P Marto, JA Anderson, KC Carrasco, RD AF Zhu, Di Wang, Zhongqiu Zhao, Jian-Jun Calimeri, Teresa Meng, Jiang Hideshima, Teru Fulciniti, Mariateresa Kang, Yue Ficarro, Scott B. Tai, Yu-Tzu Hunter, Zachary McMilin, Douglas Tong, Haoxuan Mitsiades, Constantine S. Wu, Catherine J. Treon, Steven P. Dorfman, David M. Pinkus, Geraldine Munshi, Nikhil C. Tassone, Pierfrancesco Marto, Jarrod A. Anderson, Kenneth C. Carrasco, Ruben D. TI The Cyclophilin A-CD 147 complex promotes the proliferation and homing of multiple myeloma cells SO NATURE MEDICINE LA English DT Article ID MARROW ENDOTHELIAL-CELLS; MICROENVIRONMENT; CD147; MECHANISMS; CANCER; ANGIOGENESIS; PATHOGENESIS; EXPRESSION; DISEASE; CATENIN AB B cell malignancies frequently colonize the bone marrow. The mechanisms responsible for this preferential homing are incompletely understood. Here we studied multiple myeloma (MM) as a model of a terminally differentiated B cell malignancy that selectively colonizes the bone marrow. We found that extracellular CyPA (eCyPA), secreted by bone marrow endothelial cells (BMECs), promoted the colonization and proliferation of MM cells in an in vivo scaffold system via binding to its receptor, CD147, on MM cells. The expression and secretion of eCyPA by BMECs was enhanced by BCL9, a Wnt-beta-catenin transcriptional coactivator that is selectively expressed by these cells. eCyPA levels were higher in bone marrow serum than in peripheral blood in individuals with MM, and eCyPA-CD147 blockade suppressed MM colonization and tumor growth in the in vivo scaffold system. eCyPA also promoted the migration of chronic lymphocytic leukemia and lymphoplasmacytic lymphoma cells, two other B cell malignancies that colonize the bone marrow and express CD147. These findings suggest that eCyPA-CD147 signaling promotes the bone marrow homing of B cell malignancies and offer a compelling rationale for exploring this axis as a therapeutic target for these malignancies. C1 [Zhu, Di; Wang, Zhongqiu; Zhao, Jian-Jun; Meng, Jiang; Hideshima, Teru; Fulciniti, Mariateresa; Kang, Yue; Tai, Yu-Tzu; Hunter, Zachary; McMilin, Douglas; Mitsiades, Constantine S.; Wu, Catherine J.; Treon, Steven P.; Munshi, Nikhil C.; Anderson, Kenneth C.; Carrasco, Ruben D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wang, Zhongqiu] Southern Med Univ, Nanfang Hosp, Guangdong Prov Key Lab Gastroenterol, Guangzhou, Guangdong, Peoples R China. [Calimeri, Teresa; Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy. [Calimeri, Teresa; Tassone, Pierfrancesco] Ctr Canc, Catanzaro, Italy. [Meng, Jiang] Harbin Med Univ, Affiliated Hosp 4, Harbin, Heilongjiang, Peoples R China. [Hideshima, Teru; Fulciniti, Mariateresa; Tai, Yu-Tzu; McMilin, Douglas; Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Kang, Yue] Chinese Acad Sci, Inst Biophys, Beijing 100080, Peoples R China. [Ficarro, Scott B.; Tong, Haoxuan; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ficarro, Scott B.; Tong, Haoxuan; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Dorfman, David M.; Pinkus, Geraldine; Carrasco, Ruben D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Carrasco, RD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ruben_carrasco@dfci.harvard.edu OI Hunter, Zachary/0000-0002-1689-1691 FU Multiple Myeloma Research Foundation; Doctors Cancer Foundation; National Institutes of Health [1R01 CA151391-01, 1P01 CA155258-01] FX R.D.C. is supported by a senior award from the Multiple Myeloma Research Foundation, by the Doctors Cancer Foundation, and by grants 1R01 CA151391-01 and 1P01 CA155258-01 from the National Institutes of Health. Human bone marrow-derived endothelial cell lines BMEC-60 and BMEC-1 were kindly provided by Dr. van der Schoot (University of Amsterdam, Amsterdam, the Netherlands) and Dr. Giuliani (University of Parma, Parma, Italy), respectively. NR 37 TC 11 Z9 14 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUN PY 2015 VL 21 IS 6 BP 572 EP 580 DI 10.1038/nm.3867 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CJ8UF UT WOS:000355778300013 PM 26005854 ER PT J AU Schiffer, M Teng, BN Gu, C Shchedrina, VA Kasaikina, M Pham, VA Hanke, N Rong, S Gueler, F Schroder, P Tossidou, I Park, JK Staggs, L Haller, H Erschow, S Hilfiker-Kleiner, D Wei, CL Chen, C Tardi, N Hakroush, S Selig, MK Vasilyev, A Merscher, S Reiser, J Sever, S AF Schiffer, Mario Teng, Beina Gu, Changkyu Shchedrina, Valentina A. Kasaikina, Marina Pham, Vincent A. Hanke, Nils Rong, Song Gueler, Faikah Schroder, Patricia Tossidou, Irini Park, Joon-Keun Staggs, Lynne Haller, Hermann Erschow, Sergej Hilfiker-Kleiner, Denise Wei, Changli Chen, Chuang Tardi, Nicholas Hakroush, Samy Selig, Martin K. Vasilyev, Aleksandr Merscher, Sandra Reiser, Jochen Sever, Sanja TI Pharmacological targeting of actin-dependent dynamin oligomerization ameliorates chronic kidney disease in diverse animal models SO NATURE MEDICINE LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CLATHRIN-MEDIATED ENDOCYTOSIS; KINASE-C-EPSILON; GTPASE ACTIVITY; SLIT DIAPHRAGM; GLOMERULAR BARRIER; PODOCYTE BIOLOGY; IN-VIVO; CYTOSKELETON; PROTEINURIA AB Dysregulation of the actin cytoskeleton in podocytes represents a common pathway in the pathogenesis of proteinuria across a spectrum of chronic kidney diseases (CKD). The GTPase dynamin has been implicated in the maintenance of cellular architecture in podocytes through its direct interaction with actin. Furthermore, the propensity of dynamin to oligomerize into higher-order structures in an actin-dependent manner and to cross-link actin microfilaments into higher-order structures has been correlated with increased actin polymerization and global organization of the actin cytoskeleton in the cell. We found that use of the small molecule Bis-T-23, which promotes actin-dependent dynamin oligomerization and thus increased actin polymerization in injured podocytes, was sufficient to improve renal health in diverse models of both transient kidney disease and CKD. In particular, administration of Bis-T-23 in these renal disease models restored the normal ultrastructure of podocyte foot processes, lowered proteinuria, lowered collagen IV deposits in the mesangial matrix, diminished mesangial matrix expansion and extended lifespan. These results further establish that alterations in the actin cytoskeleton of kidney podocytes is a common hallmark of CKD, while also underscoring the substantial regenerative potential of injured glomeruli and identifying the oligomerization cycle of dynamin as an attractive potential therapeutic target to treat CKD. C1 [Schiffer, Mario; Teng, Beina; Hanke, Nils; Rong, Song; Gueler, Faikah; Schroder, Patricia; Tossidou, Irini; Park, Joon-Keun; Staggs, Lynne; Haller, Hermann] Hannover Med Sch, Dept Nephrol, Hannover, Germany. [Schiffer, Mario; Schroder, Patricia; Staggs, Lynne; Haller, Hermann] Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. [Gu, Changkyu; Shchedrina, Valentina A.; Kasaikina, Marina; Pham, Vincent A.; Sever, Sanja] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Gu, Changkyu; Shchedrina, Valentina A.; Kasaikina, Marina; Pham, Vincent A.; Sever, Sanja] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Erschow, Sergej; Hilfiker-Kleiner, Denise] Hannover Med Sch, Dept Cardiol, Hannover, Germany. [Wei, Changli; Chen, Chuang; Tardi, Nicholas; Reiser, Jochen] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. [Hakroush, Samy] Univ Med Ctr Gottingen, Dept Pathol, Gottingen, Germany. [Selig, Martin K.] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA USA. [Vasilyev, Aleksandr] NYIT, COM, Dept Biomed Sci, Old Westbury, NY USA. [Merscher, Sandra] Leonard M Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL USA. RP Sever, S (reprint author), Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. EM schiffer.mario@mh-hannover.de; ssever@partners.org RI Pham, Vincent/M-5351-2013; OI Pham, Vincent/0000-0001-7083-9360; Schiffer, Mario/0000-0002-8414-1470 FU National Institutes of Health [R01 DK093773, DK087985]; NephCure Foundation; Deutsche Forschungsgemeinschaft [SCHI587/3, SCHI587/4, SCHI587/6, REBIRTH 2]; Mount Desert Island Biological Laboratory FX This work was supported by the National Institutes of Health (R01 DK093773 and DK087985 to S.S.), the NephCure Foundation (S.S.), and Deutsche Forschungsgemeinschaft (SCHI587/3, 4,6 to M.S. and REBIRTH 2 to D.H.-K. and S.E.). N.H. is the recipient of the New Investigator Award from Mount Desert Island Biological Laboratory. The DNA encoding genes for PKC epsilon and mutant with impaired kinase activity were gifts from J.-W Soh, Inha University, Incheon, South Korea. Immortalized podocytes from ACTN4 mice, ACTN4 mice and morpholino to downregulate inf2 were gifts from M. Pollak, Beth Israel Deaconess Medical Center, Boston, MA. Tg (L-FABP:DBP-EGFP) and Tg (1-fabp:DBP-EGFP) zebrafish were gifts from J. Xie and B. Anand-Apte, Cleveland Clinic, Cleveland, OH. PKC epsilonKO mice were gifts from M. Leitges, University of Oslo, Oslo, Norway. CD2APKO mice were gifts from A. Shaw, Washington University, St. Louis, MO. NR 49 TC 15 Z9 17 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUN PY 2015 VL 21 IS 6 BP 601 EP 609 DI 10.1038/nm.3843 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CJ8UF UT WOS:000355778300016 PM 25962121 ER PT J AU Zhang, S Hu, YM Huang, YW Xu, HM Wu, GX Dai, HB AF Zhang, Sai Hu, Yangmin Huang, Yuwen Xu, Huimin Wu, Gongxiong Dai, Haibin TI Heat shock protein 27 promotes cell proliferation through activator protein-1 in lung Cancer SO ONCOLOGY LETTERS LA English DT Article DE lung cancer; proliferation; heat shock protein 27; activator protein-1; c-Jun ID BREAST-CANCER; EXPRESSION; HSP27; CARCINOMA; CHEMOTHERAPY; METASTASIS; PROGNOSIS; PREDICTS; SURVIVAL; STRESS AB Heat shock protein 27 (HSP27) is an important regulator involved in the development of lung cancer. However, limited evidence exists concerning the underlying molecular mechanisms of its action. The results of the present study revealed that HSP27 was highly expressed in the lung cancer tissues of mice. In an in vitro model,the overexpression of HSP27 promoted cell proliferation, while H5P27 knockdown inhibited cell proliferation. HSP27 promoted cell proliferation in vitro by directly upregulating the expression of HSP27 target genes, which required the activation of the activator protein-1 (AP-1) signaling pathway. This was evaluated by the phosphorylation status of an important pathway component, c-Jun in lung cancer tissue and cells. These results suggested that HSP27 has a promotional role in lung cancer, and therefore indicated a novel mechanism involving lung cancer cell proliferation, which may underlie poor responses to therapy. Therefore, HSP27 may be a suitable therapeutic target for the treatment of lung cancer. C1 [Zhang, Sai] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Thorac Surg, Hangzhou 310009, Zhejiang, Peoples R China. [Hu, Yangmin; Huang, Yuwen; Xu, Huimin; Dai, Haibin] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Pharm, Hangzhou 310009, Zhejiang, Peoples R China. [Wu, Gongxiong] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Dai, HB (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Pharm, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China. EM haibindai@zju.edu.cn OI Dai, Haibin/0000-0002-5768-2714 FU National Natural Science Foundation of China [81173040, 81373391, 81302747]; Health Bureau of Zhejiang Province [2011KYA065, 2012RCA027]; Zhejiang Province Traditional Chinese Medicine Foundation of China [2011ZZ009, 2012ZB091]; Foundation of Science and Technology Department of Zhejiang Province [2014C33185] FX This study was supported by grants from the National Natural Science Foundation of China (nos. 81173040, 81373391 and 81302747), the Foundation from the Health Bureau of Zhejiang Province (nos. 2011KYA065 and 2012RCA027), the Zhejiang Province Traditional Chinese Medicine Foundation of China (nos. 2011ZZ009 and 2012ZB091) and the Foundation of Science and Technology Department of Zhejiang Province (no. 2014C33185). NR 33 TC 2 Z9 3 U1 1 U2 4 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD JUN PY 2015 VL 9 IS 6 BP 2572 EP 2576 DI 10.3892/ol.2015.3073 PG 5 WC Oncology SC Oncology GA CJ4ZS UT WOS:000355497800023 ER PT J AU Simis, M Reidler, JS Macea, DD Duarte, IM Wang, XE Lenkinski, R Petrozza, JC Fregni, F AF Simis, Marcel Reidler, Jay S. Macea, Debora Duarte Duarte, Ingrid Moreno Wang, Xiaoen Lenkinski, Robert Petrozza, John C. Fregni, Felipe TI Investigation of Central Nervous System Dysfunction in Chronic Pelvic Pain Using Magnetic Resonance Spectroscopy and Noninvasive Brain Stimulation SO PAIN PRACTICE LA English DT Article DE chronic pelvic pain; brain stimulation; transcranial direct current stimulation; tDCS; magnetic resonance spectroscopy ID POSITRON-EMISSION-TOMOGRAPHY; TRANSCRANIAL DC STIMULATION; MOTOR CORTEX STIMULATION; SPINAL-CORD-INJURY; ELECTRICAL-STIMULATION; N-ACETYLASPARTATE; NEURONAL-ACTIVITY; NEUROPATHIC PAIN; BACK-PAIN; FIBROMYALGIA AB BackgroundRecent studies demonstrate that chronic pelvic pain is associated with altered afferent sensory input resulting in maladaptive changes in the neural circuitry of pain. To better understand the central changes associated with chronic pelvic pain, we investigated the contributions of critical pain-related neural circuits using single-voxel proton magnetic resonance spectroscopy (MRS) and transcranial direct current stimulation (tDCS). MethodsWe measured concentrations of neural metabolites in 4 regions of interest (thalamus, anterior cingulate cortex, primary motor, and occipital cortex [control]) at baseline and after 10days of active or sham tDCS in patients with chronic pelvic pain. We then compared our results to those observed in healthy controls, matched by age and gender. ResultsWe observed a significant increase in pain thresholds after active tDCS compared with sham conditions. There was a correlation between metabolite concentrations at baseline and quantitative sensory assessments. Chronic pelvic pain patients had significantly lower levels of NAA/Cr in the primary motor cortex compared with healthy patients. ConclusionstDCS increases pain thresholds in patients with chronic pelvic pain. Biochemical changes in pain-related neural circuits are associated with pain levels as measured by objective pain testing. These findings support the further investigation of targeted cortical neuromodulatory interventions for chronic pelvic pain. C1 [Simis, Marcel; Reidler, Jay S.; Macea, Debora Duarte; Duarte, Ingrid Moreno; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat, Boston, MA USA. [Simis, Marcel] Santa Casa Sao Paulo Med Sch, Div Neurol, Sao Paulo, SP, Brazil. [Simis, Marcel] Univ Sao Paulo, Inst Phys Med & Rehabil, Clin Hosp, Sch Med, BR-05508 Sao Paulo, Brazil. [Wang, Xiaoen; Lenkinski, Robert] Harvard Univ, Sch Med, Dept Radiol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Petrozza, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gynecol, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. RP Fregni, F (reprint author), Spaulding Rehabil Hosp 7, Lab Neuromodulat, 9-96 13th St, Charlestown, MA 02129 USA. EM ffregni@bidmc.harvard.edu OI Reidler, Jay/0000-0002-9615-5351; Lenkinski, Robert/0000-0001-7371-5048 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) - National Institutes of Health [R21 7R21DK081773]; CAPES [9722/11-4] FX This study was funded by a Grant Number R21 7R21DK081773 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) - National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIDDK. Marcel Simis was funding by CAPES (9722/11-4). The authors report no conflict of interests. Authors are grateful to Normando Guedes and Luisa Mello Barreto for assistance with database analysis and Joao Daud Amadera for assistance with data collection. NR 39 TC 3 Z9 3 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1530-7085 EI 1533-2500 J9 PAIN PRACT JI Pain Pract. PD JUN PY 2015 VL 15 IS 5 BP 423 EP 432 DI 10.1111/papr.12202 PG 10 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CJ8BQ UT WOS:000355724500007 PM 24799153 ER PT J AU Baumer, FM Song, JW Mitchell, PD Pienaar, R Sahin, M Grant, PE Takahashi, E AF Baumer, Fiona M. Song, Jae W. Mitchell, Paul D. Pienaar, Rudolph Sahin, Mustafa Grant, P. Ellen Takahashi, Emi TI Longitudinal Changes in Diffusion Properties in White Matter Pathways of Children With Tuberous Sclerosis Complex SO PEDIATRIC NEUROLOGY LA English DT Article DE tuberous sclerosis complex; white matter; development; human; diffusion imaging; tractography; epilepsy; gender ID AUTISM SPECTRUM DISORDERS; CONSENSUS CONFERENCE; DIAGNOSTIC-CRITERIA; AGES 12; TRACTOGRAPHY; CONNECTIVITY; EPILEPSY; BRAIN; ADOLESCENTS; ARCHITECTURE AB BACKGROUND: Abnormal white matter development in patients with tuberous sclerosis complex, a multisystem hamartomatous disorder caused by aberrant neural proliferation and axonal maturation, may be associated with poorer neurocognitive outcomes. The purpose of this study is to identify predictors of longitudinal changes in diffusion properties of white matter tracts in patients with tuberous sclerosis complex. METHODS: Diffusion magnetic resonance imaging was carried out in 17 subjects with tuberous sclerosis complex (mean age, 7.2 +/- 4.4 years) with at least two magnetic resonance imaging scans (mean number of days between scans, 419.4 +/- 105.4). There were 10 males; 5 of 17 had autism spectrum disorder and 10 of 17 had epilepsy. Regions of interest were placed to delineate the internal capsule/corona radiata, cingulum, and corpus callosum. The outcomes were mean change in apparent diffusion coefficient and fractional anisotropy. Data were analyzed using Pearson's correlation and multiple linear regression analyses. RESULTS: Gender was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule, right and left cingulum bundles, and corpus callosum and a significant predictor of mean change in fractional anisotropy in the corpus callosum. Epilepsy was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule. Autism spectrum disorder was not predictive of diffusion changes in any of the studied pathways. CONCLUSION: Clinical variables, including gender and epilepsy, have an effect on the development of white matter pathways. These variables should be taken into consideration when counseling tuberous sclerosis complex patients and in future imaging studies in this population. C1 [Baumer, Fiona M.; Sahin, Mustafa] Harvard Univ, Sch Med, Dept Neurol, Boston Childrens Hosp, Boston, MA 02115 USA. [Song, Jae W.; Grant, P. Ellen; Takahashi, Emi] Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Boston Childrens Hosp, Boston, MA USA. [Mitchell, Paul D.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA 02115 USA. [Pienaar, Rudolph; Grant, P. Ellen] Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, Boston, MA 02115 USA. [Pienaar, Rudolph; Grant, P. Ellen; Takahashi, Emi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Pienaar, Rudolph; Grant, P. Ellen; Takahashi, Emi] Harvard Univ, Sch Med, Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. RP Takahashi, E (reprint author), Boston Childrens Hosp, Div Newborn Med, 1 Autumn St 456, Boston, MA 02115 USA. EM Fiona.Baumer@childrens.harvard.edu; emi.takahashioki@childrens.harvard.edu OI SAHIN, MUSTAFA/0000-0001-7044-2953 FU NIH [U01NS082320, U54 NS092090-01, P30HD018655, R01HD078561, R21HD069001]; BCH Translational Research Program FX MS was supported by NIH U01NS082320, U54 NS092090-01, P30HD018655 and BCH Translational Research Program, and ET was supported by NIH R01HD078561 and R21HD069001. Keh-Li Sheng provided technical assistance. NR 49 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 EI 1873-5150 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD JUN PY 2015 VL 52 IS 6 BP 615 EP 623 DI 10.1016/j.pediatrneurol.2015.02.004 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA CJ5ZJ UT WOS:000355572500007 PM 25817702 ER PT J AU Narayanan, S Shailam, R Grottkau, BE Nimkin, K AF Narayanan, Srikala Shailam, Randheer Grottkau, Brian E. Nimkin, Katherine TI Fishtail deformity - a delayed complication of distal humeral fractures in children SO PEDIATRIC RADIOLOGY LA English DT Article DE Fishtail deformity; Trochlea; Avascular necrosis; Magnetic resonance imaging; Distal humeral fracture; Radiography; Children ID OSTEOCHONDRITIS-DISSECANS; TROCHLEA; CHILDHOOD AB Concavity in the central portion of the distal humerus is referred to as fishtail deformity. This entity is a rare complication of distal humeral fractures in children. The purpose of this study is to describe imaging features of post-traumatic fishtail deformity and discuss the pathophysiology. We conducted a retrospective analysis of seven cases of fishtail deformity after distal humeral fractures. Seven children ages 7-14 years (five boys, two girls) presented with elbow pain and history of distal humeral fracture. Four of the seven children had limited range of motion. Five children had prior grade 3 supracondylar fracture treated with closed reduction and percutaneous pinning. One child had a medial condylar fracture and another had a lateral condylar fracture; both had been treated with conservative casting. All children had radiographs, five had CT and three had MRI. All children had a concave central defect in the distal humerus. Other imaging features included joint space narrowing with osteophytes and subchondral cystic changes in four children, synovitis in one, hypertrophy or subluxation of the radial head in three and proximal migration of the ulna in two. Fishtail deformity of the distal humerus is a rare complication of distal humeral fractures in children. This entity is infrequently reported in the radiology literature. Awareness of the classic imaging features can result in earlier diagnosis and appropriate treatment. C1 [Narayanan, Srikala; Shailam, Randheer; Nimkin, Katherine] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Imaging, Boston, MA 02114 USA. [Grottkau, Brian E.] Massachusetts Gen Hosp, Dept Orthopaed, Pediat Orthopaed, Boston, MA 02114 USA. RP Nimkin, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Pediat Imaging, 55 Fruit St, Boston, MA 02114 USA. EM knimkin@partners.org NR 19 TC 1 Z9 1 U1 0 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 JUN PY 2015 VL 45 IS 6 BP 814 EP 819 DI 10.1007/s00247-014-3249-9 PG 6 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA CJ2WQ UT WOS:000355345800005 PM 25527301 ER PT J AU Sagar, P Nimkin, K AF Sagar, Pallavi Nimkin, Katherine TI Reply to Dr. Miquel regarding velopharyngeal closure with real-time MRI SO PEDIATRIC RADIOLOGY LA English DT Letter C1 [Sagar, Pallavi; Nimkin, Katherine] Massachusetts Gen Hosp, Dept Imaging, Div Pediat Imaging, Boston, MA 02114 USA. RP Sagar, P (reprint author), Massachusetts Gen Hosp, Dept Imaging, Div Pediat Imaging, 34 Fruit St,Ellison 237, Boston, MA 02114 USA. EM psagar@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2015 VL 45 IS 6 BP 943 EP 943 DI 10.1007/s00247-014-3265-9 PG 1 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA CJ2WQ UT WOS:000355345800023 PM 25631162 ER PT J AU Kulik, A Bykov, K Choudhry, NK Bateman, BT AF Kulik, Alexander Bykov, Katsiaryna Choudhry, Niteesh K. Bateman, Brian T. TI Non-steroidal anti-inflammatory drug administration after coronary artery bypass surgery: utilization persists despite the boxed warning SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE analgesia; postoperative care; pain; coronary artery bypass graft (CABG); pharmacoepidemiology ID CARDIAC-SURGERY; GRAFT-SURGERY; INHIBITORS PARECOXIB; COX-2 INHIBITORS; KETOROLAC; PAIN; SAFETY; VALDECOXIB; ANALGESIA; DISEASE AB PurposeIn 2005, the US Food and Drug Administration (FDA) issued a boxed warning against the administration of non-steroidal anti-inflammatory drugs (NSAIDs) after coronary artery bypass graft (CABG) surgery because of cardiovascular safety concerns. We assessed utilization rates before and after the advisory and evaluated predictors of NSAID administration following CABG. MethodsWe assembled a cohort of 277576 patients who underwent CABG from 2004 to 2010. Temporal trends in NSAID exposure were evaluated, and predictors of postoperative NSAID use were identified using generalized estimating equations. ResultsOver the study period, 92938 CABG patients (33.5%) received NSAIDs following surgery. The frequency of NSAID administration declined steadily over time, from a peak of 38.9% in 2004 to a low of 29.0% in 2010 (p<0.0007). Ketorolac was the most frequent NSAID prescribed, commonly on the first postoperative day. Surgery performed after the boxed warning was independently associated with a 20% lower odds of NSAID administration [odds ratio (OR): 0.80; p=0.0003]. Other factors that predicted a lower odds of NSAID use following surgery included a history of renal disease (OR: 0.33; p<0.0001) and liver disease (OR: 0.66; p<0.0001), and the need for concurrent valve surgery (OR: 0.78; p<0.0001). A mammary graft at the time of surgery increased the odds of NSAID administration (OR: 1.23; p<0.0001). ConclusionsThe frequency of NSAID administration after CABG has declined since the FDA advisory, yet many patients continue to receive them in recent years. Our data highlight the need for future research initiatives to further define the risks associated with NSAID use in this population. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Kulik, Alexander; Bykov, Katsiaryna; Choudhry, Niteesh K.; Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA. [Kulik, Alexander] Florida Atlantic Univ, Lynn Heart & Vasc Inst, Boca Raton Reg Hosp, Boca Raton, FL 33431 USA. [Kulik, Alexander] Florida Atlantic Univ, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Kulik, A (reprint author), Boca Raton Reg Hosp, Lynn Heart & Vasc Inst, 801 Meadows Rd,Suite 104, Boca Raton, FL 33486 USA. EM alex_kulik@yahoo.com NR 21 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUN PY 2015 VL 24 IS 6 BP 647 EP 653 DI 10.1002/pds.3788 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA CK0CV UT WOS:000355872900011 PM 25907164 ER PT J AU Kudva, IT Krastins, B Torres, AG Griffin, RW Sheng, HQ Sarracino, DA Hovde, CJ Calderwood, SB John, M AF Kudva, Indira T. Krastins, Bryan Torres, Alfredo G. Griffin, Robert W. Sheng, Haiqing Sarracino, David A. Hovde, Carolyn J. Calderwood, Stephen B. John, Manohar TI The Escherichia coli O157:H7 cattle immunoproteome includes outer membrane protein A (OmpA), a modulator of adherence to bovine rectoanal junction squamous epithelial (RSE) cells SO PROTEOMICS LA English DT Article DE Cattle; GeLC-MS; MS; Immunoproteome; Norepinephrine; O157 ID III SECRETED PROTEINS; O157-H7 ADHERENCE; VIRULENCE FACTORS; TERMINAL RECTUM; STRESS-RESPONSE; FEEDLOT CATTLE; SHIGA TOXIN; BEEF-CATTLE; INFECTION; COLONIZATION AB Building on previous studies, we defined the repertoire of proteins comprising the immunoproteome (IP) of Escherichia coli O157:H7 (O157) cultured in DMEM supplemented with norepinephrine (O157 IP), a -adrenergic hormone that regulates E. coli O157 gene expression in the gastrointestinal tract, using a variation of a novel proteomics-based platform proteome mining tool for antigen discovery, called proteomics-based expression library screening (PELS; Kudva etal., 2006). The E. coli O157 IP (O157-IP) comprised 91 proteins, and included those identified previously using proteomics-based expression library screening, and also proteins comprising DMEM and bovine rumen fluid proteomes. Outer membrane protein A (OmpA), a common component of the above proteomes, and reportedly a contributor to E. coli O157 adherence to cultured HEp-2 epithelial cells, was interestingly found to be a modulator rather than a contributor to E. coli O157 adherence to bovine rectoanal junction squamous epithelial cells. Our results point to a role for yet to be identified members of the O157-IP in E. coli O157 adherence to rectoanal junction squamous epithelial cells, and additionally implicate a possible role for the outer membrane protein A regulator, TdcA, in the expression of such adhesins. Our observations have implications for the development of efficacious vaccines for preventing E. coli O157 colonization of the bovine gastrointestinal tract. C1 [Kudva, Indira T.] ARS, Food Safety & Enter Pathogens Res Unit, Natl Anim Dis Ctr, USDA, Ames, IA 50010 USA. [Krastins, Bryan; Sarracino, David A.] Harvard Partners Ctr Genet & Genom, Cambridge, MA USA. [Torres, Alfredo G.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Torres, Alfredo G.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Griffin, Robert W.; Calderwood, Stephen B.; John, Manohar] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Sheng, Haiqing; Hovde, Carolyn J.] Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83843 USA. [Calderwood, Stephen B.; John, Manohar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.; John, Manohar] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Kudva, IT (reprint author), ARS, Food Safety & Enter Pathogens Res Unit, Natl Anim Dis Ctr, USDA, Ames, IA 50010 USA. EM Indira.Kudva@ars.usda.gov FU US National Institutes of Health (NIH) [R21 AI055963]; National Research Initiative of the US Department of Agriculture Cooperative State Research, Education and Extension Service [99-35201-8539, 04-04562]; US NIH [NO1-HD-0-3309, U54-AI-57141, P20-RR16454, P20-RR15587, P20-GM103408] FX US National Institutes of Health (NIH) grants R21 AI055963 to I.T.K supported part of this work. Excellent technical assistance provided by Bryan Wheeler at the National Animal Disease Center (NADC), Ames, Iowa, with the eukaryotic cell adherence/adherence-inhibition assays is acknowledged. The Animal Resource Unit personnel at NADC, especially Dr. Rebecca Madison and Denise Chapman, are gratefully acknowledged for assisting with the collection of the bovine rectoanal junction tissues and swabs. C.J.H was supported in part by the National Research Initiative of the US Department of Agriculture Cooperative State Research, Education and Extension Service grants 99-35201-8539 and 04-04562 and US NIH grants NO1-HD-0-3309, U54-AI-57141, P20-RR16454, P20-RR15587, and P20-GM103408 NR 61 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1615-9853 EI 1615-9861 J9 PROTEOMICS JI Proteomics PD JUN PY 2015 VL 15 IS 11 BP 1829 EP 1842 DI 10.1002/pmic.201400432 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CJ8CR UT WOS:000355727400010 PM 25643951 ER PT J AU Umezawa, S Fujisawa, D Fujimori, M Ogawa, A Matsushima, E Miyashita, M AF Umezawa, Shino Fujisawa, Daisuke Fujimori, Maiko Ogawa, Asao Matsushima, Eisuke Miyashita, Mitsunori TI Prevalence, associated factors and source of support concerning supportive care needs among Japanese cancer survivors SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; cancer survivor; supportive care needs; source of support ID BREAST-CANCER; LUNG-CANCER; VERSION; HEALTH; TRENDS AB BackgroundThe current study aimed to describe cancer survivors' supportive care needs in Japan, to identify associated factors of unmet needs, and to describe the source of support that are preferred and actually used by cancer survivors. MethodsUsing a web-based questionnaire, we examined unmet supportive needs and its associated factors among 628 adult Japanese cancer survivors. The questionnaire comprised 16 items representing five domains (medical-psychological, financial, social-spiritual, sexual, and physical needs). ResultsPrevalence of unmet need ranged from 5 to 18%, depending on different domains. The prevalence was high in medical-psychological and financial domains and relatively low in physical and sexual domains. Poor performance status, psychiatric morbidity and low income status were associated with unmet needs of most domains. Most cancer survivors preferred and actually sought support from their family and friends. Financial needs were preferred to be provided by non-medical professionals. Call for peer support was intense, especially for medical-psychological, social-spiritual, and sexual needs; however, peer support was not well-provided. ConclusionsThis study illustrated characteristics of Japanese cancer survivors who are likely to have unmet needs. The study demonstrated need for expanded involvement of non-medical professionals and peer support, especially in the domains of medical-psychological, social-spiritual, financial and sexual needs. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Umezawa, Shino; Fujisawa, Daisuke; Fujimori, Maiko; Ogawa, Asao] Natl Canc Ctr Hosp East, Psychooncol Div, Kashiwa, Chiba 2778577, Japan. [Umezawa, Shino; Matsushima, Eisuke] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Div Comprehens Patient Care, Sect Liaison Psychiat & Palliat Med, Tokyo, Japan. [Fujisawa, Daisuke] Massachusetts Gen Hosp, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Fujisawa, Daisuke] Keio Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan. [Fujimori, Maiko] Natl Ctr Neurol Psychiat, Ctr Suicide Prevent, Natl Inst Mental Hlth, Tokyo, Japan. [Miyashita, Mitsunori] Tohoku Univ, Grad Sch Med, Div Palliat Nursing, Hlth Sci, Sendai, Miyagi 980, Japan. RP Fujisawa, D (reprint author), Natl Canc Ctr Hosp East, Psychooncol Div, 6-5-1 Kashiwanoha, Kashiwa, Chiba 2778577, Japan. EM dai_fujisawa@yahoo.co.jp RI Nolasco, Arlette/D-9885-2016 FU Japanese Ministry of Health Labor and Welfare [H22-005] FX The authors thank Professor Yosuke Uchitomi (Okayama University) and Justin Eusebio (Massachusetts General Hospital) for their helpful comments. This work was supported by the Grant-in-Aid from Japanese Ministry of Health Labor and Welfare [grant number H22-005]. NR 39 TC 2 Z9 2 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUN PY 2015 VL 24 IS 6 BP 635 EP 642 DI 10.1002/pon.3702 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CK1HN UT WOS:000355958000003 PM 25286187 ER PT J AU Baca, CB Vickrey, BG Vassar, S Berg, AT AF Baca, Christine B. Vickrey, Barbara G. Vassar, Stefanie Berg, Anne T. TI Disease-targeted versus generic measurement of health-related quality of life in epilepsy SO QUALITY OF LIFE RESEARCH LA English DT Article DE Epilepsy; Quality of Life in Epilepsy Inventory (QOLIE-89); SF-36; Disease targeted; Generic; Sibling control ID ADULTS; POPULATION; CHILDHOOD; INSTRUMENTS; PREDICTORS; CHILDREN; SURGERY; PEOPLE; SF-36; TIME AB To assess (1) whether the generic Short Form (SF)-36, an integrated component of the epilepsy-targeted Quality of Life in Epilepsy Inventory-89 (QOLIE-89), is able to detect differences in the health-related quality of life (HRQOL) between young adults with epilepsy and healthy sibling controls and (2) whether the generic components are as sensitive to within-disease symptom severity as the epilepsy-targeted components of the QOLIE-89 in young adults with epilepsy. A cohort of young adults with epilepsy (N = 108, age 21.6 years SD = 3.8), followed since diagnosis in a prospective community-based study of childhood-onset epilepsy, completed the QOLIE-89, an epilepsy-targeted HRQOL instrument that includes within it a generic core measure (SF-36). Sibling controls (N = 82, age = 20.7 years, SD = 2.1) completed the generic core, SF-36. Age- and gender-adjusted QOLIE-89 epilepsy-targeted and cognitive-distress composite scores and the overall score were strongly associated with seizure-free duration: seizure-free a parts per thousand yen5 years (higher HRQOL), n = 57; seizure-free 1-5 years, n = 22; or seizure-free < 1 year, n = 29 (lower HRQOL) (p < 0.001). However, on QOLIE-89 physical health and mental health composite scores, there were no differences across these seizure-free duration groups. For cases compared with sibling controls, there were no differences on SF-36 physical and mental health composite scores or the global composite score, using either classical test or item-response theory scoring procedures. While the epilepsy-targeted components of the QOLIE-89 are sensitive to seizure-related factors in young adults with epilepsy, the SF-36 generic core measures are not, thereby limiting HRQOL comparisons between young adults with epilepsy and sibling controls. C1 [Baca, Christine B.; Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Baca, Christine B.; Vickrey, Barbara G.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. [Vassar, Stefanie] Univ Calif Los Angeles, Dept Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. [Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Northwestern Mem Feinberg Sch Med, Epilepsy Ctr, Dept Pediat, Chicago, IL 60611 USA. RP Baca, CB (reprint author), Univ Calif Los Angeles, Dept Neurol, Box 951769,C-239 RNRC, Los Angeles, CA 90024 USA. EM cbower@mednet.ucla.edu FU National Institutes of Health [NINDS R37-NS31146]; NINDS; US Veterans Administration Health Services Research and Development Service; American Heart Association; UniHealth Foundation; UCLA Clinical and Translational Institute Catalyst Award [NIH/NCATS/ULITR000124]; Pediatric Epilepsy Research Foundation; [NINDS-R37-NS31146]; [NINDS R37 NS31146] FX This study is supported by a Grant from the National Institutes of Health, NINDS R37-NS31146 (PI-Berg). Dr. Baca receives support from Grant NINDS-R37-NS31146. Dr. Vickrey receives support from Grant NINDS R37 NS31146. She serves on the scientific advisory boards for the Sports Concussion Institute and is a section editor for Stroke, receives research support from NINDS, the US Veterans Administration Health Services Research and Development Service, the American Heart Association; and UniHealth Foundation, and she is a consultant to EMD Serono Canada and Genentech. Dr. Vassar received support from Grant NINDS R37 NS31146. She receives support from UCLA Clinical and Translational Institute Catalyst Award (NIH/NCATS/ULITR000124) Dr. Berg receives support from Grant NINDS-R37-NS31146 and Grant funds from the Pediatric Epilepsy Research Foundation. She serves on the Editorial Boards of Epileptic Disorders, Epilepsy and Behavior and Neurology. NR 33 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD JUN PY 2015 VL 24 IS 6 BP 1379 EP 1387 DI 10.1007/s11136-014-0867-5 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CJ9KU UT WOS:000355822000008 PM 25413780 ER PT J AU Marra, KV Wagley, S Omar, A Kinoshita, T Kovacs, KD Silva, P Kuperwaser, MC Arroyo, JG AF Marra, Kyle V. Wagley, Sushant Omar, Ahmed Kinoshita, Taiga Kovacs, Kyle D. Silva, Paolo Kuperwaser, Mark C. Arroyo, Jorge G. TI CASE-MATCHED COMPARISON OF VITRECTOMY, PERIPHERAL RETINAL ENDOLASER, AND ENDOCYCLOPHOTOCOAGULATION VERSUS STANDARD CARE IN NEOVASCULAR GLAUCOMA SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID DIODE-LASER CYCLOPHOTOCOAGULATION; BEVACIZUMAB AVASTIN INJECTION; RUBEOSIS IRIDIS; ENDOSCOPIC CYCLOPHOTOCOAGULATION; INTRAVITREAL BEVACIZUMAB; REFRACTORY GLAUCOMAS; IMPLANT; PHOTOCOAGULATION; ABLATION; EFFICACY AB Purpose: To evaluate the efficacy of combination pars plana vitrectomy, endoscopic peripheral panretinal photocoagulation, and endocyclophotocoagulation (ECP) as compared with standard care in patients with neovascular glaucoma. Methods: This age-matched case-controlled retrospective series of 54 eyes compared the clinical outcomes between a consecutive series of combination pars plana vitrectomy/panretinal photocoagulation/ECP (n = 27) versus the current standard of care (n = 27) for patients with neovascular glaucoma. "Standard" treatments for patients with neovascular glaucoma include panretinal photocoagulation, intravitreal bevacizumab, filtration surgery, pars plana vitrectomy, and Ahmed valve placement. Results: After 1 year, mean intraocular pressure reduced from 40.7 +/- 12.40 mmHg preoperatively to 12.3 +/- 4.84 mmHg (P < 0.001) in the ECP group and from 34.7 +/- 12.38 mmHg to 23.2 +/- 12.34 mmHg in the control group (P = 0.002). Compared with controls, the mean drop in intraocular pressure in the ECP group was significantly greater at all postoperative visits. Logarithm of the minimal angle of resolution visual acuity outcomes were similar in both groups. There were 2 cases (7.4%) of postoperative phthisis bulbi in each group. Conclusion: Endoscopic pars plana vitrectomy, panretinal photocoagulation, and ECP seem to control intraocular pressure to a greater extent than standard glaucoma treatments in patients with neovascular glaucoma. In this aged-matched comparative case series, there was no significant difference between the two treatments' effects on visual acuity. C1 [Marra, Kyle V.; Omar, Ahmed; Kinoshita, Taiga; Kuperwaser, Mark C.; Arroyo, Jorge G.] Harvard Univ, Div Ophthalmol, Beth Israel Deaconess Med Ctr, Retina Serv,Med Sch, Boston, MA 02215 USA. [Marra, Kyle V.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Wagley, Sushant] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Omar, Ahmed; Silva, Paolo] Harvard Univ, Beetham Eye Inst, Joslin Diabet Ctr, Sch Med, Boston, MA 02215 USA. [Omar, Ahmed] Assiut Univ, Dept Ophthalmol, Fac Med, Assiut, Egypt. [Kovacs, Kyle D.] Albert Einstein Coll Med, New York, NY USA. RP Arroyo, JG (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Retina Serv, 330 Brookline Ave,CC-5, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu FU Grimshaw-Gudewicz Charitable Foundation FX Supported by the Grimshaw-Gudewicz Charitable Foundation. NR 25 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JUN PY 2015 VL 35 IS 6 BP 1072 EP 1083 DI 10.1097/IAE.0000000000000449 PG 12 WC Ophthalmology SC Ophthalmology GA CJ7KJ UT WOS:000355673600004 PM 25621944 ER PT J AU Mothi, SS Tandon, N Padmanabhan, J Mathew, IT Clementz, B Tamminga, C Pearlson, G Sweeney, J Keshavan, MS AF Mothi, Suraj Sarvode Tandon, Neeraj Padmanabhan, Jaya Mathew, Ian T. Clementz, Brett Tamminga, Carol Pearlson, Godfrey Sweeney, John Keshavan, Matcheri S. TI Increased cardiometabolic dysfunction in first-degree relatives of patients with psychotic disorders SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Relatives; Diabetes; Hypertension; Psychotic disorder ID DRUG-NAIVE PATIENTS; BIPOLAR DISORDER; RISK-FACTORS; METABOLIC ABNORMALITIES; CARDIOVASCULAR-DISEASE; SOCIOECONOMIC-STATUS; MEDICAL COMORBIDITY; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; US ADULTS AB Introduction: Elevated prevalence of comorbid cardio-vascular and metabolic dysfunction (CMD) is consistently reported in patients with severe psychotic disorders such as schizophrenia (SZ), schizoaffective (SZA) and bipolar disorder (BP-P). Since both psychosis and CMD are substantively heritable in nature, we attempted to investigate the occurrence of CMD disorders in first-degree relatives of probands with psychosis. Methods: Our sample included 861 probands with a diagnosis of SZ (n = 354), SZA (n = 212) and BP-P (n = 295), 776 first-degree relatives of probands and 416 healthy controls. Logistic regression was used to compare prevalence of any CMD disorders (diabetes, hypertension, hyperlipidemia or coronary artery disease) across groups. Post hoc tests of independence checked for CMD prevalence across psychosis diagnosis (SZ, SZA and BP-P), both in relatives of probands and within probands themselves. Results: After controlling for potential confounders, first-degree relatives with (p < 0.001) and without (p = 0.03) Axis I non-psychotic or Axis-II cluster disorders were at a significant risk for CMD compared to controls. No significant difference (p = 0.42) was observed in prevalence of CMD between relatives of SZ, SZA and BP-P, or between psychosis diagnoses for probands (p = 0.25). Discussion: Prevalence of CMD was increased in the first-degree relatives of psychosis subjects. This finding suggests the possibility of overlapping genetic contributions to CMD and psychosis. Increased somatic disease burden in relatives of psychotic disorder probands points to need for early detection and preventive efforts in this population. (C) 2015 Elsevier B.V. All rights reserved. C1 [Mothi, Suraj Sarvode; Keshavan, Matcheri S.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Mothi, Suraj Sarvode; Tandon, Neeraj; Padmanabhan, Jaya; Mathew, Ian T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Psychiat, Boston, MA 02215 USA. [Tandon, Neeraj] Baylor Coll Med, Texas Med Ctr, Houston, TX 77030 USA. [Pearlson, Godfrey] Olin Neuropsychiat Res Ctr, Hartford, CT USA. [Pearlson, Godfrey] Yale Univ, Dept Psychiat & Neurobiol, New Haven, CT USA. [Clementz, Brett] Univ Georgia, Dept Psychol, Bioimaging Res Ctr, Athens, GA 30602 USA. [Clementz, Brett; Sweeney, John] Univ Georgia, Dept Neurosci, Bioimaging Res Ctr, Athens, GA 30602 USA. [Tamminga, Carol] UT Southwestern, Psychiat, Dallas, TX USA. RP Keshavan, MS (reprint author), Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. EM mkeshava@bidmc.harvard.edu OI Padmanabhan, Jaya/0000-0003-3958-5424 FU National Institute for Mental Health (NIMH) [MH078113, MH077945, MH077852, MH077851, MH077862, MH072767, MH083888] FX This work was supported in part by the National Institute for Mental Health (NIMH) grants MH078113, MH077945, MH077852, MH077851, MH077862, MH072767, and MH083888. NR 52 TC 4 Z9 4 U1 4 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUN PY 2015 VL 165 IS 1 BP 103 EP 107 DI 10.1016/j.schres.2015.03.034 PG 5 WC Psychiatry SC Psychiatry GA CJ5VK UT WOS:000355560100018 PM 25900543 ER PT J AU Gaffney, A Christiani, DC AF Gaffney, Adam Christiani, David C. TI Gene-Environment Interaction from International Cohorts: Impact on Development and Evolution of Occupational and Environmental Lung and Airway Disease SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE genetic susceptibility; occupational disease; environmental disease; lung disease; gene-environment interactions ID CHRONIC BERYLLIUM DISEASE; GLUTATHIONE-S-TRANSFERASE; NECROSIS-FACTOR-ALPHA; DIISOCYANATE-INDUCED ASTHMA; COAL-WORKERS PNEUMOCONIOSIS; COTTON TEXTILE WORKERS; HLA CLASS-II; N-ACETYLTRANSFERASE GENOTYPES; MICROSOMAL EPOXIDE HYDROLASE; ISOCYANATE-INDUCED ASTHMA AB Environmental and occupational pulmonary diseases impose a substantial burden of morbidity and mortality on the global population. However, it has been long observed that only some of those who are exposed to pulmonary toxicants go on to develop disease; increasingly, it is being recognized that genetic differences may underlie some of this person-to-person variability. Studies performed throughout the globe are demonstrating important gene-environment interactions for diseases as diverse as chronic beryllium disease, coal workers' pneumoconiosis, silicosis, asbestosis, byssinosis, occupational asthma, and pollution-associated asthma. These findings have, in many instances, elucidated the pathogenesis of these highly complex diseases. At the same time, however, translation of this research into clinical practice has, for good reasons, proceeded slowly. No genetic test has yet emerged with sufficiently robust berating characteristics to be clearly useful or practicable in an occupational or environmental setting. In addition, occupational genetic testing raises serious ethical and policy concerns. Therefore, the primary objective must remain ensuring that the workplace and the environment are safe for all. C1 [Gaffney, Adam; Christiani, David C.] Harvard Univ, Div Pulm & Crit Care, Dept Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02115 USA. [Gaffney, Adam; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU NHLBI NIH HHS [T32 HL116275] NR 115 TC 1 Z9 1 U1 3 U2 8 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 EI 1098-9048 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD JUN PY 2015 VL 36 IS 3 BP 347 EP 357 DI 10.1055/s-0035-1549450 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CJ3CX UT WOS:000355362100004 PM 26024343 ER PT J AU Charidimou, A Martinez-Ramirez, S Viswanathan, A AF Charidimou, Andreas Martinez-Ramirez, Sergi Viswanathan, Anand TI Waking Up MRI-Visible Perivascular Spaces and Drainage Research SO SLEEP LA English DT Editorial Material ID SMALL VESSEL DISEASE; CEREBRAL AMYLOID ANGIOPATHY; VIRCHOW-ROBIN SPACES; SLEEP; BRAIN; SEVERITY; COHORT C1 [Charidimou, Andreas; Martinez-Ramirez, Sergi; Viswanathan, Anand] Harvard Univ, Hemorrhag Stroke Res Program, Dept Neurol, Massachusetts Gen Hosp,Stroke Res Ctr,Med Sch, Boston, MA 02114 USA. RP Charidimou, A (reprint author), Harvard Univ, Sch Med, J Kistler Stroke Res Ctr, Massachusetts Gen Hosp, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM charidimou.09@ucl.ac.uk NR 18 TC 0 Z9 0 U1 1 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD JUN 1 PY 2015 VL 38 IS 6 BP 845 EP 846 AR PII sp-00233-15 DI 10.5665/sleep.4718 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ6PY UT WOS:000355617000002 PM 26039964 ER PT J AU Jafari-Khouzani, K Emblem, KE Kalpathy-Cramer, J Bjornerud, A Vangel, MG Gerstner, ER Schmainda, KM Paynabar, K Wu, O Wen, PY Batchelor, T Rosen, B Stufflebeam, SM AF Jafari-Khouzani, Kourosh Emblem, Kyrre E. Kalpathy-Cramer, Jayashree Bjornerud, Atle Vangel, Mark G. Gerstner, Elizabeth R. Schmainda, Kathleen M. Paynabar, Kamran Wu, Ona Wen, Patrick Y. Batchelor, Tracy Rosen, Bruce Stufflebeam, Steven M. TI Repeatability of Cerebral Perfusion Using Dynamic Susceptibility Contrast MRI in Glioblastoma Patients SO TRANSLATIONAL ONCOLOGY LA English DT Article ID ARTERIAL INPUT FUNCTION; BLOOD-VOLUME MAPS; VASCULAR-PERMEABILITY; CLUSTER-ANALYSIS; BRAIN-TUMORS; ENHANCED MR; GRADE; GLIOMAS; THERAPY; REPRODUCIBILITY AB OBJECTIVES: This study evaluates the repeatability of brain perfusion using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a variety of post-processing methods. METHODS: Thirty-two patients with newly diagnosed glioblastoma were recruited. On a 3-T MRI using a dual-echo, gradient-echo spin-echo DSC-MRI protocol, the patients were scanned twice 1 to 5 days apart. Perfusion maps including cerebral blood volume (CBV) and cerebral blood flow (CBF) were generated using two contrast agent leakage correction methods, along with testing normalization to reference tissue, and application of arterial input function (AIF). Repeatability of CBV and CBF within tumor regions and healthy tissues, identified by structural images, was assessed with intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs). Coefficients of variation (CVs) were reported for selected methods. RESULTS: CBV and CBF were highly repeatable within tumor with ICC values up to 0.97. However, both CBV and CBF showed lower ICCs for healthy cortical tissues (up to 0.83), healthy gray matter (up to 0.95), and healthy white matter (WM; up to 0.93). The values of CV ranged from 6% to 10% in tumor and 3% to 11% in healthy tissues. The values of RC relative to the mean value of measurement within healthy WM ranged from 22% to 42% in tumor and 7% to 43% in healthy tissues. These percentages show how much variation in perfusion parameter, relative to that in healthy WM, we expect to observe to consider it statistically significant. We also found that normalization improved repeatability, but AIF deconvolution did not. CONCLUSIONS: DSC-MRI is highly repeatable in high-grade glioma patients. C1 [Jafari-Khouzani, Kourosh; Emblem, Kyrre E.; Kalpathy-Cramer, Jayashree; Vangel, Mark G.; Wu, Ona; Rosen, Bruce; Stufflebeam, Steven M.] MIT, Harvard MIT Hlth Sci & Technol, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Cambridge, MA 02139 USA. [Emblem, Kyrre E.; Bjornerud, Atle] Oslo Univ Hosp, Rikshosp, Intervent Ctr, Oslo, Norway. [Gerstner, Elizabeth R.; Batchelor, Tracy] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Bjornerud, Atle] Univ Oslo, Dept Phys, Oslo, Norway. [Schmainda, Kathleen M.] Med Coll Wisconsin, Dept Radiol & Biophys, Milwaukee, WI 53226 USA. [Paynabar, Kamran] Georgia Inst Technol, H Milton Stewart Sch Ind & Syst Engn, Atlanta, GA 30332 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Jafari-Khouzani, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM kjafari@nmr.mgh.harvard.edu RI Emblem, Kyrre/H-6691-2012; OI Emblem, Kyrre/0000-0002-6580-9519; Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 FU NCI/NIH [R21CA117079, R01CA129371, K24CA125440]; NIH [S10RR023401, 5R01NS069696, 5R01NS060918, UL1 RR025758, R01NS059775]; Saic-Frederick Inc. [26XS263]; Norwegian Research Council [191088/V50]; Norwegian Cancer Society [3434180]; Harvard Catalyst grant [M01-RR-01066]; Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources); National Center for Advancing Translational Sciences, NIH [UL1 TR001102]; Harvard University; NCRR Shared Instrumentation Grant Program [1S10RR023401, 1S10RR023043] FX This work was supported by NCI/NIH R21CA117079, R01CA129371, and K24CA125440 (T.B.); NIH S10RR023401, 5R01NS069696, and 5R01NS060918 (S.M.S.); Saic-Frederick Inc. grant 26XS263 (T.B.); Norwegian Research Council grant 191088/V50 and Norwegian Cancer Society Grant 3434180 (K.E.E.); Harvard Catalyst grant M01-RR-01066 (T.B.); and NIH Awards UL1 RR025758 (T.B. and B.R.) and R01NS059775 (O.W.); Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program (1S10RR023401 and 1S10RR023043). NR 47 TC 5 Z9 6 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1944-7124 EI 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD JUN PY 2015 VL 8 IS 3 BP 137 EP 146 DI 10.1016/j.tranon.2015.03.002 PG 10 WC Oncology SC Oncology GA CK0VE UT WOS:000355922500001 PM 26055170 ER PT J AU McCall, KC Cheng, SC Huang, Y Kohl, NE Tupper, T Van den Abbeele, AD Zukotynski, KA Sweeney, CJ AF McCall, Keisha C. Cheng, Su-Chun Huang, Ying Kohl, Nancy E. Tupper, Tanya Van den Abbeele, Annick D. Zukotynski, Katherine A. Sweeney, Christopher J. TI [F-18]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of LAPC4-CR Castration-Resistant Prostate Cancer Xenograft Model in Soft Tissue Compartments SO TRANSLATIONAL ONCOLOGY LA English DT Article ID MALIGNANT-TUMORS; F-18-FDG PET; REPRODUCIBILITY; MITOXANTRONE; PREDNISONE; SURVIVAL; MICROPET AB Preclinical xenograft models have contributed to advancing our understanding of the molecular basis of prostate cancer and to the development of targeted therapy. However, traditional preclinical in vivo techniques using caliper measurements and survival analysis evaluate the macroscopic tumor behavior, whereas tissue sampling disrupts the microenvironment and cannot be used for longitudinal studies in the same animal. Herein, we present an in vivo study of [F-18]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) designed to evaluate the metabolism within the microenvironment of LAPC4-CR, a unique murine model of castration-resistant prostate cancer. Mice bearing LAPC4-CR subcutaneous tumors were administered [F-18]-FDG via intravenous injection. After a 60-minute distribution phase, the mice were imaged on a PET/CT scanner with submillimeter resolution; and the fused PET/CT images were analyzed to evaluate tumor size, location, and metabolism across the cohort of mice. The xenograft tumors showed [F-18]-FDG uptake that was independent of tumor size and was significantly greater than uptake in skeletal muscle and liver in mice (Wilcoxon signedrank P values of .0002 and .0002, respectively). [F-18]-FDG metabolism of the LAPC4-CR tumors was 2.1 +/- 0.8 ID/cm(3)*wt, with tumor to muscle ratio of 7.4 +/- 4.7 and tumor to liver background ratio of 6.7 +/- 2.3. Noninvasive molecular imaging techniques such as PET/CT can be used to probe the microenvironment of tumors in vivo. This study showed that [F-18]-FDG-PET/CT could be used to image and assess glucose metabolism of LAPC4-CR xenografts in vivo. Further work can investigate the use of PET/CT to quantify the metabolic response of LAPC4-CR to novel agents and combination therapies using soft tissue and possibly bone compartment xenograft models. C1 [McCall, Keisha C.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [McCall, Keisha C.; Kohl, Nancy E.; Tupper, Tanya; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Ctr Biomed Imaging Oncol, Boston, MA 02215 USA. [Cheng, Su-Chun] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Huang, Ying; Sweeney, Christopher J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Van den Abbeele, Annick D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Zukotynski, Katherine A.] Univ Toronto, Sunnybrook Hosp, Dept Med Imaging, Toronto, ON M5T 1W7, Canada. [Sweeney, Christopher J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP McCall, KC (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM kmccall@partners.org FU Dana-Farber/Harvard Cancer Center SPORE (Specialized Program of Research Excellence) in Prostate Cancer [NIH5P50 CA090381-10] FX This work was supported by the Dana-Farber/Harvard Cancer Center SPORE (Specialized Program of Research Excellence) in Prostate Cancer, Developmental Project, NIH5P50 CA090381-10. The authors also acknowledge the following individuals for their contributions: Michaela Bowden, PhD, at Dana-Farber Cancer Institute, coordinated laboratory experiments and facilitated access to histological images on LAPC4-CR tumor models; Su-Chun Cheng, PhD, Biostatistician at the Department of Biostatistics, Dana-Farber Cancer Institute, provided expert advice on statistical analysis methods; Amanda Christie, Research Technician at the CBIO/LFIC, provided advice on small-animal handling and on tumor growth patterns for Nu/Nu murine LAPC4-CR models, and prepared tumor fragments for implantation; Ying Huang, MD, PhD, Scientist at Dana-Farber Cancer Institute, performed hematoxylin staining and analysis and provided representative histological images of LAPC4-CR xenograft tumors; Li Jia, PhD, Scientist at Dana-Farber Cancer Institute, provided expertise in the LAPC4-CR cell line and prostate cancer tumor models; Paul T. Kirschmeier, PhD of the Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, and the CBIO/LFIC provided scientific advice and facilitated access to experimental data and images; Quang-De Nguyen, PhD, Director at the CBIO/LFIC, provided expert scientific advice and facilitated access to experimental data and images; Lei Qin, PhD, MRI Physicist at Department of Imaging, Dana-Farber Cancer Institute, provided imaging expertise in image acquisition and interpretation; Tanya Tupper, Research Technician at the CBIO/LFIC, conducted the preclinical data acquisition for this experiment, including small-animal handling, and subcutaneous tumor implantation, tumor growth monitoring, animal health monitoring, and in vivo PET/CT imaging of the mice; Jeffery Yap, PhD, contributed to the experiment design and defined the preclinical PET/CT imaging protocols as the Senior Diagnostic Physicist at the Department of Imaging, Dana-Farber Cancer Institute, and the CBIO/LFIC. Dr Yap is currently Associate Director of the Center for Quantitative Cancer Imaging at the Huntsman Cancer Center Institute, University of Utah. NR 22 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1944-7124 EI 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD JUN PY 2015 VL 8 IS 3 BP 147 EP 153 DI 10.1016/j.tranon.2015.03.004 PG 7 WC Oncology SC Oncology GA CK0VE UT WOS:000355922500002 PM 26055171 ER PT J AU Anupindi, SA Podberesky, DJ Towbin, AJ Courtier, J Gee, MS Darge, K Dillman, JR AF Anupindi, Sudha A. Podberesky, Daniel J. Towbin, Alexander J. Courtier, Jesse Gee, Michael S. Darge, Kassa Dillman, Jonathan R. TI Pediatric inflammatory bowel disease: imaging issues with targeted solutions SO ABDOMINAL IMAGING LA English DT Article DE Inflammatory bowel disease; CTE/MRE; Ultrasound; Fluoroscopy; Children; Pediatric concerns ID MAGNETIC-RESONANCE ENTEROGRAPHY; CONTRAST-ENHANCED ULTRASOUND; CROHNS-DISEASE; MR ENTEROGRAPHY; CT ENTEROGRAPHY; CLINICAL CHARACTERISTICS; ULCERATIVE-COLITIS; PATIENT TOLERANCE; FOLLOW-THROUGH; YOUNG-ADULTS AB To date, there have been many advances in inflammatory bowel disease (IBD) imaging in every cross-sectional imaging modality, particularly in children. The main emphasis in pediatric IBD imaging is on robust and reproducible measures of small bowel Crohn's disease inflammation, accurate diagnosis of IBD-related complications, and minimizing radiation burden to the patient, as repeat imaging is necessary over the course of their disease. In this article, we discuss the current state-of-the-art imaging techniques, in addition to routine fluoroscopy, including MR and CT enterography and bowel ultrasound. We also present the emerging use of new methods to characterize disease severity and distinguish active inflammation from fibrosis such as diffusion-weighted imaging, bowel elastography, and contrast-enhanced ultrasound. The diagnostic performance of particular examinations, their strengths and weaknesses, and role in IBD management will be discussed. Although these advanced imaging techniques applied to children are similar to those performed in adults, special considerations related to their application in pediatric patients will also be reviewed. C1 [Anupindi, Sudha A.; Darge, Kassa] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. [Podberesky, Daniel J.] Nemours Childrens Hosp, Dept Radiol, Orlando, FL 32827 USA. [Towbin, Alexander J.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH 45241 USA. [Courtier, Jesse] UCSF Benioff Childrens Hosp, Dept Radiol, San Francisco, CA 94121 USA. [Gee, Michael S.] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Imaging, Boston, MA 02114 USA. [Dillman, Jonathan R.] Univ Michigan Hlth Syst, CS Mott Childrens Hosp, Dept Radiol, Sect Pediat Radiol, Ann Arbor, MI 48109 USA. RP Anupindi, SA (reprint author), Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Radiol, 34th St & Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM anupindi@email.chop.edu OI Towbin, Alexander/0000-0003-1729-5071 NR 62 TC 6 Z9 6 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD JUN PY 2015 VL 40 IS 5 BP 975 EP 992 DI 10.1007/s00261-015-0423-y PG 18 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CJ2TI UT WOS:000355337000005 PM 25920487 ER PT J AU Suh, CH Tirumani, SH Shinagare, AB Kim, KW Rosenthal, MH Ramaiya, NH Baheti, AD AF Suh, Chong Hyun Tirumani, Sree Harsha Shinagare, Atul B. Kim, Kyung Won Rosenthal, Michael H. Ramaiya, Nikhil H. Baheti, Akshay D. TI Diagnosis and management of duodenal adenocarcinomas: a comprehensive review for the radiologist SO ABDOMINAL IMAGING LA English DT Review DE Duodenal adenocarcinoma; Small bowel; Radiology; CT ID SMALL-BOWEL ADENOCARCINOMA; SMALL-INTESTINE; PROGNOSTIC-FACTORS; NONNEUROENDOCRINE METASTASES; GASTROINTESTINAL-TRACT; SINGLE-INSTITUTION; HEPATIC RESECTION; IMAGING FEATURES; CARCINOID-TUMORS; PHASE-II AB Duodenal adenocarcinomas are the most common duodenal tumors, and represent 15-25% of small bowel carcinomas. Their management differs from other small bowel tumors, with imaging playing a very important role. In this article, we provide a comprehensive review of the diagnosis and management of duodenal adenocarcinomas, emphasizing the role of the radiologist in the same. C1 [Suh, Chong Hyun; Kim, Kyung Won] Univ Ulsan, Coll Med, Dept Radiol, Seoul, South Korea. [Suh, Chong Hyun; Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul, South Korea. [Tirumani, Sree Harsha; Shinagare, Atul B.; Rosenthal, Michael H.; Ramaiya, Nikhil H.; Baheti, Akshay D.] Harvard Univ, Dana Farber Canc Inst, Dept Imaging, Sch Med, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Rosenthal, Michael H.; Ramaiya, Nikhil H.; Baheti, Akshay D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Baheti, AD (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Imaging, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM akshaybaheti@gmail.com NR 68 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD JUN PY 2015 VL 40 IS 5 BP 1110 EP 1120 DI 10.1007/s00261-014-0309-4 PG 11 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CJ2TI UT WOS:000355337000018 PM 25427987 ER PT J AU Rosenthal, MH Kim, KW Fuchs, CS Meyerhardt, JA Ramaiya, NH AF Rosenthal, Michael H. Kim, Kyung Won Fuchs, Charles S. Meyerhardt, Jeffrey A. Ramaiya, Nikhil H. TI CT predictors of overall survival at initial diagnosis in patients with stage IV colorectal cancer SO ABDOMINAL IMAGING LA English DT Article DE Colorectal cancer; Diagnostic imaging; Patient outcome assessment; Prognosis AB We investigated whether the initial CT distribution of metastatic disease is predictive of overall survival in patients with stage IV colorectal cancer. A retrospective study of 65 patients (37 males, 28 females, mean age 56, range 28-88 years) with stage IV colorectal cancer was derived from an institutional database. Inclusion criteria required KRAS mutation testing and pretreatment CT examinations to be available (65 abdomen/pelvis, 63 chest). Disease burden was jointly characterized by two radiologists in consensus. Median follow-up was 39 months (range 8-115 months). Survival was assessed using Cox proportional hazards models. Univariate analysis showed that stratified site(s) of measurable disease and counts of measurable lesions a parts per thousand yen1 cm in the liver, peritoneum, and retroperitoneum were statistically significant risk factors for overall mortality [univariate HR 8.2 (CI 2.7-25.4) for isolated peritoneal disease, HR 1.11 per 5 lesions (CI 1.05-1.17) for liver lesions, HR 1.15 per lesion (CI 1.05-1.26) for peritoneal lesions, and HR 1.11 (CI 1.03-1.19) for retroperitoneal lymph nodes a parts per thousand yen1 cm in short axis]. The stratified site(s) of disease and counts of measurable liver lesions remained significant in the multivariate model (p < 0.0001 for isolated peritoneal disease and count of liver lesions). Thoracic metastases were not statistically significant predictors of overall mortality in this cohort. This study identified site(s) of measurable metastasis and counts of measurable liver lesions as independent predictors of overall survival. These findings may have value for future prognostic assessments once validated in a larger, independent, and potentially prospective cohort. C1 [Rosenthal, Michael H.; Kim, Kyung Won; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Fuchs, Charles S.; Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rosenthal, Michael H.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Rosenthal, Michael H.; Fuchs, Charles S.; Meyerhardt, Jeffrey A.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul, South Korea. RP Rosenthal, MH (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM michael_rosenthal@dfci.harvard.edu FU National Institutes of Health [5P50CA127003, R01CA149222, R01CA118553]; National Cancer Institute Cancer Center [5P30CA06516] FX This work was supported in part by National Institutes of Health grants 5P50CA127003, R01CA149222, R01CA118553, and National Cancer Institute Cancer Center Support Grant 5P30CA06516. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD JUN PY 2015 VL 40 IS 5 BP 1170 EP 1176 DI 10.1007/s00261-014-0272-0 PG 7 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CJ2TI UT WOS:000355337000025 PM 25326260 ER PT J AU Tirumani, SH Wagner, AJ Tirumani, H Shinagare, AB Jagannathan, JP Hornick, JL George, S Ramaiya, NH AF Tirumani, Sree Harsha Wagner, Andrew J. Tirumani, Harika Shinagare, Atul B. Jagannathan, Jyothi P. Hornick, Jason L. George, Suzanne Ramaiya, Nikhil H. TI Is the nonlipomatous component of dedifferentiated liposarcoma always soft tissue on CT? Analysis of CT densities and correlation with rate of growth in 60 patients SO ABDOMINAL IMAGING LA English DT Article DE Dedifferentiated liposarcoma; Nonlipomatous component; CT; Density ID IMAGING FINDINGS; RETROPERITONEUM; RECURRENCE; SARCOMA AB To define the various CT densities of nonlipomatous component of dedifferentiated liposarcoma (DDLPS) and to determine if the rate of growth varies with density. This study identified 60 patients with DDPLS (38 men, 22 women; mean age at diagnosis 59 years, range, 35-82 years) who had one or more resections. CT scan immediately before the surgical resection (presurgery) and up to a maximum of one year before the surgery (baseline) was reviewed by two radiologists to note the density of the nonlipomatous elements and rate of growth during that period. Clinical and histopathological data were extracted from electronic medical records. Rate of growth of various densities was compared using Kruskal-Wallis test. Three distinct densities of the nonlipomatous component were noted: soft tissue density (SD), fluid density (FD), and mixed density (MD). Of 109 lesions on the presurgery scan (SD = 78; MD = 22; FD = 9), scans at baseline were available for 72/109 lesions (SD = 49; MD = 14; FD = 9). Median growth rate/month without treatment, with chemotherapy, and with radiotherapy were 40%, 24%, and 62%, respectively, for SD lesions and 28%, 61%, and 52% for MD lesions. For FD lesions, it was 72% and 35%, respectively, without treatment and with chemotherapy. There was no statistical difference in the rate of growth of various densities. Density changed over time in 8/72 (11%) lesions, including 2/49 SD lesions (to MD), 1/14 MD lesions (to SD), and 5/9 FD lesions (to SD). DDLPS has three distinct CT densities of which soft tissue density is the most common. Despite not being statistically significant, fluid density lesions had rapid growth rate and often converted to soft tissue density in our study. C1 [Tirumani, Sree Harsha; Tirumani, Harika; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Wagner, Andrew J.; George, Suzanne] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Wagner, Andrew J.; George, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02215 USA. [Hornick, Jason L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 11 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD JUN PY 2015 VL 40 IS 5 BP 1248 EP 1254 DI 10.1007/s00261-014-0267-x PG 7 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CJ2TI UT WOS:000355337000034 PM 25287680 ER PT J AU Sharpless, J Baldwin, N Cook, R Kofman, A Morley-Fletcher, A Slotkin, R Wald, HS AF Sharpless, Joanna Baldwin, Nell Cook, Robert Kofman, Aaron Morley-Fletcher, Alessio Slotkin, Rebecca Wald, Hedy S. TI The Becoming: Students' Reflections on the Process of Professional Identity Formation in Medical Education SO ACADEMIC MEDICINE LA English DT Editorial Material AB Professional identity formation (PIF) within medical education is the multifaceted, individualized process through which students develop new ways of being in becoming physicians. Personal backgrounds, values, expectations, interests, goals, relationships, and role models can all influence PIF and may account for diversity of both experience and the active constructive process of professional formation. Guided reflection, including reflective writing, has been used to enhance awareness and meaning making within the PIF process for both students and medical educators and to shed light on what aspects of medical education are most constructive for healthy PIF. Student voices about the PIF process now emerging in the literature are often considered and interpreted by medical educators within qualitative studies or in broad theoretical overviews of PIF. In this Commentary, the authors present a chorus of individual student voices from along the medical education trajectory. Medical students (years 1-4) and a first-year resident in pediatrics respond to a variety of questions based on prevalent PIF themes extracted from the literature to reflect on their personal experiences of PIF. Topics queried included pretending in medical education, role of relationships, impact of formal and informal curricula on PIF (valuable aspects as well as suggestions for change), and navigating and developing interprofessional relationships and identities. This work aims to vividly illustrate the diverse and personal forces at play in individual students' PIF processes and to encourage future pedagogic efforts supporting healthy, integrated PIF in medical education. C1 [Sharpless, Joanna; Baldwin, Nell; Cook, Robert; Kofman, Aaron; Slotkin, Rebecca] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Morley-Fletcher, Alessio] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wald, Hedy S.] Brown Univ, Warren Alpert Med Sch, Family Med, Providence, RI 02912 USA. RP Sharpless, J (reprint author), Brown Univ, Warren Alpert Med Sch, 222 Richmond St, Providence, RI 02912 USA. EM joanna_sharpless@brown.edu NR 21 TC 6 Z9 6 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUN PY 2015 VL 90 IS 6 BP 713 EP 717 DI 10.1097/ACM.0000000000000729 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CJ1IQ UT WOS:000355237700012 PM 25881650 ER PT J AU Chan, TM Thoma, B Lin, M AF Chan, Teresa M. Thoma, Brent Lin, Michelle TI Creating, Curating, and Sharing Online Faculty Development Resources: The Medical Education in Cases Series Experience SO ACADEMIC MEDICINE LA English DT Editorial Material AB Problem It is difficult to engage clinicians in continuing medical education that does not focus on clinical expertise. Evolving online technologies (e.g., massive open online courses [MOOCs]) are disrupting and transforming medical education, but few online nonclinical professional development resources exist. Approach In August 2013, the Academic Life in Emergency Medicine Web site launched the Medical Education in Cases (MEdIC) series to engage clinicians in an online professional development exercise. Each month, a complex, realistic scenario featuring a nonclinical medical education dilemma is published with accompanying discussion questions. A weeklong discussion is moderated on Twitter and the Web site. This discussion is curated to create a community commentary, which is published alongside presolicited expert responses. Case resources are available for download. Outcomes The first six MEdIC cases (published August 2013-January 2014) emphasized different CanMEDS and/or Accreditation Council on Graduate Medical Education competencies. Median reader engagement metrics (interquartile range 25%-75%) in the first week following publication were 861 (634-1,114) pageviews, 767 (518-953) unique visitors from 326 (218-405) cities in 45 (32-50) countries, 30 (24-39) comments, 52 (40-56) tweets, 17 (13-30) Facebook Likes, and 5 (5-7) Google Plus + 1s. Next Steps The MEdIC series is proof of concept that online activities can engage clinicians in nonclinical professional development. The early experience suggests the connectivist nature of MEdIC allows for crowdsourcing solutions to ill-defined problems via the wisdom of readers. This methodology may also be effective for other nonclinical and medical education topics. C1 [Chan, Teresa M.] McMaster Univ, Dept Med, Div Emergency Med, Hamilton, ON, Canada. [Thoma, Brent] Univ Saskatchewan, Saskatoon, SK, Canada. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Learning Lab, Boston, MA 02114 USA. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Lin, Michelle] Univ Calif San Francisco, Dept Emergency Med, Med Educ, San Francisco, CA 94143 USA. RP Chan, TM (reprint author), McMaster Clin, Hamilton Gen Hosp, 237 Barton St E,Room 254, Hamilton, ON L8L 2X2, Canada. EM teresa.chan@medportal.ca OI Chan, Teresa/0000-0001-6104-462X; Thoma, Brent/0000-0003-1124-5786 FU Royal College of Physicians and Surgeons of Canada; DynaMed FX T.M. Chan has previously been supported by the Royal College of Physicians and Surgeons of Canada's Fellowship for Studies in Medical Education. M. Lin is a paid editor for DynaMed. M. Lin is editor-in-chief and T.M. Chan and B. Thoma are associate editors for the multiauthor blog Academic Life in Emergency Medicine (www.aliem.org). In addition, B. Thoma is editor-in-chief of and T.M. Chan is a managing editor for another multiauthor blog, BoringEM (www.BoringEM.org). All three authors are founding members of the MedEdLIFE Research Collaborative. None of the authors receive any financial or in-kind support for their blogging and other contributions to these Web sites. NR 5 TC 4 Z9 4 U1 2 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUN PY 2015 VL 90 IS 6 BP 785 EP 789 DI 10.1097/ACM.0000000000000692 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CJ1IQ UT WOS:000355237700025 PM 25785678 ER PT J AU Dumurgier, J Schraen, S Gabelle, A Vercruysse, O Bombois, S Laplanche, JL Peoc'h, K Sablonniere, B Kastanenka, KV Delaby, C Pasquier, F Touchon, J Hugon, J Paquet, C Lehmann, S AF Dumurgier, Julien Schraen, Susanna Gabelle, Audrey Vercruysse, Olivier Bombois, Stephanie Laplanche, Jean-Louis Peoc'h, Katell Sablonniere, Bernard Kastanenka, Ksenia V. Delaby, Constance Pasquier, Florence Touchon, Jacques Hugon, Jacques Paquet, Claire Lehmann, Sylvain TI Cerebrospinal fluid amyloid-beta 42/40 ratio in clinical setting of memory centers: a multicentric study SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; NATIONAL INSTITUTE; CSF; BIOMARKERS; DEMENTIA; DIAGNOSIS; IMPACT; TAU; DIFFERENTIATION AB Introduction: The cerebrospinal fluid (CSF) biomarkers amyloid-beta(A beta), tau and phosphorylated tau (p-tau181) are now used for the diagnosis of Alzheimer's disease (AD). A beta 40 is the most abundant A beta peptide isoform in the CSF, and the A beta 42/40 ratio has been proposed to better reflect brain amyloid production. However, its additional value in the clinical setting remains uncertain. Methods: A total of 367 subjects with cognitive disorders who underwent a lumbar puncture were prospectively included at three French memory centers (Paris-North, Lille and Montpellier; the PLM Study). The frequency of positive, negative and indeterminate CSF profiles were assessed by various methods, and their adequacies with the diagnosis of clinicians were tested using net reclassification improvement (NRI) analyses. Results: On the basis of local optimum cutoffs for A beta 42 and p-tau181, 22% of the explored patients had indeterminate CSF profiles. The systematic use of A beta 42/40 ratio instead of A beta 42 levels alone decreased the number of indeterminate profiles (17%; P = 0.03), but it failed to improve the classification of subjects (NRI = -2.1%; P = 0.64). In contrast, the use of A beta 42/40 ratio instead of A beta 42 levels alone in patients with a discrepancy between p-tau181 and A beta 42 led to a reduction by half of the number of indeterminate profiles (10%; P < 0.001) and was further in agreement with clinician diagnosis (NRI = 10.5%; P = 0.003). Conclusions: In patients with a discrepancy between CSF p-tau181 and CSF A beta 42, the assessment of A beta 42/40 ratio led to a reliable biological conclusion in over 50% of cases that agreed with a clinician's diagnosis. C1 [Dumurgier, Julien; Hugon, Jacques; Paquet, Claire] Paris Nord Ile de France St Louis Lariboisiere Fe, AP HP, CM2R, F-75010 Paris, France. [Dumurgier, Julien; Hugon, Jacques; Paquet, Claire] Univ Paris 07, INSERM U942, Biomarkers CardioNeuroVasc Dis BioCANVAS, Paris, France. [Schraen, Susanna; Sablonniere, Bernard] Univ Lille 2, Fac Med, JPArc, Inserm,UMR 1172, F-59045 Lille, France. [Schraen, Susanna; Sablonniere, Bernard] Ctr Hosp Reg Univ, Ctr Biol Pathol, F-59037 Lille, France. [Gabelle, Audrey; Touchon, Jacques] Univ Montpellier, Ctr Memoire Ressources Rech Montpellier, F-34059 Montpellier, France. [Gabelle, Audrey; Delaby, Constance; Lehmann, Sylvain] Univ Montpellier, INSERM U1040, Biochim Prote Clin IRB CCBHM, F-34059 Montpellier, France. [Vercruysse, Olivier; Bombois, Stephanie; Pasquier, Florence] Ctr Hosp Reg Univ Lille, EA 1046, Ctr Memoire Ressources Rech, Lille, France. [Laplanche, Jean-Louis; Peoc'h, Katell] Hop Univ St Louis Lariboisiere Fernand Widal, AP HP, Serv Biochim & Biol Mol, PRES Sorbonne Paris Cite, Paris, France. [Kastanenka, Ksenia V.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Kastanenka, Ksenia V.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Dumurgier, J (reprint author), Paris Nord Ile de France St Louis Lariboisiere Fe, AP HP, CM2R, 200 Rue Faubourg St Denis, F-75010 Paris, France. EM julien.dumurgier@inserm.fr RI LAPLANCHE, Jean-Louis/S-8707-2016 NR 28 TC 10 Z9 10 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PD JUN 1 PY 2015 VL 7 AR 30 DI 10.1186/s13195-015-0114-5 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ3RE UT WOS:000355400800001 PM 26034513 ER PT J AU Sarich, TC Seltzer, JH Berkowitz, SD Costin, J Curnutte, JT Gibson, CM Hoffman, M Kaminskas, E Krucoff, MW Levy, JH Mintz, PD Reilly, PA Sager, PT Singer, DE Stockbridge, N Weitz, JI Kowey, PR AF Sarich, Troy C. Seltzer, Jonathan H. Berkowitz, Scott D. Costin, James Curnutte, John T. Gibson, C. Michael Hoffman, Maureane Kaminskas, Edvardas Krucoff, Mitchell W. Levy, Jerrold H. Mintz, Paul D. Reilly, Paul A. Sager, Philip T. Singer, Daniel E. Stockbridge, Norman Weitz, Jeffrey I. Kowey, Peter R. TI Novel oral anticoagulants and reversal agents: Considerations for clinical development SO AMERICAN HEART JOURNAL LA English DT Article ID VITAMIN-K ANTAGONISTS; ATRIAL-FIBRILLATION; WARFARIN; DABIGATRAN; EFFICACY; THERAPY; STROKE; TRIAL; RIVAROXABAN; MANAGEMENT AB This white paper provides a summary of presentations and discussions that were held at an Anticoagulant-Induced Bleeding and Reversal Agents Think Tank co-sponsored by the Cardiac Safety Research Consortium and the US Food and Drug Administration (FDA) at the FDA's White Oak Headquarters on April 22, 2014. Attention focused on a development pathway for reversal agents for the novel oral anticoagulants (NOACs). This is important because anticoagulation is still widely underused for stroke prevention in patients with atrial fibrillation. Undertreatment persists, although NOACs, in general, overcome some of the difficulties associated with anticoagulation provided by vitamin K antagonists. One reason for the lack of a wider uptake is the absence of NOAC reversal agents. As there are neither widely accepted academic and industry standards nor a definitive regulatory policy on the development of such reversal agents, this meeting provided a forum for leaders in the fields of cardiovascular clinical trials and cardiovascular safety to discuss the issues and develop recommendations. Attendees included representatives from pharmaceutical companies; regulatory agencies; end point adjudication specialist groups; contract research organizations; and active, academically based physicians. There was wide and solid consensus that NOACs overall offer improvements in convenience, efficacy, and safety compared with warfarin, even without reversal agents. Still, it was broadly accepted that it would be helpful to have reversal agents available for clinicians to use. Because it is not feasible to do definitive outcomes studies demonstrating a reversal agent's clinical benefits, it was felt that these agents could be approved for use in life-threatening bleeding situations if the molecules were well characterized preclinically, their pharmacodynamic and pharmacokinetic profiles were well understood, and showed no harmful adverse events in early human testing. There was also consensus that after such approval, efforts should be made to augment the available clinical information until such time as there is a body of evidence to demonstrate real-world clinical outcomes with the reversal agents. No recommendations were made for more generalized use of these agents in the setting of non-life-threatening situations. This article reflects the views of the authors and should not be construed to represent FDA's views or policies. C1 [Sarich, Troy C.] Janssen Sci Affairs LLC, Titusville, NJ USA. [Seltzer, Jonathan H.] ACI Clin & Lankenau Heart Inst, Wynnewood, PA USA. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut Inc, Whippany, NJ USA. [Costin, James] Perosphere Inc, Danbury, CT USA. [Curnutte, John T.] Portola Pharmaceut Inc, San Francisco, CA USA. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hoffman, Maureane] Durham Vet Affairs Med Ctr, Pathol & Lab Med Serv, Durham, NC USA. [Kaminskas, Edvardas] US FDA, Div Hematol Prod, CDER, Silver Spring, MD USA. [Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Levy, Jerrold H.] Duke Univ, Sch Med, Durham, NC USA. [Mintz, Paul D.] US FDA, Div Hematol Clin Review, Off Blood Res & Review, CBER, Silver Spring, MD USA. [Reilly, Paul A.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Sager, Philip T.] Stanford Univ, San Francisco, CA USA. [Sager, Philip T.] Sager Consulting Experts, San Francisco, CA USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Prod, CDER, Silver Spring, MD USA. [Weitz, Jeffrey I.] McMaster Univ, Hamilton, ON, Canada. [Weitz, Jeffrey I.] Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada. [Kowey, Peter R.] Lankenau Heart Inst, Philadelphia, PA USA. [Kowey, Peter R.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. RP Sarich, TC (reprint author), Janssen Sci Affairs LLC, Real World Evidence, Titusville, NJ 08560 USA. EM tsarich@its.jnj.com OI Hoffman, Maureane/0000-0001-7123-0100 NR 15 TC 21 Z9 23 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JUN PY 2015 VL 169 IS 6 BP 751 EP 757 DI 10.1016/j.ahj.2015.03.010 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CJ1AK UT WOS:000355213300002 PM 26027611 ER PT J AU Wang, YL Li, ZX Xian, Y Zhao, XQ Li, H Shen, HP Wang, CX Liu, LP Wang, CJ Pan, Y Wang, D Bettger, JP Fonarow, GC Schwamm, LH Smith, SC Peterson, ED Wang, Y AF Wang, Yilong Li, Zixiao Xian, Ying Zhao, Xingquan Li, Hao Shen, Haipeng Wang, Chunxue Liu, Liping Wang, Chunjuan Pan, Yuesong Wang, David Bettger, Janet. Prvu Fonarow, Gregg C. Schwamm, Lee H. Smith, Sidney C., Jr. Peterson, Eric D. Wang, Yongjun CA Golden BRIDGE-AIS Investigators TI Rationale and design of a cluster-randomized multifaceted intervention trial to improve stroke care quality in China: The GOLDEN BRIDGE-Acute Ischemic Stroke SO AMERICAN HEART JOURNAL LA English DT Article ID CLINICAL CHARACTERISTICS; UNFRACTIONATED HEPARIN; GUIDELINES-STROKE; HEALTH-CARE; ATTACK; OUTCOMES; REGISTRY; PREVENTION; ASPIRIN; ASPIRATION AB Background Prior studies have demonstrated a significant gap between guideline-based recommendations and clinical practice in the management of acute ischemic stroke (AIS) in China. Aims This study implements a targeted multifaceted quality improvement intervention in AIS patients and identifies the feasibility and efficacy of this intervention. Design This is a multicenter, 2-arm, open-label, cluster-randomized trial involving 40 clusters (hospitals) from China National Network of Stroke Research. Hospitals are randomized to receive a targeted multifaceted quality improvement intervention (experimental group) or routine standard of care (control group). The multifaceted intervention includes an evidence-based clinical pathway, written care protocols, a quality coordinator, and a monitoring and feedback system of performance measures. The number of enrolled patients in the trial will be 4,800. Primary outcome is the measure of the adherence to AIS evidence-based performance measures including the composite measure (defined as the total number of interventions performed among eligible patients divided by the total number of possible interventions among eligible patients) and the all-or-none measure (defined as the proportion of eligible patients who receive all of the performance measure interventions for which they are eligible). Secondary patient outcomes include inhospital death; a new vascular event; disability; and all-cause death at 3, 6, and 12 months after initial symptom onset. All analyses will be performed according to the intention-to-treatment principle and accounted for clustering using generalized estimating equations. Conclusions If proven effective, this targeted multifaceted intervention model will be extended nationwide as a model to bridge the evidence-based gap in the AIS management in China. C1 [Wang, Yilong; Li, Zixiao; Li, Hao; Wang, Chunjuan; Pan, Yuesong; Wang, Yongjun] Capital Med Univ, Beijing TianTan Hosp, Dept Neurol, Tiantan Clin Trial & Res Ctr Stroke, Beijing, Peoples R China. [Wang, Yilong; Li, Zixiao; Zhao, Xingquan; Li, Hao; Wang, Chunxue; Liu, Liping; Wang, Yongjun] China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China. [Xian, Ying; Bettger, Janet. Prvu; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Zhao, Xingquan; Wang, Chunxue; Wang, Yongjun] Capital Med Univ, Beijing TianTan Hosp, Dept Neurol, Vasc Neurol, Beijing, Peoples R China. [Shen, Haipeng] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC USA. [Liu, Liping] Capital Med Univ, Beijing TianTan Hosp, Dept Neurol, Neurointens Care Unit, Beijing, Peoples R China. [Wang, Chunjuan] Beijing Inst Brain Disorders, Ctr Stroke, Beijing, Peoples R China. [Pan, Yuesong] Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R China. [Wang, David] Univ Illinois, Coll Med, Illinois Neurol Inst Stroke Network, Sisters Order St Francis Healthcare Syst 3, Peoria, IL 61656 USA. [Bettger, Janet. Prvu] Duke Univ, Sch Nursing, Durham, NC USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. RP Wang, Y (reprint author), Capital Med Univ, Beijing TianTan Hosp, Dept Neurol, Tiantan Clin Trial & Res Ctr Stroke, 6 Tiantan Xili, Beijing, Peoples R China. EM yongjunwang1962@gmail.com FU National Institute of Neurological Disorders and Stroke; Genentech FX Dr Schwamm is the chair of the GWTG-Stroke Clinical Workgroup (unpaid) and serves as a stroke system of care consultant to the Joint Commission, Center for Disease Control, and Massachusetts Department of Public Health. He is the primary investigator of a National Institute of Neurological Disorders and Stroke-funded clinical trial of extended window thrombolysis for which Genentech provides alteplase free of charge and supplemental site payments. NR 34 TC 3 Z9 3 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JUN PY 2015 VL 169 IS 6 BP 767 EP + DI 10.1016/j.ahj.2015.03.008 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CJ1AK UT WOS:000355213300004 PM 26027613 ER PT J AU Mochel, MC Pins, A Nose, V Hoang, MP AF Mochel, Mark C. Pins, Adriano Nose, Vania Hoang, Mai P. TI Loss of BAP1 Expression in Basal Cell Carcinomas in Patients With Germline BAP1 Mutations SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE BAP1; Immunohistochernistry; Basal cell carcinoma ID MALIGNANT MESOTHELIOMA; PREDISPOSE; CANCERS; UVEAL; MELANOMA; TUMORS; BRCA1; GENE AB Objectives: Patients with heterozygous germline mutations in BRCA1-associated protein 1 (BAP1), a tumor suppressor gene, develop a tumor predisposition syndrome (OMIM 614327) with increased risk of uveal and cutaneous melanomas, cutaneous atypical and epithelioid melanocytic lesions, lung adenocarcinoma, clear cell renal cell carcinoma, and other tumors. Early recognition of this syndrome is of clinical importance. In addition, screening for BAP1 mutation, loss, and inactivation by performing BAP1 immunohistochemistry on cutaneous lesions would be a simple method for screening patients suspected of having germline BAP1 mutations. Methods: We investigated BAP1 expression in seven basal cell carcinomas (BCCs) in two patients with germline BAP1 mutation and a family history of uveal melanoma. Six lesions were from the head and neck region and one from the shoulder. Thirty-one sporadic BCCs were included as controls. Results: All seven BCCs in the patients with germline BAP1 mutations exhibited loss of BAP1 nuclear staining, while 30 (97%) of 31 sporadic BCCs exhibited positive BAP 1 nuclear staining. Conclusions: Loss of BAP1 expression could be associated with the development of BCC inpatients with germline BAP1 mutations. These results suggest that BCC may be a component of the expanding category of tumors associated with this syndrome. C1 [Mochel, Mark C.; Pins, Adriano; Nose, Vania; Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pins, Adriano] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Pins, Adriano; Nose, Vania; Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@mgh.harvard.edu NR 21 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 2015 VL 143 IS 6 BP 901 EP 904 DI 10.1309/AJCPG8LFJC0DHDQT PG 4 WC Pathology SC Pathology GA CJ0HN UT WOS:000355156500018 PM 25972334 ER PT J AU Hsu, HE Shenoy, ES Kelbaugh, D Ware, W Lee, H Zakroysky, P Hooper, DC Walensky, RP AF Hsu, Heather E. Shenoy, Erica S. Kelbaugh, Douglas Ware, Winston Lee, Hang Zakroysky, Pearl Hooper, David C. Walensky, Rochelle P. TI An electronic surveillance tool for catheter-associated urinary tract infection in intensive care units SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Infection control; CAUTI; NHSN; Resources; ICU ID BLOOD-STREAM INFECTIONS; AUTOMATED SURVEILLANCE AB Background: Traditional methods of surveillance of catheter-associated urinary tract infections (CAUTIs) are error-prone and resource-intensive. To resolve these issues, we developed a highly sensitive electronic surveillance tool. Objective: To develop an electronic surveillance tool for CAUTIs and assess its performance. Methods: The study was conducted at a 947-bed tertiary care center. Patients included adults aged >= 18 years admitted to an intensive care unit between January 10 and June 30, 2012, with an indwelling urinary catheter during their admission. We identified CAUTIs using 4 methods: traditional surveillance (TS) (ie, manual chart review by ICPs), an electronic surveillance (ES) tool, augmented electronic surveillance (AES) (ie, ES with chart review on a subset of cases), and reference standard (RS) (ie, a subset of CAUTIs originally ascertained by TS or ES, confirmed by review). We assessed performance characteristics to RS for reviewed cases. Results: We identified 417 candidate CAUTIs in 308 patients; 175 (42.0%) of these candidate CAUTIs were selected for review, yielding 32 confirmed CAUTIs in 22 patients (RS). Compared with RS, the sensitivities of TS, ES, and AES were 43.8% (95% confidence interval [CI], 26.4%-62.3%), 100.0% (95% CI, 89.1%-100.0%), and 100.0% (95% CI, 89.1%-100.0%). Specificities were 82.5% (95% CI, 75.3%-88.4%), 2.8% (95% CI, 0.8%-7.0%), and 100.0% (95% CI, 97.5%-100.0%). Conclusions: Electronic CAUTI surveillance offers a streamlined approach to improve reliability and resource burden of surveillance. Copyright (C) 2015 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. C1 [Hsu, Heather E.; Shenoy, Erica S.; Lee, Hang; Hooper, David C.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Boston, MA USA. [Hsu, Heather E.] Boston Childrens Hosp, Boston Combined Residency Program Pediat, Boston, MA USA. [Hsu, Heather E.] Boston Med Ctr, Boston, MA USA. [Shenoy, Erica S.; Hooper, David C.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Shenoy, Erica S.; Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [Shenoy, Erica S.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. [Kelbaugh, Douglas] Massachusetts Gen Hosp, Partners Informat Syst, Boston, MA 02114 USA. [Kelbaugh, Douglas] Massachusetts Gen Physicians Org, Boston, MA USA. [Ware, Winston] Massachusetts Gen Hosp, Clin Care Management Unit, Boston, MA 02114 USA. [Lee, Hang; Zakroysky, Pearl] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Shenoy, ES (reprint author), Massachusetts Gen Hosp, Infect Control Unit, 55 Fruit St,Bulfinch 343, Boston, MA 02114 USA. EM eshenoy@mgh.harvard.edu FU Doris Duke Charitable Foundation; Massachusetts General Hospital Departmental Funds; National Institutes of Health Training Grant [T32 A107061, K01 AI110524]; Harvard Center for AIDS Research (RPW); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University FX This work was supported by a grant from the Doris Duke Charitable Foundation to Harvard Medical School to fund Clinical Research Fellows (HEH), Massachusetts General Hospital Departmental Funds (DCH, ESS, WW, DK, HL, and PZ), National Institutes of Health Training Grants (Nos. T32 A107061 and K01 AI110524) (ESS), and the Harvard Center for AIDS Research (RPW). Support was also received 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 No. UL1 TR001102) and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. NR 22 TC 2 Z9 3 U1 3 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD JUN PY 2015 VL 43 IS 6 BP 592 EP 599 DI 10.1016/j.ajic.2015.02.019 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CJ1RI UT WOS:000355261500010 PM 25840717 ER PT J AU Alimi, A Weeth-Feinstein, LA Stettner, A Caldera, F Weiss, JM AF Alimi, Adebisi Weeth-Feinstein, Lauren A. Stettner, Amy Caldera, Freddy Weiss, Jennifer M. TI Overlap of juvenile polyposis syndrome and cowden syndrome due to de novo chromosome 10 deletion involving BMPR1A and PTEN: Implications for treatment and surveillance SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE gastroenterology; hamartoma syndrome; multiple; intestinal polyposis; pediatrics ID GENE; MUTATIONS; 10Q23; MICRODELETIONS; PATIENT; INFANCY; DISEASE; CANCER AB We describe a patient with a severe juvenile polyposis phenotype, due to a de novo deletion of chromosome 10q22.3-q24.1. He was initially diagnosed with Juvenile polyposis syndrome (JPS) at age four after presenting with hematochezia due to multiple colonic juvenile polyps. He then re-presented at 23 years with recurrent hematochezia from juvenile polyps in his ileoanal pouch. He is one of the earliest reported cases of JPS associated with a large deletion of chromosome 10. Since his initial diagnosis of JPS further studies have confirmed an association between JPS and mutations in BMPR1A in chromosome band 10q23.2, which is in close proximity to PTEN. Mutations in PTEN cause Cowden syndrome (CS) and other PTEN hamartoma tumor syndromes. Due to the chromosome 10 deletion involving contiguous portions of BMPR1A and PTEN in our patient, he may be at risk for CS associated cancers and features, in addition to the polyps associated with JPS. This case presents new challenges in developing appropriate surveillance algorithms to account for the risks associated with each syndrome and highlights the importance of longitudinal follow-up and transitional care between pediatric and adult gastroenterology for patients with hereditary polyposis syndromes. (c) 2015 Wiley Periodicals, Inc. C1 [Alimi, Adebisi; Weeth-Feinstein, Lauren A.; Caldera, Freddy; Weiss, Jennifer M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Stettner, Amy] Univ Wisconsin, Sch Med & Publ Hlth, Dept Oncol Genet, Madison, WI USA. [Caldera, Freddy; Weiss, Jennifer M.] Univ Wisconsin, Sch Med & Publ Hlth, Div Gastroenterol & Hepatol, Madison, WI USA. [Weiss, Jennifer M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. RP Weiss, JM (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Med, Div Gastroenterol & Hepatol, 1685 Highland Ave,Room 4230, Madison, WI 53705 USA. EM jmw@medicine.wisc.edu FU American Cancer Society [MRSG-13-144-01-CPHPS]; National Institutes of Health Center for Advancing Translational Sciences [UL1TR000427]; National Cancer Institute [P30CA014520-34]; UW Health Innovation Program FX Grant sponsor: American Cancer Society; Grant number: MRSG-13-144-01-CPHPS; Grant sponsor: National Institutes of Health Center for Advancing Translational Sciences; Grant number: UL1TR000427; Grant sponsor: National Cancer Institute; Grant number: P30CA014520-34; Grant sponsor: UW Health Innovation Program. NR 19 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN PY 2015 VL 167 IS 6 BP 1305 EP 1308 DI 10.1002/ajmg.a.36876 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA CJ1WV UT WOS:000355276700019 PM 25846706 ER PT J AU Jamuar, SS Duzkale, H Duzkale, N Zhang, CS High, FA Kaban, L Bhattacharya, S Crandall, B Kantarci, S Stoler, JM Lin, AE AF Jamuar, Saumya S. Duzkale, Hatice Duzkale, Neslihan Zhang, Chengsheng High, Frances A. Kaban, Leonard Bhattacharya, Soma Crandall, Barbara Kantarci, Sibel Stoler, Joan M. Lin, Angela E. TI Deletion of chromosome 8q22.1, a critical region for Nablus mask-like facial syndrome: Four additional cases support a role of genetic modifiers in the manifestation of the phenotype SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter ID MICRODELETION C1 [Jamuar, Saumya S.; Duzkale, Hatice; Zhang, Chengsheng; High, Frances A.] Harvard Univ, Sch Med, Genet Training Program, Boston, MA USA. [Jamuar, Saumya S.] KK Womens & Childrens Hosp, Dept Paediat Med, Singapore 229899, Singapore. [Duzkale, Hatice] Yeditepe Univ, Sch Med, Dept Med Genet, Istanbul, Turkey. [Duzkale, Neslihan] Osmangazi Univ, Dept Med Genet, Sch Med, Eskisehir, Turkey. [Kaban, Leonard] Massachusetts Gen Hosp, Dept Oral Maxillofacial Surg, Boston, MA 02114 USA. [Bhattacharya, Soma] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Crandall, Barbara; Kantarci, Sibel] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Stoler, Joan M.] Boston Childrens Hosp, Div Genet, Boston, MA USA. [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. RP Jamuar, SS (reprint author), KK Womens & Childrens Hosp, Dept Paediat Med, 100 Bukit Timah Rd, Singapore 229899, Singapore. EM saumya.s.jamuar@kkh.com.sg NR 10 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN PY 2015 VL 167 IS 6 BP 1400 EP 1405 DI 10.1002/ajmg.a.36848 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CJ1WV UT WOS:000355276700036 PM 25846266 ER PT J AU Ponte, PR Koppel, P AF Ponte, Patricia Reid Koppel, Paula TI Cultivating Mindfulness to Enhance Nursing Practice SO AMERICAN JOURNAL OF NURSING LA English DT Article DE mindfulness; mindfulness-based practices; mindfulness-based stress reduction; nurse-patient relationships; stress reduction; nurse-patient communication; self-care ID STRESS REDUCTION; METAANALYSIS; NURSES; HEALTH; INTERVENTION; DEPRESSION; MEDITATION; ANXIETY; PROGRAM; EMPATHY C1 [Ponte, Patricia Reid] Patient Care Serv, Washington, DC 20420 USA. [Ponte, Patricia Reid; Koppel, Paula] Dana Farber Canc Inst, Boston, MA USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Oncol Nursing Serv, Boston, MA 02115 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Clin Serv, Boston, MA 02115 USA. RP Ponte, PR (reprint author), Patient Care Serv, Washington, DC 20420 USA. EM preidponte@partners.org NR 29 TC 3 Z9 3 U1 3 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-936X EI 1538-7488 J9 AM J NURS JI Am. J. Nurs. PD JUN PY 2015 VL 115 IS 6 BP 48 EP 55 PG 8 WC Nursing SC Nursing GA CJ2IO UT WOS:000355307700018 PM 26018005 ER PT J AU Kheirkhah, A Saboo, US Abud, TB Dohlman, TH Arnoldner, MA Hamrah, P Dana, R AF Kheirkhah, Ahmad Saboo, Ujwala S. Abud, Tulio B. Dohlman, Thomas H. Arnoldner, Michael A. Hamrah, Pedram Dana, Reza TI Reduced Corneal Endothelial Cell Density in Patients With Dry Eye Disease SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID VIVO-CONFOCAL-MICROSCOPY; SUBBASAL NERVE ALTERATIONS; IN-VIVO; NEUROTROPHIC KERATITIS; DIABETES-MELLITUS; ANTERIOR SEGMENT; WORKSHOP 2007; SUBCOMMITTEE; EPIDEMIOLOGY; INNERVATION AB PURPOSE: To evaluate corneal endothelial cell density (ECD) in patients with dry eye disease (DED) compared to an age-matched control group. DESIGN: Cross-sectional, controlled study. METHODS: This study included 90 eyes of 45 patients with moderate to severe DED (aged 53.7 +/- 9.8 years) and 30 eyes of 15 normal controls (aged 50.7 +/- 9.8 years). All subjects had a complete ophthalmic evaluation including symptom assessment using the Ocular Surface Disease Index (OSDI) and corneal fluorescein staining. In addition, laser scanning in vivo confocal microscopy was performed to measure the density of the following parameters in the central cornea: endothelial cells, subbasal nerves, and subbasal immune dendritic cells. RESULTS: Corneal ECD was significantly lower in the DED group (2595.8 +/- 356.1 cells/mm(2)) than in the control group (2812.7 +/- 395.2 cells/mm(2), P =.046). The DED group showed significantly lower corneal subbasal nerve density (17.1 +/- 6.9 mm/mm(2)) compared to the control group (24.7 +/- 4.4 mm/mm(2), P <.001). Dendritic cell density was significantly higher in the DED group than in the controls (111.7 +/- 137.3 vs 32.0 +/- 24.4 cells/mm(2), respectively, P =.002). There were statistically significant correlations between corneal ECD and dry eye severity parameters including the OSDI score (r(s) = 0.26, P =.03), and corneal fluorescein staining (r(s) = 0.28, P =.008). CONCLUSIONS: There is a significant reduction in corneal ECD in DED that correlates with clinical severity of the disease. (C) 2015 by Elsevier Inc. All rights reserved.) C1 [Kheirkhah, Ahmad; Saboo, Ujwala S.; Abud, Tulio B.; Dohlman, Thomas H.; Arnoldner, Michael A.; Hamrah, Pedram; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, Boston, MA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Reza_Dana@meei.harvard.edu FU NIH (Bethesda, Maryland) [K24-EY019098]; Falk Medical Research Trust; Massachusetts Eye and Ear Infirmary Foundation (Boston, Massachusetts) FX Funding/Support: NIH K24-EY019098 (Bethesda, Maryland), Falk Medical Research Trust, Massachusetts Eye and Ear Infirmary Foundation (Boston, Massachusetts). All authors attest that they meet the current ICMJE requirements to qualify as authors. NR 39 TC 3 Z9 3 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2015 VL 159 IS 6 BP 1022 EP 1026 DI 10.1016/j.ajo.2015.03.011 PG 5 WC Ophthalmology SC Ophthalmology GA CI9DL UT WOS:000355070500004 PM 25782347 ER PT J AU Hamrah, P Sahin, A Dastjerdi, MH Shahatit, BM Bayhan, HA Dana, R Pavan-Langston, D AF Hamrah, Pedram Sahin, Afsun Dastjerdi, Mohammad H. Shahatit, Bashar M. Bayhan, Hasan A. Dana, Reza Pavan-Langston, Deborah TI In Vivo Confocal Microscopic Changes of the Corneal Epithelium and Stroma in Patients With Herpes Zoster Ophthalmicus SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID LASER-SCANNING MICROSCOPY; NERVE GROWTH-FACTOR; RABBIT CORNEA; SJOGRENS-SYNDROME; DRY EYE; KERATITIS; MORPHOLOGY; SENSATION AB PURPOSE: To analyze the density and morphology of corneal epithelial cells and keratocytes by in vivo confocal microscopy (IVCM) in patients with herpes zoster ophthalmicus (HZO) as associated with corneal innervation. DESIGN: Prospective, controlled and masked cross-sectional study. METHODS: SETTING: Single-center study. PATIENTS: Thirty eyes with the diagnosis HZO and their contralateral clinically unaffected eyes, 15 eyes of 15 normal controts. INTERVENTION PROCEDURES: In vivo confocal microscopy and corneal esthesiometry of the central cornea. MAIN OUTCOME MEASURES: Changes in morphology and density of the superficial and basal epithelial cells and stromal keratocytes, and correlation with corneal sensation. RESULTS: The density of superficial epithelial cells in HZO eyes with severe sensation loss (766.5 +/- 25.2 cells/mm(2)) was significantly lower than both healthy control eyes (1450.23 +/- 150.83 cells/mm(2)) and contralateral unaffected eyes (1974.13 +/- 298.24 cells/mm(2)) (P =.003). Superficial epithelial cell size (1162.5 mu m(2)) was significantly larger in HZO eyes with severe loss of sensation, as compared to contralateral (441.46 +/- 298.14) or healthy eyes (407.4 +/- 47.2 mu m(2); all P <.05). The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients, controls, and contralateral unaffected eyes. Changes in superficial epithelial cell density and morphology correlated strongly with corneal sensation. " CONCLUSIONS: In vivo confocal microscopy reveals profound HZO-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. We demonstrate that these changes strongly correlate with changes in corneal innervation in eyes affected by HZO. (C) 2015 by Elsevier Inc. All rights reserved.) C1 [Hamrah, Pedram; Sahin, Afsun; Shahatit, Bashar M.; Bayhan, Hasan A.] Harvard Univ, Ocular Surface Imaging Ctr, Sch Med, Boston, MA 02114 USA. [Hamrah, Pedram; Dastjerdi, Mohammad H.; Shahatit, Bashar M.; Dana, Reza; Pavan-Langston, Deborah] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, Boston, MA 02114 USA. [Sahin, Afsun] Eskisehir Osmangazi Univ, Med Sch, Dept Ophthalmol, Eskisehir, Turkey. RP Hamrah, P (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu FU NIH (Bethesda, Maryland, USA) [K08-EY020575, K24-EY019098]; Falk Medical Research Foundation (Chicago, Ilinois, USA); Research to Prevent Blindness Career Development Award (New York, New York, USA); Johnstone Research Foundation (Chicago, Illinois, USA); Stevens Fund (Boston, Massachusetts, USA); TUBITAK (Ankara, Turkey) [111S437] FX Funding support: NIH K08-EY020575 (Bethesda, Maryland, USA) (P.H.), NIH K24-EY019098 (Bethesda, Maryland, USA) (R.D.), Falk Medical Research Foundation (Chicago, Ilinois, USA) (P.H.), Research to Prevent Blindness Career Development Award (New York, New York, USA) (P.H.), Johnstone Research Foundation (Chicago, Illinois, USA) (D.P.L.),. Stevens Fund (Boston, Massachusetts, USA) (D.P.L.), TUBITAK 111S437 (Ankara, Turkey) (A.S.). The funding organizations had no role in the design or conduct of this research. All authors attest that they meet the current ICMJE requirements to qualify as authors. NR 41 TC 5 Z9 5 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2015 VL 159 IS 6 BP 1036 EP 1044 DI 10.1016/j.ajo.2015.03.003 PG 9 WC Ophthalmology SC Ophthalmology GA CI9DL UT WOS:000355070500006 PM 25748579 ER PT J AU Jakobiec, FA Kool, M Stagner, AM Pfister, SM Eagle, RC Proia, AD Korshunov, A AF Jakobiec, Frederick A. Kool, Marcel Stagner, Anna M. Pfister, Stefan M. Eagle, Ralph C. Proia, Alan D. Korshunov, Andrey TI Intraocular Medulloepitheliomas and Embryonal Tumors With Multilayered Rosettes of the Brain: Comparative Roles of LIN28A and C19MC SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CILIARY BODY MEDULLOEPITHELIOMA; MALIGNANT TERATOID MEDULLOEPITHELIOMA; OF-THE-LITERATURE; CEREBRAL MEDULLOEPITHELIOMA; ABUNDANT NEUROPIL; TRUE ROSETTES; NEUROECTODERMAL TUMOR; OPTIC CUP; DIFFERENTIATION; AMPLIFICATION AB PURPOSE: To compare immunohistochemical and genetic overlaps and differences between intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain. " DESIGN: Retrospective histopathologic, immunohistochemical, and genetic analysis of 20 intraocular medulloepitheliomas. METHODS: (1) Review of clinical data and hematoxylin-eosin-stained sections with (2) immunohistochemical staining of paraffin sections using a polyclonal antibody against the protein LIN28A, and (3) fluorescence in situ hybridization (FISH) testing for the amplification of the genetic locus 19q13.42 involving the C19MC cluster of miRNA. Ten retinoblastomas served as controls and to determine the specificity of these biomarkers for intraocular medulloepitheliomas. " RESULTS: Nineteen of the 20 intraocular medulloepitheliomas were either diffusely or focally LIN28A positive (weak, moderate, or strong). The most intense positivity correlated with aggressive behavior such as intraocular tissue invasion or extraocular extension. None of the cases studied by FISH harbored an amplicon for C19MC. The 10 retinoblastomas were LIN28A and C19MC negative. CONCLUSION: LIN28A has a putative role in oncogenesis and is found only in embryonic cells and malignancies. Intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain both display LIN28A positivity. Only the latter, however, display amplification of the 19q13.42 locus involving C19MC, implying that other causative factors are at play in intraocular medulloepitheliomas. More aggressive tumor behavior within the eye can be partially predicted by LIN28A staining intensity. (C) 2015 by Elsevier Inc. All rights reserved. C1 [Jakobiec, Frederick A.; Stagner, Anna M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, Boston, MA USA. [Korshunov, Andrey] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany. [Korshunov, Andrey] Univ Hosp, Dept Neuropathol, Heidelberg, Germany. [Kool, Marcel; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany. [Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany. [Eagle, Ralph C.] Thomas Jefferson Univ, Wills Eye Hosp, Philadelphia, PA 19107 USA. [Proia, Alan D.] Duke Univ, Dept Pathol, Durham, NC 27706 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 328,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu RI Pfister, Stefan/F-6860-2013 OI Pfister, Stefan/0000-0002-5447-5322 NR 48 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2015 VL 159 IS 6 BP 1065 EP 1074 DI 10.1016/j.ajo.2015.03.002 PG 10 WC Ophthalmology SC Ophthalmology GA CI9DL UT WOS:000355070500010 PM 25748578 ER PT J AU Penman, A Hoadley, S Wilson, JG Taylor, HA Chen, CJ Sobrin, L AF Penman, Alan Hoadley, Suzanne Wilson, James G. Taylor, Herman A. Chen, Ching J. Sobrin, Lucia TI P-selectin Plasma Levels and Genetic Variant Associated With Diabetic Retinopathy in African Americans SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; C-REACTIVE PROTEIN; RISK-FACTORS; UNITED-STATES; FASTING GLUCOSE; RESOURCE CARE; TNF-ALPHA; POPULATION; PREVALENCE; EYE AB PURPOSE: To report the prevalence and risk factors for retinopathy in African Americans with impaired fasting glucose (IFG) and type 2 diabetes in the Jackson Heart Study and to determine if P-selectin plasma levels are independently associated with retinopathy in this population. DESIGN: Prospective, cross-sectional observational study. METHODS: SETTING: Community-based epidemiologic study. STUDY POPULATION: Total of 629 patients with type 2 diabetes and 266 participants with impaired fasting glucose. OBSERVATION PROCEDURES: Bilateral, 7-field fundus photographs were scored by masked readers for diabetic retinopathy (DR) level. Covariate data including P-selectin plasma levels and genotypes were collected in a standardized fashion. MAIN OUTCOME MEASURES: Association between risk factors, including P-selectin plasma levels and genotypes, and retinopathy. RESULTS: The prevalences of any retinopathy among participants with IFG and type 2 diabetes were 9.4% and 32.4%, respectively. Among those with type 2 diabetes, in multivariate models adjusted for age, sex, and other traditional risk factors, higher P-selectin levels were associated with any DR (odds ratio = 1.11, 95% confidence interval = 1.02-1.21, P =.02) and proliferative DR (odds ratio = 1.23, 95% confidence interval = 1.03-1.46, P =.02). To further investigate the relationship between P-selectin and DR, we examined the association between P-selectin genotype and DR. Minor allele homozygotes for the variant rs6128 were less likely to develop DR (P after Bonferroni correction = 0.03). CONCLUSIONS: Both serologic and genetic data show an association between P-selectin and DR in the Jackson Heart Study. If confirmed in other studies, this association may provide insight into the pathogenesis of retinopathy. (C) 2015 by Elsevier Inc. All rights reserved.) C1 [Penman, Alan] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA. [Hoadley, Suzanne; Chen, Ching J.] Univ Mississippi, Med Ctr, Dept Ophthalmol, Jackson, MS 39216 USA. [Taylor, Herman A.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Wilson, James G.] Univ Mississippi, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Sobrin, L (reprint author), 243 Charles St,12th Floor, Boston, MA 02114 USA. EM lucia_sobrin@meei.harvard.edu FU National Eye Institute, Bethesda, Maryland [K12-EY16335]; Research to Prevent Blindness Career Development Award and William & Mary Greve Special Scholar Award, New York, New York; Harvard Catalyst \ The Harvard Clinical and Translations Science Center Faculty Fellowship, Boston, Massachusetts; Massachusetts Lions Eye Research Fund, Abington, Massachusetts; Eleanor and Miles Shore Fellowship, Boston, Massachusetts; Sara Elizabeth O'Brien Trust, Boston, Massachusetts; National Heart, Lung and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities, Bethesda, Maryland FX Funding/Support: National Eye Institute K12-EY16335, Bethesda, Maryland; Research to Prevent Blindness Career Development Award and William & Mary Greve Special Scholar Award, New York, New York; Harvard Catalyst vertical bar The Harvard Clinical and Translations Science Center Faculty Fellowship, Boston, Massachusetts; Massachusetts Lions Eye Research Fund, Abington, Massachusetts; Eleanor and Miles Shore Fellowship, Boston, Massachusetts; Sara Elizabeth O'Brien Trust, Boston, Massachusetts. The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and HHSN268201300050C from the National Heart, Lung and Blood Institute and the National Institute on Minority Health and Health Disparities, Bethesda, Maryland. All authors attest that they meet the current ICMJE requirements to qualify as authors. NR 40 TC 5 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2015 VL 159 IS 6 BP 1152 EP 1160 DI 10.1016/j.ajo.2015.03.008 PG 9 WC Ophthalmology SC Ophthalmology GA CI9DL UT WOS:000355070500019 PM 25794792 ER PT J AU Amri, R Bordeianou, LG Sylla, P Berger, DL AF Amri, Ramzi Bordeianou, Liliana G. Sylla, Patricia Berger, David L. TI The fate of unscreened women in colon cancer: impact on staging and prognosis SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Sex disparities; Screening; Colon cancer; Baseline characteristics; Surgical stay characteristics; Outcomes ID COLORECTAL-CANCER; UNITED-STATES; CO-MORBIDITY; MORTALITY; RECOMMENDATION; SURVIVAL; PATTERNS; OUTCOMES AB BACKGROUND: Several nationwide reports show lower female participation in colon cancer screening. We therefore assessed for outcome differences in women of screening age presenting for surgical treatment of colon cancer patients. METHODS: All patients over 50 years undergoing surgery for first-onset colon cancer at Massachusetts General Hospital (2004 to 2011) were included. Differences between (unscreened) women and the remaining population in presentation characteristics and subsequent morbidity and mortality were assessed. RESULTS: We included 919 patients (49.1% female). Women were less often diagnosed through screening (26.4 vs 32.7%, P = .036). Unscreened women were at significantly higher risk (all P < .001) for having high-grade tumors (Relative risk [RR] - 1.61), lymph nodemetastasis (RR - 1.36), and distant metastasis (RR = 2.26) on pathology, leading to higher colon cancer-related mortality (RR = 1.72). CONCLUSION: Unscreened women present with more advanced colon cancer and higher mortality, confirming that disparities in screening lead to ever-increasing disparities in outcomes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Berger, David L.] Harvard Univ, Sch Med, Div Gen Surg & Gastrointestinal Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Berger, DL (reprint author), Harvard Univ, Sch Med, Div Gen Surg & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. EM dberger@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 FU 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; Dutch Cancer Society; Dutch Digestive Society; Amsterdam University Funds; Royal Netherlands Academy of Arts and Sciences; Fulbright Foundation FX This work was 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 healthcare centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic healthcare centers, or the National Institutes of Health. This work was also supported in part by the Dutch Cancer Society, the Dutch Digestive Society, the Amsterdam University Funds, the Royal Netherlands Academy of Arts and Sciences, and the Fulbright Foundation. NR 23 TC 1 Z9 1 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD JUN PY 2015 VL 209 IS 6 BP 927 EP 934 DI 10.1016/j.amjsurg.2014.09.033 PG 8 WC Surgery SC Surgery GA CI9WL UT WOS:000355120700002 PM 25724080 ER PT J AU Sahora, K Morales-Oyarvide, V Thayer, SP Ferrone, CR Warshaw, AL Lillemoe, KD Fernandez-del Castillo, C AF Sahora, Klaus Morales-Oyarvide, Vicente Thayer, Sarah P. Ferrone, Christina R. Warshaw, Andrew L. Lillemoe, Keith D. Fernandez-del Castillo, Carlos TI The effect of antecolic versus retrocolic reconstruction on delayed gastric emptying after classic non-pylorus-preserving pancreaticoduodenectomy SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Delayed gastric emptying; Pancreaticoduodenectomy; Antecolic; Retrocolic; Whipple resection; Reconstruction ID INTERNATIONAL STUDY-GROUP; PANCREATIC SURGERY ISGPS; CONSECUTIVE PATIENTS; RISK-FACTORS; DEFINITION; DUODENOJEJUNOSTOMY; ROUTE; COMPLICATIONS; METAANALYSIS; ANASTOMOSIS AB BACKGROUND: Delayed gastric emptying (DGE) after pancreaticoduodenectomy increases length of hospital stay and costs, and may be influenced by surgical techniques. METHODS: We retrospectively compared 400 patients with antecolic gastrojejunostomy with 400 patients with retrocolic gastrojejunostomy for the occurrence of DGE. RESULTS: The prevalence of DGE was 15% in the antecolic group and 21% in the retrocolic group (P = .021), and median length of stay was shorter for the former (8 vs 10 days, P = .001). The difference was statistically significant with grade A DGE (9% vs 14%, P = .038), but not B or C. In a multivariate analysis, DGE was influenced by retrocolic reconstruction, as well as older age, chronic pancreatitis, preoperative bilirubin level, a history of previous upper abdominal surgery, and postoperative pancreatic fistula. CONCLUSIONS: An antecolic gastrojejunostomy for classic non-pylorus-preserving pancreaticoduodenectomy is associated with a lower incidence of mild DGE (grade A) and a shorter length of stay. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sahora, Klaus; Morales-Oyarvide, Vicente; Thayer, Sarah P.; Ferrone, Christina R.; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM cfernandez@partners.org NR 37 TC 4 Z9 7 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD JUN PY 2015 VL 209 IS 6 BP 1028 EP 1035 DI 10.1016/j.amjsurg.2014.04.015 PG 8 WC Surgery SC Surgery GA CI9WL UT WOS:000355120700016 PM 25124295 ER PT J AU Sims, M Redmond, N Khodneva, Y Durant, RW Halanych, J Safford, MM AF Sims, Mario Redmond, Nicole Khodneva, Yulia Durant, Raegan W. Halanych, Jewell Safford, Monika M. TI Depressive symptoms are associated with incident coronary heart disease or revascularization among blacks but not among whites in the Reasons for Geographical and Racial Differences in Stroke study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Coronary disease; Epidemiology; Depressive symptoms; Myocardial infarction ID BYPASS GRAFT-SURGERY; PSYCHOSOCIAL FACTORS; AFRICAN-AMERICANS; RISK-FACTOR; CARDIOVASCULAR MORTALITY; STATISTICS-COMMITTEE; CARIBBEAN BLACKS; YOUNG-ADULTS; OLDER-ADULTS; RACE AB Purpose: To examine the association of depressive symptoms with coronary heart disease (CHD) end points by race and income. Methods: Study participants were blacks and whites (n = 24,443) without CHD at baseline from the national Reasons for Geographical and Racial Differences in Stroke cohort. Outcomes included acute CHD and CHD or revascularization. We estimated race-stratified multivariate Cox proportional hazards models of incident CHD and incident CHD or revascularization with the 4-item Center for Epidemiological Studies Depression Scale, adjusting for risk factors. Results: Mean follow-up was 4.2 +/- 1.5 years; CHD incidence was 8.3 events per 1000 person-years (n = 366) among blacks and 8.8 events per 1000 person-years (n = 613) among whites. After adjustment for age, sex, marital status, region, and socioeconomic status, depressive symptoms were significantly associated with incident CHD among blacks (hazard ratio [HR], 139; 95% confidence interval [Cl], 1.00-1.91) but not among whites (HR, 1.10; 95% Cl, 0.74-1.64). In the fully adjusted model, compared with blacks who reported no depressive symptoms, those reporting depressive symptoms had greater risk for the composite end point of CHD or revascularization (HR, 1.36; 95% CI, 1.01-1.81). Depressive symptoms were not associated with incident CHD end points among whites. Conclusions: High depressive symptoms were associated with higher risk of CHD or revascularization for blacks but not whites. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sims, Mario] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39213 USA. [Redmond, Nicole; Khodneva, Yulia; Durant, Raegan W.; Halanych, Jewell; Safford, Monika M.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA. [Durant, Raegan W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Sims, M (reprint author), Univ Mississippi, Med Ctr, Jackson Heart Study, Dept Med, 350 W Woodrow Wilson Dr, Jackson, MS 39213 USA. EM msims2@umc.edu FU National Institute of Neurological Disorders and Stroke [U01NSO41588] FX The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org. REGARDS is supported by cooperative agreement U01NSO41588 from the National Institute of Neurological Disorders and Stroke (Dr. G. Howard, PI). NR 51 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUN PY 2015 VL 25 IS 6 BP 426 EP 432 DI 10.1016/j.annepidem.2015.03.014 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CI8KM UT WOS:000355021200007 PM 25891100 ER PT J AU Serrano-Pozo, A Qian, J Monsell, SE Betensky, RA Hyman, BT AF Serrano-Pozo, Alberto Qian, Jing Monsell, Sarah E. Betensky, Rebecca A. Hyman, Bradley T. TI APOE epsilon 2 is associated with milder clinical and pathological Alzheimer disease SO ANNALS OF NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; E-EPSILON 4; CEREBRAL AMYLOID ANGIOPATHY; UNIFORM DATA SET; COGNITIVE DECLINE; NEUROPATHOLOGIC ASSESSMENT; NATIONAL INSTITUTE; TRANSGENIC MICE; APOE GENOTYPE; NEUROFIBRILLARY TANGLES AB ObjectiveThe Alzheimer disease (AD) APOE epsilon 4 risk allele associates with an earlier age at onset and increased amyloid- deposition, whereas the protective APOE epsilon 2 allele delays the onset and appears to prevent amyloid- deposition. Yet the clinical and pathological effects of APOE epsilon 2 remain uncertain because of its relative rarity. We investigated the effects of APOE epsilon 2 and epsilon 4 alleles on AD pathology and cognition in a large US data set of well-characterized AD patients. MethodsWe studied individuals from the National Alzheimer's Coordinating Center autopsy cohort across the entire clinicopathological continuum of AD. Multivariate models were built to examine the associations between APOE alleles and AD neuropathological changes, using the APOE epsilon 3/epsilon 3 group as comparator. Mediation analysis was used to estimate the direct and indirect effects of APOE alleles on AD pathology and cognition (Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination). ResultsCompared to APOE epsilon 3/epsilon 3, APOE epsilon 2 is independently associated with lower Braak neurofibrillary tangle (NFT) stages and possibly fewer neuritic plaques, but has no direct effect on cerebral amyloid angiopathy (CAA) severity, whereas APOE epsilon 4 is associated with more neuritic plaques and CAA, but has no independent effect on Braak NFT stage. Unadjusted analyses showed marked differences among APOE genotypes with respect to cognitive performance (epsilon 2>epsilon 3>epsilon 4). Mediation analysis suggests that this is largely explained through effects on pathology. InterpretationEven when adjusted for age at onset, symptom duration, and other demographic variables, APOE epsilon 2 is associated with milder AD pathology and less severe antemortem cognitive impairment compared to APOE epsilon 3 and epsilon 4 alleles, suggesting a relative neuroprotective effect of APOE epsilon 2 in AD. Ann Neurol 2015;77:917-929 C1 [Serrano-Pozo, Alberto; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Serrano-Pozo, Alberto; Betensky, Rebecca A.; Hyman, Bradley T.] Massachusetts Alzheimer Dis Res Ctr, Charlestown, MA 02129 USA. [Serrano-Pozo, Alberto] Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA. [Qian, Jing] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Monsell, Sarah E.] Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA USA. [Monsell, Sarah E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Hyman, BT (reprint author), Massachusetts Alzheimer Dis Res Ctr, 16th St,Bldg 114, Charlestown, MA 02129 USA. EM bhyman@mgh.harvard.edu OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU Massachusetts Alzheimer's Disease Research Center (NIH) [P50 AG0001534]; Harvard NeuroDiscovery Center; NIH NIA [U01 AG016976] FX This work was supported by the Massachusetts Alzheimer's Disease Research Center (NIH grant P50 AG0001534, B.T.H.) and the Harvard NeuroDiscovery Center (J.Q., R.A.B.). The NACC database is funded by NIH NIA grant U01 AG016976. NR 88 TC 20 Z9 20 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2015 VL 77 IS 6 BP 917 EP 929 DI 10.1002/ana.24369 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ1GA UT WOS:000355230100003 PM 25623662 ER PT J AU Gardner, RC Burke, JF Nettiksimmons, J Goldman, S Tanner, CM Yaffe, K AF Gardner, Raquel C. Burke, James F. Nettiksimmons, Jasmine Goldman, Sam Tanner, Caroline M. Yaffe, Kristine TI Traumatic brain injury in later life increases risk for Parkinson disease SO ANNALS OF NEUROLOGY LA English DT Article ID HEAD-INJURY; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; IMPROVES ACCURACY; SEVERITY SCORE; DEMENTIA; PARAQUAT; COHORT AB ObjectiveTraumatic brain injury (TBI) is thought to be a risk factor for Parkinson disease (PD), but results are conflicting. Many studies do not account for confounding or reverse causation. We sought to address these concerns by quantifying risk of PD after TBI compared to non-TBI trauma (NTT; defined as fractures). MethodsUsing inpatient/emergency department (ED) International Classification of Disease, Ninth Revision code data for California hospitals from 2005-2006, we identified patients aged 55 years with TBI (n=52,393) or NTT (n=113,406) and without baseline PD or dementia who survived hospitalization. Using Kaplan-Meier estimates and Cox proportional hazards models (adjusted for age, sex, race/ethnicity, income, comorbidities, health care use, and trauma severity), we estimated risk of PD after TBI during follow-up ending in 2011. We also assessed interaction with mechanism of injury (fall vs nonfall) and effect of TBI severity (mild vs moderate/severe) and TBI frequency (1 TBI vs >1 TBI). ResultsTBI patients were significantly more likely to be diagnosed with PD compared to NTT patients (1.7% vs 1.1%, p<0.001, adjusted hazard ratio [HR]=1.44, 95% confidence interval [CI]=1.31-1.58). Risk of PD was similar for TBI sustained via falls versus nonfalls (interaction p=0.6). Assessment by TBI severity (mild TBI: HR=1.24, 95% CI=1.04-1.48; moderate/severe TBI: HR=1.50, 95% CI=1.35-1.66) and TBI frequency (1 TBI: HR=1.45, 95% CI=1.30-1.60; >1 TBI: HR=1.87, 95% CI=1.58-2.21) revealed a dose response. InterpretationAmong patients aged 55 years presenting to inpatient/ED settings with trauma, TBI is associated with a 44% increased risk of developing PD over 5 to 7 years that is unlikely to be due to confounding or reverse causation. Ann Neurol 2015;77:987-995 C1 [Gardner, Raquel C.; Goldman, Sam; Tanner, Caroline M.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Gardner, Raquel C.; Nettiksimmons, Jasmine; Goldman, Sam; Tanner, Caroline M.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Burke, James F.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Burke, James F.] Ann Arbor VA Healthcare Syst, Dept Vet Affairs, VA Ctr Clin Management & Res, Ann Arbor, MI USA. [Nettiksimmons, Jasmine; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Gardner, RC (reprint author), 4150 Clement St,Neurol 127, San Francisco, CA 94121 USA. EM raquel.gardner@ucsf.edu FU Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; Medical Research Service of the San Francisco Veterans Affairs Medical Center; Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center; UCSF Pepper Center Research Career Development Core; NIH [K24 AG031155, K08 NS082597]; Department of Defense [W81XWH-12-1-0581]; Department of Veterans Affairs; California Department of Public Health; Bright Focus Foundation; Alzheimer's Association; USCF FX This study was supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment (R.C.G.); Medical Research Service of the San Francisco Veterans Affairs Medical Center (R.C.G.); Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center (R.C.G.); the UCSF Pepper Center Research Career Development Core (R.C.G.); NIH (K24 AG031155, K.Y.; K08 NS082597, J.F.B.); Department of Defense (W81XWH-12-1-0581, K.Y.); Department of Veterans Affairs (K.Y.); California Department of Public Health (K.Y.); Bright Focus Foundation (K.Y.); and Alzheimer's Association (K.Y.). [Correction added on April 27, 2015, after first online publication: USCF support added for R.C.G.]. The authors thank the Healthcare Cost and Utilization Project for compiling and managing the data used in this study. NR 39 TC 32 Z9 32 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2015 VL 77 IS 6 BP 987 EP 995 DI 10.1002/ana.24396 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ1GA UT WOS:000355230100008 PM 25726936 ER PT J AU Singh, JA Ramachandran, R AF Singh, Jasvinder A. Ramachandran, Rekha TI Does Hospital Volume Predict Outcomes and Complications After Total Shoulder Arthroplasty in the US? SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SURGEON PROCEDURE VOLUME; TOTAL KNEE ARTHROPLASTY; TOTAL HIP-REPLACEMENT; UNITED-STATES; ASSOCIATION; POPULATION; DATABASES AB ObjectiveTo assess the association of hospital procedure volume for total shoulder arthroplasty (TSA) with patient outcomes and complications. MethodsWe used the US Nationwide Inpatient Sample from 1998-2011 to study the association of hospital annual TSA procedure volume with patient characteristics and TSA outcomes, including discharge disposition (home versus inpatient facility), length of index hospitalization, postarthroplasty periprosthetic fracture, and revision. Annual hospital TSA volume was categorized as <5, 5-9, 10-14, 15-24, and 25 TSA procedures annually. ResultsPatients receiving TSA at higher volume hospitals were more likely to be female (P<0.0001) and white (P<0.0001). Compared to low volume hospitals (<5, 5-9, or 10-14 procedures annually), patients receiving TSA at higher volume hospitals (15-24 or 25 procedures annually) had significantly lower likelihood of being discharged to an inpatient medical facility: 16.5%, 13.4%, 13.0%, 12.7%, and 11.5%, respectively (P<0.0001); hospital stay above the overall median: 46.6%, 40.4%, 36.6%, 34.4%, and 29.2%, respectively (P<0.0001); postarthroplasty fracture: 1.2%, 0.8%, 0.9%, 0.6%, and 0.8%, respectively (P=0.0004); blood transfusion: 8%, 7.1%, 6.7%, 7.1%, and 5.5%, respectively (P=0.006); and TSA revision: 0.5%, 0.3%, 0.2%, 0.3%, 0.3%, respectively (P=0.045). ConclusionIn this study, we found that higher annual hospital TSA volume was associated with better TSA outcomes in the US. These findings document the impact of annual hospital TSA volume on TSA outcomes. Patients, surgeons, and policy-makers should be aware of these findings and take them into account in decision-making, policy decisions, and resource allocation. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Agency for Health Quality and Research Center for Education and Research on Therapeutics [U19-HS-021110]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [P50-AR-060772, U34-AR-062891]; National Institute on Aging [U01-AG-018947]; National Cancer Institute [U10-CA-149950]; Patient Centered Outcomes Research Institute [CE-1304-6631]; Takeda; Savient FX Dr. Singh's work was supported by the Agency for Health Quality and Research Center for Education and Research on Therapeutics (grant U19-HS-021110), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants P50-AR-060772 and U34-AR-062891), the National Institute on Aging (grant U01-AG-018947), the National Cancer Institute (grant U10-CA-149950), the Patient Centered Outcomes Research Institute (research contract CE-1304-6631), and by the resources and facilities at the VA Medical Center at Birmingham, Alabama.; Dr. Singh has received research grants (more than $10,000 each) from Takeda and Savient, honoraria (less than $10,000 each) from Allergan, Savient, and Regeneron, and (more than $10,000) from Takeda. NR 14 TC 5 Z9 5 U1 0 U2 2 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 JUN PY 2015 VL 67 IS 6 BP 885 EP 890 DI 10.1002/acr.22507 PG 6 WC Rheumatology SC Rheumatology GA CJ2QQ UT WOS:000355330000019 PM 25370499 ER PT J AU Miloslavsky, EM Specks, U Merkel, PA Seo, P Spiera, R Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Tchao, NK Ding, L Ikle, D Villareal, M Lim, N Brunetta, P Fervenza, FC Monach, PA Stone, JH AF Miloslavsky, E. M. Specks, U. Merkel, P. A. Seo, P. Spiera, R. Langford, C. A. Hoffman, G. S. Kallenberg, C. G. M. St Clair, E. W. Tchao, N. K. Ding, L. Ikle, D. Villareal, M. Lim, N. Brunetta, P. Fervenza, F. C. Monach, P. A. Stone, J. H. CA Rituximab Anca-Associated Vasculit TI Outcomes of Nonsevere Relapses in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Treated With Glucocorticoids SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID ANCA-ASSOCIATED VASCULITIS; DAILY ORAL CYCLOPHOSPHAMIDE; WEGENERS-GRANULOMATOSIS; RANDOMIZED-TRIAL; MAINTENANCE THERAPY; REMISSION; METHOTREXATE; INDUCTION; RITUXIMAB; AZATHIOPRINE AB Objective. Nonsevere relapses are more common than severe relapses in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but their clinical course and treatment outcomes remain largely unexamined. We undertook this study to analyze the outcomes of patients with nonsevere relapses in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial who were treated with prednisone according to a prespecified protocol. Methods. RAVE was a randomized, double-blind, placebo-controlled trial comparing rituximab (RTX) to cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission. Patients who experienced nonsevere relapses between months 1 and 18 were treated with a prednisone increase without a concomitant change in their nonglucocorticoid immunosuppressants, followed by a taper. Results. Forty-four patients with a first nonsevere relapse were analyzed. In comparison to the 71 patients who maintained relapse-free remission over 18 months, these patients were more likely to have proteinase 3-ANCAs, diagnoses of granulomatosis with polyangiitis (Wegener's), and a history of relapsing disease at baseline. A prednisone increase led to remission in 35 patients (80%). However, only 13 patients (30%) were able to maintain second remissions through the followup period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of them with severe disease. The mean time to second relapse was 9.4 months (4.7 months in the group treated with RTX versus 13.7 months in the group treated with CYC/AZA; P<0.01). Patients who experienced nonsevere relapses received more glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams; P<0.01). Conclusion. Treatment of nonsevere relapses in AAV with an increase in glucocorticoids is effective in restoring temporary remission in the majority of patients, but recurrent relapses within a relatively short interval remain common. Alternative treatment approaches are needed for this important subset of patients. C1 [Miloslavsky, E. M.; Stone, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Specks, U.; Fervenza, F. C.] Mayo Clin, Rochester, MN USA. [Merkel, P. A.] Univ Penn, Philadelphia, PA 19104 USA. [Seo, P.] Johns Hopkins Univ, Baltimore, MD USA. [Spiera, R.] Hosp Special Surg, New York, NY 10021 USA. [Langford, C. A.; Hoffman, G. S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kallenberg, C. G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, E. W.] Duke Univ, Med Ctr, Durham, NC USA. [Tchao, N. K.] Immune Tolerance Network, San Francisco, CA USA. [Ding, L.] NIAID, NIH, Bethesda, MD 20892 USA. [Ikle, D.; Villareal, M.] Rho, Chapel Hill, NC USA. [Lim, N.] Immune Tolerance Network, Bethesda, MD USA. [Brunetta, P.] Genentech Inc, San Francisco, CA 94080 USA. [Monach, P. A.] Boston Univ, Boston, MA 02215 USA. [Monach, P. A.] Boston Med Ctr, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2C,55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org FU Immune Tolerance Network (NIH) [N01-AI-15416, ITN021AI]; National Institute of Allergy and Infectious Diseases, NIH; Juvenile Diabetes Research Foundation; Genentech; Biogen Idec; NIH (Mayo Clinic: National Center for Research Resources Clinical and Translational Science award) [1-UL1-RR-024150-01]; NIH (Johns Hopkins University: National Center for Research Resources Clinical and Translational Science) [UL1-RR-025005, K23-AR-052820, K24-AR-049185]; NIH (Boston University: National Center for Research Resources Clinical and Translational Science) [UL1-RR-025771, M01-RR-00533, K24-AR-02224]; NIH (Cleveland Clinic: National Center for Advancing Translational Sciences) [UL1-TR-000439]; Arthritis Foundation; ChemoCentryx; GlaxoSmithKline; Eli Lilly; MedImmune FX The Rituximab in ANCA-Associated Vasculitis (RAVE) trial was performed with the support of the Immune Tolerance Network (NIH contract N01-AI-15416, protocol number ITN021AI), an international clinical research consortium headquartered at the University of California San Francisco and supported by the National Institute of Allergy and Infectious Diseases, NIH, and the Juvenile Diabetes Research Foundation. Genentech and Biogen Idec provided the study medication and partial funding for the RAVE trial. At the Mayo Clinic, Johns Hopkins University, Boston University, and the Cleveland Clinic, the RAVE trial was supported by the NIH (Mayo Clinic: National Center for Research Resources Clinical and Translational Science award 1-UL1-RR-024150-01; Johns Hopkins University: National Center for Research Resources Clinical and Translational Science award UL1-RR-025005 and career development awards K23-AR-052820 to Dr. Seo and K24-AR-049185 to Dr. Stone; Boston University: National Center for Research Resources Clinical and Translational Science award UL1-RR-025771, grant M01-RR-00533, and career development award K24-AR-02224 to Dr. Merkel; Cleveland Clinic: National Center for Advancing Translational Sciences grant UL1-TR-000439). The RAVE trial at Boston University was also supported by the Arthritis Foundation (Investigator Award to Dr. Monach).; Dr. Miloslavsky has received consulting fees, speaking fees, and/or honoraria (less than $10,000) and research funding from Genentech. Dr. Specks has received consulting fees, speaking fees, and/or honoraria from Genentech (less than $10,000). Dr. Kallenberg has received consulting fees from ChemoCentryx, GlaxoSmithKline, Eli Lilly, and MedImmune (less than $10,000 each). Dr. Brunetta owns stock or stock options in Genentech. Dr. Monach has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Genentech. Dr. Stone has received consulting fees, speaking fees, and/or honoraria from Genentech (less than $10,000). NR 27 TC 11 Z9 11 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JUN PY 2015 VL 67 IS 6 BP 1629 EP 1636 DI 10.1002/art.39104 PG 8 WC Rheumatology SC Rheumatology GA CJ2QA UT WOS:000355328400026 PM 25776953 ER PT J AU Weiss, NH Tull, MT Davis, LT Searcy, J Williams, I Gratz, KL AF Weiss, Nicole H. Tull, Matthew T. Davis, Lindsey T. Searcy, Jasmin Williams, Iman Gratz, Kim L. TI A Preliminary Experimental Investigation of Emotion Dysregulation and Impulsivity in Risky Behaviours SO BEHAVIOUR CHANGE LA English DT Article DE emotion dysregulation; impulsivity; risky behaviours; African American; experimental design ID DELIBERATE SELF-HARM; BORDERLINE PERSONALITY-DISORDER; SUBSTANCE DEPENDENT INPATIENTS; POSTTRAUMATIC-STRESS-DISORDER; SEXUAL-BEHAVIOR; SENSATION SEEKING; POSITIVE URGENCY; NEGATIVE URGENCY; RASH ACTION; ABUSE AB This prospective experimental study sought to examine the unique effects of emotion dysregulation and impulsivity on risky behaviours over time. To this end, 20 African American women enrolled in a historically Black university in the southern United States were randomly assigned to receive one of two brief empirically supported skills training modules (i.e., emotion modulation [EM] or impulsivity reduction [IR]). Participants completed measures of emotion dysregulation, impulsivity, and past-week risky behaviours before (pre-) and one week after (post-) the experimental manipulation. Participants assigned to the EM condition reported significant improvements from pre- to post-manipulation in overall emotion dysregulation (as well as all specific dimensions of emotion dysregulation other than lack of emotional awareness), as well as two dimensions of impulsivity: negative and positive urgency. Participants assigned to the IR condition reported a significant decrease in one dimension of impulsivity (lack of premeditation) from pre- to post-manipulation. Findings also revealed a significant effect of time on risky behaviours, with participants reporting significantly fewer past-week risky behaviours at the post- (vs. pre-) manipulation assessment. Finally, changes in emotion dysregulation from pre- to post-manipulation accounted for the observed reduction in risky behaviours over time (above and beyond changes in impulsivity dimensions). Results highlight the relevance of emotion dysregulation to risky behaviours and suggest that treatments targeting emotion dysregulation may be useful in reducing risky behaviours. C1 [Weiss, Nicole H.] Yale Univ, Sch Med, New Haven, CT 06511 USA. [Tull, Matthew T.; Gratz, Kim L.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [Davis, Lindsey T.] Ralph H Johnson VA Med Ctr, Savannah Primary Care Clin, Savannah, GA USA. [Searcy, Jasmin; Williams, Iman] Jackson State Univ, Dept Psychol, Jackson, MS USA. RP Weiss, NH (reprint author), Yale Univ, Sch Med, Dept Psychiat, 389 Whitney Ave, New Haven, CT 06511 USA. EM nhweiss7@gmail.com FU National Institutes of Health [T32 DA019426] FX The research described here was supported, in part, by a grant from the National Institutes of Health (T32 DA019426). NR 52 TC 2 Z9 2 U1 2 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0813-4839 EI 2049-7768 J9 BEHAV CHANGE JI Behav. Change PD JUN PY 2015 VL 32 IS 2 BP 127 EP 142 DI 10.1017/bec.2015.5 PG 16 WC Psychology, Clinical SC Psychology GA CJ3XJ UT WOS:000355417500005 ER PT J AU Sung, VMH AF Sung, Vicky M. -H. TI Mechanistic overview of ADP-ribosylation reactions SO BIOCHIMIE LA English DT Review DE ADP-ribosylation; Poly-ADP-ribosylation; Mono-ADP-ribosylation; Cyclic ADP-ribosylation; Schiff base; NAD(+) ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; PSEUDOMONAS-AERUGINOSA EXOTOXIN; TRANSITION-STATE STRUCTURE; PERTUSSIS TOXIN; RIBOSYLTRANSFERASE ACTIVITY; CRYSTAL-STRUCTURE; DIPHTHERIA-TOXIN; EUKARYOTIC ELONGATION-FACTOR-2; HUMAN CD38; POLY(ADP-RIBOSE) POLYMERASE AB ADP-ribosylation reactions consist of mono-ADP-ribosylation, poly-ADP-ribosylation and cyclic ADP-ribosylation. These reactions play essential roles in many important physiological and pathophysiological events. The types of chemical linkages, the evolutionarily conserved motif within the enzymes to determine the target specificity, stereochemistry of the ADP-ribosylated products, and the chemical reactions taking place among the enzymes and substrates are discussed. (C) 2015 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. C1 [Sung, Vicky M. -H.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sung, Vicky M. -H.] Harvard Univ, Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. RP Sung, VMH (reprint author), MGH CCIB, MCPZN 7205, 185 Cambridge St, Boston, MA 02114 USA. EM mvsung@gmail.com NR 101 TC 3 Z9 3 U1 4 U2 19 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 EI 1638-6183 J9 BIOCHIMIE JI Biochimie PD JUN PY 2015 VL 113 BP 35 EP 46 DI 10.1016/j.biochi.2015.03.016 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CJ2XQ UT WOS:000355348400005 PM 25828806 ER PT J AU Frank, E Peters, A Sylvia, LG Magalhaes, PVD Miklowitz, DJ Otto, MW Hansen, NS Dougherty, DD Berk, M Nierenberg, AA Deckersbach, T AF Frank, E. Peters, A. Sylvia, L. G. da Silva Magalhaes, P. V. Miklowitz, D. J. Otto, M. W. Hansen, N. S. Dougherty, D. D. Berk, M. Nierenberg, A. A. Deckersbach, T. TI The role of age at onset, course of illness and sleep in response to psychotherapy in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Frank, E.] Univ Pittsburgh, Pittsburgh, PA USA. [Peters, A.] Univ Illinois, Chicago, IL USA. [Sylvia, L. G.; Dougherty, D. D.; Nierenberg, A. A.; Deckersbach, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [da Silva Magalhaes, P. V.] Univ Fed Rio Grande do Sul, Porto Alegre, Brazil. [Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Otto, M. W.] Boston Univ, Boston, MA 02215 USA. [Hansen, N. S.] Univ Colorado, Boulder, CO 80309 USA. [Berk, M.] Deakin Univ, Melbourne, Vic, Australia. [Berk, M.] Univ Melbourne, Melbourne, Vic, Australia. RI Magalhaes, Pedro/A-8519-2008 OI Magalhaes, Pedro/0000-0002-5644-6357 NR 0 TC 0 Z9 0 U1 4 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 16 EP 16 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100030 ER PT J AU Miklowitz, DJ Stange, JP Sylvia, LG Magalhaes, PVD Otto, MW Frank, E Hansen, NS Dougherty, DD Berk, M Nierenberg, AA Deckersbach, T AF Miklowitz, D. J. Stange, J. P. Sylvia, L. G. da Silva Magalhaes, P. V. Otto, M. W. Frank, E. Hansen, N. S. Dougherty, D. D. Berk, M. Nierenberg, A. A. Deckersbach, T. TI Extreme attributions and affective instability predict response to psychotherapy for depression in STEP-BD SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Stange, J. P.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Sylvia, L. G.; Dougherty, D. D.; Nierenberg, A. A.; Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [da Silva Magalhaes, P. V.] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. [Otto, M. W.] Boston Univ, Boston, MA 02215 USA. [Frank, E.] Univ Pittsburgh, Pittsburgh, PA USA. [Hansen, N. S.] Univ Colorado, Boulder, CO 80309 USA. [Berk, M.] Deakin Univ, Melbourne, Vic, Australia. [Berk, M.] Univ Melbourne, Melbourne, Vic, Australia. RI Magalhaes, Pedro/A-8519-2008 OI Magalhaes, Pedro/0000-0002-5644-6357 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 16 EP 16 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100029 ER PT J AU Deckersbach, T Peters, A Sylvia, LG Magalhaes, PVD Miklowitz, DJ Otto, MW Frank, E Hansen, NS Dougherty, DD Berk, M Nierenberg, AA AF Deckersbach, T. Peters, A. Sylvia, L. G. da Silva Magalhaes, P. V. Miklowitz, D. J. Otto, M. W. Frank, E. Hansen, N. S. Dougherty, D. D. Berk, M. Nierenberg, A. A. TI Anxiety disorder and medical comorbidity predict response to psychotherapy for depression in STEP-BD SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Deckersbach, T.; Dougherty, D. D.; Nierenberg, A. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Peters, A.] Univ Illinois, Chicago, IL USA. [da Silva Magalhaes, P. V.] Univ Fed Rio Grande do Sul, Porto Alegre, Brazil. [Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Otto, M. W.] Boston Univ, Boston, MA 02215 USA. [Frank, E.] Univ Pittsburgh, Pittsburgh, PA USA. [Hansen, N. S.] Univ Colorado, Boulder, CO 80309 USA. [Berk, M.] Deakin Univ, Melbourne, Vic, Australia. [Berk, M.] Univ Melbourne, Melbourne, Vic, Australia. RI Magalhaes, Pedro/A-8519-2008 OI Magalhaes, Pedro/0000-0002-5644-6357 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 17 EP 17 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100031 ER PT J AU Nierenberg, AA McElroy, S Ketter, TA Shelton, RC Deckersbach, T Friedman, E McInnis, M Bowden, CL Tohen, M Kocsis, JH Calabrese, JR Kinrysm, G Bobo, WV Singh, V Kamali, M Kemp, D Brody, B Reilly-Harrington, NA Sylvia, LG Shesler, LW Bernstein, EE Schoenfeld, D Rabideau, DJ Leon, AC Faraone, S Thase, ME AF Nierenberg, A. A. McElroy, S. Ketter, T. A. Shelton, R. C. Deckersbach, T. Friedman, E. McInnis, M. Bowden, C. L. Tohen, M. Kocsis, J. H. Calabrese, J. R. Kinrysm, G. Bobo, W. V. Singh, V. Kamali, M. Kemp, D. Brody, B. Reilly-Harrington, N. A. Sylvia, L. G. Shesler, L. W. Bernstein, E. E. Schoenfeld, D. Rabideau, D. J. Leon, A. C. Faraone, S. Thase, M. E. TI Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic six month trial of lithium vs. quetiapine for bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Nierenberg, A. A.; Deckersbach, T.; Kinrysm, G.; Reilly-Harrington, N. A.; Sylvia, L. G.; Shesler, L. W.; Bernstein, E. E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Nierenberg, A. A.; Deckersbach, T.; Kinrysm, G.; Reilly-Harrington, N. A.; Sylvia, L. G.] Harvard Univ, Sch Med, Boston, MA USA. [McElroy, S.] Univ Cincinnati, Coll Med, Cincinnati & Lindner Ctr HOPE, Dept Psychiat & Behav Neurosci, Mason, OH USA. [Friedman, E.; Thase, M. E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Ketter, T. A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Shelton, R. C.] Univ Alabama Birmingham, Dept Psychiat, Birmingham, AL USA. [McInnis, M.; Kamali, M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Bowden, C. L.; Singh, V.] Univ Texas San Antonio, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. [Tohen, M.] Univ New Mexico, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. [Kocsis, J. H.; Brody, B.; Leon, A. C.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Calabrese, J. R.; Kemp, D.] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Bobo, W. V.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Schoenfeld, D.; Rabideau, D. J.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Faraone, S.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, S.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Thase, M. E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 25 EP 26 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100057 ER PT J AU Nierenberg, A AF Nierenberg, A. TI Challenges with outcomes for longitudinal follow up of interventions for patients with mood disorders SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Nierenberg, A.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Nierenberg, A.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 45 EP 45 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100115 ER PT J AU Nierenberg, A Peters, A Stange, J Sylvia, LG Otto, MW Miklowitz, DJ Dougherty, DD Deckersbach, T AF Nierenberg, A. Peters, A. Stange, J. Sylvia, L. G. Otto, M. W. Miklowitz, D. J. Dougherty, D. D. Deckersbach, T. TI Neural predictors of response to psychotherapy for depression in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Nierenberg, A.; Dougherty, D. D.; Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Peters, A.] Univ Illinois, Chicago, IL USA. [Stange, J.; Sylvia, L. G.] Temple Univ, Philadelphia, PA 19122 USA. [Otto, M. W.] Boston Univ, Boston, MA 02215 USA. [Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 47 EP 47 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100122 ER PT J AU Sylvia, LG Peters, A Stange, JP Peckham, A Miklowitz, DJ Otto, MW Dougherty, DD Nierenberg, A Deckersbach, T AF Sylvia, L. G. Peters, A. Stange, J. P. Peckham, A. Miklowitz, D. J. Otto, M. W. Dougherty, D. D. Nierenberg, A. Deckersbach, T. TI Cognitive functioning predicts response to psychotherapy for depression in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Sylvia, L. G.; Dougherty, D. D.; Nierenberg, A.; Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Peters, A.] Univ Illinois, Chicago, IL USA. [Stange, J. P.] Temple Univ, Philadelphia, PA 19122 USA. [Peckham, A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Otto, M. W.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 47 EP 48 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100123 ER PT J AU Dias, R Lafer, B Sachs, GS Nierenberg, AA Joffe, H AF Dias, R. Lafer, B. Sachs, G. S. Nierenberg, A. A. Joffe, H. TI Premenstrual mood symptoms after menarche association with early onset and perinatal mood disorders in women with bipolar disorder - fidings from STEP-BD SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Dias, R.; Lafer, B.] Univ Sao Paulo, Fac Med, Psychiat Bipolar Disorder Res Grp, Sao Paulo, Brazil. [Sachs, G. S.; Nierenberg, A. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA USA. [Joffe, H.] Brigham & Womens Hosp, Dept Psychiat, Womens Hormone & Aging Res Program, Boston, MA 02115 USA. OI Lafer, Beny/0000-0002-6132-9999 NR 0 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 56 EP 56 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100145 ER PT J AU Iosifescu, DV Murrough, JW Deckersbach, T Iacoviello, B Huryk, K Nierenberg, AA AF Iosifescu, D. V. Murrough, J. W. Deckersbach, T. Iacoviello, B. Huryk, K. Nierenberg, A. A. TI Galantamine-ER for cognitive deficits in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Iosifescu, D. V.; Murrough, J. W.; Iacoviello, B.; Huryk, K.] Icahn Sch Med Mt Sinai, Psychiat Mood & Anxiety Disorders Program, New York, NY 10029 USA. [Deckersbach, T.; Nierenberg, A. A.] Massachusetts Gen Hosp, Psychiat Bipolar Clin, Boston, MA 02114 USA. [Deckersbach, T.; Nierenberg, A. A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. RI Murrough, James/J-7129-2013 OI Murrough, James/0000-0001-6286-1242 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 57 EP 57 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100148 ER PT J AU Sylvia, L Gigler, ME Bernstein, E Nierenberg, A Deckersbach, T AF Sylvia, L. Gigler, M. E. Bernstein, E. Nierenberg, A. Deckersbach, T. TI A psychosocial strategy to improve cardiovascular risk factors in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Sylvia, L.; Gigler, M. E.; Bernstein, E.; Nierenberg, A.; Deckersbach, T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 75 EP 75 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100202 ER PT J AU Baek, JH Babadi, B Nierenberg, A AF Baek, J. H. Babadi, B. Nierenberg, A. TI Finding hidden patterns using network analysis of mood disorders symptoms SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Baek, J. H.; Nierenberg, A.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Babadi, B.] Harvard Univ, Ctr Brain Sci, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 85 EP 85 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100235 ER PT J AU Berk, L Gliddon, E Suppes, T Cosgrove, V Deckersbach, T Austin, D Lewis, A Lauder, S Grimm, D Berk, M AF Berk, L. Gliddon, E. Suppes, T. Cosgrove, V. Deckersbach, T. Austin, D. Lewis, A. Lauder, S. Grimm, D. Berk, M. TI Development of an online interactive self-help program for significant others: www.iCARE4bipolar.com SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Berk, L.; Austin, D.; Lewis, A.] Deakin Univ, Sch Psychol, Geelong, Vic 3217, Australia. [Gliddon, E.; Berk, M.] Deakin Univ, IMPACT Strateg Res Ctr, Geelong, Vic 3217, Australia. [Suppes, T.; Cosgrove, V.; Grimm, D.] VA Palo Alto Hlth Care Syst, Bipolar & Depress Res Program, Palo Alto, CA USA. [Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Lauder, S.] Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 94 EP 95 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100263 ER PT J AU Hall, MH Whitton, A Mallya, S Douglas, S Spencer, K Cohen, B Levy, D Smoller, J Ongur, D Pizzagalli, D AF Hall, M. H. Whitton, A. Mallya, S. Douglas, S. Spencer, K. Cohen, B. Levy, D. Smoller, J. Oenguer, D. Pizzagalli, D. TI Associations among reward-based learning, mood and anxiety symptoms, and their relation to brain neurophysiology in schizophrenia and bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Hall, M. H.; Whitton, A.; Mallya, S.; Douglas, S.; Cohen, B.; Levy, D.; Oenguer, D.; Pizzagalli, D.] Harvard Univ, McLean Hosp, Sch Med, Psychiat, Belmont, MA USA. [Spencer, K.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Psychiat, Boston, MA USA. [Smoller, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat, Boston, MA USA. RI Whitton, Alexis/H-4098-2016 OI Whitton, Alexis/0000-0002-7944-2172 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 101 EP 101 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100280 ER PT J AU Nierenberg, A Sylvia, LG Doederlein, A Edgman-Levitan, S Muskin, A Jewell, L Walker, M Goodman, D Farahbakhsh, M Tovey, R Hearing, C Montana, R Deckersbach, T AF Nierenberg, A. Sylvia, L. G. Doederlein, A. Edgman-Levitan, S. Muskin, A. Jewell, L. Walker, M. Goodman, D. Farahbakhsh, M. Tovey, R. Hearing, C. Montana, R. Deckersbach, T. TI The promise of the PCORnet MoodNetwork SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Nierenberg, A.; Sylvia, L. G.; Hearing, C.; Montana, R.; Deckersbach, T.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Nierenberg, A.; Sylvia, L. G.; Hearing, C.; Montana, R.; Deckersbach, T.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Doederlein, A.] Depress Bipolar Support Alliance, Chicago, IL USA. [Edgman-Levitan, S.] Massachusetts Gen Hosp, Stoekel Ctr Primary Care, Boston, MA 02114 USA. [Muskin, A.] Anxiety Depress Assoc Amer, Chicago, IL USA. [Jewell, L.] Depress Bipolar Support Alliance, Chicago, IL USA. [Walker, M.] Int Bipolar Fdn, San Diego, CA USA. [Goodman, D.; Farahbakhsh, M.] MoodNetwork, Boston, MA USA. [Tovey, R.] MoodNetwork, Commun, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 110 EP 111 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100308 ER PT J AU Stange, JP Kleiman, EM Sylvia, LG Magalhaes, PV Berk, M Nierenberg, AA Deckersbach, T AF Stange, J. P. Kleiman, E. M. Sylvia, L. G. Magalhaes, P. V. Berk, M. Nierenberg, A. A. Deckersbach, T. TI Mood symptoms confer risk for suicidal ideation in bipolar disorder: multi-wave data from STEP-BD SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Stange, J. P.] Temple Univ, Psychol, Philadelphia, PA 19122 USA. [Kleiman, E. M.] Harvard Univ, Psychol, Boston, MA 02115 USA. [Sylvia, L. G.; Nierenberg, A. A.; Deckersbach, T.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Sylvia, L. G.; Nierenberg, A. A.; Deckersbach, T.] Harvard Univ, Sch Med, Boston, MA USA. [Magalhaes, P. V.] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Natl Inst Translat Med, Psychiat, Porto Alegre, RS, Brazil. [Berk, M.] Barwon Hlth, Dept Clin & Biomed Sci, Melbourne, Vic, Australia. [Berk, M.] Univ Melbourne, Geelong Clin, Melbourne, Vic, Australia. RI Magalhaes, Pedro/A-8519-2008 OI Magalhaes, Pedro/0000-0002-5644-6357 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 113 EP 114 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100318 ER PT J AU Abreu, LN Lafer, B Burke, A Grunebaum, MF Sher, L Sullivan, GM Sublette, ME Pietrobon, R Vissoci, JR Mann, JJ Oquendo, MA AF Abreu, L. N. Lafer, B. Burke, A. Grunebaum, M. F. Sher, L. Sullivan, G. M. Sublette, M. E. Pietrobon, R. Vissoci, J. R. Mann, J. J. Oquendo, M. A. TI Impact of comorbid anxiety disorders in prospective suicide attempts SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Abreu, L. N.; Lafer, B.] Univ Sao Paulo, Inst Psychiat, Sao Paulo, Brazil. [Burke, A.; Grunebaum, M. F.; Sullivan, G. M.; Sublette, M. E.; Mann, J. J.; Oquendo, M. A.] New York State Psychiat Inst & Hosp, Mol Imaging & Neuropathol Div, New York, NY 10032 USA. [Sher, L.] Mt Sinai Sch Med, James J Peters Vet Adm Med Ctr, New York, NY USA. [Pietrobon, R.; Vissoci, J. R.] Duke Univ, Med Ctr, Durham, NC 27706 USA. RI Sublette, M/A-8391-2009; OI Sublette, M/0000-0001-7378-4262; Lafer, Beny/0000-0002-6132-9999 NR 0 TC 0 Z9 0 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 114 EP 114 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100320 ER PT J AU Sonpavde, G Pond, GR Fougeray, R Bellmunt, J AF Sonpavde, Guru Pond, Gregory R. Fougeray, Ronan Bellmunt, Joaquim TI Nomogram to predict the benefit from salvage systemic therapy for advanced urothelial carcinoma SO BJU INTERNATIONAL LA English DT Editorial Material ID TRANSITIONAL-CELL CARCINOMA; TRACT C1 [Sonpavde, Guru] UAB Comprehens Canc Ctr, Birmingham, AL 35294 USA. [Bellmunt, Joaquim] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Boston, MA USA. [Sonpavde, Guru; Pond, Gregory R.] McMaster Univ, Hamilton, ON, Canada. [Fougeray, Ronan] Inst Rech Pierre Fabre, Boulogne, France. [Bellmunt, Joaquim] Univ Hosp Mar IMIM, Barcelona, Spain. RP Sonpavde, G (reprint author), UAB Comprehens Canc Ctr, 1802 6th Ave S,NP2540B, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu NR 6 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD JUN PY 2015 VL 115 IS 6 BP 854 EP 855 DI 10.1111/bju.12922 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CJ1WL UT WOS:000355275600008 PM 25195625 ER PT J AU Kellogg, MD Ellervik, C Morrow, D Hsing, A Stein, E Sethi, AA AF Kellogg, Mark D. Ellervik, Christina Morrow, David Hsing, Ann Stein, Evan Sethi, Amar A. TI Preanalytical Considerations in the Design of Clinical Trials and Epidemiological Studies SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Kellogg, Mark D.; Ellervik, Christina] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Kellogg, Mark D.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Ellervik, Christina] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark. [Ellervik, Christina] Nykoebing Falster Hosp, Dept Gen Populat Study, Nykoebing Falster, Denmark. [Morrow, David] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Hsing, Ann] Canc Prevent Inst Calif, Stanford, CA USA. [Hsing, Ann] Stanford Sch Med, Epidemiol, Stanford, CA USA. [Stein, Evan] Medpace Reference Labs, Cincinnati, OH USA. [Stein, Evan] Metab & Atherosclerosis Res Ctr, Cincinnati, OH USA. [Sethi, Amar A.] Pacific Biomarkers, Seattle, WA USA. RP Kellogg, MD (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM mark.kellogg@childrens.harvard.edu NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2015 VL 61 IS 6 BP 797 EP 803 DI 10.1373/clinchem.2014.226118 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CJ1SW UT WOS:000355265800004 PM 25901083 ER PT J AU Berg, AH Powe, CE Evans, MK Wenger, J Ortiz, G Zonderman, AB Suntharalingam, P Lucchesi, K Powe, NR Karumanchi, SA Thadhani, RI AF Berg, Anders H. Powe, Camille E. Evans, Michele K. Wenger, Julia Ortiz, Guillermo Zonderman, Alan B. Suntharalingam, Pirianthini Lucchesi, Kathryn Powe, Neil R. Karumanchi, S. Ananth Thadhani, Ravi I. TI 24,25-Dihydroxyvitamin D-3 and Vitamin D Status of Community-Dwelling Black and White Americans SO CLINICAL CHEMISTRY LA English DT Article ID BONE-MINERAL DENSITY; D-BINDING PROTEIN; CHRONIC KIDNEY-DISEASE; 25-HYDROXYVITAMIN D; D SUPPLEMENTATION; D DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D; HIP-FRACTURES; ELDERLY-WOMEN; RISK AB BACKGROUND: 24,25-Dihydroxyvitamin D[24,25(OH)(2)D] is a metabolite of 25-hydroxyvitamin D (25D). Blacks frequently have low total 25D without manifestations of vitamin D deficiency, suggesting that total serum 25D may incorrectly reflect vitamin Dstatus in different racial groups. The ratio of serum 24,25(OH)(2)D to 25D [vitamin D metabolite ratio (VMR)] represents a new candidate biomarker for vitamin D status. METHODS: We measured 24,25(OH)(2)D-3 and 25D(3) by mass spectrometry in a random community cohort of black (n = 212) and white (n = 164) Americans to evaluate VMR as a marker for vitamin D status. We measured parathyroid hormone concentrations by immunoassay to compare VMR and 25D(3) against a physiological indicator of vitamin D deficiency. RESULTS: Serum 24,25(OH)(2)D-3 strongly correlated with 25D3 in both black and white study participants (r = 0.90, P < 0.001 and r = 0.86, P < 0.001 respectively). Blacks had lower mean 25D3 than whites [17.0 (7.8) vs 27.5 (11.3) ng/mL; 42.4 (19.5) vs 68.6 (28.2) nmol/L, P < 0.001] and lower mean 24,25(OH)(2)D-3 [2.1 (1.3) vs 3.6 (2.0) ng/mL; 5.1 (3.1) vs 8.7 (4.8) nmol/L, P < 0.001]. In contrast to total 25D(3) concentrations, mean VMR values were similar in blacks and whites [11.9 (4.0) vs 12.5 (3.4), P = 0.16, respectively] and were negatively correlated with parathyroid hormone concentrations in both races (r(s) = -0.26, P = 0.001, and r(s) = -0.25, P < 0.001, respectively). CONCLUSIONS: Our results provide further evidence that measurement of total 25D for assessment of vitamin D status in patients of African descent deserves reevaluation and suggest that alternative measures such as VMR should be considered. (C) 2015 American Association for Clinical Chemistry C1 [Berg, Anders H.; Suntharalingam, Pirianthini] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Berg, Anders H.; Suntharalingam, Pirianthini] Harvard Univ, Sch Med, Boston, MA USA. [Powe, Camille E.] Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02215 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA. [Wenger, Julia; Ortiz, Guillermo; Lucchesi, Kathryn; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02215 USA. [Powe, Neil R.] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Powe, Neil R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02115 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Berg, AH (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave YA309, Boston, MA 02115 USA. EM ahberg@bidmc.harvard.edu; rthadhani@mgh.harvard.edu FU National Institute on Aging Intramural Research Program at NIH [ZIA AG000513]; National Institutes of Health [K08 HL121801, K24 DK094872, R01 DK094486]; Howard Hughes Medical Institute FX National Institute on Aging Intramural Research Program at NIH, project #ZIA AG000513; A.H. Berg, K08 HL121801 from the National Institutes of Health; A. Karumanchi, Howard Hughes Medical Institute; R.I. Thadhani, K24 DK094872 and R01 DK094486 from the National Institutes of Health. Expert Testimony: None declared. NR 37 TC 15 Z9 16 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2015 VL 61 IS 6 BP 877 EP 884 DI 10.1373/clinchem.2015.240051 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CJ1SW UT WOS:000355265800014 PM 25922442 ER PT J AU Frioes, F Lourenco, P Laszczynska, O Almeida, PB Guimaraes, JT Januzzi, JL Azevedo, A Bettencourt, P AF Frioes, Fernando Lourenco, Patricia Laszczynska, Olga Almeida, Pedro-Bernardo Guimaraes, Joao-Tiago Januzzi, James L. Azevedo, Ana Bettencourt, Paulo TI Prognostic value of sST2 added to BNP in acute heart failure with preserved or reduced ejection fraction SO CLINICAL RESEARCH IN CARDIOLOGY LA English DT Article DE Acute heart failure; Biomarker; BNP; sST2; Ventricular dysfunction; Prognosis ID FAMILY-MEMBER ST2; NATRIURETIC PEPTIDE LEVELS; SOLUBLE ST2; TASK-FORCE; MORTALITY; OUTCOMES; PREVALENCE; BIOMARKERS; GUIDELINES; MANAGEMENT AB Natriuretic peptides and suppression of tumorigenicity 2 (ST2) represent two different physiopathological pathways. We evaluated the prognostic accuracy and complementarity of B-type natriuretic peptide (BNP) and soluble ST2 (sST2) plasma levels at discharge from a hospital admission for acute heart failure, both in patients with preserved (HFpEF) and depressed (HFrEF) systolic function. We enrolled 195 consecutive patients discharged alive and followed them prospectively for 6 months. The endpoint was all-cause death or hospital readmission for heart failure. Seventy-six patients had HFpEF and 119 had HFrEF, of whom 23 (30.3 %) and 43 (36.1 %) reached the combined endpoint, respectively. In both HFpEF and HFrEF, having the two biomarkers into account added prognostic information, with the highest risk in patients with both biomarkers above the median in their group (approximately 40 % hospitalization-free survival in both groups at 6 months). These associations translated into a significant fourfold increase in risk of the endpoint for one elevated biomarker and sevenfold for both biomarkers elevated in HFrEF, and no association for one elevated biomarker and fivefold increase in risk for both biomarkers elevated in HFpEF. Considering the reclassification of risk added to BNP by measurement of sST2, net reclassification index was 0.31 (p = 0.21) among patients with HFpEF and 0.70 (p < 0.001) among patients with HFrEF. sST2 provides robust prognostic information in acute heart failure with HFrEF, while this pattern was less clear in HFpEF. When sST2 was measured together with BNP, it improved prognostic accuracy in both groups, more clearly in HFrEF. C1 [Frioes, Fernando; Lourenco, Patricia; Bettencourt, Paulo] Sao Joao Hosp Ctr, Dept Internal Med, P-4200319 Oporto, Portugal. [Frioes, Fernando; Lourenco, Patricia; Bettencourt, Paulo] Univ Porto, Sch Med, Dept Med, P-4100 Oporto, Portugal. [Laszczynska, Olga; Guimaraes, Joao-Tiago; Azevedo, Ana] Univ Porto ISPUP, Inst Publ Hlth, EPIUnit, Oporto, Portugal. [Almeida, Pedro-Bernardo] Sao Joao Hosp Ctr, Dept Cardiol, P-4200319 Oporto, Portugal. [Guimaraes, Joao-Tiago] Sao Joao Hosp Ctr, Dept Pathol, P-4200319 Oporto, Portugal. [Guimaraes, Joao-Tiago] Univ Porto, Sch Med, Dept Biochem, P-4100 Oporto, Portugal. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Azevedo, Ana] Univ Porto, Sch Med, Dept Clin Epidemiol Predict Med & Publ Hlth, P-4100 Oporto, Portugal. RP Frioes, F (reprint author), Sao Joao Hosp Ctr, Dept Internal Med, Alameda Prof Hernani Monteiro, P-4200319 Oporto, Portugal. EM fbfrioes@gmail.com OI Guimaraes, Joao Tiago/0000-0003-4836-6311; Bettencourt, Paulo/0000-0003-1638-3993 FU Fundacao para a Ciencia e Tecnologia, Lisbon, Portugal [PIC/IC/82773/2007]; DeSanctis Clinical Scholar Endowment FX This study was supported by a grant from Fundacao para a Ciencia e Tecnologia, Lisbon, Portugal (PIC/IC/82773/2007). Dr Januzzi is supported in part by the DeSanctis Clinical Scholar Endowment. NR 32 TC 11 Z9 11 U1 2 U2 9 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-0684 EI 1861-0692 J9 CLIN RES CARDIOL JI Clin. Res. Cardiol. PD JUN PY 2015 VL 104 IS 6 BP 491 EP 499 DI 10.1007/s00392-015-0811-x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CJ0EK UT WOS:000355147200006 PM 25586507 ER PT J AU Etherton, MR Lyons, JL Ard, KL AF Etherton, Mark R. Lyons, Jennifer L. Ard, Kevin L. TI HIV-associated Neurocognitive Disorders and Antiretroviral Therapy: Current Concepts and Controversies SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Antiretroviral toxicity; HIV-associated neurocognitive disorder; HIV dementia; CSF escape encephalitis; CNS penetration effectiveness ID CENTRAL-NERVOUS-SYSTEM; REVERSE-TRANSCRIPTASE INHIBITORS; CEREBROSPINAL-FLUID; NEUROPSYCHIATRIC COMPLICATIONS; CNS PENETRATION; EFAVIRENZ; AIDS; RALTEGRAVIR; LAMIVUDINE; INFECTION AB Antiretroviral drugs may help prevent neurological decline in individuals with HIV infection by suppressing viral replication and associated chronic immune activation in the central nervous system. However, HIV control in the brain may come at the price of drug-induced neurotoxicity. Herein, we review recent advances in the balance between adequate viral suppression in the nervous system and adverse effects of the medications used in HIV treatment. C1 [Etherton, Mark R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Etherton, Mark R.; Lyons, Jennifer L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Etherton, Mark R.; Lyons, Jennifer L.; Ard, Kevin L.] Harvard Univ, Sch Med, Boston, MA USA. [Ard, Kevin L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Etherton, Mark R.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. RP Etherton, MR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM metherton@partners.org NR 45 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD JUN PY 2015 VL 17 IS 6 AR 28 DI 10.1007/s11908-015-0485-6 PG 6 WC Infectious Diseases SC Infectious Diseases GA CJ3YQ UT WOS:000355421000002 ER PT J AU Stewart, AF Hussain, MA Garcia-Ocana, A Vasavada, RC Bhushan, A Bernal-Mizrachi, E Kulkarni, RN AF Stewart, Andrew F. Hussain, Mehboob A. Garcia-Ocana, Adolfo Vasavada, Rupangi C. Bhushan, Anil Bernal-Mizrachi, Ernesto Kulkarni, Rohit N. TI Human beta-Cell Proliferation and Intracellular Signaling: Part 3 SO DIABETES LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; PROTEIN-COUPLED RECEPTORS; MAP KINASE PATHWAYS; PANCREATIC BETA; INSULIN-SECRETION; GLUCOSE-HOMEOSTASIS; TRANSCRIPTION FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PROLACTIN RECEPTOR; DIABETES-MELLITUS AB This is the third in a series of Perspectives on intracellular signaling pathways coupled to proliferation in pancreatic beta-cells. We contrast the large knowledge base in rodent beta-cells with the more limited human database. With the increasing incidence of type 1 diabetes and the recognition that type 2 diabetes is also due in part to a deficiency of functioning beta-cells, there is great urgency to identify therapeutic approaches to expand human beta-cell numbers. Therapeutic approaches might include stem cell differentiation, transdifferentiation, or expansion of cadaver islets or residual endogenous beta-cells. In these Perspectives, we focus on beta-cell proliferation. Past Perspectives reviewed fundamental cell cycle regulation and its upstream regulation by insulin/IGF signaling via phosphatidylinositol-3 kinase/mammalian target of rapamycin signaling, glucose, glycogen synthase kinase-3 and liver kinase B1, protein kinase C zeta, calcium-calcineurin-nuclear factor of activated T cells, epidermal growth factor/platelet-derived growth factor family members, Wnt/beta-catenin, leptin, and estrogen and progesterone. Here, we emphasize Janus kinase/signal transducers and activators of transcription, Ras/Raf/extracellular signal-related kinase, cadherins and integrins, G-protein-coupled receptors, and transforming growth factor beta signaling. We hope these three Perspectives will serve to introduce these pathways to new researchers and will encourage additional investigators to focus on understanding how to harness key intracellular signaling pathways for therapeutic human beta-cell regeneration for diabetes. C1 [Stewart, Andrew F.; Garcia-Ocana, Adolfo; Vasavada, Rupangi C.] Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, New York, NY 10029 USA. [Hussain, Mehboob A.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Hussain, Mehboob A.] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. [Bhushan, Anil] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA. [Bernal-Mizrachi, Ernesto] Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. [Bernal-Mizrachi, Ernesto] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. RP Stewart, AF (reprint author), Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, New York, NY 10029 USA. EM andrew.stewart@mssm.edu; rohit.kulkarni@joslin.harvard.edu FU NIH [R01 DK55023, U01 DK089538, R01 DK67536, R01 DK103215, R01 DK101591, R01 DK081472, P60 DK079637, R01 DK073716, R01 DK084236, R01 DK078060, R01 DK06735, DK077096]; JDRF [1-2011-603, 17-2013-416, 17-2012-37, 47-2012-750, 17-2011-595]; American Diabetes Association [1-14-BS-069] FX This work was supported by NIH grants R01 DK55023 (A.F.S.), U01 DK089538 (A.F.S.), R01 DK67536 (R.N.K.), R01 DK103215 (R.N.K.), R01 DK101591 (M.A.H.), R01 DK081472 (M.A.H.), P60 DK079637 (M.A.H.), R01 DK073716 (E.B.-M.), R01 DK084236 (E.B.-M.), R01 DK078060 (R.C.V.), R01 DK06735 (A.G.-O.), and DK077096 (A.G.-O.); JDRF grants 1-2011-603 (A.F.S.), 17-2013-416 (E.B.-M.), 17-2012-37 (R.C.V.), 47-2012-750 (R.C.V.) and 17-2011-595 (AG.-O.); and American Diabetes Association grant 1-14-BS-069. NR 118 TC 18 Z9 18 U1 1 U2 14 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 2015 VL 64 IS 6 BP 1872 EP 1885 DI 10.2337/db14-1843 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ3GH UT WOS:000355370900001 PM 25999530 ER PT J AU Pal, A Rhoads, DB Tavakkoli, A AF Pal, Atanu Rhoads, David B. Tavakkoli, Ali TI Foregut Exclusion Disrupts Intestinal Glucose Sensing and Alters Portal Nutrient and Hormonal Milieu SO DIABETES LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; GASTRIC BYPASS-SURGERY; RAT SMALL-INTESTINE; SECRETION; GLP-1; DIET; GUT; COTRANSPORTER; SGLT1; CELLS AB The antidiabetes effects of Roux-en-Y gastric bypass (RYGB) are well-known, but the underlying mechanisms remain unclear. Isolating the proximal small intestine, and in particular its luminal glucose sensors, from the nutrient stream has been proposed as a critical change, but the pathways involved are unclear. In a rodent model, we tested the effects of isolating and then stimulating a segment of proximal intestine using glucose analogs to examine their impact on glucose absorption (G(absorp)) and hormone secretion after a glucose bolus into the distal jejunum. Analogs selective for sodium-glucose cotransporter (SGLT) family members and the sweet taste receptor were tested, and measurements of the porto-systemic gradient were used to determine G(absorp) and hormone secretion, including GLP-1. Proximal intestinal isolation reduced G(absorp) and GLP-1 secretion. Stimulation of the glucose-sensing protein SGLT3 increased G(absorp) and GLP-1 secretion. These effects were abolished by vagotomy. Sweet taste receptor stimulation only increased GLP-1 secretion. This study suggests a novel role for SGLT3 in coordinating intestinal function, as reflected by the concomitant modulation of G(absorp) and GLP-1 secretion, with these effects being mediated by the vagus nerve. Our findings provide potential mechanistic insights into foregut exclusion in RYGB and identify SGLT3 as a possible antidiabetes therapeutic target. C1 [Pal, Atanu; Tavakkoli, Ali] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Pal, Atanu; Rhoads, David B.; Tavakkoli, Ali] Harvard Univ, Sch Med, Boston, MA USA. [Rhoads, David B.] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Tavakkoli, A (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM atavakkoli@partners.org FU National Institutes of Health [1R01-DK-084064] FX This study was funded by National Institutes of Health grant 1R01-DK-084064 (to A.T.). NR 32 TC 4 Z9 4 U1 1 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 2015 VL 64 IS 6 BP 1941 EP 1950 DI 10.2337/db14-1578 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ3GH UT WOS:000355370900012 PM 25576062 ER PT J AU Cook, JR Matsumoto, M Banks, AS Kitamura, T Tsuchiya, K Accili, D AF Cook, Joshua R. Matsumoto, Michihiro Banks, Alexander S. Kitamura, Tadahiro Tsuchiya, Kyoichiro Accili, Domenico TI A Mutant Allele Encoding DNA Binding-Deficient FoxO1 Differentially Regulates Hepatic Glucose and Lipid Metabolism SO DIABETES LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; FATTY LIVER-DISEASE; DE-NOVO LIPOGENESIS; FORKHEAD TRANSCRIPTION; INSULIN-RESISTANCE; FACTOR FKHR; MICE; GLUCOKINASE; INHIBITION; SENSITIVITY AB Insulin signaling in the liver blunts glucose production and stimulates triglyceride biosynthesis. FoxO1 is required for cAMP induction of hepatic glucose production and is permissive for the effect of insulin to suppress this process. Moreover, FoxO1 ablation increases lipogenesis. In this study, we investigated the pleiotropic actions of FoxO1 on glucose and lipid metabolism. To this end, we reconstituted FoxO1 function in mice with a liver-specific deletion of Foxo1 using targeted knock-in of an allele encoding a DNA binding-deficient FoxO1 mutant (L-DBD). Chow-reared L-DBD mice showed defects in hepatic glucose production but normal liver triglyceride content despite increased rates of de novo lipogenesis and impaired fatty acid oxidation in isolated hepatocytes. Gene expression studies indicated that FoxO1 regulates the expression of glucokinase via a cell-nonautonomous coregulatory mechanism, while its regulation of glucose-6-phosphatase proceeds via a cell-autonomous action as a direct transcriptional activator. These conclusions support a differential regulation of hepatic glucose and lipid metabolism by FoxO1 based on the mechanism by which it alters the expression of key target genes involved in each process. C1 [Cook, Joshua R.; Matsumoto, Michihiro; Banks, Alexander S.; Kitamura, Tadahiro; Tsuchiya, Kyoichiro; Accili, Domenico] Columbia Univ, Dept Med, New York, NY 10027 USA. [Matsumoto, Michihiro] Natl Ctr Global Hlth & Med, Diabet Res Ctr, Dept Mol Metab Regulat, Tokyo, Japan. [Banks, Alexander S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kitamura, Tadahiro] Gunma Univ, Grad Sch Med, Dept Med & Biol Sci, Maebashi, Gumma, Japan. [Tsuchiya, Kyoichiro] Tokyo Med & Dent Univ, Grad Sch, Dept Clin & Mol Endocrinol, Tokyo, Japan. RP Accili, D (reprint author), Columbia Univ, Dept Med, New York, NY 10027 USA. EM da230@columbia.edu RI Banks, Alexander/B-4832-2012 OI Banks, Alexander/0000-0003-1787-6925 FU National Institutes of Health [DK-100038, DK-57539, DK-63608] FX This work was supported by National Institutes of Health grants DK-100038, DK-57539, and DK-63608 (to Columbia University Diabetes Research Center). NR 48 TC 7 Z9 7 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 2015 VL 64 IS 6 BP 1951 EP 1965 DI 10.2337/db14-1506 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ3GH UT WOS:000355370900013 PM 25576059 ER PT J AU Stanford, KI Middelbeek, RJW Townsend, KL Lee, MY Takahashi, H So, K Hitchcox, KM Markan, KR Hellbach, K Hirshman, MF Tseng, YH Goodyear, LJ AF Stanford, Kristin I. Middelbeek, Roeland J. W. Townsend, Kristy L. Lee, Min-Young Takahashi, Hirokazu So, Kawai Hitchcox, Kristen M. Markan, Kathleen R. Hellbach, Katharina Hirshman, Michael F. Tseng, Yu-Hua Goodyear, Laurie J. TI A Novel Role for Subcutaneous Adipose Tissue in Exercise-Induced Improvements in Glucose Homeostasis SO DIABETES LA English DT Article ID MESSENGER-RNA EXPRESSION; BODY-FAT DISTRIBUTION; SKELETAL-MUSCLE; INSULIN SENSITIVITY; ENDURANCE EXERCISE; BROWN ADIPOCYTES; GENE-EXPRESSION; PPAR-GAMMA; WHITE; METABOLISM AB Exercise training improves whole-body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues, including adipose tissue. To determine whether exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from exercise-trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, 9 days post-transplantation, mice receiving scWAT from exercise-trained mice had improved glucose tolerance and enhanced insulin sensitivity compared with mice transplanted with scWAT from sedentary or sham-treated mice. Mice transplanted with scWAT from exercise-trained mice had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat-fed recipient mice were transplanted with scWAT from exercise-trained mice. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT, including the increased expression of similar to 1,550 genes involved in numerous cellular functions including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis. C1 [Stanford, Kristin I.; Middelbeek, Roeland J. W.; Townsend, Kristy L.; Lee, Min-Young; Takahashi, Hirokazu; So, Kawai; Hitchcox, Kristen M.; Markan, Kathleen R.; Hellbach, Katharina; Hirshman, Michael F.; Tseng, Yu-Hua; Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Stanford, Kristin I.; Middelbeek, Roeland J. W.; Townsend, Kristy L.; Lee, Min-Young; Takahashi, Hirokazu; Tseng, Yu-Hua; Goodyear, Laurie J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. EM laurie.goodyear@joslin.harvard.edu RI Dey, Kamalesh/E-6568-2017 FU National Institutes of Health [T32-DK-07260, F32-DK-091996, F32-DK-091048, R01-DK-077097, R01-DK-099511, R21-DK-091764, 5P30-DK-36836]; Mary K. Iacocca Fellowship; American Diabetes Association [7-08-MN-18] FX This work was supported by National Institutes of Health grants T32-DK-07260 (to K.I.S., K.L.T., and K.R.M.), F32-DK-091996 (to K.L.T.), F32-DK-091048 (to K.I.S.), R01-DK-077097 (to Y.-H.T.), R01-DK-099511 and R21-DK-091764 (to L.J.G.), and 5P30-DK-36836 (to Diabetes Research and Endocrinology Research Center, Joslin Diabetes Center). K.I.S. was also supported by the Mary K. Iacocca Fellowship. R.J.W.M. and M.-Y.L. were supported by a mentor-based fellowship (7-08-MN-18) awarded to L.J.G. from the American Diabetes Association. NR 47 TC 38 Z9 39 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 2015 VL 64 IS 6 BP 2002 EP 2014 DI 10.2337/db14-0704 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ3GH UT WOS:000355370900017 PM 25605808 ER PT J AU Kesselheim, AS Campbell, EG Schneeweiss, S Rausch, P Lappin, BM Zhou, EH Seeger, JD Brownstein, JS Woloshin, S Schwartz, LM Toomey, T Dal Pan, GJ Avorn, J AF Kesselheim, Aaron S. Campbell, Eric G. Schneeweiss, Sebastian Rausch, Paula Lappin, Brian M. Zhou, Esther H. Seeger, John D. Brownstein, John S. Woloshin, Steven Schwartz, Lisa M. Toomey, Timothy Dal Pan, Gerald J. Avorn, Jerry TI Methodological Approaches to Evaluate the Impact of FDA Drug Safety Communications SO DRUG SAFETY LA English DT Article ID NEWS MEDIA COVERAGE; PRESCRIPTION MEDICATIONS; PRIOR AUTHORIZATION; TIME-SERIES; HEALTH; ZOLPIDEM; INFORMATION; MAMMOGRAPHY; WARNINGS; INTERNET AB When the US FDA approves a new prescription drug there is still a great deal remaining to be learned about the safe and proper use of that product. When new information addressing these topics emerges post-approval, the FDA may issue a Drug Safety Communication (DSC) to alert patients and physicians. The effectiveness of the communication-how drug safety messaging conveyed in FDA DSCs changes patient or prescriber behavior-may depend on multiple factors, including the way physicians and patients learn about the information, their understanding of the issues conveyed, and their perception of the importance of the information. In 2013, the FDA issued two DSCs addressing critical new warnings related to products containing the sedative/hypnotic zolpidem. In this article, we describe a core set of research initiatives that can be used to study how zolpidem-related DSCs affected subsequent physician and patient decision making. These research initiatives include analyzing drug utilization patterns and related health outcomes; comparing zolpidem-containing products against a comparator with similar indications [eszopiclone (Lunesta)] not covered by the 2013 DSCs; and surveying patients and qualitatively evaluating the dissemination of information regarding these drugs in traditional and social-media channels. Using an integrated, multidisciplinary approach, we can obtain information that can be used to optimize regulatory communications by seeking to understand the impact of the information contained in FDA risk communications. C1 [Kesselheim, Aaron S.; Schneeweiss, Sebastian; Seeger, John D.; Toomey, Timothy; Avorn, Jerry] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, PORTAL, Boston, MA 02120 USA. [Kesselheim, Aaron S.; Campbell, Eric G.; Schneeweiss, Sebastian; Seeger, John D.; Brownstein, John S.; Toomey, Timothy; Avorn, Jerry] Harvard Univ, Sch Med, Boston, MA 02120 USA. [Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy Res, Boston, MA 02114 USA. [Rausch, Paula] US FDA, Off Commun, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lappin, Brian M.] US FDA, Off Planning, Off Commissioner, Silver Spring, MD 20993 USA. [Zhou, Esther H.; Dal Pan, Gerald J.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Brownstein, John S.] Boston Childrens Hosp, Childrens Hosp, Epidemiol Grp, Boston, MA USA. [Woloshin, Steven; Schwartz, Lisa M.] Dartmouth Inst Hlth Policy & Clin Practice, Ctr Med & Media, Lebanon, NH USA. RP Kesselheim, AS (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, PORTAL, Suite 3030,1620 Tremont St, Boston, MA 02120 USA. EM akesselheim@partners.org RI Schneeweiss, Sebastian/C-2125-2013 FU Informulary, Inc. FX Sebastian Schneeweiss is a consultant to WHISCON LLC, a consulting company specializing in the conduct of drug safety database studies. He is also a consultant to, and owns some equities in, Aetion, Inc., a software company specializing in the analyses of healthcare databases. Paula Rausch, Brian M. Lappin, Esther H. Zhou, and Gerald J. Dal Pan are employed by the FDA, which commissioned this study. John D. Seeger is a consultant to both WHISCON LLC and Optum. John S. Brownstein owns shares in, and is employed as consultant to, Epidemico, Inc., a technology company that develops social-media mining tools for drug safety. Steven Woloshin and Lisa M. Schwartz were paid under a subcontract for work on this project and are co-founders of Informulary, Inc., a company that provides data regarding the benefit, harms, and uncertainties of prescription drugs. Aaron S. Kesselheim, Eric G. Campbell, Timothy Toomey, and Jerry Avorn have no conflicts of interest that are directly relevant to the content of this study. NR 56 TC 3 Z9 3 U1 2 U2 11 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PD JUN PY 2015 VL 38 IS 6 BP 565 EP 575 DI 10.1007/s40264-015-0291-y PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA CJ0ZV UT WOS:000355211500006 PM 25968811 ER PT J AU Shamsi, MM Hassan, ZM Quinn, LS Gharakhanlou, R Baghersad, L Mahdavi, M AF Shamsi, Mahdieh Molanouri Hassan, Zuhair Mohammad Quinn, LeBris S. Gharakhanlou, Reza Baghersad, Leila Mahdavi, Mehdi TI Time course of IL-15 expression after acute resistance exercise in trained rats: effect of diabetes and skeletal muscle phenotype SO ENDOCRINE LA English DT Article DE Interleukin-15; Interleukin-6; Resistance training; Type-1 diabetes; Exercise; Myokines; Cytokines ID GENE-EXPRESSION; INTERLEUKIN-15; HYPERTROPHY; ACTIVATION; PROTEIN; MICE; PATHWAYS; CYTOKINE; ATROPHY; BIOLOGY AB Type 1 diabetes is associated with skeletal muscle atrophy. Skeletal muscle is an endocrine organ producing myokines such as interleukin-15 (IL-15) and interleukin-6 (IL-6) in response to contraction. These factors may mediate the effects of exercise on skeletal muscle metabolism and anabolic pathways. Lack of correlation between muscle IL-15 mRNA and protein levels after exercise training has been observed, while regulatory effects of IL-6 on IL-15 expression have also been suggested. This study determined post-exercise changes in muscle IL-15 and IL-6 mRNA expression and IL-15 protein levels in healthy and streptozotocin-induced diabetic rats in both the fast flexor hallucis longus (FHL) and slow soleus muscles. Resistance training preserved FHL muscle weight in diabetic rats and increased IL-15 protein levels in both the soleus and FHL muscles. However, the temporal pattern of this response was distinct in normal and diabetic rats. Moreover, discordance between post-exercise muscle IL-15 mRNA and protein expression was observed in our study, and diabetes suppressed post-exercise increases in FHL muscle IL-6 mRNA expression. Our study indicates that training, skeletal muscle phenotype, and metabolic status all influence the temporal pattern of post-exercise changes in IL-15 expression. Muscle IL-15 protein levels increase following training, suggesting this may be an adaptation contributing to increased capacity for secretion of this myokine that is not depressed by the diabetic state. C1 [Shamsi, Mahdieh Molanouri; Gharakhanlou, Reza; Baghersad, Leila] Tarbiat Modares Univ, Fac Humanities, Phys Educ & Sport Sci Dept, Tehran, Iran. [Shamsi, Mahdieh Molanouri; Hassan, Zuhair Mohammad; Gharakhanlou, Reza; Baghersad, Leila] Jala Ale Ahmad Exp, Tehran, Iran. [Hassan, Zuhair Mohammad] Tarbiat Modares Univ, Sch Med Sci, Dept Immunol, Tehran, Iran. [Quinn, LeBris S.] Univ Washington, Div Gerontol & Geriatr Med, VA Puget Sound Hlth Care Syst, Dept Med,Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Mahdavi, Mehdi] Pasteur Inst Iran, Dept Immunol, Tehran, Iran. RP Shamsi, MM (reprint author), Tarbiat Modares Univ, Fac Humanities, Phys Educ & Sport Sci Dept, Tehran, Iran. EM molanouri@modares.ac.ir; Hassan_zm@modares.ac.ir; quinnL@uw.edu; ghara_re@modares.ac.ir; l.baghersad@gmail.com; mahdavivac@gmail.com FU Research Center of Tarbiat Modares University (TMU), Tehran, Iran FX This work was supported by the Research Center of Tarbiat Modares University (TMU), Tehran, Iran. We wish to thank Professor Yaghob Fathoallahy for his help and sincere cooperation. NR 37 TC 5 Z9 5 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD JUN PY 2015 VL 49 IS 2 BP 396 EP 403 DI 10.1007/s12020-014-0501-x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ1GD UT WOS:000355230500012 ER PT J AU Dawson, AZ Walker, RJ Campbell, JA Egede, LE AF Dawson, Aprill Z. Walker, Rebekah J. Campbell, Jennifer A. Egede, Leonard E. TI Effect of perceived racial discrimination on self-care behaviors, glycemic control, and quality of life in adults with type 2 diabetes SO ENDOCRINE LA English DT Article DE Perceived racial discrimination; Self-care; Glycemic control; Type 2 diabetes ID MEDICATION ADHERENCE; RATED HEALTH; DISPARITIES; COMMUNITY; VALIDITY; STRESS; WHITES AB Objective: This study used a large sample size of black and white patients with type 2 diabetes to investigate the influence of perceived racial discrimination on biologic measures (glycemic control, blood pressure, and LDL cholesterol), the mental component of quality of life (MCS), and health behaviors known to improve diabetes outcomes. Methods: 602 patients were recruited from two adult primary care clinics in the southeastern United States. Linear regression models were used to assess the associations between perceived racial discrimination, self-care, clinical outcomes, MCS, adjusting for relevant covariates. Race-stratified models were conducted to examine differential associations by race. Results: The mean age was 61 years, with 64.9 % non-Hispanic black, and 41.6 % earning less than $20,000 annually. Perceived discrimination was significantly negatively associated with MCS (beta = -0.56, 95 % CI -0.90, 0.23), general diet (beta = -0.37, CI -0.65, -0.08), and specific diet (beta = -0.25, CI -0.47, -0.03). In African Americans, perceived discrimination was significantly associated with higher systolic blood pressure (beta = 10.17, CI 1.13, -19.22). In Whites, perceived discrimination was significantly associated with lower MCS (beta = -0.51, CI -0.89, -0.14), general diet (beta = -0.40, CI -0.69, -0.99), specific diet (beta = -0.25, CI -0.47, -0.03), and blood glucose testing (beta = -0.43, CI -0.80, -0.06).Conclusions: While no association was found with biologic measures, perceived discrimination was associated with health behaviors and the MCS. In addition, results showed a difference in influence of perceived discrimination by race. C1 [Dawson, Aprill Z.; Walker, Rebekah J.; Campbell, Jennifer A.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson VAMC, Charleston VA HSR&D COIN, HEROIC, Charleston, VA USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK09369 9-01] FX This study was supported by Grant K24DK09369 9-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). NR 29 TC 5 Z9 5 U1 3 U2 14 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD JUN PY 2015 VL 49 IS 2 BP 422 EP 428 DI 10.1007/s12020-014-0482-9 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ1GD UT WOS:000355230500015 PM 25414069 ER PT J AU Nierenberg, AA Ellard, KK AF Nierenberg, A. A. Ellard, K. K. TI Neurotic depression as the missing link: old wine with a new twist on anxiety and major depressive disorder SO EPIDEMIOLOGY AND PSYCHIATRIC SCIENCES LA English DT Editorial Material DE Neurosis; Depression; Anxiety; Emotional Processing ID ADULT HIPPOCAMPAL NEUROGENESIS; PATTERN SEPARATION; ANTIDEPRESSANT MEDICATIONS; TRANSDIAGNOSTIC TREATMENT; EMOTIONAL DISORDERS; UNIFIED PROTOCOL C1 [Nierenberg, A. A.; Ellard, K. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Suite 580,50 Staniford St, Boston, MA 02114 USA. EM anierenberg@mgh.harvard.edu NR 16 TC 0 Z9 0 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2045-7960 EI 2045-7979 J9 EPIDEMIOL PSYCH SCI JI Epidemiol. Psychiatr. Sci. PD JUN PY 2015 VL 24 IS 3 BP 230 EP 232 DI 10.1017/S2045796015000323 PG 3 WC Psychiatry SC Psychiatry GA CJ1VU UT WOS:000355273600008 PM 25997898 ER PT J AU Vo, P Bair-Merritt, M Camargo, CA AF Vo, Phuong Bair-Merritt, Megan Camargo, Carlos A. TI The potential role of vitamin D in the link between obesity and asthma severity/control in children SO EXPERT REVIEW OF RESPIRATORY MEDICINE LA English DT Review DE acute respiratory infection; asthma; children; corticosteroid responsiveness; obesity; vitamin D ID BODY-MASS INDEX; ACUTE RESPIRATORY-INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; NATURAL-KILLER-CELLS; D SUPPLEMENTATION; LUNG-FUNCTION; 25-HYDROXYVITAMIN D; TRACT INFECTION; IMMUNE FUNCTION; D DEFICIENCY AB Childhood obesity and asthma are major public health problems. Obesity is not only associated with increased risk of incident asthma, but it may worsen asthma severity/control. Although the mechanisms linking obesity with asthma expression have not been completely elucidated, evidence suggests that increased frequency of acute respiratory infection (ARI) and decreased corticosteroid responsiveness may help to explain how obesity worsens asthma expression. In addition, obese individuals have low vitamin D status, and emerging evidence suggests vitamin D affects risk of ARI and corticosteroid responsiveness in individuals with asthma. In this review, we summarize the association between obesity and asthma severity/control in children and discuss ARI and corticosteroid responsiveness as potential mediators in the obesity-asthma pathway. We also discuss the potential role of vitamin D, including a brief summary of recent randomized controlled trials of vitamin D supplementation. C1 [Vo, Phuong] Boston Med Ctr, Div Pediat Pulm & Allergy, Boston, MA 02118 USA. [Bair-Merritt, Megan] Boston Med Ctr, Div Gen Pediat, Boston, MA 02118 USA. [Camargo, Carlos A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Vo, P (reprint author), Boston Med Ctr, Div Pediat Pulm & Allergy, Boston, MA 02118 USA. EM phuong.vo@bmc.org FU Novartis; Teva FX C.A. Camargo has done asthma-related consulting for GlaxoSmithKline, Merck, Novartis and Teva and received asthma-related grants from Novartis and Teva. 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 85 TC 2 Z9 3 U1 2 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1747-6348 EI 1747-6356 J9 EXPERT REV RESP MED JI Expert Rev. Respir. Med. PD JUN PY 2015 VL 9 IS 3 BP 309 EP 325 DI 10.1586/17476348.2015.1042457 PG 17 WC Respiratory System SC Respiratory System GA CJ2MZ UT WOS:000355320300008 PM 25947112 ER PT J AU Saboo, US Amparo, F Shikari, H Jurkunas, UV Dana, R AF Saboo, Ujwala S. Amparo, Francisco Shikari, Hasanain Jurkunas, Ula V. Dana, Reza TI Outcomes of phacoemulsification in patients with chronic ocular graft-versus-host disease SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article DE Graft-versus-host disease; Cataract; Phacoemulsification; Ocular surface disease ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; POSTERIOR CAPSULE OPACIFICATION; STEM-CELL TRANSPLANTATION; QUALITY-OF-LIFE; CATARACT-SURGERY; CONTAMINATION RISK; EYE; PROBABILITY; PREVALENCE AB The purpose of this study was to evaluate the outcomes of phacoemulsification in patients with ocular graft-versus-host disease (GVHD). The occurrence of cataracts, cataract surgery, and its outcomes were analyzed in the medical records of 229 patients (458 eyes) with ocular GVHD. Outcome measures included pre- and postoperative corrected distance visual acuity (CDVA) and the rate of postoperative complications. Of the 458 eyes evaluated, 58 were pseudophakic; from the 400 phakic eyes, 238 (59 %) presented with cataracts and 62 (26 %) underwent cataract surgery. Analysis of postoperative complications and visual outcomes at 1 month was performed in 51 eyes in which detailed surgical and immediate postoperative records were available. Preoperatively, the mean CDVA was 0.67 +/- 0.57 LogMAR (Snellen 20/93), improving postoperatively to 0.17 +/- 0.18 (Snellen 20/29) at 1 month (P < 0.0001), and to 0.13 +/- 0.14 (Snellen 20/26) by the final follow-up visit (P < 0.0001). Postoperative complications included corneal epithelial defects (8 %), filamentary keratitis (6 %), worsening of corneal epitheliopathy (16 %), posterior capsular opacification (18 %), and cystoid macular edema (4 %). A corrected distance visual acuity of 20/30 or better was achieved in 87 % of the eyes; suboptimal CDVA improvement was attributable to severe ocular surface disease, pre-existing advanced glaucoma, and prior macular surgery. Phacoemulsification in patients with chronic ocular GVHD is a safe and efficacious procedure resulting in significant visual improvement. Overall, postoperative adverse events responded well to timely management. C1 [Saboo, Ujwala S.; Amparo, Francisco; Shikari, Hasanain; Jurkunas, Ula V.; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea Serv, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea Serv, Dept Ophthalmol,Med Sch, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Eye Institute, National Institutes of Health [K24-EY019098]; Research to Prevent Blindness FX This work was supported by the National Eye Institute, National Institutes of Health (Grant no: K24-EY019098), and Research to Prevent Blindness. NR 37 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X EI 1435-702X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JUN PY 2015 VL 253 IS 6 BP 901 EP 907 DI 10.1007/s00417-015-2940-3 PG 7 WC Ophthalmology SC Ophthalmology GA CJ1AM UT WOS:000355213500010 PM 25619668 ER PT J AU Khalili, H Ananthakrishnan, AN Konijeti, GG Higuchi, LM Fuchs, CS Richter, JM Tworoger, SS Hankinson, SE Chan, AT AF Khalili, Hamed Ananthakrishnan, Ashwin N. Konijeti, Gauree G. Higuchi, Leslie M. Fuchs, Charles S. Richter, James M. Tworoger, Shelley S. Hankinson, Susan E. Chan, Andrew T. TI Endogenous Levels of Circulating Androgens and Risk of Crohn's Disease and Ulcerative Colitis Among Women: A Nested Case-Control Study from the Nurses' Health Study Cohorts SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; Crohn's disease; ulcerative colitis; androgens; testosterone; Nurses' Health Study ID INFLAMMATORY-BOWEL-DISEASE; PREMENOPAUSAL WOMEN; BREAST-CANCER; HORMONE CONCENTRATIONS; POSTMENOPAUSAL WOMEN; SEX-DIFFERENCES; OLMSTED COUNTY; REPRODUCIBILITY; METAANALYSIS; TESTOSTERONE AB Background:Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC).Methods:We conducted a nested case-control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models.Results:Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39-1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21-1.15) for the third quartile, 0.22 (0.08-0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16-0.99) for the highest quintile (P-linear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (P-linear trend = 0.84). We also did not observe any association between plasma levels of sex hormone-binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all P-linear trends > 0.10).Conclusions:Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC. Further studies to understand the biological mechanisms by which endogenous androgens may mediate the etiopathogenesis of CD are warranted. C1 [Khalili, Hamed; Ananthakrishnan, Ashwin N.; Konijeti, Gauree G.; Richter, James M.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Ananthakrishnan, Ashwin N.; Konijeti, Gauree G.; Higuchi, Leslie M.; Fuchs, Charles S.; Richter, James M.; Tworoger, Shelley S.; Hankinson, Susan E.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Higuchi, Leslie M.] Boston Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Tworoger, Shelley S.; Hankinson, Susan E.; Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Tworoger, Shelley S.; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. RP Khalili, H (reprint author), Massachusetts Gen Hosp, Digest Healthcare Ctr, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM hkhalili@mgh.harvard.edu FU Crohn's and Colitis Foundation of America; American Gastroenterological Association; National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681, K08 DK064256]; [R01 CA137178]; [R01 CA050385]; [P01 CA87969]; [CA49449]; [CA67262]; [P30 DK043351]; [K24 098311]; [K23 DK091742] FX Supported by R01 CA137178, R01 CA050385, P01 CA87969, CA49449, CA67262, P30 DK043351, K23 DK099681, K08 DK064256, K24 098311, and K23 DK091742. A. T. Chan is supported by a senior investigator grant from the Crohn's and Colitis Foundation of America. H. Khalili is supported by a career development award from the American Gastroenterological Association and by the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). L. M. Higuchi is supported by National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK064256). NR 36 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUN PY 2015 VL 21 IS 6 BP 1378 EP 1385 DI 10.1097/MIB.0000000000000385 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ2LI UT WOS:000355315800021 PM 25844961 ER PT J AU Ferrero, P Iacovoni, A D'Elia, E Vaduganathan, M Gavazzi, A Senni, M AF Ferrero, Paolo Iacovoni, Attilio D'Elia, Emilia Vaduganathan, Muthiah Gavazzi, Antonello Senni, Michele TI Prognostic scores in heart failure - Critical appraisal and practical use SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Review DE Heart failure; Prognosis; Outcomes ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; CARDIAC RESYNCHRONIZATION THERAPY; IN-HOSPITAL MORTALITY; INITIATE LIFESAVING TREATMENT; RISK SCORE; PRIMARY PREVENTION; OPTIMIZE-HF; PREDICTING MORTALITY; AMBULATORY PATIENTS; ORGANIZED PROGRAM AB Survival in patients with heart failure in the last two decades has significantly improved, owing to availability of new drugs, devices, and technologies. However, these new therapeutic tools are often costly and not without attendant risks. Thus, accurate and reproducible risk stratification is required to assess appropriateness of therapy. Although a growing body of evidence has characterized various predictors of poor outcomes, the application of comprehensive prognostic models in clinical practice remains limited. Herein, we critically evaluate the utility of prognostic scores in heart failure, discussing the strategies to select the most efficient and appropriate risk estimator in the individual patient. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Ferrero, Paolo; Iacovoni, Attilio; D'Elia, Emilia; Senni, Michele] Azienda Osped Papa Giovanni XXIII, Dipartimento Cardiovasc, Bergamo, Italy. [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Gavazzi, Antonello] Azienda Osped Papa Giovanni XXIII, FROM Fdn Ric, Bergamo, Italy. [D'Elia, Emilia] Univ Pavia, Dept Internal Med, I-27100 Pavia, Italy. RP Senni, M (reprint author), Azienda Osped Papa Giovanni XXIII, Dipartimento Cardiovasc, Bergamo, Italy. EM msenni@hpg23.it OI Vaduganathan, Muthiah/0000-0003-0885-1953 FU Fondazione Credito Bergamasco (CREBERG) FX This work was supported by Fondazione Credito Bergamasco (CREBERG). NR 52 TC 8 Z9 8 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD JUN 1 PY 2015 VL 188 BP 1 EP 9 DI 10.1016/j.ijcard.2015.03.154 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CI8HW UT WOS:000355013600001 PM 25880571 ER PT J AU Bartels, CM Singh, JA Parperis, K Huber, K Rosenthal, AK AF Bartels, Christie M. Singh, Jasvinder A. Parperis, Konstantinos Huber, Karri Rosenthal, Ann K. TI Validation of Administrative Codes for Calcium Pyrophosphate Deposition A Veterans Administration Study SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE calcium pyrophosphate; chondrocalcinosis; ICD-9-CM code; veterans; CPPD disease ID SYNOVIAL-FLUID EXAMINATION; RHEUMATOID-ARTHRITIS; CRYSTALS; PREVALENCE; AFFAIRS; CHONDROCALCINOSIS; OSTEOARTHRITIS; DATABASES; DIAGNOSES; ACCURACY AB Background: Despite high prevalence, progress in calcium pyrophosphate deposition (CPPD) has been limited by poor awareness and absence of validated approaches to study it in large data sets. Objectives: We aimed to determine the accuracy of administrative codes for the diagnosis of CPPD as a foundational step for future studies. Methods: We identified all patients with an International Classification of Diseases, Ninth Revision, Clinical Modification code for chondrocalcinosis (712.1-712.39) or pseudogout/other disorders of mineral metabolism (275.49), and convenience sample selected a comparison group with gout (274.00-03 or 274.8-9), or rheumatoid arthritis (714.0) from 2009 to 2011 at a Veterans Affairs medical center. Each patient was categorized as having definite, probable, or possible CPPD or absence of CPPD based on the McCarty and Ryan criteria using chart abstracted data including crystal analysis, radiographs, and arthritis history. Results: Two hundred forty-nine patients met the clinical gold standard criteria for CPPD based on medical records, whereas 48 patients met definite criteria, 183 probable, and 18 met possible criteria. The accuracy of administrative claims with a code of 712 or 275.49 for definite or probable CPPD was as follows: 98% sensitivity (95% confidence interval, 96%-99%), 78% specificity (74%-83%), 91% positive predictive value, and 94% negative predictive value. Conclusions: At this center, single administrative code 275.49 or 712 accurately identifies patients with CPPD with a positive predictive value of 91%. These findings suggest that administrative codes can have strong clinical accuracy and merit further validation to allow adoption in future epidemiologic studies of CPPD. C1 [Bartels, Christie M.] Univ Wisconsin, Div Rheumatol, Dept Med, Madison, WI 53705 USA. [Bartels, Christie M.] William S Middleton VA Med Ctr, Madison, WI USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Div Rheumatol, Birmingham, AL 35294 USA. [Parperis, Konstantinos; Huber, Karri; Rosenthal, Ann K.] Med Coll Wisconsin, Dept Med, Div Rheumatol, Milwaukee, WI 53226 USA. [Rosenthal, Ann K.] Clement J Zablocki VA Med Ctr, Milwaukee, WI USA. RP Bartels, CM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, UWMF Centennial Bldg,1685 Highland Ave,Room 4132, Madison, WI 53705 USA. EM cb4@medicine.wisc.edu FU National Institutes of Health National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [AR062381]; Agency for Health Quality and Research Center for Education and Research on Therapeutics, NIAMS [AR062381]; National Institute of Aging; National Cancer Institute; Takeda; Savient; Regeneron; Allergan; National VA Research Service [110BX000812-01] FX C.M.B. receives support from the National Institutes of Health National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) (K23 #AR062381). J.A.S. is supported by the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, AL. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics, NIAMS (#AR062381), the National Institute of Aging, and the National Cancer Institute. J.A.S. has received research and travel grants from Takeda and Savient and consultant fees from Savient, Takeda, Regeneron, and Allergan, unrelated to this work. A.K.R. receives support from National VA Research Service (#110BX000812-01). The remaining authors declare no conflict of interest. NR 18 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 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD JUN PY 2015 VL 21 IS 4 BP 189 EP 192 DI 10.1097/RHU.0000000000000251 PG 4 WC Rheumatology SC Rheumatology GA CJ1OR UT WOS:000355253800004 PM 26010181 ER PT J AU Singh, JA Bharat, A Edwards, NL AF Singh, Jasvinder A. Bharat, Aseem Edwards, N. Lawrence TI An Internet Survey of Common Treatments Used by Patients With Gout Including Cherry Extract and Juice and Other Dietary Supplements SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article ID PERSPECTIVE; POPULATION; ADHERENCE C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Bharat, Aseem] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Bharat, Aseem] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Division of Rheumatology at the University of Alabama at Birmingham; Agency for Health Quality and Research Center for Education and Research on Therapeutics [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases [P50 AR060772, U34 AR062891]; National Institute of Aging [U01 AG018947]; National Cancer Institute [U10 CA149950]; Patient Centered Outcomes Research Institute [CE-1304-6631]; Takeda; Savient; Regeneron; Allergan; Crealta; AstraZeneca; Cymabay Pharmaceuticals FX This material is the result of work supported by research funds from the Division of Rheumatology at the University of Alabama at Birmingham and the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama. J.A.S. is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (U19 HS021110), National Institute of Arthritis, Musculoskeletal and Skin Diseases (P50 AR060772 and U34 AR062891), National Institute of Aging (U01 AG018947), and National Cancer Institute (U10 CA149950), and research contract (CE-1304-6631) from Patient Centered Outcomes Research Institute.; There are no financial conflicts related directly to this study. J.A.S. has received research and travel grants from Takeda and Savient; and consultant fees from Savient, Takeda, Regeneron, and Allergan. N.L.E. has received consultation fees from Takeda, Crealta, AstraZeneca, and Cymabay Pharmaceuticals. A.B. has no conflicts to declare. NR 11 TC 0 Z9 0 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD JUN PY 2015 VL 21 IS 4 BP 225 EP 226 DI 10.1097/RHU.0000000000000246 PG 2 WC Rheumatology SC Rheumatology GA CJ1OR UT WOS:000355253800012 PM 26010189 ER PT J AU Minshawi, NF Hurwitz, S Morriss, D McDougle, CJ AF Minshawi, Noha F. Hurwitz, Sarah Morriss, Danielle McDougle, Christopher J. TI Multidisciplinary Assessment and Treatment of Self-Injurious Behavior in Autism Spectrum Disorder and Intellectual Disability: Integration of Psychological and Biological Theory and Approach SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Intellectual disability; Self-injurious behavior; Behavior therapy; Pharmacotherapy ID PRADER-WILLI-SYNDROME; LESCH-NYHAN-SYNDROME; PERVASIVE DEVELOPMENTAL DISORDERS; MENTALLY-RETARDED CHILDREN; PATHOLOGICAL SKIN-PICKING; DU-CHAT-SYNDROME; DOUBLE-BLIND; CHALLENGING BEHAVIOR; NONCONTINGENT REINFORCEMENT; ATYPICAL ANTIPSYCHOTICS AB The objective of this review is to consider the psychological (largely behavioral) and biological [neurochemical, medical (including genetic), and pharmacological] theories and approaches that contribute to current thinking about the etiology and treatment of self-injurious behavior (SIB) in individuals with autism spectrum disorder and/or intellectual disability. Algorithms for the assessment and treatment of SIB in this context, respectively, from a multidisciplinary, integrative perspective are proposed and challenges and opportunities that exist in clinical and research settings are discussed. C1 [Minshawi, Noha F.] Indiana Univ Sch Med, Dept Psychiat, James Whitcomb Riley Hosp Children, Christian Sarkine Autism Treatment Ctr, Indianapolis, IN 46202 USA. [Hurwitz, Sarah] Indiana Univ, Sch Educ, Bloomington, IN 47405 USA. [Morriss, Danielle] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Dept Psychiat, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Dept Pediat, Lexington, MA 02421 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, MassGen Hosp Children, Lexington, MA 02421 USA. RP McDougle, CJ (reprint author), Massachusetts Gen Hosp, Lurie Ctr Autism, Dept Psychiat, One Maguire Rd, Lexington, MA 02421 USA. EM cmcdougle@partners.org NR 285 TC 8 Z9 8 U1 8 U2 28 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1541 EP 1568 DI 10.1007/s10803-014-2307-3 PG 28 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700004 PM 25395094 ER PT J AU Evers, K Steyaert, J Noens, I Wagemans, J AF Evers, Kris Steyaert, Jean Noens, Ilse Wagemans, Johan TI Reduced Recognition of Dynamic Facial Emotional Expressions and Emotion-Specific Response Bias in Children with an Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder (ASD); Dynamic facial expressions; Emotion recognition; Face perception; Response bias; Theory of mind ID 1ST-DEGREE RELATIVES; PERCEPTION; INDIVIDUALS; PHENOTYPE; INTENSITIES; CHILDHOOD; DISPLAYS; DEFICITS; PARENTS; ADULTS AB Emotion labelling was evaluated in two matched samples of 6-14-year old children with and without an autism spectrum disorder (ASD; N = 45 and N = 50, resp.), using six dynamic facial expressions. The Emotion Recognition Task proved to be valuable demonstrating subtle emotion recognition difficulties in ASD, as we showed a general poorer emotion recognition performance, in addition to some emotion-specific impairments in the ASD group. Participants' preference for selecting a certain emotion label, irrespective of the stimulus presented, played an important role in our results: response bias-corrected data still showed an overall decreased emotion recognition performance in ASD, but no emotion-specific impairments anymore. Moreover, ASD traits and empathy were correlated with emotion recognition performance. C1 [Evers, Kris; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Leuven, Belgium. [Evers, Kris; Steyaert, Jean] UPC KU Leuven, Dept Child Psychiat, Leuven, Belgium. [Evers, Kris; Steyaert, Jean; Noens, Ilse; Wagemans, Johan] Katholieke Univ Leuven, Leuven Autism Res LAuRes, Leuven, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Leuven, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Evers, K (reprint author), Katholieke Univ Leuven, Expt Psychol Lab, Tiensestr 102,Box 3711, B-3000 Leuven, Belgium. EM kris.evers@ppw.kuleuven.be FU Methusalem program by Flemish Government [METH 08/02]; Research Council of the KU Leuven [IDO/080/013]; Marguerite Marie Delacroix Support Fund [GV/B-141] FX We want to thank all participating children and their parents. Special thanks go to the participating schools, Ten Bunderen (Moorslede), De Puzzel (Kleine-Brogel) and De Schommel (Lommel). Thanks to Dr. Ervin Poljac for sharing his expertise with the Emotion Recognition Task. We thank Birgitt Haesen and the following master students for their assistance with data collection: Nele Berghmans, Stephanie Deckmyn, Sanne Drees, Tine Herreman, Ellen Janssen, Loes Steegmans, Lotte van Esch, Alysee Van Laeken, and Leen Vercammen. This research was funded by the Methusalem program by the Flemish Government (METH 08/02) awarded to J.W., by a grant from the Research Council of the KU Leuven (IDO/080/013) awarded to J.S., J.W. and I.N., and by a grant from the Marguerite Marie Delacroix Support Fund (GV/B-141) awarded to K.E. NR 44 TC 5 Z9 6 U1 7 U2 46 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1774 EP 1784 DI 10.1007/s10803-014-2337-x PG 11 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700022 PM 25563453 ER PT J AU Chen, JA Splenser, A Guillory, B Luo, JH Mendiratta, M Belinova, B Halder, T Zhang, GH Li, YP Garcia, JM AF Chen, Ji-an Splenser, Andres Guillory, Bobby Luo, Jiaohua Mendiratta, Meenal Belinova, Blaga Halder, Tripti Zhang, Guohua Li, Yi-Ping Garcia, Jose M. TI Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved SO JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE LA English DT Article DE Cachexia; Cancer; Muscle; Ghrelin; Growth hormone ID GROWTH-HORMONE SECRETAGOGUES; SKELETAL-MUSCLE; CANCER CACHEXIA; MYOBLAST DIFFERENTIATION; TRANSCRIPTION FACTORS; GENE-EXPRESSION; WEIGHT-LOSS; MICE; CELLS; CATABOLISM AB Background Cachexia and muscle atrophy are common consequences of cancer and chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake and direct effects on muscle proteolysis and protein synthesis are likely to mediate these effects, but the pathways leading to these events are not well understood. Methods We characterized molecular pathways involved in muscle atrophy induced by Lewis lung carcinoma (LLC) tumour implantation in c57/bl6 adult male mice and by administration of the chemotherapeutic agent cisplatin in mice and in C2C12 myotubes. The effects of exogenous ghrelin administration and its mechanisms of action were examined in these settings. Results Tumour implantation and cisplatin induced muscle atrophy by activating pro-inflammatory cytokines, p38-C/EBP-beta, and myostatin, and by down-regulating Akt, myoD, and myogenin, leading to activation of ubiquitin-proteasome-mediated proteolysis and muscle weakness. Tumour implantation also increased mortality. In vitro, cisplatin up-regulated myostatin and atrogin-1 by activating C/EBP-beta and FoxO1/3. Ghrelin prevented these changes in vivo and in vitro, significantly increasing muscle mass (P<0.05 for LLC and P<0.01 for cisplatin models) and grip strength (P = 0.038 for LLC and P = 0.001 for cisplatin models) and improving survival (P = 0.021 for LLC model). Conclusion Ghrelin prevents muscle atrophy by down-regulating inflammation, p38/C/EBP-beta/myostatin, and activating Akt, myogenin, and myoD. These changes appear, at least in part, to target muscle cells directly. Ghrelin administration in this setting is associated with improved muscle strength and survival. C1 [Chen, Ji-an] Third Mil Med Univ, Coll Prevent Med, Dept Hlth Educ, Chongqing, Peoples R China. [Chen, Ji-an; Splenser, Andres; Guillory, Bobby; Luo, Jiaohua; Mendiratta, Meenal; Belinova, Blaga; Halder, Tripti; Garcia, Jose M.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Ctr Translat Res Inflammatory Dis,MCL,Div Endocri, Houston, TX 77030 USA. [Luo, Jiaohua] Third Mil Med Univ, Coll Prevent Med, Dept Environm Hyg, Chongqing, Peoples R China. [Zhang, Guohua; Li, Yi-Ping] Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA. [Garcia, Jose M.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Garcia, Jose M.] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. RP Garcia, JM (reprint author), Michael E DeBakey VA Med Ctr, Div Endocrinol Diabet & Metab, 2002 Holcombe Blvd,Bldg 109,Rm 210, Houston, TX 77030 USA. EM Jgarcia1@bcm.edu FU US Department of Veterans Affairs [I01-BX000507, I01 CX000174]; Caroline Wiess Law Fund for Molecular Medicine; National Institutes of Health [AG040583, AR063786]; National Institute of aging [T32AG000183]; National Natural Science Foundation of China [81072262, 81372944]; Vanderbilt MMPC [U24 DK59637]; Vanderbilt University Medical Center Hormone Assay and Analytical Services Core (National Institutes of Health) [DK059637, DK020593]; University of Virginia [DK076037]; Baylor Diabetes & Endocrinology Research Center [P30 DK079638] FX US Department of Veterans Affairs (Merit grants I01-BX000507 and I01 CX000174, Merit Review Entry Program and a South-central healthcare network career development award); Caroline Wiess Law Fund for Molecular Medicine; National Institutes of Health (AG040583 to J.M.G. and AR063786 to Y.P.L); National Institute of aging (T32AG000183) to B.G.; National Natural Science Foundation of China (81072262 and 81372944) to J.A.C; Vanderbilt MMPC (supported in part by U24 DK59637); Vanderbilt University Medical Center Hormone Assay and Analytical Services Core (supported by National Institutes of Health grants DK059637 and DK020593); University of Virginia (DK076037); and Baylor Diabetes & Endocrinology Research Center (P30 DK079638). NR 52 TC 19 Z9 20 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2190-5991 EI 2190-6009 J9 J CACHEXIA SARCOPENI JI J. Caxhexia Sarcopenia Muscle PD JUN PY 2015 VL 6 IS 2 BP 132 EP 143 DI 10.1002/jcsm.12023 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CJ2UP UT WOS:000355340500003 PM 26136189 ER PT J AU Fisichella, PM Orthopoulos, G Holmstrom, A Patti, MG AF Fisichella, P. Marco Orthopoulos, George Holmstrom, Amy Patti, Marco G. TI The Surgical Management of Achalasia in the Morbid Obese Patient SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Obesity; Morbid obesity; Esophageal achalasia; Heller myotomy; Dor fundoplication; Roux-en-Y gastric bypass ID GASTROESOPHAGEAL-REFLUX DISEASE; LAPAROSCOPIC HELLER MYOTOMY; GASTRIC BYPASS AB Morbid obesity and achalasia may coexist in the same patient. The surgical management of the morbidly obese patient with achalasia is complex, and the most effective treatment still remains controversial. The goal of our report is to provide our evidence-based approach for the surgical management of the patient with achalasia and morbid obesity. Three main surgical approaches have been used for the concomitant treatment of morbid obesity and achalasia: 1) a laparoscopic Heller myotomy and a laparoscopic Roux-en-Y gastric bypass (LRYGB); 2) a laparoscopic Heller myotomy with bilio-pancreatic diversion; and 3) a laparoscopic Heller myotomy with a sleeve gastrectomy. Our approach of choice is the first one discussed, that is the laparoscopic Heller myotomy with a LRYGB, as this approach can provide excellent relief of symptoms and control of reflux while at the same time treating obesity and its comorbidities. Achalasia and obesity can coexist, albeit infrequently. A laparoscopic Heller myotomy with a LRYGB allows the simultaneous treatment of both diseases. When a morbidly obese patient with achalasia chooses to have a myotomy alone and not a LRYGB, a thorough discussion of the risks and benefits should occur and the autonomy of the patient's decision-making should be respected. C1 [Fisichella, P. Marco] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Dept Surg, West Roxbury, MA 02132 USA. [Orthopoulos, George; Holmstrom, Amy] Boston Univ, Med Ctr, Boston, MA USA. [Patti, Marco G.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Patti, Marco G.] Univ Chicago, Pritzker Sch Med, Ctr Esophageal Dis, Chicago, IL 60637 USA. RP Fisichella, PM (reprint author), Harvard Univ, Sch Med, Boston VA Healthcare Syst, Dept Surg, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM marco6370@yahoo.com NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUN PY 2015 VL 19 IS 6 BP 1139 EP 1143 DI 10.1007/s11605-015-2790-7 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CJ2WB UT WOS:000355344300021 PM 25759076 ER PT J AU Neuhaus, V Kadzielski, JJ Mudgal, CS AF Neuhaus, V. Kadzielski, J. J. Mudgal, C. S. TI The role of arthrodesis of the wrist in spastic disorders SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Article DE Arthrodesis; outcome; spastic deformities; wrist ID IN-PALM DEFORMITY; CEREBRAL-PALSY; UPPER EXTREMITY; HAND AB We investigated the functional and radiographic outcome of wrist arthrodesis in 11 adults with spastic wrist deformities, carried out by one surgeon between 2003 and 2012. The underlying cause of spasticity was a cerebrovascular insult in five, traumatic brain injury in four, and cerebral palsy in two patients. A dorsal plate and local bone graft was used in all patients. The mean radiographic flexion deformity significantly improved from 67 degrees pre-operatively to 4 degrees of dorsal angulation post-operatively. Thumb-in-palm deformity was more pronounced in three patients after the operation. The functional House score improved in all patients an average of two levels (range 1-3). Level of evidence: IV (Case series). C1 [Neuhaus, V.; Kadzielski, J. J.; Mudgal, C. S.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 FU 'Gottfried und Julia Bangerter-Rhyner-Stiftung', Switzerland FX V. Neuhaus was supported by the 'Gottfried und Julia Bangerter-Rhyner-Stiftung', Switzerland, for Scientific Research. No other funding to declare. NR 15 TC 1 Z9 1 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 EI 2043-6289 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD JUN PY 2015 VL 40 IS 5 BP 512 EP 517 DI 10.1177/1753193414530193 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CI8BW UT WOS:000354993500010 PM 24692187 ER PT J AU Bell, DL Kimberly, WT Yoo, AJ Leslie-Mazwi, TM Rabinov, JD Bell, JE Mehta, BP Hirsch, JA AF Bell, Donnie L. Kimberly, W. Taylor Yoo, Albert J. Leslie-Mazwi, Thabele M. Rabinov, James D. Bell, Jania E. Mehta, Brijesh P. Hirsch, Joshua A. TI Low neurologic intensive care unit hemoglobin as a predictor for intra-arterial vasospasm therapy and poor discharge modified Rankin Scale in aneurysmal subarachnoid haemorrhage-induced cerebral vasospasm SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article DE Aneurysm; Hemorrhage; Subarachnoid ID CELL TRANSFUSION INCREASES; ENDOVASCULAR TREATMENT; BLOOD-TRANSFUSION; OXYGEN DELIVERY; ANEMIA; MANAGEMENT; ISCHEMIA; OUTCOMES; STROKE AB Background Intra-arterial vasospasm therapy (IAVT) with vasodilators, balloon angioplasty, and cerebral blood flow augmentation devices are therapies for aneurysmal subarachnoid hemorrhage-induced symptomatic cerebral vasospasm refractory to maximal medical management. Our aim was to identify clinical factors predictive of IAVT and/or poor outcome. Methods A cross-sectional retrospective analysis was performed of 130 patients with aneurysmal subarachnoid hemorrhage including patients without and with symptomatic cerebral vasospasm requiring IAVT. The data were analysed by Student t test, univariate analysis and binary logistic regression. Results The meanSD patient age was 54 +/- 12.2years, admission hemoglobin was 13.6 +/- 1.5g/dL, and neurologic intensive care unit (NICU) hemoglobin 11 +/- 1.4g/dL. The median Hunt and Hess grade was 2 (range 1,4), Fisher grade 3 (range 3,3), and discharge modified Rankin Scale (mRS) 0.5 (range 0,2). Lower mean NICU hemoglobin was found in patients receiving IAVT than in those not receiving IAVT (M=10.4 +/- 0.9g/dL vs M=11.2 +/- 1.4g/dL, t(115)=-2.52, p=0.01). Further, lower mean NICU hemoglobin was associated with increased IAVT (=-0.3, p<0.01) and higher discharge mRS (=-0.5, p<0.01). In binary logistic regression, lower mean NICU hemoglobin was an independent predictor of IAVT (OR 0.6, 95% CI 0.4 to 0.9, p<0.05) as well as poor discharge mRS (OR 0.6, 95% CI 0.4 to 0.9, p<0.05). Hunt and Hess grade was also an independent predictor of these outcomes. Conclusions Lower mean hemoglobin during the acute phase of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm is an independent predictor of IAVT and poor discharge mRS. This relationship warrants further evaluation. C1 [Bell, Donnie L.; Yoo, Albert J.; Rabinov, James D.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Neuroendovasc Program, Boston, MA 02114 USA. [Bell, Donnie L.; Kimberly, W. Taylor; Yoo, Albert J.; Leslie-Mazwi, Thabele M.; Rabinov, James D.; Mehta, Brijesh P.; Hirsch, Joshua A.] Harvard Med Sch, Boston, MA USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Neurocrit Care, Dept Neurol, Boston, MA 02114 USA. [Leslie-Mazwi, Thabele M.; Mehta, Brijesh P.] Massachusetts Gen Hosp, Neurocrit Care & Neuroendovasc Program, Dept Neurol & Radiol, Boston, MA 02114 USA. RP Bell, DL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroendovasc Program, 55 Fruit St,GRB 241, Boston, MA 02114 USA. EM dbell3@partners.org FU David Heitman Neurovascular Foundation FX WTK is funded by the David Heitman Neurovascular Foundation. NR 31 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUN PY 2015 VL 7 IS 6 BP 438 EP 442 DI 10.1136/neurintsurg-2014-011164 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA CJ0YZ UT WOS:000355208800013 PM 24814068 ER PT J AU Kilbane, C Ramirez-Zamora, A Ryapolova-Webb, E Qasim, S Glass, GA Starr, PA Ostrem, JL AF Kilbane, Camilla Ramirez-Zamora, Adolfo Ryapolova-Webb, Elena Qasim, Selman Glass, Graham A. Starr, Philip A. Ostrem, Jill L. TI Pallidal stimulation for Holmes tremor: clinical outcomes and single-unit recordings in 4 cases SO JOURNAL OF NEUROSURGERY LA English DT Article DE Holmes tremor; deep brain stimulation; neurophysiology; oscillation; globus pallidus; Parkinson's disease; functional neurosurgery ID DEEP BRAIN-STIMULATION; NUCLEUS VENTRALIS INTERMEDIUS; MULTIPLE-SCLEROSIS; THALAMIC-STIMULATION; MIDBRAIN TREMOR; PARKINSONS-DISEASE; NEURONAL DISCHARGE; POSTTRAUMATIC TREMOR; STEREOTAXIC SURGERY; MOVEMENT-DISORDERS AB OBJECT Holmes tremor (HT) is characterized by irregular, low-frequency (< 4.5 Hz) tremor occurring at rest, with posture, and with certain actions, often affecting proximal muscles. Previous reports have tended to highlight the use of thalamic deep brain stimulation (DBs) in cases of medication-refractory HT. In this study, the authors report the clinical outcome and analysis of single-unit recordings in patients with medication-refractory HT treated with globus pallidus internus (GPi) DBS. METHODS The authors retrospectively reviewed the medical charts of 4 patients treated with pallidal DBS for medication-refractory HT at the University of California, San Francisco, and San Francisco Veterans Affairs Medical Center. Clinical outcomes were measured at baseline and after surgery using an abbreviated motor-severity Fahn-Tolosa-Marin (FTM) tremor rating scale. Intraoperative microelectrode recordings were performed with patients in the awake state. The neurophysiological characteristics identified in HT were then also compared with characteristics previously described in Parkinson's disease (PD) studied at the authors' institution. RESULTS The mean percentage improvement in tremor motor severity was 78.87% (range 59.9%-94.4%) as measured using the FTM tremor rating scale, with an average length of follow-up of 33.75 months (range 18-52 months). Twenty-eight GPi neurons were recorded intraoperatively in the resting state and 13 of these were also recorded during contralateral voluntary arm movement. The mean firing rate at rest in HT was 56.2 +/- 28.5 Hz, and 63.5 +/- 19.4 Hz with action, much lower than the GPi recordings in PD. GPi unit oscillations of 2-8 Hz were prominent in both patients with HT and those with PD, but in HT, unlike PD, these oscillations were not suppressed by voluntary movement. CONCLUSIONS The efficacy of GPi DBS exceeded that reported in prior studies of ventrolateral thalamus DBS and suggest GPi may be a better target for treating HT. These clinical and neurophysiological findings help illuminate evolving models of HT and highlight the importance of cerebellar basal ganglia interactions. C1 [Kilbane, Camilla] Stanford Univ, Dept Neurol, Med Ctr, Stanford, CA 94305 USA. [Ostrem, Jill L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94115 USA. [Ryapolova-Webb, Elena; Qasim, Selman; Starr, Philip A.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94115 USA. [Glass, Graham A.; Starr, Philip A.; Ostrem, Jill L.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Ramirez-Zamora, Adolfo] Albany Med Coll, Albany, NY 12208 USA. RP Ostrem, JL (reprint author), Univ Calif San Francisco, Surg Movement Disorder Ctr, 1635 Divisadero St,Ste 520-530, San Francisco, CA 94115 USA. EM jill.ostrem@ucsf.edu OI Qasim, Salman/0000-0001-8739-5962; Ramirez-Zamora, Adolfo/0000-0001-9253-3899 NR 68 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 2015 VL 122 IS 6 BP 1306 EP 1314 DI 10.3171/2015.2.JNS141098 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CI8OK UT WOS:000355031400007 PM 25794341 ER PT J AU Morgan, JH Kallen, MA Okike, K Lee, OC Vrahas, MS AF Morgan, Jordan H. Kallen, Michael A. Okike, Kanu Lee, Olivia C. Vrahas, Mark S. TI PROMIS Physical Function Computer Adaptive Test Compared With Other Upper Extremity Outcome Measures in the Evaluation of Proximal Humerus Fractures in Patients Older Than 60 Years SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE outcome measures; patient-reported outcomes; PROMIS; computer adaptive testing; physical function; trauma ID FUNCTION ITEM BANK; MUSCULOSKELETAL FUNCTION ASSESSMENT; INFORMATION-SYSTEM PROMIS; SHOULDER ASSESSMENT; HAND QUESTIONNAIRE; INTERNAL-FIXATION; OPEN REDUCTION; RESPONSIVENESS; DISABILITIES; PLATE AB Objectives:To compare the PROMIS Physical Function Computer Adaptive Test (PROMIS PF CAT) to commonly used traditional PF measures for the evaluation of patients with proximal humerus fractures.Design:Prospective.Setting:Two Level I trauma centers.Patients/Participants:Forty-seven patients older than 60 years with displaced proximal humerus fractures treated between 2006 and 2009.Intervention:Evaluation included completion of the PROMIS PF CAT, the Constant Shoulder Score, the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Short Musculoskeletal Functional Assessment (SMFA).Main Outcome Measurement:Observed correlations among the administered PF outcome measures.Results:On average, patients responded to 86 outcome-related items for this study: 4 for the PROMIS PF CAT (range: 4-8 items), 6 for the Constant Shoulder Score, 30 for the DASH, and 46 for the SMFA. Time to complete the PROMIS PF CAT (median completion time = 98 seconds) was significantly less than that for the DASH (median completion time = 336 seconds, P < 0.001) and for the SMFA (median completion time = 482 seconds, P < 0.001). PROMIS PF CAT scores correlated statistically significantly and were of moderate-to-high magnitude with all other PF outcome measure scores administered.Conclusions:This study suggests using the PROMIS PF CAT as a sole PF outcome measure can yield an assessment of upper extremity function similar to those provided by traditional PF measures, while substantially reducing patient assessment time. C1 [Morgan, Jordan H.; Vrahas, Mark S.] Harvard Univ, Dept Orthopaed Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Kallen, Michael A.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Okike, Kanu] Univ Maryland, Sch Med, Dept Orthopaed Surg, Baltimore, MD 21201 USA. [Lee, Olivia C.] Louisiana State Univ, Hlth Sci Ctr, Dept Orthopaed Surg, New Orleans, LA USA. RP Morgan, JH (reprint author), 55 Fruit St,Yawkey Ctr Suite 3C, Boston, MA 02114 USA. EM jhmorgan@partners.org OI Okike, Kanu/0000-0001-9310-9969 FU Orthopaedic Research and Education Foundation; Massachusetts General Hospital Orthopaedic Academic Enrichment Fund FX Supported in part by research grants from the Orthopaedic Research and Education Foundation and the Massachusetts General Hospital Orthopaedic Academic Enrichment Fund. NR 32 TC 7 Z9 7 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD JUN PY 2015 VL 29 IS 6 BP 257 EP 263 DI 10.1097/BOT.0000000000000280 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA CI7WW UT WOS:000354977000005 PM 26001348 ER PT J AU Benzing, T Wilhoit, C Wright, S McCann, A Lessner, S Brothers, TE AF Benzing, Travis Wilhoit, Cameron Wright, Sharee McCann, Aaron Lessner, Susan Brothers, Thomas E. TI Standard duplex criteria overestimate the degree of stenosis after eversion carotid endarterectomy SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ARTERY STENOSIS; CT ANGIOGRAPHY; FOLLOW-UP; SYMPTOMATIC PATIENTS; VELOCITY CRITERIA; PATCH CLOSURE; ULTRASOUND; TRIAL; BIFURCATION; SONOGRAPHY AB Objective: The eversion technique for carotid endarterectomy (eCEA) offers an alternative to longitudinal arteriotomy and patch closure (pCEA) for open carotid revascularization. In some reports, eCEA has been associated with a higher rate of >50% restenosis of the internal carotid when it is defined as peak systolic velocity (PSV) >125 cm/s by duplex imaging. Because the conformation of the carotid bifurcation may differ after eCEA compared with native carotid arteries, it was hypothesized that standard duplex criteria might not accurately reflect the presence of restenosis after eCEA. Methods: In a case-control study, the outcomes of all patients undergoing carotid endarterectomy by one surgeon during the last 10 years were analyzed retrospectively, with a primary end point of PSV >125 cm/s. Duplex flow velocities were compared with luminal diameter measurements for any carotid computed tomography arteriography or magnetic resonance angiography study obtained within 2 months of duplex imaging, with the degree of stenosis calculated by the methodology used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) as well as cross-sectional area (CSA) reduction. Simulations were generated and analyzed by computational model simulations of the eCEA and pCEA arteries. Results: Eversion and longitudinal arteriotomy with patch techniques were used in 118 and 177 carotid arteries, respectively. Duplex follow-up was available in 90 eCEA arteries at a median of 16 (range, 2-136) months and in 150 pCEA arteries at a median of 41 (range, 3-115) months postoperatively. PSV >125 cm/s was present at some time during follow-up in 31% of eCEA and pCEA carotid arteries, each, and in the most recent duplex examination in 7% after eCEA and 21% after pCEA (P = . 003), with no eCEA and two pCEA arteries occluding completely during follow-up (P = .29). In 19 carotid arteries with PSV >125 cm/s after angle correction (median, 160 cm/s; interquartile range, 146-432 cm/s) after eCEA that were subsequently examined by axial imaging, the mean percentage stenosis was 8% +/- 11% by NASCET, 11% +/- 5% by ECST, and 20% +/- 9% by CSA criteria. For eight pCEA arteries with PSV >125 cm/s (median velocity, 148 cm/s; interquartile range, 139-242 cm/s), the corresponding NASCET, ECST, and CSA stenoses were 8% +/- 35%, 26% +/- 32%, and 25% +/- 33%, respectively. NASCET internal carotid diameter reduction of at least 50% was noted by axial imaging after two of the eight pCEAs, and the PSV exceeded 200 cm/s in each case. Conclusions: The presence of hemodynamically significant carotid artery restenosis may be overestimated by standard duplex criteria after eCEA and perhaps after pCEA. Insufficient information currently exists to determine what PSV does correspond to hemodynamically significant restenosis. C1 [Brothers, Thomas E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Benzing, Travis; Wilhoit, Cameron; Wright, Sharee; Brothers, Thomas E.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [McCann, Aaron; Lessner, Susan] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC USA. RP Brothers, TE (reprint author), 25 Courtenay Dr,Ste 7018, Charleston, SC 29425 USA. EM brothete@musc.edu OI Lessner, Susan/0000-0002-8409-5216 FU Research Program for Medical Students at USC School of Medicine FX P.A.McC. was supported by the Research Program for Medical Students at USC School of Medicine. NR 39 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2015 VL 61 IS 6 BP 1457 EP 1463 DI 10.1016/j.jvs.2015.01.039 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CI8JL UT WOS:000355018500010 PM 25758452 ER PT J AU Phan, AT Halperin, DM Chan, JA Fogelman, DR Hess, KR Malinowski, P Regan, E Ng, CS Yao, JC Kulke, MH AF Phan, Alexandria T. Halperin, Daniel M. Chan, Jennifer A. Fogelman, David R. Hess, Kenneth R. Malinowski, Paige Regan, Eileen Ng, Chaan S. Yao, James C. Kulke, Matthew H. TI Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study SO LANCET ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; PLUS OCTREOTIDE; II TRIAL; BEVACIZUMAB; SUNITINIB; EVEROLIMUS; COMBINATION; SORAFENIB; CAPECITABINE; TEMOZOLOMIDE AB Background Treatment options for advanced, well-differentiated neuroendocrine tumours (NETs) remain scarce. Pazopanib is an orally bioavailable, small molecule, multitargeted kinase inhibitor that inhibits VEGF receptors 1, 2, and 3. We did a study of the efficacy of pazopanib with depot octreotide in patients with advanced NETs. Methods We did a parallel cohort study of patients with metastatic or locally advanced grade 1-2 carcinoid tumours or pancreatic NETs, by use of a single-group, two-stage design. Patients received pazopanib 800 mg orally once per day and octreotide at their preprotocol dosage. The primary endpoint was the proportion of patients achieving an objective response, as assessed by investigators, by intention-to-treat analysis. This study is registered with ClinicalTrials.gov, identifier NCT00454363, and was completed in March, 2014. Findings Between April 12, 2007, and July 2, 2009, we enrolled 52 patients, including 32 individuals with pancreatic NETs and 20 individuals with carcinoid tumours. Seven (21.9%, 95% CI 11.0-38.8) of 32 patients with pancreatic NETs achieved an objective response. We detected no responses in the first stage of the cohort with carcinoid tumours, and we terminated accrual at 20 patients. Toxic effects included one patient with grade 4 hypertriglyceridaemia and one with grade 4 thrombosis, with the most common grade three events being aminotransferase increases and neutropenia, each of which happened in 3 patients. In all 52 patients, the most frequently observed toxic effects were fatigue (39 [75%]), nausea (33 [63%]), diarrhoea (33 [63%]), and hypertension (28 [54%]). Interpretation Treatment with pazopanib is associated with tumour response for patients with pancreatic NETs, but not for carcinoid tumours; a randomised controlled phase 3 study to assess pazopanib in advanced pancreatic NETs is warranted. C1 [Phan, Alexandria T.; Halperin, Daniel M.; Fogelman, David R.; Yao, James C.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Hess, Kenneth R.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Ng, Chaan S.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Chan, Jennifer A.; Malinowski, Paige; Regan, Eileen; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Yao, JC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. EM jyao@mdanderson.org OI Halperin, Daniel M/0000-0002-3113-930X FU United States National Cancer Institute of the National Institutes of Health [US NCI-CTEP N01CM-2011-00039]; US National Cancer Institute of the National Institutes of Health FX US National Cancer Institute of the National Institutes of Health. NR 34 TC 23 Z9 23 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUN PY 2015 VL 16 IS 6 BP 695 EP 703 DI 10.1016/S1470-2045(15)70136-1 PG 9 WC Oncology SC Oncology GA CJ1MB UT WOS:000355246600054 PM 25956795 ER PT J AU Lin, NU Lee, EQ Aoyama, H Barani, IJ Barboriak, DP Baumert, BG Bendszus, M Brown, PD Camidge, DR Chang, SM Dancey, J de Vries, EGE Gaspar, LE Harris, GJ Hodi, FS Kalkanis, SN Linskey, ME Macdonald, DR Margolin, K Mehta, MP Schiff, D Soffietti, R Suh, JH van den Bent, MJ Vogelbaum, MA Wen, PY AF Lin, Nancy U. Lee, Eudocia Q. Aoyama, Hidefumi Barani, Igor J. Barboriak, Daniel P. Baumert, Brigitta G. Bendszus, Martin Brown, Paul D. Camidge, D. Ross Chang, Susan M. Dancey, Janet de Vries, Elisabeth G. E. Gaspar, Laurie E. Harris, Gordon J. Hodi, F. Stephen Kalkanis, Steven N. Linskey, Mark E. Macdonald, David R. Margolin, Kim Mehta, Minesh P. Schiff, David Soffietti, Riccardo Suh, John H. van den Bent, Martin J. Vogelbaum, Michael A. Wen, Patrick Y. CA Response Assessment Neuro-Oncology TI Response assessment criteria for brain metastases: proposal from the RANO group SO LANCET ONCOLOGY LA English DT Review ID GAMMA-KNIFE RADIOSURGERY; VOLUMETRIC DATA ERRORS; SOLID TUMORS; CLINICAL-TRIALS; BREAST-CANCER; PHASE-II; GUIDELINES; MR AB CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials. C1 [Lin, Nancy U.; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lee, Eudocia Q.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Aoyama, Hidefumi] Niigata Univ, Grad Sch Med & Dent Sci, Dept Radiol, Chuo Ku, Niigata, Japan. [Barani, Igor J.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Barboriak, Daniel P.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Baumert, Brigitta G.] MediClin Robert Janker Clin, Dept Radiat Oncol, Bonn, Germany. [Baumert, Brigitta G.] Univ Bonn, Med Ctr, Cooperat Unit Neurooncol, Bonn, Germany. [Bendszus, Martin] Heidelberg Univ, Dept Neuroradiol, Heidelberg, Germany. [Brown, Paul D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Camidge, D. Ross] Univ Colorado, Sch Med, Div Med Oncol, Denver, CO USA. [Chang, Susan M.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Dancey, Janet] Queens Univ, Ontario Inst Canc Res, NCIC Clin Trials Grp, Kingston, ON, Canada. [de Vries, Elisabeth G. E.] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands. [Gaspar, Laurie E.] Univ Colorado Denver, Dept Radiat Oncol, Aurora, CO USA. [Harris, Gordon J.] Massachusetts Gen Hosp, MGH Imaging Lab 3D, Boston, MA 02114 USA. [Kalkanis, Steven N.] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. [Linskey, Mark E.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Linskey, Mark E.] UC Irvine Med Ctr, Orange, CA USA. [Macdonald, David R.] Univ Western Ontario, Dept Oncol, London Reg Canc Program, London Hlth Sci Ctr, London, ON, Canada. [Margolin, Kim] Stanford Univ, Div Oncol, Stanford, CA 94305 USA. [Mehta, Minesh P.] Univ Maryland, Sch Med, Maryland Proton Treatment Ctr, Baltimore, MA USA. [Schiff, David] Univ Virginia, Div Neurooncol, Charlottesville, VA USA. [Soffietti, Riccardo] Univ Turin, Dept Neurol Neurooncol, Turin, Italy. [Suh, John H.] Cleveland Clin, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, Dept Radiat Oncol T28, Cleveland, OH 44106 USA. [Vogelbaum, Michael A.] Cleveland Clin, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, Dept Neurosurg ND40, Cleveland, OH 44106 USA. [van den Bent, Martin J.] Erasmus Univ, Med Ctr, Dr Daniel Den Hoed Canc Ctr, Neurooncol Unit, Rotterdam, Netherlands. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM nlin@partners.org RI Aoyama, Hidefumi/D-3635-2016 OI Aoyama, Hidefumi/0000-0002-8437-7491 FU Breast Cancer Research Foundation FX We thank Patricia Cortazar, Suzanne Demko, Ruthann Giusti, Patricia Keegan, and Richard Pazdur from the US Food and Drug Administration for their feedback regarding these proposed radiographic criteria. This work was supported in part by the Breast Cancer Research Foundation (grant to NUL), but this support did not directly influence the writing of this manuscript or the decision to submit it for publication. NR 22 TC 38 Z9 38 U1 4 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUN PY 2015 VL 16 IS 6 BP E270 EP E278 PG 9 WC Oncology SC Oncology GA CJ1MB UT WOS:000355246600024 PM 26065612 ER PT J AU Kidia, K Ndhlovu, C Jombo, S Abas, M Makadzange, AT AF Kidia, Khameer Ndhlovu, Chiratidzo Jombo, Shamiso Abas, Melanie Makadzange, Azure T. TI The mental health of HIV-positive adolescents SO LANCET PSYCHIATRY LA English DT Editorial Material ID CHALLENGES; COUNTRIES; INFECTION; DISORDERS; AFRICA; CARE C1 [Kidia, Khameer] Icahn Sch Med Mt Sinai, Arnhold Global Hlth Inst, New York, NY 10029 USA. [Kidia, Khameer; Ndhlovu, Chiratidzo; Jombo, Shamiso; Abas, Melanie; Makadzange, Azure T.] Univ Zimbabwe, Coll Hlth Sci, Harare, Zimbabwe. [Abas, Melanie] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Makadzange, Azure T.] Ragon Inst Massachusetts Gen Hosp Harvard Med Sch, Boston, MA USA. RP Kidia, K (reprint author), Icahn Sch Med Mt Sinai, Arnhold Global Hlth Inst, New York, NY 10029 USA. EM kkidia@gmail.com FU GSK Consulting FX ATM reports personal fees from GSK Consulting, outside the submitted work. KK, CN, SJ, and MA declare no competing interests. NR 12 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD JUN PY 2015 VL 2 IS 6 BP 487 EP 488 PG 3 WC Psychiatry SC Psychiatry GA CJ0UI UT WOS:000355193600009 PM 26360431 ER PT J AU Iezzoni, LI Yu, J Wint, AJ Smeltzer, SC Ecker, JL AF Iezzoni, Lisa I. Yu, Jun Wint, Amy J. Smeltzer, Suzanne C. Ecker, Jeffrey L. TI Health Risk Factors and Mental Health Among US Women with and without Chronic Physical Disabilities by Whether Women are Currently Pregnant SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Disability; Pregnancy; Health risks; Mental health; National Health Interview Survey ID PRENATAL SMOKING; MATERNAL OBESITY; PREVALENCE; DELIVERY; DEPRESSION; MORTALITY; ACCESS; CARE AB Growing numbers of reproductive-age US women with chronic physical disabilities (CPD) raise questions about their pregnancy experiences. Little is known about the health risks of women with versus without CPD by current pregnancy status. We analyzed cross-sectional, nationally-representative National Health Interview Survey data from 2006 to 2011, which includes 47,629 civilian, noninstitutionalized women ages 18-49. NHIS asks about specified movement difficulties, current pregnancy, and various health and health risk indicators, including tobacco use and body mass index (BMI). We used responses from eight movement difficulty and other questions to identify women with mobility difficulties caused by chronic physical health conditions. Across all women regardless of CPD, women reporting current pregnancy are significantly less likely to currently smoke tobacco and report certain mental health problems. Among currently pregnant women only, women with CPD are more likely to smoke cigarettes every day (12.2 %) versus 6.3 % for pregnant women without CPD (p a parts per thousand currency sign 0.001). Among currently pregnant women, 17.7 % of women with CPD have BMIs in the non-overweight range, compared with 40.1 % of women without CPD (p a parts per thousand currency sign 0.0001). Currently pregnant women with CPD are significantly more likely to report having any mental health problems, 66.6 % compared with 29.7 % among women without CPD (p a parts per thousand currency sign 0.0001). For all women, currently pregnant women appear to have fewer health risks and mental health concerns than nonpregnant women. Among pregnant women, women with CPD have higher rates than other women of health risk factors that could affect maternal and infant outcomes. C1 [Iezzoni, Lisa I.; Yu, Jun; Wint, Amy J.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Smeltzer, Suzanne C.] Villanova Univ, Ctr Nursing Res, Coll Nursing, Villanova, PA 19085 USA. [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Ecker, Jeffrey L.] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@mgh.harvard.edu FU Eunice Kennedy Shriver National Institute for Child Health and Human Development [5R21HD068756-02] FX Eunice Kennedy Shriver National Institute for Child Health and Human Development, Grant No. 5R21HD068756-02. NR 33 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 EI 1573-6628 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD JUN PY 2015 VL 19 IS 6 BP 1364 EP 1375 DI 10.1007/s10995-014-1641-6 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CJ1CU UT WOS:000355220400019 PM 25421328 ER PT J AU Kressin, NR Lasser, KE Paasche-Orlow, M Allison, J Ash, AS Adams, WG Shanahan, CW Legler, A Pizer, SD AF Kressin, Nancy R. Lasser, Karen E. Paasche-Orlow, Michael Allison, Jeroan Ash, Arlene S. Adams, William G. Shanahan, Christopher W. Legler, Aaron Pizer, Steven D. TI Clinical Operations Variables are Associated With Blood Pressure Outcomes SO MEDICAL CARE LA English DT Article DE hypertension; normalization of uncontrolled blood pressure; clinical operations ID DIABETES-MELLITUS; HEALTH SYSTEMS; HYPERTENSION; TRIAL; MANAGEMENT AB Background: Uncontrolled blood pressure (BP), among patients diagnosed and treated for the condition, remains an important clinical challenge; aspects of clinical operations could potentially be adjusted if they were associated with better outcomes. Objectives: To assess clinical operations factors' effects on normalization of uncontrolled BP. Research Design: Observational cohort study. Subjects: Patients diagnosed with hypertension from a large urban clinical practice (2005-2009). Measures: We obtained clinical data on BP, organized by person-month, and administrative data on primary care provider (PCP) staffing. We assessed the resolution of an episode of uncontrolled BP as a function of time-varying covariates including practice-level appointment volume, individual clinicians' appointment volume, overall practice-level PCP staffing, and number of unique PCPs. Results: Among the 7409 unique patients representing 50,403 person-months, normalization was less likely for the patients in whom the episode starts during months when the number of unique PCPs were high [the top quintile of unique PCPs was associated with a 9 percentage point lower probability of normalization (P < 0.01) than the lowest quintile]. Practice appointment volume negatively affected the likelihood of normalization [episodes starting in months with the most appointments were associated with a 6 percentage point reduction in the probability of normalization (P = 0.01)]. Neither clinician appointment volume nor practice clinician staffing levels were significantly associated with the probability of normalization. Conclusions: Findings suggest that clinical operations factors can affect clinical outcomes like BP normalization, and point to the importance of considering outcome effects when organizing clinical care. C1 [Kressin, Nancy R.; Legler, Aaron; Pizer, Steven D.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Kressin, Nancy R.; Lasser, Karen E.; Paasche-Orlow, Michael; Shanahan, Christopher W.] Boston Univ, Sch Med, Sect Gen Internal Med, Boston, MA 02118 USA. [Allison, Jeroan; Ash, Arlene S.] Univ Massachusetts, Sch Med, Quantitat Hlth Sci, Worcester, MA USA. [Adams, William G.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Pizer, Steven D.] Northeastern Univ, Sch Pharm, Boston, MA 02115 USA. RP Kressin, NR (reprint author), 150 South Huntington Ave,Bldg 9 152c, Boston, MA 02130 USA. EM nkressin@bu.edu OI Shanahan, Christopher/0000-0001-9067-5922 FU NIH/NHLBI [RC2HL101628]; Veterans Affairs Health Services Research and Development Service [RCS-02-066-1] FX Supported by funding from the NIH/NHLBI (RC2HL101628, N.R.K., PI). N.R.K. is supported in part by a Research Career Scientist award from the Veterans Affairs Health Services Research and Development Service (RCS-02-066-1). NR 16 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JUN PY 2015 VL 53 IS 6 BP 480 EP 484 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CI4NI UT WOS:000354726500003 PM 25974844 ER PT J AU Burke, RE Juarez-Colunga, E Levy, C Prochazka, AV Coleman, EA Ginde, AA AF Burke, Robert E. Juarez-Colunga, Elizabeth Levy, Cari Prochazka, Allan V. Coleman, Eric A. Ginde, Adit A. TI Patient and Hospitalization Characteristics Associated With Increased Postacute Care Facility Discharges From US Hospitals SO MEDICAL CARE LA English DT Article DE post-acute care; nursing home; geriatrics ID POST-ACUTE CARE; COMMUNITY-ACQUIRED PNEUMONIA; SKILLED NURSING FACILITIES; PROSPECTIVE-PAYMENT SYSTEM; UNITED-STATES; CONTROLLED-TRIAL; SEVERE SEPSIS; CRITICAL PATHWAY; OLDER; IMPAIRMENT AB Background/Objectives: The number of patients discharged to postacute care (PAC) facilities after hospitalization increased by 50% nationally between 1996 and 2010. We sought to describe payors and patients most affected by this trend and to identify diagnoses for which PAC facility care may be substituting for continued hospital care. Design: Retrospective analysis of the National Hospital Discharge Survey from 1996 to 2010. Setting: Adult discharges from a national sample of non-Federal hospitals. Participants/Exposures: Adults admitted and discharged to a PAC facility between 1996 and 2010. Our analysis includes 2.99 million sampled discharges, representative of 386 million discharges nationally. Measurements: Patient demographic and hospitalization characteristics, including length of stay (LOS) and diagnoses treated. Results: More than half (50.7%) of all patients discharged to PAC facilities were 80 years old or older in 2010; 40% of hospitalizations in this age group ended with a PAC stay. Decreases in LOS and increases in PAC facility use were consistent across payors and patient demographics. PAC facilities may be substituting for continued inpatient care for patients with pneumonia, hip fracture, and sepsis as these diagnoses demonstrated the clearest trends of decreasing LOS and increasing discharges to PAC facilities. Conclusions: The rise in discharges to PAC facilities is occurring in all age groups and payors, though the predominant population is the very old Medicare patient, for whom successful rehabilitation may be most unsure. PAC facility care may be increasingly substituted for prolonged hospitalizations for patients with pneumonia, hip fracture, and sepsis. C1 [Burke, Robert E.; Prochazka, Allan V.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs Med Ctr, Denver, CO USA. [Burke, Robert E.; Prochazka, Allan V.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Denver, CO USA. [Juarez-Colunga, Elizabeth] Univ Colorado, Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Levy, Cari; Coleman, Eric A.] Univ Colorado, Sch Med, Div Hlth Care Policy & Res, Aurora, CO USA. [Ginde, Adit A.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. RP Burke, RE (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM robert.burke5@va.gov RI bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017 FU Colorado Clinical Translational Science Institute [NIH UL1 TR001082]; VA HSR&D Center for Innovation: Value-Centered and Value-Driven Care; NIH [K23AG040708] FX R.E.B., E.J.-C., A.V.P., and A.A.G. were supported by the Colorado Clinical Translational Science Institute (NIH UL1 TR001082) and R.E.B., C.L., and A.V.P. by the VA HSR&D Center for Innovation: Value-Centered and Value-Driven Care. A.A.G. was supported by NIH grant K23AG040708. These sponsors had no role in the design, conduct, analysis, interpretation, or presentation of the study. NR 34 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JUN PY 2015 VL 53 IS 6 BP 492 EP 500 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CI4NI UT WOS:000354726500005 PM 25906015 ER PT J AU Kutney-Lee, A Stimpfel, AW Sloane, DM Cimiotti, JP Quinn, LW Aiken, LH AF Kutney-Lee, Ann Stimpfel, Amy Witkoski Sloane, Douglas M. Cimiotti, Jeannie P. Quinn, Lisa W. Aiken, Linda H. TI Changes in Patient and Nurse Outcomes Associated With Magnet Hospital Recognition SO MEDICAL CARE LA English DT Article DE nursing; Magnet hospitals; outcomes; quality of care ID QUALITY-OF-CARE; PRACTICE ENVIRONMENT; WORK ENVIRONMENTS; MORTALITY; EDUCATION; FAILURE; RATES; COST AB Background: Research has documented an association between Magnet hospitals and better outcomes for nurses and patients. However, little longitudinal evidence exists to support a causal link between Magnet recognition and outcomes. Objective: To compare changes over time in surgical patient outcomes, nurse-reported quality, and nurse outcomes in a sample of hospitals that attained Magnet recognition between 1999 and 2007 with hospitals that remained non-Magnet. Research Design: Retrospective, 2-stage panel design using 4 secondary data sources. Subjects: One hundred thirty-six Pennsylvania hospitals (11 emerging Magnets and 125 non-Magnets). Measures: American Nurses Credentialing Center Magnet recognition; risk-adjusted rates of surgical 30-day mortality and failure-to-rescue, nurse-reported quality measures, and nurse outcomes; the Practice Environment Scale of the Nursing Work Index. Methods: Fixed-effects difference models were used to compare changes in outcomes between emerging Magnet hospitals and hospitals that remained non-Magnet. Results: Emerging Magnet hospitals demonstrated markedly greater improvements in their work environments than other hospitals. On average, the changes in 30-day surgical mortality and failure-to-rescue rates over the study period were more pronounced in emerging Magnet hospitals than in non-Magnet hospitals, by 2.4 fewer deaths per 1000 patients (P<0.01) and 6.1 fewer deaths per 1000 patients (P=0.02), respectively. Similar differences in the changes for emerging Magnet hospitals and non-Magnet hospitals were observed in nurse-reported quality of care and nurse outcomes. Conclusions: In general, Magnet recognition is associated with significant improvements over time in the quality of the work environment, and in patient and nurse outcomes that exceed those of non-Magnet hospitals. C1 [Kutney-Lee, Ann; Sloane, Douglas M.; Aiken, Linda H.] Univ Penn, Sch Nursing, Ctr Hlth Outcomes & Policy Res, Philadelphia, PA 19104 USA. [Stimpfel, Amy Witkoski] NYU, Coll Nursing, New York, NY USA. [Cimiotti, Jeannie P.] Univ Florida, Coll Nursing, Gainesville, FL 32611 USA. [Quinn, Lisa W.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Kutney-Lee, A (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Outcomes & Policy Res, 418 Curie Blvd Claire M Fagin Hall,Room 385, Philadelphia, PA 19104 USA. EM akutney@nursing.upenn.edu FU American Nurses Foundation [NINR R01-NR-004513, T32-NR007104]; Robert Wood Johnson Foundation FX Supported by grants from the American Nurses Foundation (Margretta Madden Styles Credentialing Research Award and Sayre Memorial Scholarship (Kutney-Lee, PI)), NINR R01-NR-004513(Aiken, PI), T32-NR007104 (Aiken, PI), and the Robert Wood Johnson Foundation. NR 45 TC 16 Z9 16 U1 3 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JUN PY 2015 VL 53 IS 6 BP 550 EP 557 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CI4NI UT WOS:000354726500013 PM 25906016 ER PT J AU Caan, B LaCroix, AZ Joffe, H Guthrie, KA Larson, JC Carpenter, JS Cohen, LS Freeman, EW Manson, JE Newton, K Reed, S Rexrode, K Shifren, J Sternfeld, B Ensrud, K AF Caan, Bette LaCroix, Andrea Z. Joffe, Hadine Guthrie, Katherine A. Larson, Joseph C. Carpenter, Janet S. Cohen, Lee S. Freeman, Ellen W. Manson, JoAnn E. Newton, Katherine Reed, Susan Rexrode, Kathy Shifren, Jan Sternfeld, Barbara Ensrud, Kris TI Effects of estrogen and venlafaxine on menopause-related quality of life in healthy postmenopausal women with hot flashes: a placebo-controlled randomized trial SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Estrogen; Venlafaxine; Menopause; Quality of life; Pain; Stress ID PAINFUL PHYSICAL SYMPTOMS; MAJOR DEPRESSIVE DISORDER; VASOMOTOR SYMPTOMS; PERCEIVED STRESS; CLINICAL-TRIAL; UNITED-STATES; ESCITALOPRAM; INDEX; DULOXETINE; SEVERITY AB Objective: This study aims to evaluate the effects of low-dose estradiol (E-2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes. Methods: A double-blind, placebo-controlled, randomized trial of low-dose oral 17 beta-E-2 0.5 mg/day and venlafaxine XR 75 mg/day, versus identical placebo, was conducted among 339 women (aged 40-62 y) experiencing two or more vasomotor symptoms (VMS) per day (mean [SD], 8.07 [5.29]) who were recruited at three clinical sites from November 2011 to October 2012. The primary trial outcome, as reported previously, was frequency of VMS at 8 weeks. Here, we report on secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and from measures of pain (Pain, Enjoyment in life, and General activity scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder Questionnaire-7), and perceived stress (Perceived Stress Scale). Results: Treatment with both E-2 and venlafaxine resulted in significantly greater improvement in quality of life, as measured by total MENQOL scores, compared with placebo (E-2: mean difference at 8 wk, -0.4; 95% CI, -0.7 to -0.2; P < 0.001; venlafaxine: mean difference at 8 wk, -0.2; 95% CI, -0.5 to 0.0; P = 0.04). Quality-of-life domain analyses revealed that E-2 had beneficial treatment effects on all domains of the MENQOL except for the psychosocial domain, whereas venlafaxine benefits were observed only in the psychosocial domain. Neither E-2 nor venlafaxine improved pain, anxiety, or depressive symptoms, although baseline symptom levels were low. Modest benefits were observed for perceived stress with venlafaxine. Conclusions: Both low-dose E-2 and venlafaxine are effective pharmacologic agents for improving menopause-related quality of life in healthy women with VMS. C1 [Caan, Bette; Sternfeld, Barbara] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [LaCroix, Andrea Z.] Univ Calif San Diego, San Diego, CA 92103 USA. [Joffe, Hadine; Manson, JoAnn E.; Rexrode, Kathy] Brigham & Womens Hosp, Boston, MA 02115 USA. [Joffe, Hadine] Dana Farber Canc Inst, Boston, MA 02115 USA. [Guthrie, Katherine A.; Larson, Joseph C.] Fred Hutchinson Canc Res Ctr, MsFLASH Coordinating Ctr, Seattle, WA 98104 USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Cohen, Lee S.; Shifren, Jan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cohen, Lee S.; Manson, JoAnn E.; Rexrode, Kathy] Harvard Univ, Sch Med, Boston, MA USA. [Freeman, Ellen W.] Univ Penn Sch Med, Dept Obstet Gynecol, Philadelphia, PA USA. [Freeman, Ellen W.] Univ Penn Sch Med, Dept Psychiat, Philadelphia, PA USA. [Newton, Katherine] Grp Hlth Res Inst, Seattle, WA USA. [Reed, Susan] Univ Washington Sch Med, Seattle, WA USA. [Ensrud, Kris] Univ Minnesota, VA Med Ctr, Minneapolis, MN USA. RP Caan, B (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM bette.caan@kp.org OI Rexrode, Kathryn/0000-0003-3387-8429 FU National Institute on Aging; Eunice Kennedy Shriver National Institute of Child Health and Development; National Center for Complementary and Alternative Medicine; Office of Research on Women's Health [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700] FX This study was supported by a cooperative agreement issued by the National Institute on Aging, in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Center for Complementary and Alternative Medicine, and the Office of Research on Women's Health (grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700). NR 26 TC 2 Z9 2 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2015 VL 22 IS 6 BP 607 EP 615 DI 10.1097/gme.0000000000000364 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CJ1IU UT WOS:000355238100006 PM 25405571 ER PT J AU Kural, C Akatay, AA Gaudin, R Chen, BC Legant, WR Betzig, E Kirchhausen, T AF Kural, Comert Akatay, Ahmet Ata Gaudin, Raphael Chen, Bi-Chang Legant, Wesley R. Betzig, Eric Kirchhausen, Tom TI Asymmetric formation of coated pits on dorsal and ventral surfaces at the leading edges of motile cells and on protrusions of immobile cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; PLASMA-MEMBRANE AREA; MIGRATING CELLS; DYNAMIN RECRUITMENT; LIVING CELLS; GROWTH CONE; MOVEMENTS; FIBROBLASTS; ACTIN; LOCALIZATION AB Clathrin/AP2-coated vesicles are the principal endocytic carriers originating at the plasma membrane. In the experiments reported here, we used spinning-disk confocal and lattice light-sheet microscopy to study the assembly dynamics of coated pits on the dorsal and ventral membranes of migrating U373 glioblastoma cells stably expressing AP2 tagged with enhanced green fluorescence (AP2-EGFP) and on lateral protrusions from immobile SUM159 breast carcinoma cells, gene-edited to express AP2-EGFP. On U373 cells, coated pits initiated on the dorsal membrane at the front of the lamellipodium and at the approximate boundary between the lamellipodium and lamella and continued to grow as they were swept back toward the cell body; coated pits were absent from the corresponding ventral membrane. We observed a similar dorsal/ventral asymmetry on membrane protrusions from SUM159 cells. Stationary coated pits formed and budded on the remainder of the dorsal and ventral surfaces of both types of cells. These observations support a previously proposed model that invokes net membrane deposition at the leading edge due to an imbalance between the endocytic and exocytic membrane flow at the front of a migrating cell. C1 [Kural, Comert; Gaudin, Raphael; Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kural, Comert; Gaudin, Raphael; Kirchhausen, Tom] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Kural, Comert] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA. [Akatay, Ahmet Ata] Ohio State Univ, Biophys Grad Program, Columbus, OH 43210 USA. [Chen, Bi-Chang; Legant, Wesley R.; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA. [Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kural.1@osu.edu; kirchhausen@crystal.harvard.edu RI Chen , Bi-Chang /F-3480-2014 FU Helen Hay Whitney Foundation Fellowship; National Institutes of Health [GM-075252, U54 AI057159]; Janelia Visitor Program; Howard Hughes Medical Institute FX We thank Eric Marino for maintaining the Imaging Resource used in this study, Patrick Reeves for generating the expression plasmid for LifeAct, and members of our laboratory for helpful discussions. C.K. was a recipient of a Helen Hay Whitney Foundation Fellowship. This work was supported in part by National Institutes of Health grants GM-075252 (to T.K.) and U54 AI057159 (New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility). B.-C.C., W.R.L, and E.B. were funded by the Howard Hughes Medical Institute. T.K. gratefully acknowledges support from the Janelia Visitor Program. NR 56 TC 10 Z9 10 U1 0 U2 7 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUN 1 PY 2015 VL 26 IS 11 BP 2044 EP 2053 DI 10.1091/mbc.E15-01-0055 PG 10 WC Cell Biology SC Cell Biology GA CJ1LP UT WOS:000355245400007 PM 25851602 ER PT J AU Guan, Y Meurer, M Raghavan, S Rebane, A Lindquist, JR Santos, S Kats, I Davidson, MW Mazitschek, R Hughes, TE Drobizhev, M Knop, M Shah, JV AF Guan, Yinghua Meurer, Matthias Raghavan, Sarada Rebane, Aleksander Lindquist, Jake R. Santos, Sofia Kats, Ilia Davidson, Michael W. Mazitschek, Ralph Hughes, Thomas E. Drobizhev, Mikhail Knop, Michael Shah, Jagesh V. TI Live-cell multiphoton fluorescence correlation spectroscopy with an improved large Stokes shift fluorescent protein SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CROSS-CORRELATION SPECTROSCOPY; 2-PHOTON EXCITATION; LIVING CELLS; IN-VIVO; MICROSCOPY; EVOLUTION; MECHANISM; DIFFUSION; DYNAMICS; VARIANT AB We report an improved variant of mKeima, a monomeric long Stokes shift red fluorescent protein, hmKeima8.5. The increased intracellular brightness and large Stokes shift (similar to 180 nm) make it an excellent partner with teal fluorescent protein (mTFP1) for multiphoton, multicolor applications. Excitation of this pair by a single multiphoton excitation wavelength (MPE, 850 nm) yields well-separable emission peaks (similar to 120-nm separation). Using this pair, we measure homo- and hetero-oligomerization interactions in living cells via multiphoton excitation fluorescence correlation spectroscopy (MPE-FCS). Using tandem dimer proteins and small-molecule inducible dimerization domains, we demonstrate robust and quantitative detection of intracellular protein-protein interactions. We also use MPE-FCCS to detect drug-protein interactions in the intracellular environment using a Coumarin 343 (C343)-conjugated drug and hmKeima8.5 as a fluorescence pair. The mTFP1/hmKeima8.5 and C343/hmKeima8.5 combinations, together with our calibration constructs, provide a practical and broadly applicable toolbox for the investigation of molecular interactions in the cytoplasm of living cells. C1 [Guan, Yinghua; Shah, Jagesh V.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Guan, Yinghua; Shah, Jagesh V.] Brigham & Womens Hosp, Renal Div, Boston, MA 02115 USA. [Meurer, Matthias; Raghavan, Sarada; Kats, Ilia; Knop, Michael] Heidelberg Univ, Zentrum Mol Biol, D-69120 Heidelberg, Germany. [Meurer, Matthias; Raghavan, Sarada; Kats, Ilia; Knop, Michael] Deutsch Krebsforschungszentrum, DKFZ ZMBH Allianz, D-69120 Heidelberg, Germany. [Rebane, Aleksander; Drobizhev, Mikhail] Montana State Univ, Dept Phys, Bozeman, MT 59717 USA. [Lindquist, Jake R.; Hughes, Thomas E.] Montana State Univ, Dept Cell Biol & Neurosci, Bozeman, MT 59717 USA. [Santos, Sofia; Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Santos, Sofia] Univ Lisbon, Fac Farm, Inst Invest Med, P-1640003 Lisbon, Portugal. [Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. [Mazitschek, Ralph] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Knop, M (reprint author), Heidelberg Univ, Zentrum Mol Biol, D-69120 Heidelberg, Germany. EM m.knop@zmbh.uni-heidelberg.de; jagesh@hms.harvard.edu OI Hughes, Thomas/0000-0001-5880-9951 FU National Institutes of Health [NS083875, GM098083, GM77238]; FP7 EU Marie Curie Grant (Penelope); Beckman Laser SPARK Fellowship; Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BD/80162/2011] FX We thank the Shah lab for helpful comments and also acknowledge the help of Geoffrey Wicks. This work was supported by funding from the National Institutes of Health (NS083875 to T.H., GM098083 to M.D., and GM77238 to J.V.S.), an FP7 EU Marie Curie Grant (Penelope) to M.K., a Beckman Laser SPARK Fellowship to Y.G., and SFRH/BD/80162/2011 from Fundacao para a Ciencia e Tecnologia, Portugal, to S.A.S. NR 36 TC 3 Z9 3 U1 6 U2 26 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUN 1 PY 2015 VL 26 IS 11 BP 2054 EP 2066 DI 10.1091/mbc.E14-10-1473 PG 13 WC Cell Biology SC Cell Biology GA CJ1LP UT WOS:000355245400008 PM 25877871 ER PT J AU Zhang, J Dong, YL Zhou, C Zhang, YY Xie, ZC AF Zhang, Jie Dong, Yuanlin Zhou, Chen Zhang, Yiying Xie, Zhongcong TI Anesthetic Sevoflurane Reduces Levels of Hippocalcin and Postsynaptic Density Protein 95 SO MOLECULAR NEUROBIOLOGY LA English DT Article DE Anesthetic; Sevoflurane; Hippocalcin; Postsynaptic density protein 95 ID ISOFLURANE INDUCES APOPTOSIS; EARLY EXPOSURE; RAT-BRAIN; MICE; ACTIVATION; CALCIUM; MEMANTINE; PATHWAY; AGE; NEURODEGENERATION AB Sevoflurane, the commonly used inhalation anesthetic in children, has been shown to enhance cytosolic calcium levels and induce cognitive impairment in young mice. However, the downstream consequences of the sevoflurane-induced elevation in cytosolic calcium levels and the upstream mechanisms of the sevoflurane-induced cognitive impairment remain largely to be determined. Hippocalcin is one of the neuronal calcium sensor proteins, and also binds to postsynaptic density protein 95 (PSD-95). We therefore set out to determine the effects of sevoflurane on the levels of hippocalcin and PSD-95 in vitro and in vivo. Hippocampus neurons from mice and 6-day-old mice were treated with 4.1 % sevoflurane for 6 h or 3 % sevoflurane 2 h daily for 3 days, respectively. We then measured the levels of hippocalcin and PSD-95, and assessed whether BAPTA, an intracellular calcium chelator, and memantine, a partial antagonist of the NMDA receptor, could inhibit the sevoflurane's effects. We found that sevoflurane decreased the levels of hippocalcin and PSD-95 in the neurons; and decreased the levels of hippocalcin and PSD-95 in the hippocampus of mice immediately after the anesthesia, but only the PSD-95 levels three weeks after the anesthesia. BAPTA inhibited the sevoflurane's effects in the neurons. Memantine attenuated the sevoflurane-induced reductions in the levels of hippocalcin and PSD-95, as well as the sevoflurane-induced cognitive impairment in mice. These data suggested that sevoflurane decreased the levels of hippocalcin and PSD-95, which could serve as one of bridge mechanisms between the sevoflurane-induced elevation of cytosolic calcium levels and the sevoflurane-induced cognitive impairment. C1 [Zhang, Jie; Dong, Yuanlin; Zhou, Chen; Zhang, Yiying; Xie, Zhongcong] Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Zhang, Jie; Dong, Yuanlin; Zhou, Chen; Zhang, Yiying; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Zhang, Jie] Huazhong Univ Sci & Technol, Dept Anesthesiol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@mgh.harvard.edu FU National Institutes of Health, Bethesda, Maryland [R21AG038994, R01 GM088801, R01 AG041274]; Alzheimer's Association, Chicago, Illinois; Cure Alzheimer's Fund, Wellesley, Massachusetts FX This research was supported by R21AG038994, R01 GM088801 and R01 AG041274 from National Institutes of Health, Bethesda, Maryland, Investigator-initiated Research grant from Alzheimer's Association, Chicago, Illinois, and Cure Alzheimer's Fund, Wellesley, Massachusetts to Zhongcong Xie. Anesthetic sevoflurane was generously provided by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. NR 44 TC 3 Z9 5 U1 3 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD JUN PY 2015 VL 51 IS 3 BP 853 EP 863 DI 10.1007/s12035-014-8746-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CI3CM UT WOS:000354625100002 PM 24870966 ER PT J AU Depeille, P Henricks, LM van de Ven, RAH Lemmens, E Wang, CY Matli, M Werb, Z Haigis, KM Donner, D Warren, R Roose, JP AF Depeille, Philippe Henricks, Linda M. van de Ven, Robert A. H. Lemmens, Ed Wang, Chih-Yang Matli, Mary Werb, Zena Haigis, Kevin M. Donner, David Warren, Robert Roose, Jeroen P. TI RasGRP1 opposes proliferative EGFR-SOS1-Ras signals and restricts intestinal epithelial cell growth SO NATURE CELL BIOLOGY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; FACTOR RECEPTOR; COLORECTAL-CANCER; RAS ACTIVATION; EGF RECEPTOR; COLON-CANCER; FEEDBACK ACTIVATION; ACQUIRED-RESISTANCE; TUMOR PROGRESSION; GENE-EXPRESSION AB The character of EGFR signals can influence cell fate but mechanistic insights into intestinal EGFR-Ras signalling are limited. Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of EGFR but act in functional opposition. RasGRP1 is expressed in intestinal crypts where it restricts epithelial growth. High RasGRP1 expression in colorectal cancer (CRC) patient samples correlates with a better clinical outcome. Biochemically, we find that RasGRP1 creates a negative feedback loop that limits proliferative EGFR-SOS1-Ras signals in CRC cells. Genetic Rasgrp1 depletion from mice with either an activating mutation in KRas or with aberrant Wnt signalling due to a mutation in Apc resulted in both cases in exacerbated Ras-ERK signalling and cell proliferation. The unexpected opposing cell biological effects of EGFR-RasGRP1 and EGFR-SOS1 signals in the same cell shed light on the intricacy of EGFR-Ras signalling in normal epithelium and carcinoma. C1 [Depeille, Philippe; Henricks, Linda M.; van de Ven, Robert A. H.; Lemmens, Ed; Wang, Chih-Yang; Werb, Zena; Roose, Jeroen P.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. [Wang, Chih-Yang] Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med, Tainan 70101, Taiwan. [Matli, Mary; Donner, David; Warren, Robert] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. RP Depeille, P (reprint author), Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. EM philippe.depeille@ucsf.edu; jeroen.roose@ucsf.edu FU Sandler Program in Basic Science (start-up); NIH-NCI Physical Science Oncology Center grant [U54CA143874]; NIH grant [1P01AI091580-01]; Gabrielle's Angel Foundation grant; ECSI; ACS grant; UCSF Research Allocation Program (RAP) pilot grant; NCI [R01 CA057621, K01CA118425]; Jeannik M. Littlefield foundation; Ministry of Science and Technology, Taiwan [104-2917-1-006-002]; KWF (Dutch Cancer Society); Saal an Zwanenberg Foundation FX The authors thank J. Stone, T. Jacks and A. Ma for Rasgrp1-deficient, KRASLSL-G12D and VillinCre mice, A. Karnczis and O. Yilmaz for helpful comments on the intestinal hyperplasia, L. Westerveld for technical support, and A. Balmain, M. McMahon, C. Bonnans, N. Duesbery and O. Klein for critically reading the manuscript. Our research was supported by the Sandler Program in Basic Science (start-up), NIH-NCI Physical Science Oncology Center grant U54CA143874, NIH grant 1P01AI091580-01, a Gabrielle's Angel Foundation grant, a ECSI, ACS grant, and a UCSF Research Allocation Program (RAP) pilot grant (all to J.P.R.), as well as by grants from the NCI (R01 CA057621 to Z.W. and K01CA118425 to K.M.H.), from the Jeannik M. Littlefield foundation (to R.W.), and from the Ministry of Science and Technology, Taiwan (104-2917-1-006-002 to C-Y.W.), and by the KWF (Dutch Cancer Society) (R.A.H.v.d.V., L.M.H.) and Saal an Zwanenberg Foundation (L.M.H.). NR 69 TC 6 Z9 6 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUN PY 2015 VL 17 IS 6 BP 804 EP + DI 10.1038/ncb3175 PG 27 WC Cell Biology SC Cell Biology GA CJ1XD UT WOS:000355277500012 PM 26005835 ER PT J AU Surakka, I Horikoshi, M Magi, R Sarin, AP Mahajan, A Lagou, V Marullo, L Ferreira, T Miraglio, B Timonen, S Kettunen, J Pirinen, M Karjalainen, J Thorleifsson, G Hagg, S Hottenga, JJ Isaacs, A Ladenvall, C Beekman, M Esko, T Ried, JS Nelson, CP Willenborg, C Gustafsson, S Westra, HJ Blades, M de Craen, AJM de Geus, EJ Deelen, J Grallert, H Hamsten, A Havulinna, AS Hengstenberg, C Houwing-Duistermaat, JJ Hypponen, E Karssen, LC Lehtimaki, T Lyssenko, V Magnusson, PKE Mihailov, E Muller-Nurasyid, M Mpindi, JP Pedersen, NL Penninx, BWJH Perola, M Pers, TH Peters, A Rung, J Smit, JH Steinthorsdottir, V Tobin, MD Tsernikova, N van Leeuwen, EM Viikari, JS Willems, SM Willemsen, G Schunkert, H Erdmann, J Samani, NJ Kaprio, J Lind, L Gieger, C Metspalu, A Slagboom, PE Groop, L van Duijn, CM Eriksson, JG Jula, A Salomaa, V Boomsma, DI Power, C Raitakari, OT Ingelsson, E Jarvelin, MR Thorsteinsdottir, U Franke, L Ikonen, E Kallioniemi, O Pietiainen, V Lindgren, CM Stefansson, K Palotie, A McCarthy, MI Morris, AP Prokopenko, I Ripatti, S AF Surakka, Ida Horikoshi, Momoko Magi, Reedik Sarin, Antti-Pekka Mahajan, Anubha Lagou, Vasiliki Marullo, Letizia Ferreira, Teresa Miraglio, Benjamin Timonen, Sanna Kettunen, Johannes Pirinen, Matti Karjalainen, Julia Thorleifsson, Gudmar Hagg, Sara Hottenga, Jouke-Jan Isaacs, Aaron Ladenvall, Claes Beekman, Marian Esko, Tonu Ried, Janina S. Nelson, Christopher P. Willenborg, Christina Gustafsson, Stefan Westra, Harm-Jan Blades, Matthew de Craen, Anton J. M. de Geus, Eco J. Deelen, Joris Grallert, Harald Hamsten, Anders Havulinna, Aki S. Hengstenberg, Christian Houwing-Duistermaat, Jeanine J. Hypponen, Elina Karssen, Lennart C. Lehtimaki, Terho Lyssenko, Valeriya Magnusson, Patrik K. E. Mihailov, Evelin Muller-Nurasyid, Martina Mpindi, John-Patrick Pedersen, Nancy L. Penninx, Brenda W. J. H. Perola, Markus Pers, Tune H. Peters, Annette Rung, Johan Smit, Johannes H. Steinthorsdottir, Valgerdur Tobin, Martin D. Tsernikova, Natalia van Leeuwen, Elisabeth M. Viikari, Jorma S. Willems, Sara M. Willemsen, Gonneke Schunkert, Heribert Erdmann, Jeanette Samani, Nilesh J. Kaprio, Jaakko Lind, Lars Gieger, Christian Metspalu, Andres Slagboom, P. Eline Groop, Leif van Duijn, Cornelia M. Eriksson, Johan G. Jula, Antti Salomaa, Veikko Boomsma, Dorret I. Power, Christine Raitakari, Olli T. Ingelsson, Erik Jarvelin, Marjo-Riitta Thorsteinsdottir, Unnur Franke, Lude Ikonen, Elina Kallioniemi, Olli Pietiainen, Vilja Lindgren, Cecilia M. Stefansson, Kari Palotie, Aarno McCarthy, Mark I. Morris, Andrew P. Prokopenko, Inga Ripatti, Samuli CA ENGAGE Consortium TI The impact of low-frequency and rare variants on lipid levels SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; IN-VITRO; HETEROGENEITY; EXPRESSION; SIALOMUCIN; SEQUENCE; DISEASE; GLUCOSE; GENES; LIVER AB Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing. C1 [Surakka, Ida; Sarin, Antti-Pekka; Miraglio, Benjamin; Timonen, Sanna; Kettunen, Johannes; Pirinen, Matti; Isaacs, Aaron; Mpindi, John-Patrick; Perola, Markus; Kaprio, Jaakko; Groop, Leif; Kallioniemi, Olli; Pietiainen, Vilja; Palotie, Aarno; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Surakka, Ida; Sarin, Antti-Pekka; Kettunen, Johannes; Havulinna, Aki S.; Perola, Markus; Kaprio, Jaakko; Eriksson, Johan G.; Jula, Antti; Salomaa, Veikko; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Helsinki, Finland. [Horikoshi, Momoko; Mahajan, Anubha; Lagou, Vasiliki; Ferreira, Teresa; Ingelsson, Erik; Lindgren, Cecilia M.; McCarthy, Mark I.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Horikoshi, Momoko; Lagou, Vasiliki; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Magi, Reedik; Esko, Tonu; Mihailov, Evelin; Perola, Markus; Tsernikova, Natalia; Metspalu, Andres; Morris, Andrew P.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Marullo, Letizia] Univ Ferrara, Genet Sect, Dept Life Sci & Biotechnol, I-44100 Ferrara, Italy. [Karjalainen, Julia; Westra, Harm-Jan; Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet Amgen Inc, Reykjavik, Iceland. [Hagg, Sara; Gustafsson, Stefan; Magnusson, Patrik K. E.; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Hagg, Sara; Gustafsson, Stefan; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol, Uppsala, Sweden. [Hagg, Sara; Gustafsson, Stefan; Ingelsson, Erik] Uppsala Univ, Sci Life Lab, Uppsala, Sweden. [Hottenga, Jouke-Jan; de Geus, Eco J.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Dept Biol Psychol, Amsterdam, Netherlands. [Hottenga, Jouke-Jan; de Geus, Eco J.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Isaacs, Aaron; Karssen, Lennart C.; van Leeuwen, Elisabeth M.; Willems, Sara M.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Isaacs, Aaron] Ctr Med Syst Biol, Leiden, Netherlands. [Ladenvall, Claes; Lyssenko, Valeriya; Groop, Leif] Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Skane Univ Hosp, Malmo, Sweden. [Beekman, Marian; de Craen, Anton J. M.; Deelen, Joris; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Beekman, Marian; Deelen, Joris; Slagboom, P. Eline] Netherlands Consortium Hlth Ageing, Leiden, Netherlands. [Esko, Tonu; Pers, Tune H.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Esko, Tonu; Pers, Tune H.] Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Esko, Tonu; Pers, Tune H.; Lindgren, Cecilia M.; Palotie, Aarno] Broad Inst & MIT Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Esko, Tonu] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Ried, Janina S.; Muller-Nurasyid, Martina; Gieger, Christian] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany. [Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, Leicester Cardiovasc Dis Biomed Res Unit, NIHR, Leicester, Leics, England. [Erdmann, Jeanette] Univ Lubeck, Inst Integrat & Experimentelle Genom, Lubeck, Germany. [Willenborg, Christina; Erdmann, Jeanette] Deutsches Zentrum Herz Kreislauf Forsch DZHK, Lubeck, Germany. [Willenborg, Christina; Erdmann, Jeanette] Deutsches Zentrum Herz Kreislauf Forsch DZHK, Kiel, Germany. [Blades, Matthew] Univ Leicester, BBASH, Leicester, Leics, England. [de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Grallert, Harald; Peters, Annette; Gieger, Christian] Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany. [Grallert, Harald] German Ctr Diabet Res DZD, Neuherberg, Germany. [Grallert, Harald; Peters, Annette; Gieger, Christian] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany. [Hamsten, Anders] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden. [Hengstenberg, Christian; Peters, Annette; Schunkert, Heribert] Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany. [Hengstenberg, Christian; Muller-Nurasyid, Martina; Schunkert, Heribert] Munich Heart Alliance, Deutsches Zentrum Herz Kreislauf Forsch DZHK, Munich, Germany. [Houwing-Duistermaat, Jeanine J.] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands. [Hypponen, Elina; Power, Christine] UCL, Inst Child Hlth, Populat Policy & Practice, London, England. [Hypponen, Elina] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia. [Hypponen, Elina] Univ S Australia, Sch Populat Hlth, Adelaide, SA 5001, Australia. [Hypponen, Elina] Univ S Australia, Sansom Inst, Adelaide, SA 5001, Australia. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lyssenko, Valeriya] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Muller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Muller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany. [Penninx, Brenda W. J. H.; Smit, Johannes H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Perola, Markus] Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland. [Rung, Johan] European Bioinformat Inst, Hinxton, England. [Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester, Leics, England. [Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma S.] Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland. [Kaprio, Jaakko; Ripatti, Samuli] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden. [Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.] Helsinki Univ Hosp, Unit Primary Hlth Care, Helsinki, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli T.] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland. [Raitakari, Olli T.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC,HPA,Ctr Environm & Hlth, London, England. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Ikonen, Elina] Univ Helsinki, Inst Biomed, Anat, Helsinki, Finland. [Ikonen, Elina] Minerva Fdn, Helsinki, Finland. [Palotie, Aarno] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. [Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton, England. RP Ripatti, S (reprint author), Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. EM samuli.ripatti@fimm.fi RI Grallert, Harald/B-3424-2013; Ripatti, Samuli/H-9446-2014; Peters, Annette/A-6117-2011; Hypponen, Elina/B-2596-2014; Franke, Lude/P-7036-2016; Karjalainen, Juha/P-8624-2016; Slagboom, P. Eline/R-4790-2016; Magnusson, Patrik/C-4458-2017; Erdmann, Jeanette/P-7513-2014; OI Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Eriksson, Johan/0000-0002-2516-2060; Pirinen, Matti/0000-0002-1664-1350; Kaprio, Jaakko/0000-0002-3716-2455; Karssen, Lennart C./0000-0002-1959-342X; de Geus, Eco/0000-0001-6022-2666; Kallioniemi, Olli/0000-0002-3231-0332; Peters, Annette/0000-0001-6645-0985; Ripatti, Samuli/0000-0002-0504-1202; Hypponen, Elina/0000-0003-3670-9399; Franke, Lude/0000-0002-5159-8802; Slagboom, P. Eline/0000-0002-2875-4723; Erdmann, Jeanette/0000-0002-4486-6231; Gieger, Christian/0000-0001-6986-9554; Magi, Reedik/0000-0002-2964-6011; Esko, Tonu/0000-0003-1982-6569 FU European Union's Seventh Framework Programme (FP7), ENGAGE Consortium [HEALTH-F4-2007-201413]; Helsinki University Doctoral Programme in Biomedicine (DPBM); Manpei Suzuki Diabetes Foundation; Wellcome Trust [WT098017, WT090532, WT064890]; European Union's Seventh Framework Programme (FP7), ENGAGE project [HEALTH-F4-2007-201413]; ENGAGE Exchange and Mobility Program; UK Medical Research Council Senior Clinical Fellowship [G0902313]; Sigrid Juselius Foundation; RFBR (Russian Foundation for Basic Research)-Helmholtz Joint Research Group [12-04-91322]; European Union's Seventh Framework Programme (FP7-Health-F5) [305280]; European Union's Seventh Framework Programme [305280, 313010, 261433]; Finnish Academy [269517, 139635]; Yrjo Jahnsson Foundation; Juho Vainio Foundation; British Heart Foundation (BHF); BHF; NIHR Leicester Cardiovascular Biomedical Research Unit; Finnish Foundation for Cardiovascular Research; Academy of Finland Centre of Excellence in Biomembrane Research [272130]; Academy of Finland [263841, 251217, 255847]; University of Helsinki Postdoctoral Researcher grant; Magnus Ehrnrooth Foundation; Kymenlaakso Cultural Foundation; European Union's Seventh Framework Programme (FP7) [258068]; EU-FP7-Systems Microscopy Network of Excellence; Center of Excellence in Complex Disease Genetics; European Union's Seventh Framework Programme project ENGAGE [201413]; European Union's Seventh Framework Programme project BioSHaRE [261433]; Biocentrum Helsinki FX We acknowledge CSC (IT Center for Science) and the Technology Centre of the Institute for Molecular Medicine for computational services. The High-Throughput Biomedicine Unit of the Institute for Molecular Medicine Finland, R. Kovanen and A. Uro are acknowledged for technical expertise. M. Jauhiainen is acknowledged for sharing his expertise in the manuscript writing process. This research was supported through funds from the European Union's Seventh Framework Programme (FP7/2007-2013), ENGAGE Consortium, grant agreement HEALTH-F4-2007-201413. LS. was partly funded by the Helsinki University Doctoral Programme in Biomedicine (DPBM). M.H. was funded by a Manpei Suzuki Diabetes Foundation Grant-in-Aid for young scientists working abroad. A.P.M. and A. Mahajan acknowledge funding from the Wellcome Trust under awards WT098017, WT090532 and WT064890. V. Lagou, L.M., S.H. and I.P. were funded in part through the European Union's Seventh Framework Programme (FP7/2007-2013), ENGAGE project, grant agreement HEALTH-F4-2007-201413. L.M. was in part sponsored by '5 per mile' contribution assigned to the University of Ferrara, income tax return year 2009, and in part by the ENGAGE Exchange and Mobility Program for ENGAGE training funds. M.D.T. holds a UK Medical Research Council Senior Clinical Fellowship (G0902313). S.T. is supported by the Sigrid Juselius Foundation. J.S.R. and C.G. have received funding from a grant from the RFBR (Russian Foundation for Basic Research)-Helmholtz Joint Research Group (12-04-91322). C.G. received funding from the European Union's Seventh Framework Programme (FP7-Health-F5-2012) under grant agreement 305280 (MIMOmics). M. Perola has been supported by the European Union's Seventh Framework Programme (grant agreements 313010; BBMRI-LPC, 305280; MIMOmics, and 261433; BioSHaRE-BU), Finnish Academy grant 269517, the Yrjo Jahnsson Foundation and the Juho Vainio Foundation. N.J.S. holds a chair funded by the British Heart Foundation (BHF) and is an NIHR Senior Investigator. C.P.N. is funded by the BHF and was preciously funded by the NIHR Leicester Cardiovascular Biomedical Research Unit. V. Salomaa was supported by the Finnish Foundation for Cardiovascular Research and the Finnish Academy (grant 139635). E. Ikonen was supported by the Academy of Finland Centre of Excellence in Biomembrane Research (272130), the Academy of Finland (263841) and the Sigrid Juselius Foundation. V.P. was supported by a University of Helsinki Postdoctoral Researcher grant, the Magnus Ehrnrooth Foundation and the Kymenlaakso Cultural Foundation. O.K., J.-P.M. and V.P. have received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement 258068; EU-FP7-Systems Microscopy Network of Excellence. S.R. was supported by the Academy of Finland (251217 and 255847), the Center of Excellence in Complex Disease Genetics, the European Union's Seventh Framework Programme projects ENGAGE (201413) and BioSHaRE (261433), the Finnish Foundation for Cardiovascular Research, Biocentrum Helsinki and the Sigrid Juselius Foundation. Cohort-specific acknowledgments are provided in the Supplementary Note. NR 34 TC 31 Z9 31 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUN PY 2015 VL 47 IS 6 BP 589 EP 597 DI 10.1038/ng.3300 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CJ3LW UT WOS:000355386500009 PM 25961943 ER PT J AU Rock, JM Lang, UF Chase, MR Ford, CB Gerrick, ER Gawande, R Coscolla, M Gagneux, S Fortune, SM Lamers, MH AF Rock, Jeremy M. Lang, Ulla F. Chase, Michael R. Ford, Christopher B. Gerrick, Elias R. Gawande, Richa Coscolla, Mireia Gagneux, Sebastien Fortune, Sarah M. Lamers, Meindert H. TI DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader SO NATURE GENETICS LA English DT Article ID POLYMERASE-III; ESCHERICHIA-COLI; IDENTIFICATION; EVOLUTION; REPAIR; MOTIF AB The DNA replication machinery is an important target for antibiotic development in increasingly drug-resistant bacteria, including Mycobacterium tuberculosis(1). Although blocking DNA replication leads to cell death, disrupting the processes used to ensure replication fidelity can accelerate mutation and the evolution of drug resistance. In Escherichia coli, the proofreading subunit of the replisome, the epsilon exonuclease, is essential for high-fidelity DNA replication(2); however, we find that the corresponding subunit is completely dispensable in M. tuberculosis. Rather, the mycobacterial replicative polymerase DnaE1 itself encodes an editing function that proofreads DNA replication, mediated by an intrinsic 3'-5' exonuclease activity within its PHP domain. Inactivation of the DnaE1 PHP domain increases the mutation rate by more than 3,000-fold. Moreover, phylogenetic analysis of DNA replication proofreading in the bacterial kingdom suggests that Escherichia coli is a phylogenetic outlier and that PHP domain-mediated proofreading is widely conserved and indeed may be the ancestral prokaryotic proofreader. C1 [Rock, Jeremy M.; Chase, Michael R.; Ford, Christopher B.; Gerrick, Elias R.; Gawande, Richa; Fortune, Sarah M.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Lang, Ulla F.; Lamers, Meindert H.] MRC, Mol Biol Lab, Cambridge CB2 2QH, England. [Ford, Christopher B.; Fortune, Sarah M.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Coscolla, Mireia; Gagneux, Sebastien] Swiss Trop & Publ Hlth Inst, Basel, Switzerland. [Coscolla, Mireia; Gagneux, Sebastien] Univ Basel, Basel, Switzerland. [Fortune, Sarah M.] Massachusetts Gen Hosp, Harvard & Massachusetts Inst Technol, Ragon Inst Massachusetts, Cambridge, MA USA. RP Fortune, SM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM sfortune@hsph.harvard.edu; mlamers@mrc-lmb.cam.ac.uk FU Helen Hay Whitney fellowship; US National Institutes of Health Director's New Innovator Award [1DP20D001378]; National Institute of Allergy and Infectious Diseases (NIAID) [U19AI076217, AI109755-01]; Doris Duke Charitable Foundation [2010054]; UK Medical Research Council grant [MC_U105197143] FX We thank E. Rubin, B. Bloom, D. Boyd, J. McKenzie, D. Warner and B. Javid for comments, B. Jacobs (Albert Einstein College of Medicine) and M. Wilmans (European Molecular Biology Laboratory) for bacterial strains, and T. Baker (University of Auckland) for plasmids. This work was supported by a Helen Hay Whitney fellowship to J.M.R., US National Institutes of Health Director's New Innovator Award 1DP20D001378, subcontracts from National Institute of Allergy and Infectious Diseases (NIAID) U19AI076217 and AI109755-01, the Doris Duke Charitable Foundation under grant 2010054 to S.M.F. and a UK Medical Research Council grant to M.H.L. (MC_U105197143). NR 21 TC 7 Z9 7 U1 4 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUN PY 2015 VL 47 IS 6 BP 677 EP 681 DI 10.1038/ng.3269 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA CJ3LW UT WOS:000355386500022 PM 25894501 ER PT J AU Chittajallu, DR Florian, S Kohler, RH Iwamoto, Y Orth, JD Weissleder, R Danuser, G Mitchison, TJ AF Chittajallu, Deepak R. Florian, Stefan Kohler, Rainer H. Iwamoto, Yoshiko Orth, James D. Weissleder, Ralph Danuser, Gaudenz Mitchison, Timothy J. TI In vivo cell-cycle profiling in xenograft tumors by quantitative intravital microscopy SO NATURE METHODS LA English DT Article ID ANTIMITOTIC DRUGS; CANCER-CELLS; SINGLE-CELL; SEGMENTATION; NUCLEI; TARGET; CLASSIFICATION; RECONSTRUCTION; MICROTUBULES; PACLITAXEL AB Quantification of cell-cycle state at a single-cell level is essential to understand fundamental three-dimensional (3D) biological processes such as tissue development and cancer. Analysis of 3D in vivo images, however, is very challenging. Today's best practice, manual annotation of select image events, generates arbitrarily sampled data distributions, which are unsuitable for reliable mechanistic inferences. Here, we present an integrated workflow for quantitative in vivo cell-cycle profiling. It combines image analysis and machine learning methods for automated 3D segmentation and cell-cycle state identification of individual cell-nuclei with widely varying morphologies embedded in complex tumor environments. We applied our workflow to quantify cell-cycle effects of three antimitotic cancer drugs over 8 d in HT-1080 fibrosarcoma xenografts in living mice using a data set of 38,000 cells and compared the induced phenotypes. In contrast to results with 2D culture, observed mitotic arrest was relatively low, suggesting involvement of additional mechanisms in their antitumor effect in vivo. C1 [Chittajallu, Deepak R.; Danuser, Gaudenz] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Florian, Stefan; Weissleder, Ralph; Mitchison, Timothy J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02138 USA. [Kohler, Rainer H.; Iwamoto, Yoshiko; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Orth, James D.] Univ Colorado, Mol Cellular & Dev Biol, Boulder, CO 80309 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02138 USA. EM stefan_florian@hms.harvard.edu; rweissleder@mgh.harvard.edu; gaudenz.danuser@utsouthwestern.edu FU DFG (Deutsche Forschungsgemeinschaft) [FL 820/1-1]; US National Institutes of Health [R01-CA164448, S10RR0266360, PO1-CA139980]; Nikon Imaging Center at Harvard Medical School FX S.F. was supported by a research fellowship (FL 820/1-1) from the DFG (Deutsche Forschungsgemeinschaft). This project was supported by US National Institutes of Health grants R01-CA164448, S10RR0266360 and PO1-CA139980. We thank P. Choi for helpful discussions. We are grateful for the support of The Nikon Imaging Center at Harvard Medical School. We thank K. Krukenberg (Harvard Medical School) for the MCF7 and T47D cell lines stably expressing H2B-GFP; P. Keller (Howard Hughes Medical Institute, Janelia Research Campus) for Drosophila, mouse and zebrafish data sets; M. Sebas for surgical implantation of the DSCs; and J. Moore for assistance with flow cytometry. The FUCCI viral particles were a kind gift from P. Jorgensen, A. Tzur and M. Chung (Harvard Medical School) generated with vectors kindly provided by the laboratory of A. Miyawaki (RIKEN Brain Science Institute). The H2B-CFP construct was obtained from A. Loewer (Max Delbrueck Center). NR 46 TC 19 Z9 19 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JUN PY 2015 VL 12 IS 6 BP 577 EP + DI 10.1038/nmeth.3363 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CJ1MQ UT WOS:000355248100029 PM 25867850 ER PT J AU Garfield, AS Li, C Madara, JC Shah, BP Webber, E Steger, JS Campbell, JN Gavrilova, O Lee, CE Olson, DP Elmquist, JK Tannous, BA Krashes, MJ Lowell, BB AF Garfield, Alastair S. Li, Chia Madara, Joseph C. Shah, Bhavik P. Webber, Emily Steger, Jennifer S. Campbell, John N. Gavrilova, Oksana Lee, Charlotte E. Olson, David P. Elmquist, Joel K. Tannous, Bakhos A. Krashes, Michael J. Lowell, Bradford B. TI A neural basis for melanocortin-4 receptor-regulated appetite SO NATURE NEUROSCIENCE LA English DT Article ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MELANOCYTE-STIMULATING HORMONE; PROTEIN-COUPLED RECEPTORS; AGOUTI-RELATED PROTEIN; PARABRACHIAL NUCLEUS; FEEDING-BEHAVIOR; AGRP NEURONS; RNA-SEQ; LATERAL HYPOTHALAMUS; FRAMESHIFT MUTATION AB Pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus (ARC) are oppositely regulated by caloric depletion and coordinately stimulate and inhibit homeostatic satiety, respectively. This bimodality is principally underscored by the antagonistic actions of these ligands at downstream melanocortin-4 receptors (MC4R) in the paraventricular nucleus of the hypothalamus (PVH). Although this population is critical to energy balance, the underlying neural circuitry remains unknown. Using mice expressing Cre recombinase in MC4R neurons, we demonstrate bidirectional control of feeding following real-time activation and inhibition of PVHMC4R neurons and further identify these cells as a functional exponent of ARC(AgRP) neuron-driven hunger. Moreover, we reveal this function to be mediated by a PVHMC4R -> lateral parabrachial nucleus (LPBN) pathway. Activation of this circuit encodes positive valence, but only in calorically depleted mice. Thus, the satiating and appetitive nature of PVHMC4R -> LPBN neurons supports the principles of drive reduction and highlights this circuit as a promising target for antiobesity drug development. C1 [Garfield, Alastair S.; Madara, Joseph C.; Shah, Bhavik P.; Steger, Jennifer S.; Campbell, John N.; Olson, David P.; Lowell, Bradford B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. [Garfield, Alastair S.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland. [Li, Chia; Webber, Emily; Krashes, Michael J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Li, Chia; Webber, Emily; Krashes, Michael J.] NIDA, NIH, Baltimore, MD USA. [Gavrilova, Oksana] NIDDK, Mouse Metab Core, NIH, Bethesda, MD 20892 USA. [Lee, Charlotte E.; Elmquist, Joel K.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hypothalam Res, Dallas, TX 75390 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Lowell, Bradford B.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Lowell, BB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. EM agarfiel@staffmail.ed.ac.uk; michael.krashes@nih.gov; blowell@bidmc.harvard.edu FU Boston Area Diabetes Endocrinology Research Center [BADERC P30 DK057521]; University of Edinburgh; US National Institutes of Health [R01 DK096010, R01 DK089044, R01 DK071051, R01 DK075632, R37 DK053477, F32 DK089710, K08 DK071561, R01 DK088423, R37 DK0053301]; US National Institutes of Health (BNORC Transgenic Core) [P30 DK046200]; US National Institutes of Health (BADERC Transgenic Core) [P30 DK057521]; American Heart Association [14POST20100011]; viral vector production core [P30 NS045776]; American Diabetes Association; NIH, NIDDK [DK075087, DK075088] FX The authors gratefully acknowledge the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Mouse Metabolism Core for technical support, V. Petkova and the Beth Israel Deaconess Medical Center Molecular Medicine Core Facility for assistance with quantitative PCR and sample preparation, and D. Morse for the production of the rabies virus. Sequencing and initial data processing were performed at Massachusetts General Hospital's Next-Gen Sequencing Core. Sequencing was supported in part by funding from the Boston Area Diabetes Endocrinology Research Center (BADERC P30 DK057521). This work was supported by the University of Edinburgh Chancellor's Fellowship (A.S.G.); US National Institutes of Health grants to B.B.L. (R01 DK096010, R01 DK089044, R01 DK071051, R01 DK075632, R37 DK053477, BNORC Transgenic Core P30 DK046200, BADERC Transgenic Core P30 DK057521), to M.J.K. (F32 DK089710), to D.P.O. (K08 DK071561) and to J.K.E. (R01 DK088423 and R37 DK0053301); American Heart Association Postdoctoral Fellowship 14POST20100011 to J.N.C.; viral vector production core P30 NS045776 to B.A.T.; and an American Diabetes Association Mentor-Based Fellowship to B.P.S. and B.B.L. This research was supported, in part, by the Intramural Research Program of the NIH, NIDDK (DK075087, DK075088). NR 63 TC 50 Z9 50 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUN PY 2015 VL 18 IS 6 BP 863 EP U299 DI 10.1038/nn.4011 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CJ1CB UT WOS:000355218300014 PM 25915476 ER PT J AU Adamala, K Engelhart, AE Kamat, NP Jin, L Szostak, JW AF Adamala, Katarzyna Engelhart, Aaron E. Kamat, Neha P. Jin, Lin Szostak, Jack W. TI Construction of a liposome dialyzer for the preparation of high-value, small-volume liposome formulations SO NATURE PROTOCOLS LA English DT Article ID MODEL PROTOCELLS; DRUG-DELIVERY; RNA; EFFICIENT; VESICLES; PROTEIN; CELLS AB The liposome dialyzer is a small-volume equilibrium dialysis device, built from commercially available materials, that is designed for the rapid exchange of small volumes of an extraliposomal reagent pool against a liposome preparation. The dialyzer is prepared by modification of commercially available dialysis cartridges (Slide-A-Lyzer cassettes), and it consists of a reactor with two 300-mu l chambers and a 1.56-cm(2) dialysis surface area. The dialyzer is prepared in three stages: (i) disassembling the dialysis cartridges to obtain the required parts, (ii) assembling the dialyzer and (iii) sealing the dialyzer with epoxy. Preparation of the dialyzer takes similar to 1.5 h, not including overnight epoxy curing. Each round of dialysis takes 1-24 h, depending on the analyte and membrane used. We previously used the dialyzer for small-volume non-enzymatic RNARNARNA synthesis reactions inside fatty acid vesicles. In this protocol, we demonstrate other applications, including removal of unencapsulated calcein from vesicles, remote loading and vesicle microscopy. C1 [Adamala, Katarzyna] MIT, Media Lab, Cambridge, MA 02139 USA. [Engelhart, Aaron E.; Kamat, Neha P.; Jin, Lin; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Engelhart, Aaron E.; Kamat, Neha P.; Jin, Lin; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu RI Kamat, Neha/L-2799-2016; OI Adamala, Kate/0000-0003-1066-7207 FU National Aeronautics and Space Administration (NASA) [NNX07AJ09G]; Simons Foundation [290363]; Tosteson Fellowship from the Massachusetts General Hospital Executive Committee on Research FX This work was supported in part by The National Aeronautics and Space Administration (NASA) Exobiology grant NNX07AJ09G to J.W.S. and in part by a grant (290363) from the Simons Foundation to J.W.S. A.E.E. and N.P.K. were supported by appointments to the NASA Postdoctoral Program, administered by Oak Ridge Associated Universities through a contract with NASA. A.E.E. was supported by a Tosteson Fellowship from the Massachusetts General Hospital Executive Committee on Research. J.W.S. is an Investigator of the Howard Hughes Medical Institute. NR 21 TC 0 Z9 0 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD JUN PY 2015 VL 10 IS 6 BP 927 EP 938 DI 10.1038/nprot.2015.054 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CJ1LN UT WOS:000355245200008 PM 26020615 ER PT J AU Bacher, D Jarosiewicz, B Masse, NY Stavisky, SD Simeral, JD Newell, K Oakley, EM Cash, SS Friehs, G Hochberg, LR AF Bacher, Daniel Jarosiewicz, Beata Masse, Nicolas Y. Stavisky, Sergey D. Simeral, John D. Newell, Katherine Oakley, Erin M. Cash, Sydney S. Friehs, Gerhard Hochberg, Leigh R. TI Neural Point-and-Click Communication by a Person With Incomplete Locked-In Syndrome SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE ALS; stroke; spinal cord injury; paralysis; assistive technology; text entry ID BRAIN-COMPUTER INTERFACE; CORTICAL CONTROL; MOVEMENT SIGNAL; TETRAPLEGIA; PEOPLE; DEVICES; HUMANS; DESIGN; SYSTEM; BCI AB A goal of brain-computer interface research is to develop fast and reliable means of communication for individuals with paralysis and anarthria. We evaluated the ability of an individual with incomplete locked-in syndrome enrolled in the BrainGate Neural Interface System pilot clinical trial to communicate using neural point-and-click control. A general-purpose interface was developed to provide control of a computer cursor in tandem with one of two on-screen virtual keyboards. The novel BrainGate Radial Keyboard was compared to a standard QWERTY keyboard in a balanced copy-spelling task. The Radial Keyboard yielded a significant improvement in typing accuracy and speedenabling typing rates over 10 correct characters per minute. The participant used this interface to communicate face-to-face with research staff by using text-to-speech conversion, and remotely using an internet chat application. This study demonstrates the first use of an intracortical brain-computer interface for neural point-and-click communication by an individual with incomplete locked-in syndrome. C1 [Bacher, Daniel; Stavisky, Sergey D.; Simeral, John D.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Jarosiewicz, Beata; Masse, Nicolas Y.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Bacher, Daniel; Jarosiewicz, Beata; Masse, Nicolas Y.; Simeral, John D.; Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Jarosiewicz, Beata; Stavisky, Sergey D.; Simeral, John D.; Hochberg, Leigh R.] Dept Vet Affairs Med Ctr, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Simeral, John D.; Newell, Katherine; Oakley, Erin M.; Cash, Sydney S.; Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney S.; Hochberg, Leigh R.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Friehs, Gerhard] Rhode Isl Hosp, Dept Neurosurg, Providence, RI USA. RP Bacher, D (reprint author), 2 Stimson Ave,Box 1994, Providence, RI USA. EM daniel_bacher@brown.edu FU NIH: NIDCD [R01DC009899]; NICHD-NCMRR [N01HD53403, N01HD10018]; Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs [B6453R, A6779I, B6310N]; Doris Duke Charitable Foundation; Craig H. Neilsen Foundation; MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; Cyberkinetics Neurotechnology Systems (CKI) FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by NIH: NIDCD (R01DC009899) and NICHD-NCMRR (N01HD53403, N01HD10018); Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs (Merit Review Awards B6453R and A6779I; Career Development Transition Award B6310N); Doris Duke Charitable Foundation; Craig H. Neilsen Foundation; and the MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke. The pilot clinical trial into which participant S3 was recruited was sponsored in part by Cyberkinetics Neurotechnology Systems (CKI). The BrainGate clinical trial is directed by Massachusetts General Hospital. NR 33 TC 8 Z9 9 U1 4 U2 20 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 EI 1552-6844 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD JUN PY 2015 VL 29 IS 5 BP 462 EP 471 DI 10.1177/1545968314554624 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CJ3WI UT WOS:000355414600008 PM 25385765 ER PT J AU Maurovich-Horvat, P Kallianos, K Engel, LC Szymonifka, J Schlett, CL Koenig, W Hoffmann, U Truong, QA AF Maurovich-Horvat, Pal Kallianos, Kimberly Engel, Leif-Christopher Szymonifka, Jackie Schlett, Christopher L. Koenig, Wolfgang Hoffmann, Udo Truong, Quynh A. TI Relationship of thoracic fat depots with coronary atherosclerosis and circulating inflammatory biomarkers SO OBESITY LA English DT Article ID EPICARDIAL ADIPOSE-TISSUE; VISCERAL ABDOMINAL FAT; DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; PERICARDIAL FAT; HEART-DISEASE; ARTERY-DISEASE; IN-VIVO; ASSOCIATION AB ObjectiveThe aim of the study was to determine the relationship of various thoracic fat depots with the presence and extent of coronary artery plaque and circulating biomarkers. MethodsIn 342 patients (5211 years, 61% male, BMI 29.15.9 kg/m(2)) with coronary computed tomography (CT), angiography, we measured the fat volume in four thoracic depots (pericoronary, epicardial, periaortic, extracardiac), assessed coronary plaque, and determined the circulating levels of C-reactive protein, tumor necrosis factor alpha, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and adiponectin. The extent of coronary plaque was classified into three groups: 0, 1-3, and >3 segments. ResultsPatients with plaque (n =169, 49%) had higher volumes of all four fat depots as compared to patients without plaque (all P<0.01), despite similar BMI (P=0.18). Extracardiac fat was most strongly correlated with BMI (r=0.45, P<0.001), while pericoronary fat was least (r=0.21, P<0.001). Only pericoronary fat remained associated with coronary plaque in adjusted analyses. Inflammatory biomarkers showed a positive correlation with pericoronary fat (all P<0.0001), whereas adiponectin was not associated with this fat compartment (P=0.60) and showed a negative correlation with all other fat depots (all P<0.001). ConclusionsPericoronary fat is independently associated with coronary artery disease (CAD). Its correlation with inflammatory biomarkers suggests that while systemic inflammation plays a role in the pathogenesis of CAD, there are additional local effects that may exist. C1 [Maurovich-Horvat, Pal; Kallianos, Kimberly; Engel, Leif-Christopher; Schlett, Christopher L.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Div Cardiol, Boston, MA USA. [Maurovich-Horvat, Pal; Kallianos, Kimberly; Engel, Leif-Christopher; Schlett, Christopher L.; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Maurovich-Horvat, Pal] Semmelweis Univ, Heart & Vasc Ctr, MTA SE Lendulet Cardiovasc Imaging Res Grp, H-1085 Budapest, Hungary. [Szymonifka, Jackie] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Schlett, Christopher L.] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Truong, Quynh A.] New York Presbyterian Hosp, Dept Radiol, New York, NY 10032 USA. [Truong, Quynh A.] Weill Cornell Med Coll, Dalio Inst Cardiovasc Imaging, New York, NY USA. RP Truong, QA (reprint author), New York Presbyterian Hosp, Dept Radiol, New York, NY 10032 USA. EM qat9001@med.cornell.edu FU NIH [R01 HL080053, K23HL098370, L30HL093896]; Siemens Medical Solutions; General Electrics Healthcare; University of Ulm Medical Centre FX This work was supported by NIH R01 HL080053, Siemens Medical Solutions, and General Electrics Healthcare. Dr. Truong received support from NIH grants K23HL098370 and L30HL093896. Additional funds for biomarker determination came from the University of Ulm Medical Centre. NR 32 TC 6 Z9 6 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JUN PY 2015 VL 23 IS 6 BP 1178 EP 1184 DI 10.1002/oby.21080 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CJ0FG UT WOS:000355150300008 PM 25960369 ER PT J AU Long, MT Pedley, A Massaro, JM Hoffmann, U Esliger, DW Vasan, RS Fox, CS Murabito, JM AF Long, Michelle T. Pedley, Alison Massaro, Joseph M. Hoffmann, Udo Esliger, Dale W. Vasan, Ramachandran S. Fox, Caroline S. Murabito, Joanne M. TI Hepatic steatosis is associated with lower levels of physical activity measured via accelerometry SO OBESITY LA English DT Article ID FATTY LIVER-DISEASE; ALL-CAUSE MORTALITY; UNITED-STATES; RISK-FACTORS; WEIGHT-LOSS; INSULIN SENSITIVITY; EXERCISE; ADULTS; POPULATION; HEALTH AB ObjectivePrior studies on the association of physical activity (PA) and nonalcoholic fatty liver disease are limited by reliance on subjective measures of PA. We examined the association between objectively measured PA and hepatic steatosis defined by computed tomography (CT). MethodsWe conducted a cross-sectional study of 1,060 Framingham Heart Study participants who participated in the Multidetector CT 2 substudy and who underwent assessment of PA via accelerometry. Hepatic steatosis was estimated by liver attenuation, as measured by CT. We explored the relationship between liver attenuation and PA using multivariable regression models. ResultsIn multivariable-adjusted models, we observed an inverse association between PA and liver attenuation. Each 30 minutes/day increase in moderate to vigorous PA (MVPA) was associated with a reduced odds of hepatic steatosis (OR = 0.62, P < 0.001). This association was attenuated and no longer statistically significant after adjustment for body mass index (BMI) (OR = 0.77, P = 0.05) or visceral adipose tissue (VAT) (OR = 0.83, P = 0.18). Participants who met the national PA recommendations of engaging in 150 minutes/week of MVPA had the lowest odds of hepatic steatosis, even after adjusting for BMI (OR = 0.63, P = 0.007) or VAT (OR = 0.67, P = 0.03). ConclusionsThere is an inverse association between PA and hepatic steatosis. Participants who met the national PA guidelines had the lowest prevalence of hepatic steatosis. C1 [Long, Michelle T.] Boston Univ, Sch Med, Boston Med Ctr, Div Gastroenterol, Boston, MA 02118 USA. [Long, Michelle T.; Pedley, Alison; Massaro, Joseph M.; Vasan, Ramachandran S.; Fox, Caroline S.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Esliger, Dale W.] Univ Loughborough, Sch Sport Exercise & Hlth Sci, Loughborough, Leics, England. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. EM murabito@bu.edu OI Long, Michelle/0000-0001-6131-3981; Ramachandran, Vasan/0000-0001-7357-5970 FU Boston University School of Medicine; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Division of Intramural Research of the National Heart, Lung, and Blood Institute; NIH [1RO1-AG-047645]; Boston University Clinical and Translational Science Institute [UL1-TR000157] FX This work was supported by the Boston University School of Medicine, the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195), and the Division of Intramural Research of the National Heart, Lung, and Blood Institute. We received additional support from the NIH grant 1RO1-AG-047645. Dr. Long is supported in part by the Boston University Clinical and Translational Science Institute (grant UL1-TR000157). NR 39 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JUN PY 2015 VL 23 IS 6 BP 1259 EP 1266 DI 10.1002/oby.21058 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CJ0FG UT WOS:000355150300019 PM 25959049 ER PT J AU Bellucci, R Martin, A Bommarito, D Wang, K Hansen, SH Freeman, GJ Ritz, J AF Bellucci, Roberto Martin, Allison Bommarito, Davide Wang, Kathy Hansen, Steen H. Freeman, Gordon J. Ritz, Jerome TI Interferon-gamma-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression SO ONCOIMMUNOLOGY LA English DT Article DE IFN gamma; JAK1/JAK2; NK cells; PD-1/PD-L1 ID NATURAL-KILLER-CELL; I ANTIGEN-EXPRESSION; MELANOMA-CELLS; IFN-GAMMA; INTERLEUKIN-10 SECRETION; MALIGNANT-MELANOMA; ANTI-PD-1 ANTIBODY; SIGNALING PATHWAY; B7 FAMILY; CANCER AB Inhibition of JAK1 or JAK2 in human tumor cells was previously shown to increase susceptibility of these cells to NK cell lysis. In the present study, we examined the cellular mechanisms that mediate this effect in hematopoietic tumor cell lines and primary tumor cells. Incubation of tumor cells with supernatant from activated NK cells or interferon-gamma (IFN)-induced activation of pSTAT1 and increased expression of PD-L1 without altering expression of other activating or inhibitory NK cell ligands. These functional effects were blocked by chemical JAK inhibition or shRNAs targeting JAK1, JAK2 or STAT1. Inhibition of IFN signaling also prevented the upregulation of PD-L1 and blocking PD-L1 resulted in increased tumor lysis by NK cells. These results show that NK cell activation and secretion of IFN results in activation of JAK1, JAK2 and STAT1 in tumor cells, resulting in rapid up-regulation of PD-L1 expression. Increased expression of PD-L1 results in increased resistance to NK cell lysis. Blockade of JAK pathway activation prevents increased PD-L1 expression resulting in increased susceptibility of tumor cells to NK cell activity. These observations suggest that JAK pathway inhibitors as well as PD-1 and PD-L1 antibodies may work synergistically with other immune therapies by preventing IFN-induced inhibition of NK cell-mediated tumor cell lysis. C1 [Bellucci, Roberto; Martin, Allison; Bommarito, Davide; Wang, Kathy; Freeman, Gordon J.; Ritz, Jerome] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bellucci, Roberto; Hansen, Steen H.; Freeman, Gordon J.; Ritz, Jerome] Brigham & Womans Hosp, Dept Med, Boston, MA USA. [Bellucci, Roberto; Hansen, Steen H.; Freeman, Gordon J.; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA USA. [Hansen, Steen H.] Childrens Hosp Boston, GI Cell Biol Res Lab, Boston, MA USA. [Freeman, Gordon J.; Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Bellucci, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Roberto_Bellucci@dfci.harvard.edu; Jerome_Ritz@dfci.harvard.edu FU NIH [R21 AI088521, CA078378, CA142106, CA183560, CA163125, P50 CA101942, RO1 CA142647]; International Myeloma Foundation (IMF); Multiple Myeloma Research Foundation (MMRF); Claudia Adams Barr Research Program FX This work was supported by NIH Grants R21 AI088521 (R.B.), CA078378, CA142106, CA183560 (J.R.), CA163125, P50 CA101942 (G.F.), RO1 CA142647 (S.H.H.). International Myeloma Foundation (IMF), Multiple Myeloma Research Foundation (MMRF) and Claudia Adams Barr Research Program (R.B.). NR 51 TC 25 Z9 25 U1 1 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD JUN PY 2015 VL 4 IS 6 DI 10.1080/2162402X.2015.1008824 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CJ0XK UT WOS:000355203300014 ER PT J AU Suryadevara, CM Gedeon, PC Sanchez-Perez, L Verla, T Alvarez-Breckenridge, C Choi, BD Fecci, PE Sampson, JH AF Suryadevara, Carter M. Gedeon, Patrick C. Sanchez-Perez, Luis Verla, Terence Alvarez-Breckenridge, Christopher Choi, Bryan D. Fecci, Peter E. Sampson, John H. TI Are BiTEs the "missing link" in cancer therapy? SO ONCOIMMUNOLOGY LA English DT Review DE bispecific antibodies; immunotherapy; malignancies; T lymphocytes ID SINGLE-CHAIN ANTIBODY; MHC CLASS-I; CHIMERIC ANTIGEN RECEPTOR; MODIFIED T-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROGRESSION-FREE SURVIVAL; METASTATIC MELANOMA; TUMOR-REGRESSION; DOWN-REGULATION; BISPECIFIC ANTIBODY AB Conventional treatment for cancer routinely includes surgical resection and some combination of chemotherapy and radiation. These approaches are frequently accompanied by unintended and highly toxic collateral damage to healthy tissues, which are offset by only marginal prognostic improvements in patients with advanced cancers. This unfortunate balance has driven the development of novel therapies that aim to target tumors both safely and efficiently. Over the past decade, mounting evidence has supported the therapeutic utility of T-cell-centered cancer immunotherapy, which, in its various iterations, has been shown capable of eliciting highly precise and robust antitumor responses both in animal models and human trials. The identification of tumor-specific targets has further fueled a growing interest in T-cell therapies given their potential to circumvent the non-specific nature of traditional treatments. Of the several strategies geared toward achieving T-cell recognition of tumor, bispecific antibodies (bsAbs) represent a novel class of biologics that have garnered enthusiasm in recent years due to their versatility, specificity, safety, cost, and ease of production. Bispecific T-cell Engagers (BiTEs) are a subclass of bsAbs that are specific for CD3 on one arm and a tumor antigen on the second. As such, BiTEs function by recruiting and activating polyclonal populations of T-cells at tumor sites, and do so without the need for co-stimulation or conventional MHC recognition. Blinatumomab, a well-characterized BiTE, has emerged as a promising recombinant bscCD19xCD3 construct that has demonstrated remarkable antitumor activity in patients with B-cell malignancies. This clinical success has resulted in the rapid extension of BiTE technology against a greater repertoire of tumor antigens and the recent US Food and Drug Administration's (FDA) accelerated approval of blinatumomab for the treatment of a rare form of acute lymphoblastic leukemia (ALL). In this review, we dissect the role of T-cell therapeutics in the new era of cancer immunotherapy, appraise the value of CAR T-cells in the context of solid tumors, and discuss why the BiTE platform may rescue several of the apparent deficits and shortcomings of competing immunotherapies to support its widespread clinical application. C1 [Suryadevara, Carter M.; Gedeon, Patrick C.; Sanchez-Perez, Luis; Verla, Terence; Fecci, Peter E.; Sampson, John H.] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg,Duke Brain Tumor Immunotherapy Prog, Durham, NC 27710 USA. [Suryadevara, Carter M.; Sampson, John H.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Suryadevara, Carter M.; Gedeon, Patrick C.; Sanchez-Perez, Luis; Verla, Terence; Fecci, Peter E.; Sampson, John H.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Gedeon, Patrick C.; Sampson, John H.] Duke Univ, Dept Biomed Engn, Durham, NC 27710 USA. [Alvarez-Breckenridge, Christopher; Choi, Bryan D.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Alvarez-Breckenridge, Christopher; Choi, Bryan D.] Harvard Univ, Sch Med, Boston, MA USA. RP Suryadevara, CM (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg,Duke Brain Tumor Immunotherapy Prog, Durham, NC 27710 USA. EM carter.suryadevara@duke.edu RI Gedeon, Patrick/G-6563-2013 OI Gedeon, Patrick/0000-0002-5387-1833 NR 110 TC 5 Z9 5 U1 1 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD JUN PY 2015 VL 4 IS 6 DI 10.1080/2162402X.2015.1008339 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CJ0XK UT WOS:000355203300005 ER PT J AU Duchin, KS Asefzadeh, B Poulaki, V Rett, D Marescalchi, P Cavallerano, A AF Duchin, Kyla S. Asefzadeh, Baharak Poulaki, Vasiliki Rett, Douglas Marescalchi, Paul Cavallerano, Anthony TI Teleretinal Imaging for Detection of Referable Macular Degeneration SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE teleretinal; macular degeneration; screening; visual impairment; aging population; nonmydriatic ID DIABETIC-RETINOPATHY; PREMATURITY DIAGNOSIS; CLINICAL-TRIAL; NURSING-HOME; RELIABILITY; TELEMEDICINE; SPECIFICITY; SENSITIVITY; PREVALENCE; DEPRESSION AB Purpose. The purpose of this study was to determine the sensitivity and specificity for detection of referable age-related macular degeneration (AMD) using an existing nonmydriatic telemedicine pathway for diabetic retinopathy screening with comparison to same-day face-to-face examination by a retina specialist. Methods. Subjects in this study underwent nonmydriatic and mydriatic digital retinal imaging on the same day as stereoscopic dilated examination of the macula by a retina specialist and the level of AMD was recorded for each eye. Images were graded by two trained readers as nonreferable or referable (AREDS [Age-Related Eye Disease Study] grading of level 3 or greater). Sensitivity and specificity were calculated by comparing referral recommendations between each reader and the retina specialist ("gold standard"). Results. There were 47 subjects (94 eyes) enrolled in the study. Sensitivity for nonreferable AMD with nonmydriatic imaging was 1.0 (reader 1) and 1.0 (reader 2), whereas specificity was 0.75 (reader 1) and 0.91 (reader 2). Sensitivity for referable AMD with nonmydriatic imaging was 0.84 (reader 1) and 0.88 (reader 2), whereas specificity was 0.81 (reader 1) and 0.81 (reader 2). Conclusions. Our study showed that nonmydriatic digital retinal imaging had excellent sensitivity and specificity in identifying referable and nonreferable AMD using an existing validated telemedicine pathway for diabetic retinopathy screening. C1 [Duchin, Kyla S.] VA Maine Healthcare Syst, Augusta, ME USA. [Asefzadeh, Baharak; Poulaki, Vasiliki; Rett, Douglas; Marescalchi, Paul; Cavallerano, Anthony] VA Boston Healthcare Syst, Boston, MA USA. RP Duchin, KS (reprint author), Togus VAMC Lewiston Auburn CBOC, 15 Challenger Dr, Lewiston, ME 04240 USA. EM Kyla.Duchin@va.gov NR 30 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-5488 EI 1538-9235 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD JUN PY 2015 VL 92 IS 6 BP 714 EP 718 PG 5 WC Ophthalmology SC Ophthalmology GA CJ0DA UT WOS:000355141900014 PM 25955641 ER PT J AU Frederick, MJ Lin, AM Neuman, R Smith, BL Austen, WG Colwell, AS AF Frederick, Michael J. Lin, Alex M. Neuman, Robert Smith, Barbara L. Austen, William G., Jr. Colwell, Amy S. TI Nipple-Sparing Mastectomy in Patients with Previous Breast Surgery: Comparative Analysis of 775 Immediate Breast Reconstructions SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID REDUCTION; COMPLICATIONS; MAMMAPLASTY; MASTOPEXY; OUTCOMES AB Background: An increasing number of women are candidates for nipple preservation with mastectomy. It is unclear how previous breast surgery impacts nipple-sparing mastectomy and immediate breast reconstruction. Methods: A single-institution retrospective review was performed between June of 2007 and June of 2013. Results: Four hundred forty-four patients underwent 775 immediate breast reconstructions after nipple-sparing mastectomy. Of these, 160 patients and 187 reconstructions had previous breast surgery, including 154 lumpectomies, 27 breast augmentations, and six reduction mammaplasties. Two hundred eighty-four patients with 588 reconstructions without previous breast surgery served as the control group. The previous breast surgery patients were older (49.6 years versus 45.8 years; p < 0.001) but otherwise had similar demographics. Previous breast surgery reconstructions were more often unilateral, therapeutic, and associated with preoperative radiotherapy (p < 0.001 for each). Extension of breast scars was common with previous breast surgery, whereas the inframammary incision was most frequent if no scars were present (p < 0.001). Multivariate regression analysis showed that previous breast surgery was not a significant risk factor for ischemic complications or nipple loss. Subgroup analysis showed extension of prior irradiated incisions was predictive of skin flap necrosis (OR, 9.518; p = 0.05). A higher number of lumpectomy patients had preoperative radiotherapy (41 versus 11; p < 0.001), and patients with breast augmentation had more single-stage reconstructions (85.2 percent versus 62.9 percent; p = 0.02). Conclusion: Nipple-sparing mastectomy and immediate reconstruction can be performed in patients with prior breast surgery with no significant increase in nipple loss or ischemic complications. C1 [Frederick, Michael J.; Lin, Alex M.; Neuman, Robert; Smith, Barbara L.; Austen, William G., Jr.; Colwell, Amy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. RP Colwell, AS (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM acolwell@partners.org NR 22 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2015 VL 135 IS 6 BP 954E EP 962E DI 10.1097/PRS.0000000000001283 PG 9 WC Surgery SC Surgery GA CJ1EM UT WOS:000355225000002 PM 26017611 ER PT J AU Eberlin, KR Kobraei, EM Nyame, TT Bloom, JM Upton, J AF Eberlin, Kyle R. Kobraei, Edward M. Nyame, Theodore T. Bloom, Jacob M. Upton, Joseph, III TI Salvage Palmar Fasciectomy after Initial Treatment with Collagenase Clostridium Histolyticum SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID DUPUYTRENS-DISEASE; NONSURGICAL TREATMENT; FOLLOW-UP; CONTRACTURE; FASCIOTOMY; DIAGNOSIS AB Background: Collagenase clostridium histolyticum was approved for clinical use in 2010 and has become an accepted treatment modality for Dupuytren's contracture. Because longitudinal experience with injectable collagenase remains limited, the effect of treatment on future surgery is not well defined. Methods: A retrospective review of the senior author's practice from February of 2010 through March of 2014 was performed. Eleven patients were identified who had digital or palmar fasciectomy after at least one previous injection of collagenase clostridium histolyticum. Cases were reviewed for functional outcomes and operative difficulty. Results: Seven metacarpophalangeal joints and 12 proximal interphalangeal joints in 11 patients were treated. Nine of the 11 patients were referred to the senior author after collagenase clostridium histolyticum injections by other hand surgeons; two patients had previous injections by the senior author. The average interval between most recent injection and salvage fasciectomy was 12 months. Intraoperative findings demonstrated disruption of normal architecture and areolar tissue, with extensive scar in the dissection planes after previous injection. Mean preoperative/postinjection joint contracture for metacarpophalangeal and proximal interphalangeal joints was 42 and 60 degrees, respectively; after surgery, joint contractures were 0 and 21 degrees, respectively. Significant improvement in postoperative range of motion was seen for both metacarpophalangeal and proximal interphalangeal joints after palmar fasciectomy. Conclusions: Collagenase clostridium histolyticum injections may produce a -deeply scarred bed and increase the technical difficulty of salvage fasciectomy. However, results of palmar fasciectomy are comparable to those of primary fasciectomy even in the setting of recurrent or progressive disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Eberlin, KR (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Wang Ambulatory Care Ctr 435, 15 Parkman St, Boston, MA 02114 USA. EM keberlin@mgh.harvard.edu NR 23 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2015 VL 135 IS 6 BP 1000E EP 1006E DI 10.1097/PRS.0000000000001282 PG 7 WC Surgery SC Surgery GA CJ1EM UT WOS:000355225000007 PM 26017606 ER PT J AU Garcia, RM Hadlock, TA Klebuc, MJ Simpson, RL Zenn, MR Marcus, JR AF Garcia, Ryan M. Hadlock, Tessa A. Klebuc, Michael J. Simpson, Roger L. Zenn, Michael R. Marcus, Jeffrey R. TI Contemporary Solutions for the Treatment of Facial Nerve Paralysis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID MASSETERIC NERVE; MUSCLE TRANSFER; DYNAMIC REANIMATION; GRADING SYSTEM; BELLS-PALSY; MOTOR-NERVE; ANASTOMOSIS; FACE; SURGERY; MANAGEMENT AB Learning Objectives: After reviewing this article, the participant should be able to: 1. Understand the most modern indications and technique for neurotization, including masseter-to-facial nerve transfer (fifth-to-seventh cranial nerve transfer). 2. Contrast the advantages and limitations associated with contiguous muscle transfers and free-muscle transfers for facial reanimation. 3. Understand the indications for a two-stage and one-stage free gracilis muscle transfer for facial reanimation. 4. Apply nonsurgical adjuvant treatments for acute facial nerve paralysis. Summary: Facial expression is a complex neuromotor and psychomotor process that is disrupted in patients with facial paralysis breaking the link between emotion and physical expression. Contemporary reconstructive options are being implemented in patients with facial paralysis. While static procedures provide facial symmetry at rest, true "facial reanimation" requires restoration of facial movement. Contemporary treatment options include neurotization procedures (a new motor nerve is used to restore innervation to a viable muscle), contiguous regional muscle transfer (most commonly temporalis muscle transfer), microsurgical free muscle transfer, and nonsurgical adjuvants used to balance facial symmetry. Each approach has advantages and disadvantages along with ongoing controversies and should be individualized for each patient. Treatments for patients with facial paralysis continue to evolve in order to restore the complex psychomotor process of facial expression. C1 Duke Univ, Med Ctr, Div Plast & Reconstruct Surg, Dept Surg, Durham, NC 27710 USA. Massachusetts Eye & Ear Infirm, Boston, MA USA. Baylor Coll Med, Methodist Hosp, Dept Surg, Div Plast & Reconstruct Surg, Houston, TX 77030 USA. Nassau Univ, Med Ctr, Div Plast Surg, Dept Surg, E Meadow, NY 11554 USA. RP Marcus, JR (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Plast Reconstruct Oral & Maxillofacial Surg, 2301 Erwin Rd, Durham, NC 27710 USA. EM jeffrey.marcus@duke.edu NR 67 TC 6 Z9 7 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2015 VL 135 IS 6 BP 1025E EP 1046E DI 10.1097/PRS.0000000000001273 PG 22 WC Surgery SC Surgery GA CJ1EM UT WOS:000355225000010 PM 26017609 ER PT J AU Menendez, ME Ring, D Harris, MB Cha, TD AF Menendez, Mariano E. Ring, David Harris, Mitchel B. Cha, Thomas D. TI Predicting In-Hospital Mortality in Elderly Patients With Cervical Spine Fractures A Comparison of the Charlson and Elixhauser Comorbidity Measures SO SPINE LA English DT Article DE Charlson; Elixhauser; comorbidity; risk adjustment; mortality; cervical spine fractures; trauma ID ADMINISTRATIVE DATA; ORTHOPEDIC-SURGERY; COMPLICATIONS; OUTCOMES; ADJUSTMENT; INJURIES; INDEX; STABILIZATION; EPIDEMIOLOGY; ARTHROPLASTY AB Study Design. Retrospective analysis of nationally representative data collected for the National Hospital Discharge Survey. Objective. To compare the performance of the Charlson and Elixhauser comorbidity-based measures for predicting in-hospital mortality after cervical spine fractures. Summary of Background Data. Mortality occurring as a consequence of cervical spine fractures is very high in the elderly. The Charlson comorbidity measure has been associated with an increased risk of mortality, but its predictive accuracy has yet to be compared with the more recent and increasingly used Elixhauser measure. Methods. Using the National Hospital Discharge Survey for the years 1990 through 2007, we identified all patients aged 65 years or older hospitalized with a diagnosis of cervical spine fracture. The association of each Charlson and Elixhauser comorbidity with mortality was assessed in bivariate analysis using chi(2) tests. Two main multivariable logistic regression models were constructed, with in-hospital mortality as the dependent variable and 1 of the 2 comorbidity-based measures (as well as age, sex, and year of admission) as independent variables. A base model that included only age, sex, and year of admission was also evaluated. The discriminative ability of the models was quantified using the area under the receiver operating characteristic curve (AUC). Results. Among an estimated 111,564 patients admitted for cervical spine fractures, 7.6% died in the hospital. Elixhauser comorbidity adjustment provided better prediction of in-hospital case mortality (AUC = 0.852, 95% confidence interval: 0.848-0.856) than the Charlson model (AUC = 0.823, 95% confidence interval: 0.819-0.828) and the base model with no comorbidities (AUC = 0.785, 95% confidence interval: 0.781-0.790). In terms of relative improvement in predictive ability, the Elixhauser model performed 43% better than the Charlson model. Conclusion. The Elixhauser comorbidity risk adjustment method performed numerically better than the widely used Charlson measure in predicting in-hospital mortality after cervical spine fractures. C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Harris, Mitchel B.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Cha, Thomas D.] Massachusetts Gen Hosp, Orthopaed Spine Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Cha, TD (reprint author), Massachusetts Gen Hosp, Orthopaed Spine Serv, Yawkey Ctr, Ste 3A,55 Fruit St, Boston, MA 02114 USA. EM tcha@partners.org NR 46 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 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JUN 1 PY 2015 VL 40 IS 11 BP 809 EP 815 DI 10.1097/BRS.0000000000000892 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CJ3IV UT WOS:000355377500016 PM 25785957 ER PT J AU Ni, JQ Wang, X Wood, KB AF Ni, Jianqiang Wang, Xin Wood, Kirkham B. TI Re: Can Spontaneous Correction Loss of the Minor Cures Be Ignored at the Final Follow-up? SO SPINE LA English DT Letter ID ADOLESCENT IDIOPATHIC SCOLIOSIS; SELECTIVE ANTERIOR FUSION; CURVES C1 [Ni, Jianqiang] Yuhuangding Hosp, Dept Orthoped, Yantai, Shandong, Peoples R China. [Wang, Xin] Yuhuangding Hosp, Yantai, Shandong, Peoples R China. [Wood, Kirkham B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA USA. RP Ni, JQ (reprint author), Yuhuangding Hosp, Dept Orthoped, Yantai, Shandong, Peoples R China. NR 4 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 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JUN 1 PY 2015 VL 40 IS 11 BP 863 EP 863 DI 10.1097/BRS.0000000000000907 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CJ3IV UT WOS:000355377500024 PM 25816138 ER PT J AU Smith, EE Schwamm, LH AF Smith, Eric E. Schwamm, Lee H. TI Endovascular Clot Retrieval Therapy Implications for the Organization of Stroke Systems of Care in North America SO STROKE LA English DT Article DE quality improvement; stroke ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; CLINICAL-OUTCOMES; UNITED-STATES; GUIDELINES; TRENDS; CENTERS; ACCESS; TRIAL; TIMES AB Endovascular acute ischemic stroke therapy is now proven by randomized controlled trials to produce large, clinically meaningful benefits. In response, stroke systems of care must change to increase timely and equitable access to this therapy. In this review, we provide a North American perspective on implications for stroke systems, focusing on the United States and Canada, accompanied by initial recommendations for changes. Most urgently, every community must create access to a hospital that can safely and quickly provide intravenous tissue-type plasminogen activator and immediately transfer appropriate patients onward to a more capable center as required. Safe and effective therapy in the community setting will be ensured by certification programs, performance measurement, and data entry into registries. C1 [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 2T9, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 2T9, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. RP Smith, EE (reprint author), Univ Calgary, Foothills Hosp, Dept Clin Neurosci, 1403 29 St NW, Calgary, AB T2N 2T9, Canada. EM eesmith@ucalgary.ca FU Genentech FX Dr Smith is a member of the Get With The Guidelines (GWTG) Steering Committee, AHA Scientific Oversight Committee and co-Chair of the Canadian Stroke Best Practice Recommendations. Dr Schwamm is chair of the GWTG Stroke Clinical Workgroup, PI of the National Institutes of Health and Genentech-funded MR WITNESS phase 2 safety trial of extended window alteplase, a member of the DIAS-3 and 4 international steering committee (Lundbeck), the Data Safety Monitoring Board of the Penumbra 3D Separator trial (Penumbra), and a stroke systems consultant to the Massachusetts Department of Public Health. NR 25 TC 19 Z9 20 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUN PY 2015 VL 46 IS 6 BP 1462 EP + DI 10.1161/STROKEAHA.115.008385 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CI7KI UT WOS:000354941800022 PM 25944330 ER PT J AU Rutten-Jacobs, LCA Traylor, M Adib-Samii, P Thijs, V Sudlow, C Rothwell, PM Boncoraglio, G Dichgans, M Bevan, S Meschia, J Levi, C Rost, NS Rosand, J Hassan, A Markus, HS AF Rutten-Jacobs, Loes C. A. Traylor, Matthew Adib-Samii, Poneh Thijs, Vincent Sudlow, Cathie Rothwell, Peter M. Boncoraglio, Giorgio Dichgans, Martin Bevan, Steve Meschia, James Levi, Christopher Rost, Natalia S. Rosand, Jonathan Hassan, Ahamad Markus, Hugh S. TI Common NOTCH3 Variants and Cerebral Small-Vessel Disease SO STROKE LA English DT Article DE CADASIL; cerebral small vessel diseases; genetic association studies; stroke, lacunar ID MATTER HYPERINTENSITY VOLUME; GENETIC-VARIATION; LACUNAR STROKE; ASSOCIATION; LEUKOARAIOSIS; CADASIL; LINKAGE AB Background and Purpose-The most common monogenic cause of cerebral small-vessel disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH3 gene mutations. It has been hypothesized that more common variants in NOTCH3 may also contribute to the risk of sporadic small-vessel disease. Previously, 4 common variants (rs10404382, rs1043994, rs10423702, and rs1043997) were found to be associated with the presence of white matter hyperintensity in hypertensive community-dwelling elderly. Methods-We investigated the association of common single nucleotide polymorphisms (SNPs) in NOTCH3 in 1350 patients with MRI-confirmed lacunar stroke and 7397 controls, by meta-analysis of genome-wide association study data sets. In addition, we investigated the association of common SNPs in NOTCH3 with MRI white matter hyperintensity volumes in 3670 white patients with ischemic stroke. In each analysis, we considered all SNPs within the NOTCH3 gene, and within 50-kb upstream and downstream of the coding region. A total of 381 SNPs from the 1000 genome population with a mean allele frequency >0.01 were included in the analysis. A significance level of P<0.0015 was used, adjusted for the effective number of independent SNPs in the region using the Galwey method. Results-We found no association of any common variants in NOTCH3 (including rs10404382, rs1043994, rs10423702, and rs1043997) with lacunar stroke or white matter hyperintensity volume. We repeated our analysis stratified for hypertension but again found no association. Conclusions-Our study does not support a role for common NOTCH3 variation in the risk of sporadic small-vessel disease. C1 [Rutten-Jacobs, Loes C. A.; Traylor, Matthew; Bevan, Steve; Markus, Hugh S.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0QQ, England. [Adib-Samii, Poneh] St Georges Univ London, Dept Clin Neurosci, Stroke & Dementia Res Ctr, London, England. [Thijs, Vincent] KULeuven, Dept Expt Neurol, Leuven, Belgium. [Thijs, Vincent] Katholieke Univ Leuven, Leuven Res Inst Neurosci & Dis, Leuven, Belgium. [Thijs, Vincent] VIB, Vesalius Res Ctr, Neurobiol Lab, Leuven, Belgium. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Neuroimaging Sci, Edinburgh, Midlothian, Scotland. [Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Rothwell, Peter M.] Univ Oxford, Nuffield Dept Neurosci, Stroke Prevent Res Unit, Oxford, England. [Boncoraglio, Giorgio] Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy. [Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Meschia, James] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Levi, Christopher] Univ Newcastle, Hunter Med Res Inst, Dept Neurol, Ctr Clin Epidemiol & Biostat, Callaghan, NSW 2308, Australia. [Levi, Christopher] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Rost, Natalia S.; Rosand, Jonathan] Ctr Human Genet Res, Dept Neurol, Boston, MA USA. [Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hassan, Ahamad] Leeds Teaching Hosp NHS Trust, Leeds Gen Infirm, Dept Neurol, Leeds, W Yorkshire, England. RP Rutten-Jacobs, LCA (reprint author), Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0QQ, England. EM LR406@medschl.cam.ac.uk RI Thijs, Vincent/C-3647-2009; Boncoraglio, Giorgio/B-8647-2011; OI Thijs, Vincent/0000-0002-6614-8417; Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Rutten-Jacobs, Loes/0000-0003-3223-885X FU Wellcome Trust [WT072952]; Stroke Association [TSA 2010/01]; Stroke Association Grant [TSA 2013/01]; Massachusetts General Hospital-Deane Institute for the Integrative Study of Atrial Fibrillation and Stroke; National Institute of Neurological Disorders and Stroke [U01 NS069208, R01 NS082285-01]; Stroke Association/British Heart Foundation [TSA BHF 2010/01]; Medical Research Council (United Kingdom); National Institute for Health Research Cambridge University Hospitals Comprehensive Biomedical Research Centre; National Institute for Health Research Senior Investigator award; Clinical Investigator Grant from the scientific research fund; Fonds Wetenschappelijk Onderzoek Flanders FX Collection of the UK Young Lacunar Stroke DNA Study (DNA lacunar) was primarily supported by the Wellcome Trust (WT072952) with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA lacunar samples, and Dr Traylor, was supported by a Stroke Association Grant (TSA 2013/01). Funding for the genotyping at Massachusetts General Hospital was provided by the Massachusetts General Hospital-Deane Institute for the Integrative Study of Atrial Fibrillation and Stroke and the National Institute of Neurological Disorders and Stroke (U01 NS069208). Dr Rutten-Jacobs was supported by a project grant from the Stroke Association/British Heart Foundation grant (TSA BHF 2010/01). Dr Adib-Samii was supported by a Medical Research Council (United Kingdom) training fellowship. Drs Markus and Bevan were supported by the National Institute for Health Research Cambridge University Hospitals Comprehensive Biomedical Research Centre. Dr Markus was supported by a National Institute for Health Research Senior Investigator award. Dr Thijs was supported by a Clinical Investigator Grant from the scientific research fund, Fonds Wetenschappelijk Onderzoek Flanders. Dr Rost was supported by a National Institute of Neurological Disorders and Stroke grant (R01 NS082285-01). The sponsors of the study had no role in the study design, data collection, data analysis, interpretation, writing of the article, or the decision to submit the article for publication. NR 19 TC 3 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUN PY 2015 VL 46 IS 6 BP 1482 EP + DI 10.1161/STROKEAHA.114.008540 PG 24 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CI7KI UT WOS:000354941800025 PM 25953367 ER PT J AU Wayangankar, SA Kennedy, KF Aronow, HD Rundback, J Tafur, A Drachman, D Patel, B Sivaram, CA Latif, F AF Wayangankar, Siddharth A. Kennedy, Kevin F. Aronow, Herbert D. Rundback, John Tafur, Alfonso Drachman, Douglas Patel, Bhavin Sivaram, Chittur A. Latif, Faisal TI Racial/Ethnic Variation in Carotid Artery Revascularization Utilization and Outcomes Analysis From the National Cardiovascular Data Registry SO STROKE LA English DT Article DE endarterectomy, carotid; stroke ID CASCADE RANDOMIZED-TRIAL; QUALITY IMPROVEMENT PROGRAM; ACUTE MYOCARDIAL-INFARCTION; BYPASS SURGERY ANALYSIS; VEIN GRAFT DISEASE; ATRIAL-FIBRILLATION; ETHNIC DISPARITIES; PREDICTING STROKE; VASCULAR-DISEASE; STATIN THERAPY AB Background and Purpose-It is not known whether racial or ethnic disparities observed with other revascularization procedures are also seen with carotid artery stenting (CAS) and endarterectomy (CEA). Methods-We compared the utilization and outcomes of CAS and CEA across racial/ethnic groups within the CARE Registry between May 2007 and December 2012. Results-Between 2007 and 2012, of the 13 129 patients who underwent CAS, majority were non-Hispanic whites (89.3%), followed by blacks (4.4%), Hispanics (4.3%), and other groups (2.0%). A similar distribution was observed among the 10 953 patients undergoing CEA (non-Hispanic whites, 92.6%; blacks, 3.5%; Hispanics, 2.8%; and other groups, 1.1%). During this time period, a trend toward proportionate increase in CAS utilization was observed in non-Hispanic whites and other groups, whereas the opposite was observed among Hispanics and blacks. This trend persisted even when hospitals performing both CAS and CEA were exclusively analyzed. Adherence to antiplatelet and statin therapy was significantly lower among blacks post CEA. In-hospital major adverse cardiac and cerebrovascular events remained comparable across groups post CAS and CEA. At 30 days, the incidence of stroke (7.2%) and major adverse cardiac and cerebrovascular events (8.8%) was higher among blacks post CEA (P<0.05), after risk adjustment. Conclusion-During the study period, utilization of CAS and CEA was highest among non-Hispanic whites. There was a trend toward increased CAS utilization over time among non-Hispanic whites and other groups, and a trend toward increased CEA utilization among Hispanics and blacks. In-hospital major adverse cardiac and cerebrovascular events remained comparable between groups, whereas 30-day major adverse cardiac and cerebrovascular events were significantly higher in blacks. C1 [Wayangankar, Siddharth A.] Cleveland Clin Fdn, Cleveland, OH USA. [Kennedy, Kevin F.] St Lukes Hosp, Mid Amer Heart & Vasc Inst, Kansas City, MO USA. [Aronow, Herbert D.] Michigan Heart & Vasc Inst, Ypsilanti, MI USA. [Rundback, John] Holy Name Med Ctr, Teaneck, NJ USA. [Tafur, Alfonso; Patel, Bhavin; Sivaram, Chittur A.; Latif, Faisal] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Tafur, Alfonso; Patel, Bhavin; Sivaram, Chittur A.; Latif, Faisal] Vet Affairs Med Ctr, Boston, MA USA. [Drachman, Douglas] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Latif, F (reprint author), OUHSC, Dept Med, Cardiovasc Dis Sect, 920 Stanton L Young Blvd,POB 26901,WP3010, Oklahoma City, OK 73104 USA. EM faisal-latif@ouhsc.edu FU American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR) FX This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR). NR 35 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 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUN PY 2015 VL 46 IS 6 BP 1525 EP + DI 10.1161/STROKEAHA.115.009013 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CI7KI UT WOS:000354941800032 PM 25953368 ER PT J AU Ernst, M Yoo, AJ Kriston, L Schonfeld, MH Vettorazzi, E Fiehler, J AF Ernst, Marielle Yoo, Albert J. Kriston, Levente Schoenfeld, Michael H. Vettorazzi, Eik Fiehler, Jens TI Is Visual Evaluation of Aneurysm Coiling a Reliable Study End Point? Systematic Review and Meta-Analysis SO STROKE LA English DT Article DE intracranial aneurysm; meta-analysis; reliability of results ID TIME-OF-FLIGHT; DIGITAL-SUBTRACTION-ANGIOGRAPHY; COILED INTRACRANIAL ANEURYSMS; ENHANCED MR-ANGIOGRAPHY; MAGNETIC-RESONANCE ANGIOGRAPHY; GUGLIELMI DETACHABLE COILS; IMAGING FOLLOW-UP; BARE PLATINUM COILS; ENDOVASCULAR TREATMENT; CEREBRAL ANEURYSMS AB Background and Purpose-Angiographic occlusion as a surrogate marker of satisfactory aneurysm treatment is commonly used in clinical trials although some pitfalls have to be considered. To investigate the inter-rater reliability of visual rating of aneurysm occlusion as study end point, we performed a systematic review and meta-analysis. Methods-Electronic databases (MEDLINE, EMBASE, PubMed, and the Cochrane Library) were searched up to June 2014. Assessment of risk for bias was based on the Quality Appraisal Tool for Studies of Diagnostic Reliability and the Guidelines for Reporting Reliability and Agreement studies. Inter-rater reliability estimates were pooled across studies using meta-analysis, and the influence of several factors (eg, imaging methods, grading scales, and occlusion rate) was tested with meta-regression. Results-From 1193 titles, 644 abstracts and 87 full-text versions were reviewed. Twenty-six articles met the inclusion criteria and provided 77 reliability estimates. Twenty-one different rating scales were used, and statistical analysis varied. Mean inter-rater agreement of the pooled studies was substantial (kappa=0.65; 95% confidence interval, 0.60-0.69). Reliability varied significantly as a function of imaging methods, grading scales, occlusion rates, and their interaction. Observer agreement substantially increased with increasing occlusion rate in digital subtraction angiography but not in MR angiography. Reliability was higher in studies using 2- or 3-value grading scales than in studies with 4-value grading scales. Conclusions-There is significant heterogeneity between studies evaluating the reliability of visual evaluation of aneurysm coiling. On the basis of our analysis, we found that the combination of magnetic resonance angiography, 3-value grading scale, and 2 trained raters seems most promising for usage as surrogate study end points. C1 [Ernst, Marielle; Schoenfeld, Michael H.; Fiehler, Jens] Univ Med Ctr Hamburg Eppendorf, Dept Diagnost & Intervent Neuroradiol, D-20246 Hamburg, Germany. [Kriston, Levente] Univ Med Ctr Hamburg Eppendorf, Dept Med Psychol, D-20246 Hamburg, Germany. [Vettorazzi, Eik] Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, D-20246 Hamburg, Germany. [Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Ernst, M (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Diagnost & Intervent Neuroradiol, Haus Ost 22,O 22,Martinistr 52, D-20246 Hamburg, Germany. EM m.ernst@uke.de RI Kriston, Levente/D-1713-2013; OI Kriston, Levente/0000-0003-0748-264X; Vettorazzi, Eik/0000-0002-3737-6402 FU Microvention, Inc. FX Dr Fiehler consults for Company Microvention, Stryker, Codman and is speaker for Covidien. Dr Yoo has received research funding from Microvention, Inc. The other authors report no conflicts. NR 51 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUN PY 2015 VL 46 IS 6 BP 1574 EP + DI 10.1161/STROKEAHA.114.008513 PG 16 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CI7KI UT WOS:000354941800039 PM 25944331 ER PT J AU Yan, P Zhu, A Liao, F Xiao, QL Kraft, AW Gonzales, E Perez, R Greenberg, SM Holtzman, DM Lee, JM AF Yan, Ping Zhu, Alec Liao, Fan Xiao, Qingli Kraft, Andrew W. Gonzales, Ernie Perez, Ron Greenberg, Steven M. Holtzman, David M. Lee, Jin-Moo TI Minocycline Reduces Spontaneous Hemorrhage in Mouse Models of Cerebral Amyloid Angiopathy SO STROKE LA English DT Article DE apolipoproteins E; cerebral amyloid angiopathy; cerebral hemorrhage; gliosis; matrix metalloproteinase-9; minocycline ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MICE; A-BETA; MICROGLIAL ACTIVATION; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; MATRIX METALLOPROTEINASES; INTRACEREBRAL HEMORRHAGE; COGNITIVE IMPAIRMENT; PARKINSONS-DISEASE AB Background and Purpose-Cerebral amyloid angiopathy (CAA) is a common cause of recurrent intracerebral hemorrhage in the elderly. Previous studies have shown that CAA induces inflammation and expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (gelatinases) in amyloid-laden vessels. Here, we inhibited both using minocycline in CAA mouse models to determine whether spontaneous intracerebral hemorrhage could be reduced. Methods-Tg2576 (n=16) and 5xFAD/ApoE4 knockin mice (n=16), aged 17 and 12 months, respectively, were treated with minocycline (50 mg/kg, IP) or saline every other day for 2 months. Brains were extracted and stained with X-34 (to quantify amyloid), Perls' blue (to quantify hemorrhage), and immunostained to examined beta-amyloid peptide load, gliosis (glial fibrillary acidic protein [GFAP], Iba-1), and vascular markers of blood-brain barrier integrity (zonula occludins-1 [ZO-1] and collagen IV). Brain extracts were used to quantify mRNA for a variety of inflammatory genes. Results-Minocycline treatment significantly reduced hemorrhage frequency in the brains of Tg2576 and 5xFAD/ApoE4 mice relative to the saline-treated mice, without affecting CAA load. Gliosis (GFAP and Iba-1 immunostaining), gelatinase activity, and expression of a variety of inflammatory genes (matrix metalloproteinase-9, NOX4, CD45, S-100b, and Iba-1) were also significantly reduced. Higher levels of microvascular tight junction and basal lamina proteins were found in the brains of minocycline-treated Tg2576 mice relative to saline-treated controls. Conclusions-Minocycline reduced gliosis, inflammatory gene expression, gelatinase activity, and spontaneous hemorrhage in 2 different mouse models of CAA, supporting the importance of matrix metalloproteinase-related and inflammatory pathways in intracerebral hemorrhage pathogenesis. As a Food and Drug Administration-approved drug, minocycline might be considered for clinical trials to test efficacy in preventing CAA-related intracerebral hemorrhage. C1 [Yan, Ping; Zhu, Alec; Liao, Fan; Xiao, Qingli; Kraft, Andrew W.; Gonzales, Ernie; Perez, Ron; Holtzman, David M.; Lee, Jin-Moo] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, Dept Neurol, St Louis, MO 63110 USA. [Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Philip Kistler Stroke Res Ctr, Boston, MA USA. RP Lee, JM (reprint author), Washington Univ, Sch Med, Hope Ctr Neurol Disorders, Dept Neurol, 660 S Euclid Ave,Campus Box 8111, St Louis, MO 63110 USA. EM leejm@neuro.wustl.edu OI Liao, Fan/0000-0003-4874-460X FU National Institutes of Health (NIH) [R01 NS084028, R21 NS082529]; Argo E. & Edna Edwards Landau Fund; Lillian Straus Fund; Cure Alzheimer's fund; JPB Foundation; NIH [R01 NS090934] FX This work was supported by National Institutes of Health (NIH) R01 NS084028, R21 NS082529, the Argo E. & Edna Edwards Landau Fund, and the Lillian Straus Fund (to Dr Lee), a grant from the Cure Alzheimer's fund, the JPB Foundation and NIH R01 NS090934 (to Dr Holtzman). NR 59 TC 5 Z9 5 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUN PY 2015 VL 46 IS 6 BP 1633 EP + DI 10.1161/STROKEAHA.115.008582 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CI7KI UT WOS:000354941800048 PM 25944329 ER PT J AU Min, CH Zhu, XP Grogg, K El Fakhri, G Winey, B Paganetti, H AF Min, Chul Hee Zhu, Xuping Grogg, Kira El Fakhri, Georges Winey, Brian Paganetti, Harald TI A Recommendation on How to Analyze In-Room PET for In Vivo Proton Range Verification Using a Distal PET Surface Method SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE proton therapy; in-room PET; in vivo range; distal PET surface; Monte Carlo simulation ID POSITRON-EMISSION-TOMOGRAPHY; RADIATION-THERAPY; BEAM THERAPY; IMPLEMENTATION AB We describe the rationale and implementation of a method for analyzing in-room positron emission tomography (PET) data to verify the proton beam range. The method is based on analyzing distal PET surfaces after passive scattering proton beam delivery. Typically in vivo range verification is done by comparing measured and predicted PET distribution for a single activity level at a selected activity line along the beam passage. In the method presented here, we suggest using a middle point method based on dual PET activity levels to minimize the uncertainty due to local variations in the PET activity. Furthermore, we introduce 2-dimensional (2D) PET activity level surfaces based on 3-dimensional maps of the PET activities along the beam passage. This allows determining not only average range differences but also range difference distributions as well as root mean square deviations (RMSDs) for a more comprehensive range analysis. The method is demonstrated using data from 8 patients who were scanned with an in-room PET scanner. For each of the 8 patients, the average range difference was less than 5 mm and the RMSD was 4 to 11 mm between the measured and simulated PET activity level surfaces for single-field treatments. An ongoing protocol at our institution allows the use of a single field for patients being imaged for the PET range verification study at 1 fraction during their treatment course. Visualizing the range difference distributions using the PET surfaces offers a convenient visual verification of range uncertainties in 2D. Using the distal activity level surfaces of simulated and measured PET distributions at the middle of 25% and 50% activity level is a robust method for in vivo range verification. C1 [Min, Chul Hee; Winey, Brian; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Min, Chul Hee; Zhu, Xuping; Grogg, Kira; El Fakhri, Georges; Winey, Brian; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Min, Chul Hee] Yonsei Univ, Dept Radiol Sci, Wonju, Kangwon, South Korea. [Min, Chul Hee] Yonsei Univ, Res Inst Hlth Sci, Wonju, Kangwon, South Korea. [Zhu, Xuping; Grogg, Kira; El Fakhri, Georges] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@partners.org FU NIH [P01CA21239, R21CA153455, R21EB12823] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by NIH grants P01CA21239, R21CA153455, and R21EB12823. NR 18 TC 1 Z9 1 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-0346 EI 1533-0338 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD JUN PY 2015 VL 14 IS 3 BP 320 EP 325 DI 10.1177/1533034614547457 PG 6 WC Oncology SC Oncology GA CJ1VL UT WOS:000355272600008 PM 25246517 ER PT J AU Godwin, BD Simianu, VV Drake, FT Dighe, M Flum, D Bhargava, P AF Godwin, Benjamin David Simianu, Vlad Valentin Drake, Frederick Thurston Dighe, Manjiri Flum, David Bhargava, Puneet TI Is There a Need to Standardize Reporting Terminology in Appendicitis? SO ULTRASOUND QUARTERLY LA English DT Editorial Material ID LOWER QUADRANT PAIN; SUSPECTED APPENDICITIS; CLINICAL-OUTCOMES; RADIOLOGY; DIAGNOSIS; IMPROVE; SONOGRAPHY; CLARITY; IMPACT; SCORE AB While computed tomography (CT) remains the most accurate and widely used modality for appendicitis imaging, ultrasound has developed its own niche role, especially in the pediatric population and in premenopausal women. Ultrasound is commonly used as the initial imaging test when available, with indeterminate or clinically equivocal cases proceeding to CT. To avoid the radiation and time and cost of CT, ultrasound needs to be improved. While previous studies have focused on improving the diagnostic accuracy of ultrasound through better patient selection and technique, relatively little attention has been brought to the ultrasound report, which often serves as the sole mode of communication between the radiologist and the clinician. Standardization of reporting and terminology has been found to improve patient outcomes and management in breast imaging. A standardized report for appendicitis has the potential to decrease confusion and increase accuracy. A potential format could include a standardized list of the presence or absence of imaging findings associated with appendicitis, with a final summary or score indicating the likelihood of appendicitis being present. Aggregation of data over time through use of a common format could help guide radiologist recommendations based on which imaging findings are present. Overall, a standardized report could help increase the value of ultrasound, leading to improved radiologist-clinician communication, better patient outcomes, and decreased costs. C1 [Godwin, Benjamin David; Dighe, Manjiri] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Simianu, Vlad Valentin; Drake, Frederick Thurston; Flum, David] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. RP Godwin, BD (reprint author), 1959 NE Pacific St,RR 215,UW Mailbox 357115, Seattle, WA 98195 USA. EM benjag@uw.edu FU NIDDK NIH HHS [T32 DK070555] NR 22 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 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD JUN PY 2015 VL 31 IS 2 BP 92 EP 94 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ0CS UT WOS:000355140900003 PM 26002523 ER PT J AU Wiecek, E Lashkari, K Dakin, SC Bex, P AF Wiecek, Emily Lashkari, Kameran Dakin, Steven C. Bex, Peter TI Metamorphopsia and interocular suppression in monocular and binocular maculopathy SO ACTA OPHTHALMOLOGICA LA English DT Letter ID SURGERY; PHP C1 [Wiecek, Emily; Lashkari, Kameran; Bex, Peter] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Wiecek, Emily; Lashkari, Kameran; Bex, Peter] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Wiecek, Emily; Dakin, Steven C.] UCL, Inst Ophthalmol, London, England. [Dakin, Steven C.] Moorfields Eye Hosp NHS Fdn Trust, NIHR, Biomed Res Ctr, London, England. [Dakin, Steven C.] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1, New Zealand. [Bex, Peter] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. RP Wiecek, E (reprint author), 125 Nightingale,360 Huntington Ave, Boston, MA 02115 USA. EM emilywiecek@gmail.com OI Dakin, Steven/0000-0002-3548-9104 FU NEI NIH HHS [R01 EY019281, R01 EY021553] NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-375X EI 1755-3768 J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD JUN PY 2015 VL 93 IS 4 BP E318 EP E320 DI 10.1111/aos.12559 PG 4 WC Ophthalmology SC Ophthalmology GA CI3GH UT WOS:000354635300021 PM 25271099 ER PT J AU Nardi, V Pulluqi, O Abramson, JS Dal Cin, P Hasserjian, RP AF Nardi, Valentina Pulluqi, Olja Abramson, Jeremy S. Dal Cin, Paola Hasserjian, Robert P. TI Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; RISK-FACTORS; INVOLVEMENT; IMPACT; CLASSIFICATION; ABERRATIONS; PROGNOSIS; RITUXIMAB; BIOPSY AB Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma. Am. J. Hematol. 90:529-533, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Nardi, Valentina; Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nardi, Valentina; Abramson, Jeremy S.; Dal Cin, Paola; Hasserjian, Robert P.] Harvard Univ, Sch Med, Boston, MA USA. [Pulluqi, Olja; Dal Cin, Paola] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 224, Boston, MA 02114 USA. EM rhasserjian@mgh.harvard.edu NR 23 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2015 VL 90 IS 6 BP 529 EP 533 DI 10.1002/ajh.24008 PG 5 WC Hematology SC Hematology GA CI5OK UT WOS:000354806500019 PM 25776302 ER PT J AU Leblebjian, H Noonan, K Paba-Prada, C Treon, SP Castillo, JJ Ghobrial, IM AF Leblebjian, Houry Noonan, Kimberly Paba-Prada, Claudia Treon, Steven P. Castillo, Jorge J. Ghobrial, Irene M. TI Cyclophosphamide, bortezomib, and dexamethasone combination in waldenstrom macroglobulinemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID DIAGNOSED MULTIPLE-MYELOMA; PHASE-II TRIAL; INHIBITOR EVEROLIMUS; INDUCTION; CYBORD C1 [Leblebjian, Houry; Noonan, Kimberly; Paba-Prada, Claudia; Treon, Steven P.; Castillo, Jorge J.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM JorgeJ_castillo@dfci.harvard.edu; irene_ghobrial@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 8 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2015 VL 90 IS 6 BP E122 EP E123 DI 10.1002/ajh.23985 PG 2 WC Hematology SC Hematology GA CI5OK UT WOS:000354806500004 PM 25703132 ER PT J AU Mahal, BA Cooperberg, MR Aizer, AA Ziehr, DR Hyatt, AS Choueiri, TK Hu, JC Sweeney, CJ Beard, CJ D'Amico, AV Martin, NE Orio, PF Trinh, QD Nguyen, PL AF Mahal, Brandon A. Cooperberg, Matthew R. Aizer, Ayal A. Ziehr, David R. Hyatt, Andrew S. Choueiri, Toni K. Hu, Jim C. Sweeney, Christopher J. Beard, Clair J. D'Amico, Anthony V. Martin, Neil E. Orio, Peter F., III Quoc-Dien Trinh Nguyen, Paul L. TI Who Bears the Greatest Burden of Aggressive Treatment of Indolent Prostate Cancer? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Health policy; Low-risk; Overtreatment; Population health; Prostate-specific antigen; Prostatic neoplasms ID ACTIVE SURVEILLANCE; INITIAL TREATMENT; RISK-ASSESSMENT; TIME TRENDS; HEALTH-CARE; MEN; MANAGEMENT; OUTCOMES; RACE AB PURPOSE: The long-term prostate cancer-specific survival for patients initially managed with active surveillance for low-risk prostate cancer ranges from 97% to 100%. We characterized factors that are associated with aggressive treatment with radical prostatectomy or radiation for indolent prostate cancer (defined as screening-detected, low-risk disease). METHODS: The Surveillance, Epidemiology, and End Results Program was used to extract a cohort of 39,803 men diagnosed with prostate-specific antigenedetected, low-risk prostate cancer (clinical category T1c, Gleason score <= 6, and prostate-specific antigen <10) from 2004 to 2010. After socioeconomic profiles were generated from county-linked education and income data, multivariable logistic regression was used to determine whether there were any factors associated with high rates of aggressive treatment. RESULTS: The rate of aggressive treatment among all men with indolent prostate cancer was 64.3%. Greater rates of aggressive treatment were experienced by men with high socioeconomic status, Caucasian men, and married men (P < .001 for all cases). The increased adjusted odds for receipt of aggressive therapy were 1.25 (95% confidence interval [CI], 1.17-1.32; P < .001), 1.26 (95% CI, 1.21-1.32; P < .001), and 1.88 (95% CI, 1.80-1.97; P < .001) for men with high socioeconomic status, Caucasian men, and married men, respectively, compared with men with low socioeconomic status, non-Caucasian men, and unmarried men, respectively. CONCLUSIONS: Although men with high socioeconomic status, Caucasian men, and married men often receive the highest quality health care and have the best outcomes for many cancers, it seems that they are most at risk for the avoidable potential harms of aggressive treatment of indolent prostate cancer. Future policy should encourage more stringent guidelines for deferred treatment and culturally and sociodemo-graphically competent counseling of active surveillance. (C) 2015 Elsevier Inc. All rights reserved. C1 [Mahal, Brandon A.; Ziehr, David R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cooperberg, Matthew R.] Univ Calif San Francisco, Dept Urol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Cooperberg, Matthew R.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Epidemiol & Publ Hlth, San Francisco, CA USA. [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA USA. [Hyatt, Andrew S.; Beard, Clair J.; D'Amico, Anthony V.; Martin, Neil E.; Orio, Peter F., III; Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Hu, Jim C.] Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU David and Cynthia Chapin; Prostate Cancer Foundation; Fitz's Cancer Warriors; Hugh Simons in honor of Frank and Anne Simons 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 31 TC 6 Z9 6 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUN PY 2015 VL 128 IS 6 BP 609 EP 616 DI 10.1016/j.amjmed.2014.12.030 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CI6NR UT WOS:000354877200020 PM 25644324 ER PT J AU Luce, JC Mix, J Mathews, K Goldstein, R Niewczyk, P DiVita, MA Gerrard, P Sheridan, RL Ryan, CM Kowalske, K Zafonte, R Schneider, JC AF Luce, John C. Mix, Jacqueline Mathews, Katie Goldstein, Richard Niewczyk, Paulette DiVita, Margaret A. Gerrard, Paul Sheridan, Robert L. Ryan, Colleen M. Kowalske, Karen Zafonte, Ross Schneider, Jeffrey C. TI Inpatient Rehabilitation Experience of Children with Burn Injuries: A 10-yr Review of the Uniform Data System for Medical Rehabilitation SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Pediatrics; Burns; Rehabilitation; Outcome Measures ID FUNCTIONAL INDEPENDENCE MEASURE; WEEFIM; POPULATION; INSTRUMENT; ETIOLOGY; OUTCOMES AB Objective This study aimed to describe the pediatric burn inpatient rehabilitation population and short-term functional outcomes using the Uniform Data System for Medical Rehabilitation. Design This is a secondary analysis of data from the Uniform Data System for Medical Rehabilitation database between 2002 and 2011 included children younger than 18 yrs at time of admission to inpatient rehabilitation with primary diagnosis of burn injury. Demographic, medical, and functional data were evaluated. Function was assessed with the Functional Independence Measure or the WeeFIM. Results A total of 509 children were included, of whom 124 were evaluated with Functional Independence Measure and 385 with WeeFIM. The mean age of the population was 8.6 yrs and most were boys (72%). The mean length of stay for the population was 35 days. Functional status improved significantly from admission to discharge; most gains were in the motor subscore. Most patients were discharged home (95%). Of those discharged home, most (96%) went home with family. Conclusions Children receiving multidisciplinary inpatient rehabilitation make significant functional improvements in total functional scores and in both motor and cognitive subscores. Most patients are discharged home with family. This study advances understanding of pediatric burn post-acute care outcomes. C1 [Luce, John C.; Mathews, Katie; Goldstein, Richard; Gerrard, Paul; Zafonte, Ross; Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Luce, John C.; Gerrard, Paul; Ryan, Colleen M.; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Boston, MA USA. [Mix, Jacqueline; Niewczyk, Paulette; DiVita, Margaret A.] SUNY Buffalo, Uniform Data Syst Med Rehabil, Buffalo, NY 14260 USA. [Niewczyk, Paulette] Daeman Coll, Dept Hlth Care Studies, Amherst, NY USA. [DiVita, Margaret A.] SUNY Coll Cortland, Dept Hlth, Cortland, NY USA. [Gerrard, Paul] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Gerrard, Paul] Newton Wellesley Hosp, Spine Ctr, Newton, MA USA. [Sheridan, Robert L.; Ryan, Colleen M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sheridan, Robert L.; Ryan, Colleen M.; Schneider, Jeffrey C.] Shriners Hosp Children, Boston, MA USA. [Kowalske, Karen] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. RP Schneider, JC (reprint author), Spaulding Rehabil Hosp, 300 First Ave, Charlestown, MA 02129 USA. FU Department of Education, NIDRR [H133A120034] FX The contents of this manuscript were developed in part under a grant from the Department of Education, NIDRR grant number H133A120034. However, the contents do not necessarily represent the policy of the Department of Education, and endorsement by the Federal Government should not be assumed. MAD is an employee of Uniform Data Systems for Medical Rehabilitation and her job responsibilities include research. Presented as a poster presentation at the American Burn Association's 46th Annual Meeting in Boston, MA, on March 27, 2014. NR 28 TC 3 Z9 3 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JUN PY 2015 VL 94 IS 6 BP 436 EP 443 DI 10.1097/PHM.0000000000000195 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CI6ON UT WOS:000354879900009 PM 25251252 ER PT J AU Rosow, C AF Rosow, Carl TI Portable Infrared Pupillometry: Ready for Prime Time? SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID PHARMACOKINETICS; PHARMACODYNAMICS C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Rosow, C (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM crosow@partners.org NR 5 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2015 VL 120 IS 6 BP 1184 EP 1185 DI 10.1213/ANE.0000000000000724 PG 2 WC Anesthesiology SC Anesthesiology GA CI6JD UT WOS:000354864100005 PM 25988627 ER PT J AU Lesicka, A Feinman, JW Thiele, K Andrawes, MN AF Lesicka, Agnieszka Feinman, Jared W. Thiele, Karl Andrawes, Michael N. TI Echocardiographic Artifact Induced by HeartWare Left Ventricular Assist Device SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID IMPLANTATION; SUPPORT C1 [Lesicka, Agnieszka; Andrawes, Michael N.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Feinman, Jared W.] Hosp Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Thiele, Karl] Philips Med Syst, Andover, MA USA. RP Lesicka, A (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, 55 Fruit St,GRB 444, Boston, MA 02114 USA. EM agnes.lesicka@gmail.com NR 7 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2015 VL 120 IS 6 BP 1208 EP 1211 DI 10.1213/ANE.0000000000000664 PG 4 WC Anesthesiology SC Anesthesiology GA CI6JD UT WOS:000354864100010 PM 25988632 ER PT J AU Lovich, MA Pezone, MJ Maslov, MY Murray, MR Wakim, MG Peterfreund, RA AF Lovich, Mark A. Pezone, Matthew J. Maslov, Mikhail Y. Murray, Michael R. Wakim, Matthew G. Peterfreund, Robert A. TI Infusion System Carrier Flow Perturbations and Dead-Volume: Large Effects on Drug Delivery In Vitro and Hemodynamic Responses in a Swine Model SO ANESTHESIA AND ANALGESIA LA English DT Article ID DYNAMICS; IMPACT; RATES; SET AB BACKGROUND: We have previously shown that, at constant carrier flow, drug infusion systems with large dead-volumes (V) slow the time to steady-state drug delivery in vitro and pharmacodynamic effect in vivo compared to those with smaller V. In this study, we tested whether clinically relevant alterations in carrier flow generate perturbations in drug delivery and pharmacodynamic effect, and how these might be magnified when V is large. METHODS: Drug delivery in vitro or mean arterial blood pressure (MAP) and ventricular contractility (max dP/dt) in a swine model were quantified during an infusion of norepinephrine (fixed rate 3 mL/h) with a crystalloid carrier (10 mL/h). The carrier flow was transiently halted for either 10 minutes or 20 minutes and then restarted. In separate experiments, a second drug infusion (50 mL over 10 minutes) was introduced into the same catheter lumen used by a steady-state norepinephrine infusion. The resulting perturbations in drug delivery and biologic effect were compared between drug infusion systems with large and small V. RESULTS: Halting carrier flow immediately decreased drug delivery in vitro, and MAP and max dP/dt. These returned to steady state before restarting carrier flow with the small, but not the large, V. Resuming carrier flow after 10 minutes resulted in a transient increase in drug delivery in vitro and max dP/dt in vivo, which were of longer duration and greater area under the curve (AUC) for larger V. MAP also increased for longer duration for larger V. Resuming the carrier flow after 20 minutes resulted in greater AUCs for drug delivery, MAP, and max dP/dt for the larger V. Adding a second infusion to a steady-state norepinephrine plus carrier flow initially resulted in a drug bolus in vitro and augmented contractility response in vivo, both greater with a larger V. Steady-state drug delivery resumed before the secondary infusion finished. After the end of the secondary infusion drug delivery, MAP and max dP/dt decreased over minutes. Drug delivery and max dP/dt returned to steady state more quickly with the small V. CONCLUSIONS: Stopping and resuming a carrier flow, or introducing a second medication infusion, impacts drug delivery in vitro and biologic response in vivo. Infusion systems with small dead-volumes minimize these perturbations and dampen the resulting hemodynamic instability. Alterations in carrier flow impact drug delivery, resulting in substantial effects on physiologic responses. Therefore, infusion systems for vasoactive drugs should be configured with small V when possible. C1 [Lovich, Mark A.; Pezone, Matthew J.; Maslov, Mikhail Y.; Murray, Michael R.; Wakim, Matthew G.] Steward St Elizabeths Med Ctr, Dept Anesthesiol Pain Med & Crit Care, Brighton, MA 02135 USA. [Peterfreund, Robert A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Lovich, MA (reprint author), Steward St Elizabeths Med Ctr, Dept Anesthesiol Pain Med & Crit Care, 736 Cambridge St,CMP 2, Brighton, MA 02135 USA. EM mark.lovich@steward.org FU Doran International, Toussieu, France; Department of Anesthesiology, Pain Medicine and Critical Care, Steward St. Elizabeth's Medical Center, Boston, MA FX In part by Doran International, Toussieu, France, and in part by the Department of Anesthesiology, Pain Medicine and Critical Care, Steward St. Elizabeth's Medical Center, Boston, MA. NR 15 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2015 VL 120 IS 6 BP 1255 EP 1263 DI 10.1213/ANE.0000000000000654 PG 9 WC Anesthesiology SC Anesthesiology GA CI6JD UT WOS:000354864100015 PM 25811259 ER PT J AU Cheng, KA Kurtis, B Babayeva, S Zhuge, J Tantchou, I Cai, DM Lafaro, RJ Fallon, JT Zhong, MH AF Cheng, Katherine A. Kurtis, Boaz Babayeva, Sabina Zhuge, Jian Tantchou, Irlna Cai, Dongming Lafaro, Rocco J. Fallon, John T. Zhong, Minghao TI Heterogeneity of TERT promoter mutations status in squamous cell carcinomas of different anatomical sites SO ANNALS OF DIAGNOSTIC PATHOLOGY LA English DT Article DE TERT promoter mutations; Squamous cell carcinoma; Heterogeneity ID DISEASE RECURRENCE; MELANOMA; CANCER; COMMON AB Squamous cell carcinoma (SCC) can arise from different anatomical sites including the skin, head and neck, lung, esophagus, genital area, and so on. Despite the same histopathologic features and immunohistochemistry profile, the SCCs of different body sites can show tremendous differences in their presenting symptoms, risk factor associations, natural history, prognosis, and response to treatment. This may reflect the fact that SCCs are heterogenous and likely have unique molecular characteristics at different anatomical sites. Recurrent somatic mutations in the TERT promoter region were first reported in human melanomas. Subsequently, other tumors including cutaneous SCC were found to demonstrate high frequencies of the same mutations. However, the incidences of TERT promoter mutation in noncutaneous SCCs have not been systemically studied. We investigated the TERT promoter mutation status among SCCs from different sites. We collected 84 cases of SCC from the skin (27), head and neck (12), lung (25), and cervix (10), as well as 10 cases of urothelial carcinoma with squamous differentiation (UC-SqD). We found that the frequencies of TERT promoter mutation among SCC of different sits are quite heterogenous: similar to 70% in skin SCC and UC-SqD, 16.67% in head and neck SCC, and 0% in lung and cervix SCC. These results may support the hypothesis of different carcinogenesis mechanisms of SCC in different sites. It also indicates that TERT promoter mutation could be a biomarker for distinguishing skin SCC or UC-SqD vs pulmonary SCC. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cheng, Katherine A.; Kurtis, Boaz; Babayeva, Sabina; Zhuge, Jian; Fallon, John T.; Zhong, Minghao] New York Med Coll, Westchester Med Ctr, Dept Pathol, Valhalla, NY 10595 USA. [Cheng, Katherine A.] New York Med Coll, Westchester Med Ctr, Dept Oncol, Valhalla, NY 10595 USA. [Tantchou, Irlna; Lafaro, Rocco J.] New York Med Coll, Westchester Med Ctr, Dept Surg, Valhalla, NY 10595 USA. [Cai, Dongming] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Cai, Dongming] James J Peters VA Med Ctr, New York, NY USA. RP Zhong, MH (reprint author), New York Med Coll, Westchester Med Ctr, Dept Pathol, 100 Woods Rd, Valhalla, NY 10595 USA. EM ZhongM@WCMC.com FU Pathology Department at Westchester Medical Center/New York Medical College; New York Medical College summer research program FX This study is supported by resident research fund from Pathology Department at Westchester Medical Center/New York Medical College. K.C. was supported by The New York Medical College summer research program. NR 10 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1092-9134 EI 1532-8198 J9 ANN DIAGN PATHOL JI Ann. Diagn. Pathol. PD JUN PY 2015 VL 19 IS 3 BP 146 EP 148 DI 10.1016/j.anndiagpath.2015.03.005 PG 3 WC Pathology SC Pathology GA CI8OT UT WOS:000355032300010 PM 25862495 ER PT J AU Carruthers, MN Topazian, MD Khosroshahi, A Witzig, TE Wallace, ZS Hart, PA Deshpande, V Smyrk, TC Chari, S Stone, JH AF Carruthers, Mollie N. Topazian, Mark D. Khosroshahi, Arezou Witzig, Thomas E. Wallace, Zachary S. Hart, Philip A. Deshpande, Vikram Smyrk, Thomas C. Chari, Suresh Stone, John H. TI Rituximab for IgG4-related disease: a prospective, open-label trial SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article DE B cells; Inflammation; Treatment ID IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; SERUM IGG4 LEVELS; AUTOIMMUNE PANCREATITIS; SYSTEMIC-DISEASE; CLINICAL PROFILE; THERAPY; MULTICENTER; VASCULITIS; G4 AB Objectives To evaluate the efficacy of rituximab (RTX) in IgG4-related disease (IgG4-RD) in an open-label pilot trial. Methods We treated 30 IgG4-RD patients with two doses of RTX (1000 mg each). The participants were either treated with RTX alone (n = 26; 87%) or required to discontinue baseline glucocorticoids (GC) within 2months (n = 4; 13%). Disease activity was measured by the IgG4-RD Responder Index (IgG4-RD RI) and physician's global assessment (PGA). Disease response was defined as the improvement of the IgG4-RD RI by two points. The primary outcome, measured at 6months, was defined as: (1) decline of the IgG4-RD RI 2 points compared with baseline; (2) no disease flares before month 6; and (3) no GC use between months 2 and 6. Complete remission was defined as an IgG4-RD RI score of 0 with no GC use. Results Disease responses occurred in 97% of participants. The baseline IgG4-RD RI and PGA values, 117 and 6322mm, respectively, declined to 1 +/- 2 and 11 +/- 16mm at 6months (both p<0.00001). The primary outcome was achieved by 23 participants (77%). Fourteen (47%) were in complete remission at 6months, and 12 (40%) remained in complete remission at 12 months. Among the 19 with elevated baseline serum IgG4, IgG4 concentrations declined from a mean of 911mg/dL (range 138-4780mg/dL) to 422mg/dL (range 56-2410mg/dL) at month 6 (p<0.05). However, only 8 (42%) of the 19 achieved normal values. Conclusions RTX appears to be an effective treatment for IgG4-RD, even without concomitant GC therapy. Trial registration number ClinicalTrials.gov identifier: NCT01584388. C1 [Carruthers, Mollie N.; Wallace, Zachary S.; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. [Carruthers, Mollie N.; Wallace, Zachary S.; Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. [Topazian, Mark D.; Hart, Philip A.; Chari, Suresh] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Khosroshahi, Arezou] Emory Univ, Sch Med, Dept Med, Div Rheumatol, Atlanta, GA USA. [Witzig, Thomas E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Deshpande, Vikram] Mayo Clin, Dept Pathol, Rochester, MN USA. [Smyrk, Thomas C.] Mayo Clin, Div Hematol, Rochester, MN USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org RI Hart, Phil/A-9842-2016 OI Hart, Phil/0000-0003-4346-6196 FU Genentech FX This study was supported by Genentech. JHS has served as a consultant to Genentech in the area of IgG4-related disease. NR 28 TC 70 Z9 78 U1 2 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2015 VL 74 IS 6 BP 1171 EP 1177 DI 10.1136/annrheumdis-2014-206605 PG 7 WC Rheumatology SC Rheumatology GA CH9QO UT WOS:000354371200033 PM 25667206 ER PT J AU Goodman, JH Prager, J Goldstein, R Freeman, M AF Goodman, Janice H. Prager, Joanna Goldstein, Richard Freeman, Marlene TI Perinatal Dyadic Psychotherapy for postpartum depression: a randomized controlled pilot trial SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Postpartum depression; Intervention; Psychotherapy; Mother-infant relationship; Postpartum anxiety ID MOTHER-INFANT INTERACTIONS; ANTENATAL RISK-FACTORS; POSTNATAL DEPRESSION; MATERNAL DEPRESSION; CHILD-DEVELOPMENT; PSYCHOLOGICAL TREATMENT; AT-RISK; WOMEN; METAANALYSIS; BEHAVIOR AB An integrated approach addressing maternal depression and associated mother-infant relationship dysfunction may improve outcomes. This study tested Perinatal Dyadic Psychotherapy (PDP), a dual-focused mother-infant intervention to prevent/decrease maternal postpartum depression and improve aspects of the mother-infant relationship related to child development. Women recruited from hospital postpartum units were screened using a three-stage process. Forty-two depressed first-time mothers and their 6-week-old infants were enrolled and randomized to receive the PDP intervention or usual care plus depression monitoring by phone. The intervention consisted of eight home-based, nurse-delivered mother-infant sessions consisting of (a) supportive, relationship-based, mother-infant psychotherapy, and (b) a developmentally based infant-oriented component focused on promoting positive mother-infant interactions. Data collected at baseline, post-intervention, and three-month follow-up included measures of maternal depression, anxiety, maternal self-esteem, parenting stress, and mother-infant interaction. Depression and anxiety symptoms and diagnoses decreased significantly, and maternal self-esteem increased significantly across the study time frame with no between-group differences. There were no significant differences between groups on parenting stress or mother-infant interaction at post-intervention and follow-up. No participants developed onset of postpartum depression during the course of the study. PDP holds potential for treating depression in the context of the mother-infant relationship; however, usual care plus depression monitoring showed equal benefit. Further research is needed to explore using low-intensity interventions as a first step in a stepped care approach and to determine what subset of at-risk or depressed postpartum mothers might benefit most from the PDP intervention. C1 [Goodman, Janice H.; Prager, Joanna] MGH Inst Hlth Profess, Sch Nursing, Boston, MA 02129 USA. [Goldstein, Richard] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Freeman, Marlene] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Goodman, JH (reprint author), MGH Inst Hlth Profess, Sch Nursing, 36 1st Ave, Boston, MA 02129 USA. EM jgoodman@mghihp.edu FU Robert Wood Johnson Foundation; National Institute of Child Health and Development [1R21HD065156-01] FX Support for this study was provided by grants to J. Goodman from the Robert Wood Johnson Foundation and from the National Institute of Child Health and Development (1R21HD065156-01). We wish to acknowledge the valuable contributions of our research team: Jennifer Bernard, Laura Betz, Melissa Burnett, Kayse Eichelberger, Mary Ellen Flanagan, Avery Forget, Christine Godbout, Carol Gordon, Deborah Koopman, Francesca Longo, Stephanie Lubin-Levy, Rebecca Petersen, Rachael Phillips, and Gabrielle Santangelo. NR 93 TC 5 Z9 5 U1 9 U2 22 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD JUN PY 2015 VL 18 IS 3 BP 493 EP 506 DI 10.1007/s00737-014-0483-y PG 14 WC Psychiatry SC Psychiatry GA CI4GS UT WOS:000354707100009 PM 25522664 ER PT J AU Vantler, M Jesus, J Leppanen, O Scherner, M Berghausen, EM Mustafov, L Chen, X Kramer, T Zierden, M Gerhardt, M ten Freyhaus, H Blaschke, F Sterner-Kock, A Baldus, S Zhao, JJ Rosenkranz, S AF Vantler, Marius Jesus, Joana Leppaenen, Olli Scherner, Maximilian Berghausen, Eva Maria Mustafov, Lenard Chen, Xin Kramer, Tilmann Zierden, Mario Gerhardt, Maximilian ten Freyhaus, Henrik Blaschke, Florian Sterner-Kock, Anja Baldus, Stephan Zhao, Jean J. Rosenkranz, Stephan TI Class IA Phosphatidylinositol 3-Kinase Isoform p110 alpha Mediates Vascular Remodeling SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE neointima; p110 alpha; p110 delta; phosphatidylinositol 3 '-kinase (PI3K); tyrosine kinase; vascular remodeling; vascular smooth muscle cells ID MUSCLE-CELL PROLIFERATION; DRUG-ELUTING STENT; PHOSPHOINOSITIDE 3-KINASE; SMOOTH-MUSCLE; NEOINTIMA FORMATION; IN-VIVO; MIGRATION; PI3K; MECHANISMS; PATHWAY AB Objective-Neointima formation after vascular injury remains a significant problem in clinical cardiology, and current preventive strategies are suboptimal. Phosphatidylinositol 3'-kinase is a central downstream mediator of growth factor signaling, but the role of phosphatidylinositol 3'-kinase isoforms in vascular remodeling remains elusive. We sought to systematically characterize the precise role of catalytic class IA phosphatidylinositol 3'-kinase isoforms (p110 alpha, p110 beta, p110 delta), which signal downstream of receptor tyrosine kinases, for vascular remodeling in vivo. Approach and Results-Western blot analyses revealed that all 3 isoforms are abundantly expressed in smooth muscle cells. To analyze their significance for receptor tyrosine kinases-dependent cellular responses, we used targeted gene knockdown and isoform-specific small molecule inhibitors of p110 alpha (PIK-75), p110 beta (TGX-221), and p110 delta (IC-87114), respectively. We identified p110 alpha to be crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of rat, murine, and human smooth muscle cells, whereas p110 beta and p110 delta activities were dispensable. Surprisingly, p110 delta exerted noncatalytic functions in smooth muscle cell proliferation, but had no effect on migration. Based on these results, we generated a mouse model of smooth muscle cell-specific p110 alpha deficiency (sm-p110 alpha(-/-)). Targeted deletion of p110 alpha in sm-p110 alpha(-/-) mice blunted growth factor-induced cellular responses and abolished neointima formation after balloon injury of the carotid artery in mice. In contrast, p110 delta deficiency did not affect vascular remodeling in vivo. Conclusions-Receptor tyrosine kinases-induced phosphatidylinositol 3'-kinase signaling via the p110 alpha isoform plays a central role for vascular remodeling in vivo. Thus, p110 alpha represents a selective target for the prevention of neointima formation after vascular injury, whereas p110 beta and p110 delta expression and activity do not play a significant role. C1 [Vantler, Marius; Jesus, Joana; Berghausen, Eva Maria; Mustafov, Lenard; Chen, Xin; Kramer, Tilmann; Zierden, Mario; Gerhardt, Maximilian; ten Freyhaus, Henrik; Baldus, Stephan; Rosenkranz, Stephan] Univ Cologne, Innere Med Klin 3, D-50935 Cologne, Germany. [Vantler, Marius; Jesus, Joana; Berghausen, Eva Maria; Mustafov, Lenard; Chen, Xin; Kramer, Tilmann; Zierden, Mario; Gerhardt, Maximilian; ten Freyhaus, Henrik; Baldus, Stephan; Rosenkranz, Stephan] Univ Cologne, CMMC, D-50935 Cologne, Germany. [Leppaenen, Olli] Uppsala Univ, Cty Council Gavleborg, Ctr R&D, Gavle, Sweden. [Scherner, Maximilian] Univ Cologne, Klin Herz & Thoraxchirurg, D-50935 Cologne, Germany. [ten Freyhaus, Henrik; Baldus, Stephan; Rosenkranz, Stephan] Univ Cologne, CCRC, D-50935 Cologne, Germany. [Blaschke, Florian] Charite, Kardiol Klin, D-13353 Berlin, Germany. [Sterner-Kock, Anja] Univ Cologne, Inst Expt Med, D-50935 Cologne, Germany. [Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Rosenkranz, S (reprint author), Univ Cologne, Herzzentrum, Innere Med Klin 3, Kerpener St 62, D-50935 Cologne, Germany. EM stephan.rosenkranz@uk-koeln.de RI 刘, 李陆/H-8469-2015 FU Deutsche Forschungsgemeinschaft (DFG) [SFB-612]; Center for Molecular Medicine, University of Cologne (CMMC) [A6] FX This study was supported in part by the Deutsche Forschungsgemeinschaft (DFG, SFB-612, Project B12, to S. Rosenkranz) and by the Center for Molecular Medicine, University of Cologne (CMMC, project A6). NR 41 TC 1 Z9 2 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2015 VL 35 IS 6 BP 1434 EP 1444 DI 10.1161/ATVBAHA.114.304887 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CI5SU UT WOS:000354820600019 PM 25908763 ER PT J AU Tawakol, A Singh, P Mojena, M Pimentel-Santillana, M Emami, H MacNabb, M Rudd, JHF Narula, J Enriquez, JA Traves, PG Fernandez-Velasco, M Bartrons, R Martin-Sanz, P Fayad, ZA Tejedor, A Bosca, L AF Tawakol, Ahmed Singh, Parmanand Mojena, Marina Pimentel-Santillana, Maria Emami, Hamed MacNabb, Megan Rudd, James H. F. Narula, Jagat Enriquez, Jose A. Traves, Paqui G. Fernandez-Velasco, Maria Bartrons, Ramon Martin-Sanz, Paloma Fayad, Zahi A. Tejedor, Alberto Bosca, Lisardo TI HIF-1 alpha and PFKFB3 Mediate a Tight Relationship Between Proinflammatory Activation and Anerobic Metabolism in Atherosclerotic Macrophages SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE anoxia; atherosclerosis; energy metabolism; macrophages; positron-emission tomography ID GM-CSF; 6-PHOSPHOFRUCTO-2-KINASE PFKFB3; OXIDATIVE-METABOLISM; TUMOR-GROWTH; HELA-CELLS; HYPOXIA; INFLAMMATION; GLYCOLYSIS; CANCER; EXPRESSION AB Objective-Although it is accepted that macrophage glycolysis is upregulated under hypoxic conditions, it is not known whether this is linked to a similar increase in macrophage proinflammatory activation and whether specific energy demands regulate cell viability in the atheromatous plaque. Approach and Results-We studied the interplay between macrophage energy metabolism, polarization, and viability in the context of atherosclerosis. Cultured human and murine macrophages and an in vivo murine model of atherosclerosis were used to evaluate the mechanisms underlying metabolic and inflammatory activity of macrophages in the different atherosclerotic conditions analyzed. We observed that macrophage energetics and inflammatory activation are closely and linearly related, resulting in dynamic calibration of glycolysis to keep pace with inflammatory activity. In addition, we show that macrophage glycolysis and proinflammatory activation mainly depend on hypoxia-inducible factor and on its impact on glucose uptake, and on the expression of hexokinase II and ubiquitous 6-phosphofructo-2-kinase. As a consequence, hypoxia potentiates inflammation and glycolysis mainly via these pathways. Moreover, when macrophages' ability to increase glycolysis through 6-phosphofructo-2-kinase is experimentally attenuated, cell viability is reduced if subjected to proinflammatory or hypoxic conditions, but unaffected under control conditions. In addition to this, granulocytemacrophage colony-stimulating factor enhances anerobic glycolysis while exerting a mild proinflammatory activation. Conclusions-These findings, in human and murine cells and in an animal model, show that hypoxia potentiates macrophage glycolytic flux in concert with a proportional upregulation of proinflammatory activity, in a manner that is dependent on both hypoxia-inducible factor -1 alpha and 6-phosphofructo-2-kinase. C1 [Tawakol, Ahmed; Singh, Parmanand; Emami, Hamed; MacNabb, Megan] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Tawakol, Ahmed; Singh, Parmanand; Emami, Hamed; MacNabb, Megan] Harvard Univ, Sch Med, Boston, MA USA. [Singh, Parmanand] New York Presbyterian Hosp, Div Cardiol, Weill Cornell Med Coll, New York, NY USA. [Mojena, Marina; Pimentel-Santillana, Maria; Traves, Paqui G.; Fernandez-Velasco, Maria; Martin-Sanz, Paloma; Bosca, Lisardo] Inst Invest Biomed Alberto Sols CSIC UAM, Madrid, Spain. [Mojena, Marina; Pimentel-Santillana, Maria; Traves, Paqui G.; Fernandez-Velasco, Maria; Martin-Sanz, Paloma; Bosca, Lisardo] Inst Salud Carlos III, Ctr Invest Red Enfermedades Hepat & Digest CIBERH, Madrid, Spain. [Mojena, Marina; Tejedor, Alberto] Hosp Gen Univ Gregorio Maranon, Madrid, Spain. [Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. [Narula, Jagat; Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Enriquez, Jose A.] Ctr Nacl Invest Cardiovasc, Madrid, Spain. [Traves, Paqui G.] Salk Inst Biol Studies, La Jolla, CA 92037 USA. [Fernandez-Velasco, Maria] Hosp Univ La Paz, Idipaz, Madrid, Spain. [Bartrons, Ramon] Univ Barcelona, Dept Ciencies Fisiol 2, Unitat Bioquim & Biol Mol, Barcelona, Spain. RP Tawakol, A (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM atawakol@partners.org; lbosca@iib.uam.es RI Bosca, Lisardo/A-2059-2008; Enriquez, Jose Antonio/M-8468-2016; Pimentel-Santillana, Maria/L-9437-2014 OI Bosca, Lisardo/0000-0002-0253-5469; Enriquez, Jose Antonio/0000-0002-3671-2961; Pimentel-Santillana, Maria/0000-0003-1179-4259 FU NHLBI [HL122177, 5T32 HL076136]; Cambridge Biomedical Research Centre; British Heart Foundation; HEFCE (Higher Education Funding Council for England); National Institutes of Health (NIH)/National Heart Lung and Blood Institute (NHLBI) [R01 HL071021, R01 HL078667]; NIH/NIBIB (National Institute of Biomedical Imaging and Bioengineering) [R01 EB009638]; NIH/NHLBI Program of Excellence in Nanotechnology (PEN) Award [HHSN268201000045C]; MINECO (Ministerio de Economia y Competitividad) [BFU2011-24760, SAF2014-52492, IPT2012-1331 to 060000]; ISCIII (Instituto de Salud Carlos III) [FIS-RIC RD12/0042/0019] FX Dr Tawakol is supported in part by NHLBI (HL122177). Dr Rudd is supported, in part, by the Cambridge Biomedical Research Centre, the British Heart Foundation and HEFCE (Higher Education Funding Council for England). Dr Fayad is supported by National Institutes of Health (NIH)/National Heart Lung and Blood Institute (NHLBI) R01 HL071021, R01 HL078667; NIH/NIBIB (National Institute of Biomedical Imaging and Bioengineering) R01 EB009638 and NIH/NHLBI Program of Excellence in Nanotechnology (PEN) Award, contract HHSN268201000045C. Dr Singh was supported by a grant from the NHLBI (5T32 HL076136). Dr Bosca was supported by BFU2011-24760, SAF2014-52492, IPT2012-1331 to 060000, and FIS-RIC RD12/0042/0019 from MINECO (Ministerio de Economia y Competitividad) and ISCIII (Instituto de Salud Carlos III), respectively. NR 46 TC 24 Z9 25 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2015 VL 35 IS 6 BP 1463 EP 1471 DI 10.1161/ATVBAHA.115.305551 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CI5SU UT WOS:000354820600022 PM 25882065 ER PT J AU Beaudoin, M Gupta, RM Won, HH Lo, KS Do, R Henderson, CA Lavoie-St-Amour, C Langlois, S Rivas, D Lehoux, S Kathiresan, S Tardif, JC Musunuru, K Lettre, G AF Beaudoin, Melissa Gupta, Rajat M. Won, Hong-Hee Lo, Ken Sin Do, Ron Henderson, Christopher A. Lavoie-St-Amour, Claire Langlois, Simon Rivas, Daniel Lehoux, Stephanie Kathiresan, Sekar Tardif, Jean-Claude Musunuru, Kiran Lettre, Guillaume TI Myocardial Infarction-Associated SNP at 6p24 Interferes With MEF2 Binding and Associates With PHACTR1 Expression Levels in Human Coronary Arteries SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coronary artery disease; genetic association studies; myocardial infarction ID GENOME-WIDE ASSOCIATION; HUMAN ENDOTHELIAL-CELLS; CARDIOVASCULAR-DISEASE; SUSCEPTIBILITY LOCI; GENETIC-VARIATION; VARIANTS; RISK; TORCETRAPIB; REGULATOR; DYNAMICS AB Objective-Coronary artery disease (CAD), including myocardial infarction (MI), is the main cause of death in the world. Genome-wide association studies have identified dozens of single nucleotide polymorphisms (SNPs) associated with CAD/MI. One of the most robust CAD/MI genetic associations is with intronic SNPs in the gene PHACTR1 on chromosome 6p24. How these PHACTR1 SNPs influence CAD/MI risk, and whether PHACTR1 itself is the causal gene at the locus, is currently unknown. Approach and Results-Using genetic fine-mapping and DNA resequencing experiments, we prioritized an intronic SNP (rs9349379) in PHACTR1 as causal variant. We showed that this variant is an expression quantitative trait locus for PHACTR1 expression in human coronary arteries. Experiments in endothelial cell extracts confirmed that alleles at rs9349379 are differentially bound by the transcription factors myocyte enhancer factor-2. We engineered a deletion of this myocyte enhancer factor-2-binding site using CRISPR/Cas9 genome-editing methodology. Heterozygous endothelial cells carrying this deletion express 35% less PHACTR1. Finally, we found no evidence that PHACTR1 expression levels are induced when stimulating human endothelial cells with vascular endothelial growth factor, tumor necrosis factor-a, or shear stress. Conclusions-Our results establish a link between intronic SNPs in PHACTR1, myocyte enhancer factor-2 binding, and transcriptional functions at the locus, PHACTR1 expression levels in coronary arteries and CAD/MI risk. Because PHACTR1 SNPs are not associated with the traditional risk factors for CAD/MI (eg, blood lipids or pressure, diabetes mellitus), our results suggest that PHACTR1 may influence CAD/MI risk through as yet unknown mechanisms in the vascular endothelium. C1 [Beaudoin, Melissa; Lo, Ken Sin; Lavoie-St-Amour, Claire; Langlois, Simon; Tardif, Jean-Claude; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Gupta, Rajat M.; Henderson, Christopher A.; Musunuru, Kiran] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, England. [Gupta, Rajat M.; Henderson, Christopher A.; Musunuru, Kiran] Harvard Stem Cell Inst, Cambridge, MA USA. [Gupta, Rajat M.; Musunuru, Kiran] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Won, Hong-Hee; Do, Ron; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Won, Hong-Hee; Do, Ron; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Won, Hong-Hee; Do, Ron; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Won, Hong-Hee; Do, Ron; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Rivas, Daniel; Lehoux, Stephanie] McGill Univ, Lady Davis Inst Med Res, Montreal, PQ, Canada. [Tardif, Jean-Claude; Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. RP Beaudoin, M (reprint author), Montreal Heart Inst, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada. EM guillaume.lettre@umontreal.ca FU Centre of Excellence in Personalized Medicine; Fonds de Recherche Sante Quebec; Canadian Institute of Health Research [CIHR-MOP136979]; Montreal Heart Institute Foundation; National Heart, Lung, and Blood Institute; National Human Genome Research Institute of the US National Institutes of Health (NIH); Massachusetts General Hospital (MGH); Howard Goodman Fellowship from MGH; Donovan Family Foundation [R01HL107816]; Transatlantic Networks of Excellence award from Fondation Leducq; CIHR; US National Institutes of Health (NIH) [R01-GM104464]; Cardiovascular Program Pilot Grant from the Harvard Stem Cell Institute; LaDue Fellowship at Harvard University; Sarnoff Foundation Scholar Award; American Heart Association [15POST23280019]; [CIHR-MOP102489]; [RC2 HL-103010]; [RC2 HL-102923]; [RC2 HL-102924]; [RC2 HL-102925]; [RC2 HL-102926]; [5U54HG003067-11] FX This work was funded by the Centre of Excellence in Personalized Medicine, the Fonds de Recherche Sante Quebec, the Canadian Institute of Health Research (CIHR-MOP136979), and the Montreal Heart Institute Foundation (to G. Lettre), and the CIHR-MOP102489 (to S. Lehoux). S. Lehoux, J.-C. Tardif, and G. Lettre are Canada Research Chair holders. Sequencing of PHACTR1 was performed by the Myocardial Infarction Genetics Exome Sequencing Consortium with support from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute of the US National Institutes of Health (NIH). Grant support included RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2 HL-102926, and 5U54HG003067-11. S. Kathiresan is supported by a Research Scholar award from the Massachusetts General Hospital (MGH), the Howard Goodman Fellowship from MGH, the Donovan Family Foundation, R01HL107816, and a Transatlantic Networks of Excellence award from Fondation Leducq. R. Do is supported by a Banting Fellowship from the CIHR. K. Musunuru is supported by Grant R01-GM104464 from the US National Institutes of Health (NIH) and a Cardiovascular Program Pilot Grant from the Harvard Stem Cell Institute. R.M. Gupta is supported by the LaDue Fellowship at Harvard University and the Sarnoff Foundation Scholar Award. H.-H. Won is supported by a postdoctoral award from the American Heart Association (15POST23280019). NR 42 TC 15 Z9 15 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2015 VL 35 IS 6 BP 1472 EP 1479 DI 10.1161/ATVBAHA.115.305534 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CI5SU UT WOS:000354820600023 PM 25838425 ER PT J AU Bernstein, EE Nierenberg, AA Deckersbach, T Sylvia, LG AF Bernstein, Emily E. Nierenberg, Andrew A. Deckersbach, Thilo Sylvia, Louisa G. TI Eating behavior and obesity in bipolar disorder SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE bipolar disorder; body mass index; eating pathology; weight gain ID DIETARY RESTRAINT; WEIGHT-GAIN; METABOLIC SYNDROME; HEALTH; DISINHIBITION; INTERVENTION; ASSOCIATION; PREVALENCE; OLANZAPINE; HUNGER AB Objectives: Individuals with bipolar disorder are more frequently overweight or obese than the general population, but the reasons for this association are unknown. The aim of this study is to further understand the etiology of overweight and obesity in bipolar disorder. Methods: We invited patients in a specialty outpatient bipolar clinic to complete the Eating Inventory. Patients provided self-reported restraint, disinhibition, and perceived hunger as well as general perceptions of dietary intake. Results: Sixty-two individuals (37 female) between the ages of 18 and 67 (M = 41.5, SD = 13.38) and with an average body mass index (BMI) of 27.18 (SD = 5.71) completed the survey. Disinhibition and perceived hunger were positively correlated with BMI and self-reported difficulty eating healthy foods. Restraint was positively correlated with healthy eating (ps < .05). Stepwise linear regressions revealed that hunger was the most significant predictor of BMI (F(1) = 8.134, p = .006). Those participants with bipolar I or II disorder reported greater hunger scores (p < .01) and difficulty eating healthily (p < .05) than those without a full diagnosis. Conclusions: These results suggest that disinhibition and perception of hunger may be linked to the disproportionately high rate of obesity in bipolar disorder. C1 [Bernstein, Emily E.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.; Deckersbach, Thilo; Sylvia, Louisa G.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Bernstein, EE (reprint author), Harvard Univ, Dept Psychol, Psych Dept, William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM ebernstein@fas.harvard.edu FU National Institute of Mental Health [5K23MH091182-02] FX This study was supported in part by the National Institute of Mental Health, grant no. 5K23MH091182-02. NR 34 TC 3 Z9 3 U1 4 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD JUN PY 2015 VL 49 IS 6 BP 566 EP 572 DI 10.1177/0004867414565479 PG 7 WC Psychiatry SC Psychiatry GA CI5CB UT WOS:000354769400009 PM 25586751 ER PT J AU Sher, L AF Sher, Leo TI Brief psychotic disorder and suicidal behavior SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter ID OBSESSIVE-COMPULSIVE DISORDER C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 3 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD JUN PY 2015 VL 49 IS 6 BP 578 EP 578 DI 10.1177/0004867415569804 PG 1 WC Psychiatry SC Psychiatry GA CI5CB UT WOS:000354769400014 PM 25648142 ER PT J AU Jefferson, AL Gifford, KA Damon, S Chapman, GW Liu, DD Sparling, J Dobromyslin, V Salat, D AF Jefferson, Angela L. Gifford, Katherine A. Damon, Stephen Chapman, G. William Liu, Dandan Sparling, Jamie Dobromyslin, Vitaly Salat, David CA Alzheimer's Dis Neuroimaging TI Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Mild cognitive impairment; White matter; Tissue contrast; Imaging markers ID NEUROIMAGING INITIATIVE ADNI; MAGNETIC-RESONANCE IMAGES; ALZHEIMERS-DISEASE; CORTICAL THICKNESS; CEREBRAL-CORTEX; SIGNAL INTENSITY; MRI; DEMENTIA; SEGMENTATION; RELIABILITY AB The clinical relevance of gray/white matter contrast ratio (GWR) in mild cognitive impairment (MCI) remains unknown. This study examined baseline GWR and 3-year follow-up diagnostic status in MCI. Alzheimer's Disease Neuroimaging Initiative MCI participants with baseline 1.5 T MRI and 3-year follow-up clinical data were included. Participants were categorized into two groups based on 3-year follow-up diagnoses: 1) non-converters (n = 69, 75 +/- 7, 26 % female), and 2) converters (i.e., dementia at follow-up; n = 69, 75 +/- 7, 30 % female) who were matched on baseline age and Mini-Mental State Examination scores. Groups were compared on FreeSurfer generated baseline GWR from structural images in which higher values represent greater tissue contrast. A general linear model, adjusting for APOE-status, scanner type, hippocampal volume, and cortical thickness, revealed that converters evidenced lower GWR values than non-converters (i.e., more degradation in tissue contrast; p = 0.03). Individuals with MCI who convert to dementia have lower baseline GWR values than individuals who remain diagnostically stable over a 3-year period, statistically independent of cortical thickness or hippocampal volume. C1 [Jefferson, Angela L.; Gifford, Katherine A.; Damon, Stephen; Chapman, G. William] Vanderbilt Univ, Med Ctr, Dept Neurol, Vanderbilt Memory & Alzheimers Ctr, Nashville, TN 37203 USA. [Sparling, Jamie] Boston Univ, Sch Med, Boston, MA 02118 USA. [Dobromyslin, Vitaly; Salat, David] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Liu, Dandan] Vanderbilt Univ, Dept Biostat, Nashville, TN 37235 USA. [Salat, David] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Salat, David] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Jefferson, AL (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, Vanderbilt Memory & Alzheimers Ctr, 2525 West End Ave,12th Floor Suite 1200, Nashville, TN 37203 USA. EM angela.jefferson@vanderbilt.edu FU Paul B. Beeson Career Development Award in Aging [K23-AG030962]; Alzheimer's Association [IIRG-08-88733, R01-AG034962, R01-HL111516, K24-AG046373]; American Federation for Aging Research Medical Student Training in Aging Research Grant [T35-AG038027]; Vanderbilt Memory & Alzheimer's Center; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; Northern California Institute for Research and Education; NIH [P30 AG010129, K01 AG030514]; [R01-NR010827] FX This research was supported by K23-AG030962 (Paul B. Beeson Career Development Award in Aging; ALJ); Alzheimer's Association IIRG-08-88733 (ALJ); R01-AG034962 (ALJ); R01-HL111516 (ALJ); K24-AG046373 (ALJ); American Federation for Aging Research Medical Student Training in Aging Research Grant (JS; T35-AG038027); R01-NR010827 (DS); and the Vanderbilt Memory & Alzheimer's Center. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, by the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec, Inc.; Bristol-Myers Squibb Company; Eisai, Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development, LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; Servier; Synarc, Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study Rev October 16, 2012 at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514. NR 42 TC 2 Z9 2 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2015 VL 9 IS 2 BP 141 EP 148 DI 10.1007/s11682-014-9291-2 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA CI7TB UT WOS:000354966600001 PM 24493370 ER PT J AU McGregor, KM Sudhyadhom, A Nocera, J Seff, A Crosson, B Butler, AJ AF McGregor, Keith M. Sudhyadhom, Atchar Nocera, Joe Seff, Ari Crosson, Bruce Butler, Andrew J. TI Reliability of negative BOLD in ipsilateral sensorimotor areas during unimanual task activity SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE fMRI; Ipsilateral inhibition; Negative BOLD; Reliability; Sensorimotor activity ID UNILATERAL HAND MOVEMENTS; PRIMARY SOMATOSENSORY CORTEX; PRIMARY MOTOR CORTEX; INTERHEMISPHERIC INHIBITION; MIRROR MOVEMENTS; MULTIPLE-SCLEROSIS; NEURONAL INHIBITION; SIGNAL CHANGES; AGE; ACTIVATION AB Research using functional magnetic resonance imaging has for numerous years now reported the existence of a negative blood oxygenation level dependent (BOLD) response. Based on accumulating evidence, this negative BOLD signal appears to represent an active inhibition of cortical areas in which it is found during task activity. This particularly important with respect to motor function given that it is fairly well-established that, in younger adults, the ipsilateral sensorimotor cortex exhibits negative BOLD during unimanual movements in fMRI. This interhemispheric suppression of cortical activity may have useful implications for our understanding of both basic motor function and rehabilitation of injury or disease. However, to date, we are aware of no study that has tested the reliability of evoked negative BOLD in ipsilateral sensorimotor cortex in individuals across sessions. The current study employs a unimanual finger opposition task previously shown to evoke negative BOLD in ipsilateral sensorimotor cortex across three sessions. Reliability metrics across sessions indicates that both the magnitude and location of ipsilateral sensorimotor negative BOLD response is relatively stable over each of the three sessions. Moreover, the volume of negative BOLD in ipsilateral cortex was highly correlated with volume of positive BOLD activity in the contralateral primary motor cortex. These findings show that the negative BOLD signal can be reliably evoked in unimanual task paradigms, and that the signal dynamic could represent an active suppression of the ipsilateral sensorimotor cortex originating from the contralateral motor areas. C1 [McGregor, Keith M.; Nocera, Joe; Seff, Ari; Crosson, Bruce; Butler, Andrew J.] US Dept Vet Affairs, Ctr Visual & Neurocognit, Atlanta, GA USA. [McGregor, Keith M.; Nocera, Joe; Crosson, Bruce] Emory Univ, Dept Neurol, Decatur, GA 30033 USA. [Sudhyadhom, Atchar] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Butler, Andrew J.] Georgia State Univ, Dept Phys Therapy, Atlanta, GA 30303 USA. RP McGregor, KM (reprint author), Emory Univ, Dept Neurol, 1518 Clifton Rd NE, Decatur, GA 30033 USA. EM keith.mcgregor@emory.edu OI McGregor, Keith/0000-0003-3654-351X FU Department of Veteran Affairs (VA) Rehabilitation R&D Center of Excellence [F2182C]; Career Development Award Level-2 award; Senior Research Career Scientist award [B6364L] FX The contents do not represent the views of the Department of Veterans Affairs or the United States Government. This work was supported by a Department of Veteran Affairs (VA) Rehabilitation R&D Center of Excellence #F2182C, Career Development Award Level-2 (KMM) and Senior Research Career Scientist (BC: #B6364L) awards. NR 61 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2015 VL 9 IS 2 BP 245 EP 254 DI 10.1007/s11682-014-9302-3 PG 10 WC Neuroimaging SC Neurosciences & Neurology GA CI7TB UT WOS:000354966600010 PM 24788334 ER PT J AU Yang, JC Papadimitriou, G Eckbo, R Yeterian, EH Liang, LC Dougherty, DD Bouix, S Rathi, Y Shenton, M Kubicki, M Eskandar, EN Makris, N AF Yang, Jimmy C. Papadimitriou, George Eckbo, Ryan Yeterian, Edward H. Liang, Lichen Dougherty, Darin D. Bouix, Sylvain Rathi, Yogesh Shenton, Martha Kubicki, Marek Eskandar, Emad N. Makris, Nikos TI Multi-tensor investigation of orbitofrontal cortex tracts affected in subcaudate tractotomy SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Psychosurgery; Diffusion tensor imaging; Diffusion tractography; Obsessive-compulsive disorder; Deep brain stimulation ID OBSESSIVE-COMPULSIVE DISORDER; DEEP BRAIN-STIMULATION; PREFRONTAL CORTICAL PROJECTIONS; GLUCOSE METABOLIC-RATE; CEREBRAL WHITE-MATTER; TERM-FOLLOW-UP; RHESUS-MONKEY; TOPOGRAPHIC PARCELLATION; SYMPTOM PROVOCATION; MACAQUE MONKEYS AB Subcaudate tractotomy (SCT) is a neurosurgical lesioning procedure that can reduce symptoms in medically intractable obsessive compulsive disorder (OCD). Due to the putative importance of the orbitofrontal cortex (OFC) in symptomatology, fibers that connect the OFC, SCT lesion, and either the thalamus or brainstem were investigated with two-tensor tractography using an unscented Kalman filter approach. From this dataset, fibers were warped to Montreal Neurological Institute space, and probability maps with center-of-mass analysis were subsequently generated. In comparing fibers from the same OFC region, including medial OFC (mOFC), central OFC (cOFC), and lateral OFC (lOFC), the area of divergence for fibers connected with the thalamus versus the brainstem is posterior to the anterior commissure. At the anterior commissure, fibers connected with the thalamus run dorsal to those connected with the brainstem. As OFC fibers travel through the ventral aspect of the internal capsule, lOFC fibers are dorsal to cOFC and mOFC fibers. Using neuroanatomical comparison, tracts coursing between the OFC and thalamus are likely part of the anterior thalamic radiations, while those between the OFC and brainstem likely belong to the medial forebrain bundle. These data support the involvement of the OFC in OCD and may be relevant to creating differential lesional procedures of specific tracts or to developing deep brain stimulation programming paradigms. C1 [Papadimitriou, George; Liang, Lichen; Makris, Nikos] Massachusetts Gen Hosp, Dept Psychiat, Ctr Morphometr Anal, A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Papadimitriou, George; Liang, Lichen; Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Yang, Jimmy C.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Eckbo, Ryan; Bouix, Sylvain; Rathi, Yogesh; Shenton, Martha; Kubicki, Marek] Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Yang, Jimmy C.; Dougherty, Darin D.; Bouix, Sylvain; Rathi, Yogesh; Shenton, Martha; Kubicki, Marek; Eskandar, Emad N.; Makris, Nikos] Harvard Univ, Sch Med, Boston, MA USA. [Yeterian, Edward H.] Colby Coll, Dept Psychol, Waterville, ME 04901 USA. [Shenton, Martha] VA Boston Healthcare Syst, Brockton, MA USA. RP Makris, N (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Morphometr Anal, A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM nikos@cma.mgh.harvard.edu FU [R01DA027804]; [R21EB016449] FX R01DA027804 (NM), R21EB016449 (NM) NR 72 TC 1 Z9 1 U1 7 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2015 VL 9 IS 2 BP 342 EP 352 DI 10.1007/s11682-014-9314-z PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CI7TB UT WOS:000354966600019 PM 25103312 ER PT J AU Leyland-Jones, B Gray, KP Abramovitz, M Bouzyk, M Young, B Long, B Kammler, R Dell'Orto, P Biasi, MO Thurlimann, B Lyng, MB Ditzel, HJ Harvey, VJ Neven, P Treilleux, I Rasmussen, BB Maibach, R Price, KN Coates, AS Goldhirsch, A Pagani, O Viale, G Rae, JM Regan, MM AF Leyland-Jones, Brian Gray, Kathryn P. Abramovitz, Mark Bouzyk, Mark Young, Brandon Long, Bradley Kammler, Roswitha Dell'Orto, Patrizia Biasi, Maria Olivia Thuerlimann, Beat Lyng, Maria B. Ditzel, Henrik J. Harvey, Vernon J. Neven, Patrick Treilleux, Isabelle Rasmussen, Birgitte Bruun Maibach, Rudolf Price, Karen N. Coates, Alan S. Goldhirsch, Aron Pagani, Olivia Viale, Giuseppe Rae, James M. Regan, Meredith M. TI CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE CYP19A1; Aromatase inhibitor; Musculoskeletal side effects; Bone side effects; Letrozole; Tamoxifen ID SINGLE-NUCLEOTIDE POLYMORPHISM; AROMATASE INHIBITOR; GENETIC-VARIATION; ADVERSE EVENTS; RISK; LETROZOLE; REGION; CARCINOMA; TAMOXIFEN; VARIANTS AB To determine whether CYP19A1 polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Tumors were genotyped for six CYP19A1 polymorphisms using PCR-based methods. Associations with breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI), musculoskeletal and bone adverse events (AEs) were assessed using Cox proportional hazards models. All statistical tests were two-sided. No association between the CYP19A1 genotypes and BCFI or DRFI was observed overall. A reduced risk of a breast cancer event for tamoxifen-treated patients with rs700518 variants was observed (BCFI CC/TC vs. TT: HR 0.53, 95 % CI 0.34-0.82, interaction P = 0.08), but not observed for letrozole-treated patients. There was an increased risk of musculoskeletal AEs for patients with rs700518 variants CC/TC versus TT (HR 1.22, 95 % CI 1.03-1.45, P = 0.02), regardless of treatment. Tamoxifen-treated patients with rs4646 variants had a reduced risk of bone AEs (AA/CA vs. CC: HR 0.76, 95 % CI 0.59-0.98), whereas an increase of minor allele (C) of rs10046 was associated with an increased risk of bone AEs (HR 1.28, 95 % CI 1.07-1.52). rs936308 variants were associated with a reduced risk of bone AEs in letrozole-treated patients (GG/GC vs. CC: HR 0.73, 95 % CI 0.54-0.99), different from in tamoxifen-treated patients (GG/GC vs. CC: HR 1.32, 95 % CI 0.92-1.90, interaction P = 0.01). CYP19A1 rs700518 variants showed associations with BCFI, DRFI, in tamoxifen treated patients and musculoskeletal AEs regardless of treatment. SNPs rs4646, rs10046, and rs936308 were associated with bone AEs. C1 [Leyland-Jones, Brian; Young, Brandon] Avera Canc Inst, Sioux Falls, SD 57105 USA. [Gray, Kathryn P.; Price, Karen N.; Regan, Meredith M.] Dana Farber Canc Inst, Int Breast Canc Study Grp IBCSG Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gray, Kathryn P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Abramovitz, Mark] VM Inst Res, Montreal, PQ, Canada. [Bouzyk, Mark] AKESOgen Inc, Norcross, GA USA. [Long, Bradley] Univ Chicago, Dept Pathol, Genom Mol Pathol, Chicago, IL 60637 USA. [Kammler, Roswitha] IBCSG Coordinating Ctr, Bern, Switzerland. [Kammler, Roswitha] Cent Pathol Off, Bern, Switzerland. [Dell'Orto, Patrizia; Viale, Giuseppe] Univ Milan, IBCSG Cent Pathol Off, Div Pathol, Milan, Italy. [Dell'Orto, Patrizia; Viale, Giuseppe] Univ Milan, Lab Med, European Inst Oncol, Milan, Italy. [Biasi, Maria Olivia] European Inst Oncol, Div Pathol, Milan, Italy. [Biasi, Maria Olivia] European Inst Oncol, Lab Med, Milan, Italy. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Lyng, Maria B.; Ditzel, Henrik J.] Univ Southern Denmark, Inst Mol Med, Odense, Denmark. [Ditzel, Henrik J.] Odense Univ Hosp, Dept Oncol, DK-5000 Odense, Denmark. [Harvey, Vernon J.] Auckland City Hosp, Auckland, New Zealand. [Neven, Patrick] Univ Leuven, Dept Oncol, KU Leuven, Leuven, Belgium. [Neven, Patrick] Univ Hosp Leuven, Multidisciplinary Breast Ctr, Leuven, Belgium. [Treilleux, Isabelle] Ctr Leon Berard, F-69373 Lyon, France. [Rasmussen, Birgitte Bruun] Herlev Hosp, DK-2730 Herlev, Denmark. [Maibach, Rudolf] IBCSG Coordinating Ctr, Bern, Switzerland. [Price, Karen N.] IBCSG Stat Ctr, Frontier Sci & Technol Res Fdn, Boston, MA USA. [Coates, Alan S.] Int Breast Canc Study Grp, Sydney, NSW, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Pagani, Olivia] Swiss Grp Clin Canc Res SAKK, Inst Oncol Southern Switzerland IOSI, Viganello, Switzerland. [Pagani, Olivia] IBCSG Osped Italiano, Viganello, Switzerland. [Rae, James M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA USA. RP Leyland-Jones, B (reprint author), Avera Canc Inst, 1000 E 23rd St, Sioux Falls, SD 57105 USA. EM bleylandj@aol.com; pkruan@jimmy.harvard.edu; mark.abramovitz@gmail.com; mbouzyk@akesogen.com; Brandon.Young@avera.org; bradley.long@uchospitals.edu; rosita.kammler@ibcsg.org; patrizia.dellorto@ieo.it; olivia.biasi@ieo.it; beat.thuerlimann@kssg.ch; mlyng@health.sdu.dk; hditzel@health.sdu.dk; vernonh@adhb.govt.nz; patrick.neven@uzleuven.be; isabelle.treilleux@lyon.unicancer.fr; birgitte.bruun.rasmussen@regionh.dk; rudolf.maibach@ibcsg.org; price@jimmy.harvard.edu; alan.coates@ibcsg.org; aron.goldhirsch@ibcsg.org; Olivia.pagani@ibcsg.org; giuseppe.viale@ieo.it; jimmyrae@med.umich.edu; mregan@jimmy.harvard.edu OI Ditzel, Henrik J./0000-0003-3927-5135 FU Novartis; Susan G. Komen for the Cure Promise Grant [KG080081]; Breast Cancer Research Foundation (BCRF) [N003173]; National Institutes of Health [1RO1GM099143]; IBCSG: United States National Cancer Institute [CA75362] FX The BIG 1-98 trial is registered at ClinicalTrials.gov (Identifier NCT00004205). We are indebted to the women, physicians, nurses, and data managers who participated in this clinical trial; to the many pathologists who submitted tumor blocks; to the BIG 1-98 Steering Committee; to Novartis for funding of the clinical trial and of the collection of tumor blocks; to the IBCSG for the design of the trial, coordination, data management, medical review, and statistical support; to the IBCSG Central Pathology Office for collection and processing of tumor blocks; to the BIG-198 Collaborative Group (members who submitted tumor blocks are listed in Supplementary Appendix, available online); to Susan G. Komen for the Cure Promise Grant. The translational research, including DNA extraction and genotyping, was funded by Susan G. Komen for the Cure Promise Grant (KG080081 to GV, OP, MMR) and by The Breast Cancer Research Foundation (BCRF) (N003173 to JMR), the National Institutes of Health (1RO1GM099143 to JMR). The Breast International Group (BIG) 1-98 trial was funded by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Other support for the IBCSG: United States National Cancer Institute (CA75362 to MMR). NR 30 TC 3 Z9 3 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2015 VL 151 IS 2 BP 373 EP 384 DI 10.1007/s10549-015-3378-3 PG 12 WC Oncology SC Oncology GA CI1JC UT WOS:000354499200015 PM 25935582 ER PT J AU Swaroop, MN Ferguson, CM Horick, NK Skolny, MN Miller, CL Jammallo, LS Brunelle, CL O'Toole, JA Isakoff, SJ Specht, MC Taghian, AG AF Swaroop, Meyha N. Ferguson, Chantal M. Horick, Nora K. Skolny, Melissa N. Miller, Cynthia L. Jammallo, Lauren S. Brunelle, Cheryl L. O'Toole, Jean A. Isakoff, Steven J. Specht, Michelle C. Taghian, Alphonse G. TI Impact of adjuvant taxane-based chemotherapy on development of breast cancer-related lymphedema: results from a large prospective cohort SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Lymphedema; Breast cancer; Taxane chemotherapy; Arm swelling; Quality of life ID REPORTED ARM-LYMPHEDEMA; QUALITY-OF-LIFE; RISK-FACTORS; NODE DISSECTION; FLUID RETENTION; OPTOELECTRONIC VOLUMETRY; RADIATION-THERAPY; RANDOMIZED-TRIALS; LIMB VOLUME; FOLLOW-UP AB Taxane-based chemotherapy for the treatment of breast cancer is associated with fluid retention in the extremities; however, its association with development of breast cancer-related lymphedema is unclear. We sought to determine if adjuvant taxane-based chemotherapy increased risk of lymphedema or mild swelling of the upper extremity. 1121 patients with unilateral breast cancer were prospectively screened for lymphedema with perometer measurements. Lymphedema was defined as a relative volume change (RVC) of a parts per thousand yen10 % from preoperative baseline. Mild swelling was defined as RVC 5- < 10 %. Clinicopathologic characteristics were obtained via medical record review. Kaplan-Meier and Cox proportional hazard analyses were performed to determine lymphedema rates and risk factors. 29 % (324/1121) of patients were treated with adjuvant taxane-based chemotherapy. The 2-year cumulative incidence of lymphedema in the overall cohort was 5.27 %. By multivariate analysis, axillary lymph node dissection (ALND) (p < 0.0001), higher body mass index (p = 0.0007), and older age at surgery (p = 0.04) were significantly associated with increased risk of lymphedema; however, taxane chemotherapy was not significant when compared to no chemotherapy and non-taxane chemotherapy (HR 1.14, p = 0.62; HR 1.56, p = 0.40, respectively). Chemotherapy with docetaxel was significantly associated with mild swelling on multivariate analysis in comparison to both no chemotherapy and non-taxane chemotherapy groups (HR 1.63, p = 0.0098; HR 2.15, p = 0.02, respectively). Patients who receive taxane-based chemotherapy are not at an increased risk of lymphedema compared to patients receiving no chemotherapy or non-taxane adjuvant chemotherapy. Those treated with docetaxel may experience mild swelling, but this does not translate into subsequent lymphedema. C1 [Swaroop, Meyha N.; Ferguson, Chantal M.; Skolny, Melissa N.; Miller, Cynthia L.; Jammallo, Lauren S.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Horick, Nora K.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Brunelle, Cheryl L.; O'Toole, Jean A.] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Specht, Michelle C.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org FU National Cancer Institute [R01CA139118, P50CA089393]; Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema FX The study described was supported by Award Number R01CA139118 (AGT), Award Number P50CA089393 (AGT) from the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 67 TC 8 Z9 8 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2015 VL 151 IS 2 BP 393 EP 403 DI 10.1007/s10549-015-3408-1 PG 11 WC Oncology SC Oncology GA CI1JC UT WOS:000354499200017 PM 25940996 ER PT J AU Lim, LS Ling, LH Cheung, CMG Ong, PG Gong, LL Tai, ES Mathur, R Wong, D Foulds, W Wong, TY AF Lim, Laurence S. Ling, Lieng H. Cheung, Chui Ming Gemmy Ong, Peng Guan Gong, Lingli Tai, E. Shyong Mathur, Ranjana Wong, Doric Foulds, Wallace Wong, Tien Yin TI Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTIMA-MEDIA THICKNESS; UNITED-STATES; NITRIC-OXIDE; DYSFUNCTION; MELLITUS; VASODILATION; HUMANS AB Background To investigate possible associations between diabetic retinopathy (DR) and systemic vascular endothelial function and arterial stiffness measured using reactive hyperaemia peripheral arterial tonometry. Methods This was a cross-sectional observational clinical study. Subjects with diabetes were recruited and DR was graded from retinal photographs. Systemic endothelial function was measured using reactive hyperaemia peripheral arterial tonometry (EndoPAT) and expressed as the reactive hyperaemia index (RHI). Peripheral arterial stiffness was measured using the same device and expressed as the augmentation index (AI). Results In total, 164 eyes of 95 Chinese patients were evaluated. The mean age of the subject eyes was 60.1 +/- 8.2 years and 76.8% were men. The mean duration of diabetes was 15.5 +/- 9.8 years, and the mean HbA1c was 8.1 +/- 1.4%. In age-gender-adjusted models, increasing severity of DR was associated with increasing mean RHI (p= 0.001) and increasing mean AI (p< 0.001). In multivariate models, adjusting additionally for smoking, mean duration of diabetes, HbA1c and hypertension, the associations with RHI and AI persisted (p= 0.011 and 0.001, respectively). In analyses of the dichotomous outcomes clinically significant macular oedema (CSME), moderate DR and vision-threatening DR, AI was a significant predictor of CSME and vision-threatening DR. In multivariate-adjusted models, for every SD increase in AI, the odds of having CSME was 1.78 times higher (95% CI 1.05 to 2.99; p= 0.029). For every SD increase in AI, the odds of having vision-threatening DR was 1.73 times higher (95% CI 1.17 to 2.56; p= 0.003). Conclusions Subjects with more severe DR have larger peripheral reactive hyperaemic responses and greater peripheral vascular stiffness. These findings support the link between the microvascular changes of diabetes and macrovascular disease. C1 [Lim, Laurence S.; Cheung, Chui Ming Gemmy; Ong, Peng Guan; Tai, E. Shyong; Mathur, Ranjana; Wong, Doric; Foulds, Wallace; Wong, Tien Yin] Singapore Natl Eye Ctr, Duke NUS Gradate Med Sch, Singapore Eye Res Inst, Singapore 168751, Singapore. [Lim, Laurence S.; Cheung, Chui Ming Gemmy; Wong, Tien Yin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore. [Lim, Laurence S.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. [Ling, Lieng H.] Natl Univ Heart Ctr, Dept Cardiac, Singapore, Singapore. [Ling, Lieng H.; Gong, Lingli] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. RP Wong, TY (reprint author), Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore. EM tien_yin_wong@nuhs.edu.sg OI Tai, E Shyong/0000-0003-2929-8966 FU National Medical Research Council [R710/60/2009] FX This study was supported by National Medical Research Council grant R710/60/2009. NR 27 TC 5 Z9 5 U1 1 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 2015 VL 99 IS 6 BP 837 EP 841 DI 10.1136/bjophthalmol-2014-306075 PG 5 WC Ophthalmology SC Ophthalmology GA CI7NO UT WOS:000354950600022 PM 25488949 ER PT J AU Kanellopoulos, AJ Asimellis, G Salvador-Culla, B Chodosh, J Ciolino, JB AF Kanellopoulos, Anastasios John Asimellis, George Salvador-Culla, Borja Chodosh, James Ciolino, Joseph B. TI High-irradiance CXL combined with myopic LASIK: flap and residual stroma biomechanical properties studied ex-vivo SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID COLLAGEN CROSS-LINKING; IN-SITU KERATOMILEUSIS; FEMTOSECOND LASER; CORNEAL STROMA; PHOTOREFRACTIVE KERATECTOMY; UV ABSORBENCY; KERATOCONUS; RIBOFLAVIN; RESISTANCE; EPITHELIUM AB Background/aims To evaluate ex vivo biomechanical and enzymatic digestion resistance differences between standard myopic laser in-situ keratomileusis (LASIK) compared with LASIK+ CXL, in which high-irradiance cross-linking (CXL) is added. Methods Eight human donor corneas were subjected to femtosecond-assisted myopic LASIK. Group A (n=4) served as a control group (no CXL). The corneas in LASIK+ CXL group B were subjected to concurrent prophylactic high-irradiance CXL (n=4). Saline-diluted (0.10%) riboflavin was instilled on the stroma, subsequently irradiated with UV-A through the repositioned flap. The cornea stroma and flap specimens were separately subjected to transverse biaxial resistance measurements; biomechanical differences were assessed via stress and Young's shear modulus. Subsequently, the specimens were subjected to enzymatic degradation. Results For the corneal stroma specimen, stress at 10% strain was 128 +/- 11 kPa for control group A versus 293 +/- 20 kPa for the LASIK+ CXL group B (relative difference Delta =+ 129%, p< 0.05). The stress in group B was also increased at 20% strain by + 68% (p< 0.05). Shear modulus in group B was increased at 10% strain by + 79%, and at 20% strain by + 48% (both statistically significant, p< 0.05). The enzymatic degradation time to dissolution was 157.5 +/- 15.0 min in group A versus 186.25 +/- 7.5 min in group B (Delta=+ 18%, p= 0.014). For the flaps, both biomechanical, as well as enzymatic degradation tests showed no significant differences. Conclusions LASIK+ CXL appears to provide significant increase in underlying corneal stromal rigidity, up to + 130%. Additionally, there is significant relevant enzymatic digestion resistance confirmatory to the above. LASIK flaps appear unaffected biomechanically by the LASIK+ CXL procedure, suggesting effective CXL just under the flap. C1 [Kanellopoulos, Anastasios John; Asimellis, George] Laservis Gr Eye Inst, Athens, Greece. [Kanellopoulos, Anastasios John] NYU, Sch Med, Dept Ophthalmol, New York, NY 10012 USA. [Salvador-Culla, Borja; Chodosh, James; Ciolino, Joseph B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Cornea & Refract Surg, Boston, MA USA. RP Kanellopoulos, AJ (reprint author), NYU, Sch Med, Dept Ophthalmol, New York, NY 10012 USA. EM ajk@brilliantvision.com OI Asimellis, George/0000-0002-9620-3878 NR 38 TC 10 Z9 10 U1 1 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 2015 VL 99 IS 6 BP 870 EP 874 DI 10.1136/bjophthalmol-2014-306411 PG 5 WC Ophthalmology SC Ophthalmology GA CI7NO UT WOS:000354950600028 PM 25795914 ER PT J AU Matulonis, UA Oza, AM Ho, TW Ledermann, JA AF Matulonis, Ursula A. Oza, Amit M. Ho, Tony W. Ledermann, Jonathan A. TI Intermediate clinical endpoints: A bridge between progression-free survival and overall survival in ovarian cancer trials SO CANCER LA English DT Review DE clinical trial; ovarian cancer; progression-free survival; surrogate endpoints; survival ID PHASE-III TRIAL; CELL LUNG-CANCER; RESISTANT PROSTATE-CANCER; OLAPARIB MAINTENANCE THERAPY; RANDOMIZED CONTROLLED-TRIALS; METASTATIC BREAST-CANCER; INDIVIDUAL PATIENT DATA; EPITHELIAL OVARIAN; COLORECTAL-CANCER; 1ST-LINE CHEMOTHERAPY AB Ovarian cancer patients are usually diagnosed at an advanced stage, experience recurrence after platinum-based chemotherapy, and eventually develop resistance to chemotherapy. Overall survival (OS), which has improved in recent years as more active treatments have been incorporated into patient care, is regarded as the most clinically relevant endpoint in ovarian cancer trials. However, although there remains a significant need for new treatments that prolong OS further without compromising quality of life, it has become increasingly difficult to detect an OS benefit for investigational treatments because of the use of multiple lines of chemotherapy to treat ovarian cancer. Progression-free survival (PFS), which measures the time to disease progression or death, is unaffected by postprogression therapies but does not evaluate the long-term impact of investigational treatments on tumor biology and responses to future therapies. Recent clinical trials of targeted agents in relapsed ovarian cancer have shown improvements in PFS but not OS, and this is possibly reflective of the long postprogression survival (PPS) period associated with this disease. Intermediate endpoints such as the time to second disease progression or death and the time to second subsequent therapy or death may provide supportive evidence for clinically meaningful PFS improvements and may be used to determine whether these improvements persist beyond the first disease progression and throughout subsequent lines of therapy. For clinical trials that have settings with a long PPS duration and/or involve multiple rounds of postprogression therapy, a primary endpoint of PFS supported by intermediate clinical endpoints and OS may provide a more comprehensive approach for evaluating efficacy. Cancer 2015;121:1737-1746. (c) 2015 American Cancer Society. Overall survival is regarded as the most clinically relevant endpoint in trials of ovarian cancer, but it may be confounded by multiple lines of subsequent therapy. A primary endpoint of progression-free survival supported by intermediate clinical endpoints and overall survival provides a more comprehensive approach for evaluating efficacy. C1 [Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Oza, Amit M.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Ho, Tony W.] AstraZeneca, Wilmington, DE USA. [Ledermann, Jonathan A.] UCL, UCL Canc Inst, London, England. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ursula_matulonis@dfci.harvard.edu OI Ho, Tony/0000-0002-3489-3594 FU AstraZeneca FX AstraZeneca provided funding for this study. NR 57 TC 9 Z9 9 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2015 VL 121 IS 11 BP 1737 EP 1746 DI 10.1002/cncr.29082 PG 10 WC Oncology SC Oncology GA CI5SO UT WOS:000354819900008 PM 25336142 ER PT J AU Stagl, JM Bouchard, LC Lechner, SC Blomberg, BB Gudenkauf, LM Jutagir, DR Gluck, S Derhagopian, RP Carver, CS Antoni, MH AF Stagl, Jamie M. Bouchard, Laura C. Lechner, Suzanne C. Blomberg, Bonnie B. Gudenkauf, Lisa M. Jutagir, Devika R. Glueck, Stefan Derhagopian, Robert P. Carver, Charles S. Antoni, Michael H. TI Long-term psychological benefits of cognitive-behavioral stress management for women with breast cancer: 11-year follow-up of a randomized controlled trial SO CANCER LA English DT Article DE breast neoplasms; cognitive therapy; depression; follow-up studies; psychological stress; quality of life; relaxation therapy; survivors ID QUALITY-OF-LIFE; PSYCHOSOCIAL INTERVENTIONS; META-ANALYSIS; DEPRESSION; SURVIVORS; SYMPTOMS; ANXIETY; THERAPY; METAANALYSIS; PREVALENCE AB BACKGROUNDBreast cancer survivors experience long-term physical and psychological sequelae after their primary treatment that negatively influence their quality of life (QOL) and increase depressive symptoms. Group-based cognitive-behavioral stress management (CBSM) delivered after surgery for early-stage breast cancer was previously associated with better QOL over a 12-month follow-up and with fewer depressive symptoms up to 5 years after study enrollment. This 8- to 15-year follow-up (median, 11 years) of a previously conducted trial (NCT01422551) evaluated whether women in this cohort receiving CBSM had fewer depressive symptoms and better QOL than controls at an 8- to 15-year follow-up. METHODSWomen with stage 0 to IIIb breast cancer were initially recruited 2 to 10 weeks after surgery and randomized to a 10-week CBSM intervention or a 1-day psychoeducational control group. One hundred women (51 CBSM patients and 49 controls) were recontacted 8 to 15 years after study enrollment to participate in a follow-up assessment. The Center for Epidemiologic Studies-Depression (CES-D) scale and the Functional Assessment of Cancer Therapy-Breast (FACT-B) were self-administered. Multiple regression was employed to evaluate group differences on the CES-D scale and FACT-B over and above effects of confounding variables. RESULTSParticipants assigned to CBSM reported significantly lower depressive symptoms (d, 0.63; 95% confidence interval [CI], 0.56-0.70) and better QOL (d, 0.58; 95% CI, 0.52-0.65) above the effects of the covariates. CONCLUSIONSWomen who received CBSM after surgery for early-stage breast cancer reported lower depressive symptoms and better QOL than the control group up to 15 years later. Early implementation of cognitive-behavioral interventions may influence long-term psychosocial functioning in breast cancer survivors. Cancer 2015;121:1873-1881. (c) 2015 American Cancer Society. Women in a randomized controlled trial receiving cognitive-behavioral stress management (CBSM) after surgery for early-stage breast cancer are evaluated at an 8- to 15-year follow-up (median, 11 years). Women in the CBSM group report fewer depressive symptoms and better quality of life than a control group up to 15 years later. C1 [Stagl, Jamie M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bouchard, Laura C.; Gudenkauf, Lisa M.; Jutagir, Devika R.; Carver, Charles S.; Antoni, Michael H.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Lechner, Suzanne C.; Antoni, Michael H.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Lechner, Suzanne C.; Blomberg, Bonnie B.; Glueck, Stefan; Carver, Charles S.; Antoni, Michael H.] Univ Miami, Miller Sch Med, Sylvester Canc Ctr, Miami, FL 33136 USA. [Blomberg, Bonnie B.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Derhagopian, Robert P.] Baptist Hlth Breast Ctr, Miami, FL USA. RP Antoni, MH (reprint author), Univ Miami, Dept Psychol, 5665 Ponce De Leon Blvd, Coral Gables, FL 33124 USA. EM mantoni@miami.edu OI Jacobs, Jamie M./0000-0001-9740-624X FU National Cancer Institute of the National Institutes of Health [R01-CA-064710] FX This study was funded by the National Cancer Institute of the National Institutes of Health (R01-CA-064710). NR 40 TC 7 Z9 7 U1 3 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2015 VL 121 IS 11 BP 1873 EP 1881 DI 10.1002/cncr.29076 PG 9 WC Oncology SC Oncology GA CI5SO UT WOS:000354819900024 PM 25809235 ER PT J AU Mack, JW Walling, A Dy, S Antonio, ALM Adams, J Keating, NL Tisnado, D AF Mack, Jennifer W. Walling, Anne Dy, Sydney Antonio, Anna Liza M. Adams, John Keating, Nancy L. Tisnado, Diana TI Patient beliefs that chemotherapy may be curative and care received at the end of life among patients with metastatic lung and colorectal cancer SO CANCER LA English DT Article DE chemotherapy; communication; end of life; informed consent; palliative ID OF-LIFE; SURVEILLANCE CONSORTIUM; MEDICARE BENEFICIARIES; PROSPECTIVE COHORT; OUTCOMES RESEARCH; MENTAL-HEALTH; NEAR-DEATH; PLACE; ASSOCIATIONS; DISCUSSIONS AB BACKGROUNDMany patients with incurable cancer inaccurately believe that chemotherapy may cure them. Little is known about how such beliefs affect choices for care at the end of life. This study assessed whether patients with advanced cancer who believed that chemotherapy might offer a cure were more likely to receive chemotherapy in the last month of life and less likely to enroll in hospice care before death. METHODSThis study examined patients diagnosed with stage IV lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance consortium, a population- and health system-based prospective cohort study. Among 722 patients who completed a baseline survey and died during the study period, logistic regression was used to assess the association of understanding goals of chemotherapy with chemotherapy use in the last month of life and hospice enrollment before death; adjustments were made for patient and tumor characteristics. RESULTSOne-third of the patients (33%) recognized that chemotherapy was not at all likely to cure their cancer. After adjustments, such patients were no less likely than other patients to receive end-of-life chemotherapy (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.84-2.09), but they were more likely than other patients to enroll in hospice (OR, 1.97; 95% CI, 1.37-2.82). CONCLUSIONSAn understanding of the purpose of chemotherapy for incurable cancer is a critical aspect of informed consent. Still, advanced cancer patients who were well informed about chemotherapy's goals received late-life chemotherapy at rates similar to those for other patients. An understanding of the incurable nature of cancer, however, is associated with increased hospice enrollment before death, and this suggests important care outcomes beyond chemotherapy use. Cancer 2015;121:1891-1897. (c) 2015 American Cancer Society. An understanding of the purpose of chemotherapy for incurable cancer is a critical aspect of informed consent. Patients with advanced cancer who are well informed about chemotherapy's goals receive late-life chemotherapy at rates similar to those for other patients, but they are more likely to enroll in hospice before death. This suggests important care outcomes beyond chemotherapy use. C1 [Mack, Jennifer W.] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02215 USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02215 USA. [Walling, Anne; Antonio, Anna Liza M.; Adams, John] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Walling, Anne; Antonio, Anna Liza M.; Adams, John] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Dy, Sydney] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Antonio, Anna Liza M.] Univ Calif Los Angeles, Los Angeles Fielding Sch Publ Hlth, Los Angeles, CA USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Tisnado, Diana] Calif State Univ Fullerton, Dept Hlth Sci, Fullerton, CA 92634 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_mack@dfci.harvard.edu FU National Cancer Institute [U01CA093344, U01CA093332, U01CA093324, U01CA093348, U01CA093329, U01CA093339, U01CA093326, R01CA164021-01A1, K24CA181510]; Department of Veterans Affairs [CRS 02-164]; American Cancer Society [119663-RSG-10-176-01-PCSM]; National Institutes of Health/National Center for Advancing Translational Science (University of California Los Angeles Clinical and Translational Institute) [UL1TR000123] FX The work of the Cancer Care Outcomes Research and Surveillance consortium was supported by grants from the National Cancer Institute to the statistical coordinating center (U01CA093344) and the National Cancer Institute-supported primary data collection and research centers (Dana-Farber Cancer Institute/Cancer Research Network, U01CA093332; Harvard Medical School/Northern California Cancer Center, U01CA093324; RAND/University of California Los Angeles, U01CA093348; University of Alabama at Birmingham, U01CA093329; University of Iowa, U01CA093339; and University of North Carolina, U01CA093326) and by a grant from the Department of Veterans Affairs to the Durham Veterans Affairs Medical Center (CRS 02-164). Additional support for this project was provided by the American Cancer Society (119663-RSG-10-176-01-PCSM), the National Institutes of Health/National Center for Advancing Translational Science (University of California Los Angeles Clinical and Translational Institute Connections grant UL1TR000123 to Anne Walling), and the National Cancer Institute (R01CA164021-01A1 and K24CA181510 to Nancy L. Keating). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the American Cancer Society, the National Cancer Institute, or the National Institutes of Health. NR 29 TC 10 Z9 10 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2015 VL 121 IS 11 BP 1891 EP 1897 DI 10.1002/cncr.29250 PG 7 WC Oncology SC Oncology GA CI5SO UT WOS:000354819900026 PM 25677655 ER PT J AU Ananthakrishnan, AN Kwon, J Raffals, L Sands, B Stenson, WF McGovern, D Kwon, JH Rheaume, RL Sandler, RS AF Ananthakrishnan, Ashwin N. Kwon, Jennifer Raffals, Laura Sands, Bruce Stenson, William F. McGovern, Dermot Kwon, John H. Rheaume, Robert L. Sandler, Robert S. TI Variation in Treatment of Patients With Inflammatory Bowel Diseases at Major Referral Centers in the United States SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Sinai Helmsley Alliance for Research Excellence (SHARE) Consortium; IBD; Practice Variation; Anti-TNF Agent ID CROHNS-DISEASE; ULCERATIVE-COLITIS; HOSPITAL VOLUME; MANAGEMENT; MORTALITY; RECURRENCE; CONSENSUS; OUTCOMES; CHILDREN; SURGERY AB We performed a prospective study of patients with inflammatory bowel diseases to examine variations in treatment among medical centers. In a prospective cohort study of 1659 patients with Crohn's disease and 946 patients with ulcerative colitis seen at 7 high-volume referral centers, we collected data on demographics, disease characteristics, and medical and surgical treatments. We used logistic regression to determine differences in treatment among centers, controlling for potential confounders. We found significant variations among centers in the treatment of Crohn's disease with immunomodulators (odds ratio [OR], 3.34; 95% confidence interval [CI], 2.09-5.32) but not anti-tumor necrosis factor agents (OR, 1.64; 95% CI, 0.97-2.77). There was less variation in the treatment of ulcerative colitis; we found no difference in use of immunomodulators (OR, 1.83; 95% CI, 1.00-3.36) or anti-tumor necrosis factor therapy (OR, 0.81; 95% CI, 0.40-1.65). The development and implementation of evidence-based standards of care for inflammatory bowel disease may help reduce variation and improve outcomes. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Kwon, Jennifer; Sands, Bruce] Icahn Sch Med Mt Sinai, Henry D Janowitz Div Gastroenterol, New York, NY 10029 USA. [Raffals, Laura] Mayo Clin, Div Gastroenterol, Rochester, MN USA. [Stenson, William F.] Washington Univ, Div Gastroenterol, St Louis, MO USA. [McGovern, Dermot] Cedars Sinai Med Ctr, Inflammatory Bowel Dis & Immunobiol Res Inst, Los Angeles, CA 90048 USA. [Kwon, John H.] Univ Chicago, Div Gastroenterol Hepatol & Nutr, Chicago, IL 60637 USA. [Rheaume, Robert L.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Sandler, Robert S.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU Leona M. and Harry B. Helmsley Charitable Trust FX This work was supported by the Leona M. and Harry B. Helmsley Charitable Trust. NR 20 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2015 VL 13 IS 6 BP 1197 EP 1200 DI 10.1016/j.cgh.2014.11.020 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CI5TZ UT WOS:000354824000033 PM 25460565 ER PT J AU Horowitz, D Guyer, M Sanders, K AF Horowitz, Deborah Guyer, Margaret Sanders, Kathy TI Psychosocial approaches to violence and aggression: contextually anchored and trauma-informed interventions SO CNS SPECTRUMS LA English DT Article DE Aggression; prevention; psychosocial; trauma informed; violence; violence assessment ID RISK-ASSESSMENT; BEHAVIOR; CHILDHOOD; OFFENDERS; SETTINGS; WARDS AB Psychosocial interventions are part of the complex understanding and treatment of violent behavior in our state mental health hospitals. A comprehensive assessment of violence and aggression includes attention to all 3 domains of prevention and assessment (primary-institutional, secondary-structural, and tertiary-direct). Trauma experiences and their consequences may include behavioral violence and aggression. The authors' premise is that trauma is a universal component in the individual assessment of violent behavior. Therapeutic interventions must include a trauma-informed formulation to be effective. Organizational commitment to trauma-informed, person-centered, recovery-oriented (TPR) care is crucial to the efficacy of any of the interventions discussed. Thus, the dynamic nature of the individual, interpersonal, environmental, and cultural factors associated with the daily operations of the inpatient unit need to be assessed through the lens of primary and secondary violence prevention, building on the recognition that the majority of persons served and staff have significant trauma histories. Once a compassionate, respectful, empathic, and empowering approach is embraced by leadership and staff, the work with individuals can proceed more effectively. Interventions used include a variety of cognitive-behavioral, interpersonal, and somatosensory therapies. These interventions, when effectively applied, result in more self-esteem, self-mastery, self-control for the person served, and diminished behavioral violence. C1 [Horowitz, Deborah] Massachusetts Dept Mental Hlth, Off Training & Dev, Westborough, MA USA. [Guyer, Margaret] Massachusetts Dept Mental Hlth, Cent Off Res Review Comm, Boston, MA 02114 USA. [Guyer, Margaret] Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02115 USA. [Guyer, Margaret] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Sanders, Kathy] Massachusetts Dept Mental Hlth, Clin & Profess Serv, Boston, MA 02114 USA. [Sanders, Kathy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Sanders, K (reprint author), Massachusetts Dept Mental Hlth, 25 Staniford St, Boston, MA 02114 USA. EM kathy.sanders@massmail.state.ma.us NR 54 TC 2 Z9 2 U1 1 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2015 VL 20 IS 3 BP 190 EP 199 DI 10.1017/S1092852915000280 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CI7XP UT WOS:000354979800006 PM 25959809 ER PT J AU Rosell, DR Siever, LJ AF Rosell, Daniel R. Siever, Larry J. TI The neurobiology of aggression and violence SO CNS SPECTRUMS LA English DT Review DE Amgydala; cortisol; dopamine; intermittent explosive disorder (IED); monoamine oxidase A (MAOA); orbitofrontal cortex; serotonin; testosterone; tryptophan hydroxylase 2 (TPH2); vasopressin ID BORDERLINE PERSONALITY-DISORDER; SEROTONIN TRANSPORTER GENE; MONOAMINE-OXIDASE-A; 1B RECEPTOR GENE; IMPAIRED IMPULSE CONTROL; IPSAPIRONE CHALLENGE CORRELATE; ALCOHOL-HEIGHTENED AGGRESSION; POSITRON-EMISSION-TOMOGRAPHY; CALLOUS-UNEMOTIONAL TRAITS; ACUTE TRYPTOPHAN DEPLETION AB Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala-frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field. C1 [Rosell, Daniel R.; Siever, Larry J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Rosell, Daniel R.; Siever, Larry J.] Icahn Sch Med Mt Sinai, Special Evaluat Program Mood & Personal Disorders, New York, NY 10029 USA. [Siever, Larry J.] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. [Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN3, Bronx, NY USA. RP Siever, LJ (reprint author), James J Peters Dept Vet Affairs Med Ctr, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM larry.siever@va.gov FU National Institute of Mental Health [MH63875]; Department of Veterans Affairs Office of Academic Affiliations Psychiatric Research/Neurosciences Advanced Fellowship FX Writing of this manuscript was supported by Grant MH63875 from the National Institute of Mental Health to Larry J. Siever. Writing of this manuscript was also supported by The Department of Veterans Affairs Office of Academic Affiliations Psychiatric Research/Neurosciences Advanced Fellowship. NR 249 TC 22 Z9 22 U1 17 U2 103 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2015 VL 20 IS 3 BP 254 EP 279 DI 10.1017/S109285291500019X PG 26 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CI7XP UT WOS:000354979800014 PM 25936249 ER PT J AU Chang, VS Dhaliwal, DK Raju, L Kowalski, RP AF Chang, Victoria S. Dhaliwal, Deepinder K. Raju, Leela Kowalski, Regis P. TI Antibiotic Resistance in the Treatment of Staphylococcus aureus Keratitis: a 20-Year Review SO CORNEA LA English DT Article DE Staphylococcus keratitis; MRSA; MSSA; antimicrobials ID BACTERIAL KERATITIS; SUSCEPTIBILITY PATTERNS; METHICILLIN-RESISTANCE; SHIFTING TRENDS; INFECTIONS; BACTEREMIA; VIRULENCE; MRSA; FLUOROQUINOLONES; CIPROFLOXACIN AB Purpose: We compared the resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) keratitis isolates with the common topically applied ophthalmic antimicrobials. Methods: We reviewed the antibiotic susceptibility results of 122 MRSA and 276 MSSA keratitis isolates from January 1993 to November 2012. In vitro susceptibility testing of each Staphylococcus aureus (SA) isolate was performed using Kirby-Bauer disk diffusion based on modified serum interpretations for cefoxitin, bacitracin, cefazolin, ciprofloxacin, gatifloxacin, gentamicin, moxifloxacin, ofloxacin, polymyxin B, sulfamethoxazole, tobramycin, and trimethoprim. Results: MRSA represented 30.7% (122 of 398) of the total SA isolates. All the SA isolates were susceptible to vancomycin, whereas they were less susceptible to the fluoroquinolones than to the nonfluoroquinolones. In comparison with MSSA, MRSA was significantly more resistant to all the antibiotics tested other than polymyxin B (both equally resistant) and vancomycin (both equally susceptible) (P < 0.001). Besides vancomycin, MRSA demonstrated the best susceptibilities to sulfamethoxazole (94.3%), bacitracin (89.3%), trimethoprim (88.5%), and gentamicin (86.1%). Additionally, MRSA was found to be significantly more resistant to the second-generation fluoroquinolones (ciprofloxacin and ofloxacin) than to the fourth-generation fluoroquinolones (moxifloxacin and gatifloxacin). An increase in resistance to the fourth-generation fluoroquinolones was detected for both MRSA and MSSA over the study period. Conclusions: The in vitro susceptibilities of commonly used topical antibiotics differ for MRSA and MSSA isolates; thus, successful treatment of bacterial keratitis should be supported with laboratory studies. Vancomycin remains the treatment of choice for MRSA keratitis. The empiric use of second-generation fluoroquinolones seems to be contraindicated in the treatment of MRSA keratitis. C1 [Chang, Victoria S.; Dhaliwal, Deepinder K.; Raju, Leela; Kowalski, Regis P.] UPMC, Dept Ophthalmol, Charles T Campbell Ophthalm Microbiol Lab, Ophthalmol & Visual Sci Res Ctr, Pittsburgh, PA USA. RP Chang, VS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM victoriaschang@gmail.com FU Eye and Ear Foundation of Pittsburgh, Pittsburgh, PA; National Institutes of Health [P30 EY008098, UL1TR000005]; Research to Prevent Blindness, Inc, New York, NY FX Supported by The Eye and Ear Foundation of Pittsburgh, Pittsburgh, PA, a National Institutes of Health core grant for vision research P30 EY008098, and, an unrestricted grant from Research to Prevent Blindness, Inc, New York, NY. Statistical analysis was performed in part by the University of Pittsburgh's Clinical and Translational Science Institute with the support of the National Institutes of Health through grant UL1TR000005. NR 43 TC 8 Z9 8 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD JUN PY 2015 VL 34 IS 6 BP 698 EP 703 PG 6 WC Ophthalmology SC Ophthalmology GA CH8VB UT WOS:000354313100021 PM 25811722 ER PT J AU Sadeh, N McNiel, DE AF Sadeh, Naomi McNiel, Dale E. TI Posttraumatic Stress Disorder Increases Risk of Criminal Recidivism Among Justice-Involved Persons With Mental Disorders SO CRIMINAL JUSTICE AND BEHAVIOR LA English DT Article DE recidivism risk; trauma; substance use; mental illness; criminal justice system ID VIOLENT BEHAVIOR; SUBSTANCE USE; JAIL INMATES; ILLNESS; PTSD; VICTIMIZATION; OFFENDERS; TRAUMA; SYMPTOMS; PATHWAYS AB Posttraumatic stress disorder (PTSD) is a potentially important, yet understudied, mental disorder to consider in models of criminal recidivism. The present study sought to address this gap in the literature with a large-scale secondary analysis of observational data from a sample of justice-involved persons with mental disorders. Administrative data were reviewed for 771 adult jail detainees with mental disorders. Hierarchical logistic regression models showed that PTSD was associated with a greater likelihood of general (arrest for any new charge) and serious (arrest for a new felony charge) recidivism during the year following the index arrest, after controlling for risk conferred by a recent history of arrest, demographic characteristics, and other mental disorders. Furthermore, risk of rearrest for new charges was comparable for PTSD and substance use disorders. Findings show that PTSD increases risk of both general and serious recidivism and suggest it should be considered in interventions to reduce justice-system involvement. C1 [Sadeh, Naomi] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McNiel, Dale E.] Univ Calif San Francisco, Dept Psychiat, Sch Med, San Francisco, CA 94143 USA. RP Sadeh, N (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,116B-2, Boston, MA 02130 USA. EM naomisadeh@gmail.com OI Sadeh, Naomi/0000-0002-8101-3190 NR 47 TC 0 Z9 0 U1 2 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0093-8548 EI 1552-3594 J9 CRIM JUSTICE BEHAV JI Crim. Justice Behav. PD JUN PY 2015 VL 42 IS 6 BP 573 EP 586 DI 10.1177/0093854814556880 PG 14 WC Psychology, Clinical; Criminology & Penology SC Psychology; Criminology & Penology GA CI6EM UT WOS:000354851500001 ER PT J AU Kotloff, RM Blosser, S Fulda, GJ Malinoski, D Ahya, VN Angel, L Byrnes, MC DeVita, MA Grissom, TE Halpern, SD Nakagawa, TA Stock, PG Sudan, DL Wood, KE Anillo, SJ Bleck, TP Eidbo, EE Fowler, RA Glazier, AK Gries, C Hasz, R Herr, D Khan, A Landsberg, D Lebovitz, DJ Levine, DJ Mathur, M Naik, P Niemann, CU Nunley, DR O'Connor, KJ Pelletier, SJ Rahman, O Ranjan, D Salim, A Sawyer, RG Shafer, T Sonneti, D Spiro, P Valapour, M Vikraman-Sushama, D Whelan, TPM AF Kotloff, Robert M. Blosser, Sandralee Fulda, Gerard J. Malinoski, Darren Ahya, Vivek N. Angel, Luis Byrnes, Matthew C. DeVita, Michael A. Grissom, Thomas E. Halpern, Scott D. Nakagawa, Thomas A. Stock, Peter G. Sudan, Debra L. Wood, Kenneth E. Anillo, Sergio J. Bleck, Thomas P. Eidbo, Elling E. Fowler, Richard A. Glazier, Alexandra K. Gries, Cynthia Hasz, Richard Herr, Dan Khan, Akhtar Landsberg, David Lebovitz, Daniel J. Levine, Deborah Jo Mathur, Mudit Naik, Priyumvada Niemann, Claus U. Nunley, David R. O'Connor, Kevin J. Pelletier, Shawn J. Rahman, Omar Ranjan, Dinesh Salim, Ali Sawyer, Robert G. Shafer, Teresa Sonneti, David Spiro, Peter Valapour, Maryam Vikraman-Sushama, Deepak Whelan, Timothy P. M. CA Soc Critical Care Med Amer Coll Chest Phys Assoc Organ Procurement Org Donor TI Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement SO CRITICAL CARE MEDICINE LA English DT Article DE critical care; organ donor; organ transplantation ID BRAIN-DEAD DONORS; ORTHOTOPIC LIVER-TRANSPLANTATION; HEART-BEATING DONORS; HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL; ANTIBODY-POSITIVE DONORS; SINGLE-CENTER EXPERIENCE; DELAYED GRAFT FUNCTION; TASK-FORCE RECOMMENDATIONS; OF-WISCONSIN EXPERIENCE AB This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus. C1 [Kotloff, Robert M.; Valapour, Maryam] Cleveland Clin, Dept Pulm Med, Cleveland, OH 44106 USA. [Blosser, Sandralee] Penn State Hershey Med Ctr, Div Pulm Allergy & Crit Care Med, Hershey, PA USA. [Blosser, Sandralee] Pittsburgh Crit Care Assoc, Pittsburgh, PA USA. [Fulda, Gerard J.] Christiana Care Hlth Syst, Dept Surg, Newark, DE USA. [Malinoski, Darren] Portland VA Med Ctr, Dept Surg, Portland, OR USA. [Ahya, Vivek N.; Halpern, Scott D.] Hosp Univ Penn, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. [Angel, Luis; Levine, Deborah Jo] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA. [Byrnes, Matthew C.] Univ Minnesota, Med Ctr, Dept Surg, Minneapolis, MN 55455 USA. [DeVita, Michael A.] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, Dept Gen Surg, New York, NY 10032 USA. [Grissom, Thomas E.] Univ Maryland, Med Ctr, Dept Anesthesiol, Baltimore, MD 21201 USA. [Nakagawa, Thomas A.] Wake Forest Baptist Hlth Med Ctr, Pediat Crit Care Sect, Winston Salem, NC USA. [Stock, Peter G.; Niemann, Claus U.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Sudan, Debra L.; Vikraman-Sushama, Deepak] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Wood, Kenneth E.] Geisinger Med Ctr, Danville, PA 17822 USA. [Anillo, Sergio J.] SUNY Buffalo, Buffalo, NY 14260 USA. [Bleck, Thomas P.] Rush Med Coll, Dept Neurol, Chicago, IL 60612 USA. [Eidbo, Elling E.; Fowler, Richard A.] Assoc Organ Procurement Organizat, Vienna, VA USA. [Glazier, Alexandra K.] New England Organ Bank Inc, Waltham, MA USA. [Gries, Cynthia] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Hasz, Richard] Gift Life, Philadelphia, PA USA. [Herr, Dan] Univ Maryland, Med Ctr, Dept Med, Baltimore, MD 21201 USA. [Khan, Akhtar] Allegheny Gen Hosp, Dept Surg, Pittsburgh, PA 15212 USA. [Landsberg, David] SUNY Upstate Med Ctr, Dept Emergency Med, Syracuse, NY USA. [Lebovitz, Daniel J.] Akron Childrens Hosp, Dept Pediat Crit Care Med, Akron, OH USA. [Mathur, Mudit] Loma Linda Univ, Childrens Hosp, Dept Crit Care Med, Loma Linda, CA 92350 USA. [Nunley, David R.] Univ Louisville Hosp, Div Pulm & Crit Care Med, Louisville, KY USA. [O'Connor, Kevin J.] LifeCtr Northwest, Bellevue, WA USA. [Pelletier, Shawn J.; Sawyer, Robert G.] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA USA. [Rahman, Omar] Indiana Univ Hlth Syst, Pulm & Crit Care, Indianapolis, IN USA. [Ranjan, Dinesh] Oscar G Johnson Vet Adm Med Ctr, Dept Surg, Iron Mt, MI USA. [Salim, Ali] Brigham & Womens Hosp, Trauma Burns & Surg Crit Care Div, Boston, MA 02115 USA. [Shafer, Teresa] Texas Transplantat Soc, Austin, TX USA. [Sonneti, David] Univ Wisconsin, Div Pulm & Crit Care Med, Madison, WI USA. [Spiro, Peter] Harlem Hosp Med Ctr, Dept Pulm, New York, NY USA. [Whelan, Timothy P. M.] Med Univ S Carolina, Div Pulm Crit Care & Sleep Med, Charleston, SC 29425 USA. RP Kotloff, RM (reprint author), Cleveland Clin, Dept Pulm Med, Cleveland, OH 44106 USA. EM kotlofr@ccf.org FU Society of Critical Care Medicine; American College of Chest Physicians; Association of Organ Procurement Organizations; Health Resources and Services Administration (HRSA); Agency for Healthcare Research and Quality grants; AOPO; Washington Regional Transplant Community; PneumRx; National Heart, Lung and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX Supported, in part, by the Society of Critical Care Medicine, American College of Chest Physicians, and Association of Organ Procurement Organizations.; Dr. Malinoski consulted for the Organ Donation and Transplantation Alliance, lectured for multiple organ procurement organizations, and disclosed government work. His institution received grant support from Health Resources and Services Administration (HRSA). Dr. Ahya consulted for Catapult Consulting (the entity is contracted by Centers for Medicare and Medicaid Services to review lung transplant programs with lower than expected outcomes) and received royalties from UptoDate (Lung Transplant section in UptoDate). Dr. Byrnes is employed by the Saint Catherine Hospital. Dr. Nakagawa received royalties from UpToDate and consulted for the U.S. Department of Health and Human Services, HRSA, and the Organ Donation and Transplantation Alliance. Dr. Wood and his institution received grant support from Agency for Healthcare Research and Quality grants. Mr. Eidbo has disclosed that he is executive director of the Association of Organ Procurement Organizations (AOPO). Mr. Fowler received support for article writing/review from the AOPO (led AOPO's expert review of the article and associated revisions), consulted for the AOPO (independent consultant-relevant client during the time period) and the Washington Regional Transplant Community (independent consultant-relevant client during the time period), and has stock in Johnson & Johnson. Dr. Gries received support for travel from American Society of Transplantation (travel to Board of Directors meeting, travel to give talk). Her institution received grant support from PneumRx. Dr. Mathur is employed by the Faculty Physicians and Surgeons of Loma Linda University School of Medicine. His institution received grant support from the National Heart, Lung and Blood Institute (the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials). Dr. Niemann served as a board member for the International Liver Transplant Society, consulted for MedSleuth, is employed by University of California, San Francisco, has stock options with MedSleuth (nothing paid), and received support for article research from HRSA. He and his institution received grant support from HRSA. Dr. Salim's institution received grant support from National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Sonetti is employed by the University of Wisconsin Hospital and Clinic, University of Wisconsin Medical Foundation, and the William S. Middleton Memorial Veteran Hospital (Madison, WI). Dr. Valapour is employed by the University of Minnesota and the Cleveland Clinic and received support for article research from the National Institutes of Health (the topic was covered by this article but the funding was not for this particular project). She and her institution received Federal grant support (investigator for Scientific Registry of Transplant Recipients). Dr. Whelan consulted for LifePoint (Organ Procurement Organization of South Carolina). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 311 TC 25 Z9 26 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2015 VL 43 IS 6 BP 1291 EP 1325 DI 10.1097/CCM.0000000000000958 PG 35 WC Critical Care Medicine SC General & Internal Medicine GA CI4LL UT WOS:000354720300039 PM 25978154 ER PT J AU Villar, J Kacmarek, RM AF Villar, Jesus Kacmarek, Robert M. TI New Classification of Acute Respiratory Distress Syndrome: Not So Convincing Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID ACUTE MYOCARDIAL-INFARCTION; MEDICAL THERAPY C1 [Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesiol, Boston, MA 02115 USA. RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. NR 8 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 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2015 VL 43 IS 6 BP E214 EP E215 DI 10.1097/CCM.0000000000000983 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA CI4LL UT WOS:000354720300016 PM 25978179 ER PT J AU Spoont, MR Nelson, DB Murdoch, M Sayer, NA Nugent, S Rector, T Westermeyer, J AF Spoont, Michele R. Nelson, David B. Murdoch, Maureen Sayer, Nina A. Nugent, Sean Rector, Thomas Westermeyer, Joseph TI ARE THERE RACIAL/ETHNIC DISPARITIES IN VA PTSD TREATMENT RETENTION? SO DEPRESSION AND ANXIETY LA English DT Article DE PTSD; posttraumatic stress disorder; adherence; ethnicity; race; health services; treatment ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE PATIENTS; OF-VETERANS-AFFAIRS; MENTAL-HEALTH-SERVICES; UNITED-STATES; DEPRESSION TREATMENT; PROLONGED EXPOSURE; PSYCHOTROPIC MEDICATION; RACIAL-DIFFERENCES; CLINICAL-RESEARCH AB BackgroundChronic posttraumatic stress disorder (PTSD) can result in significant social and physical impairments. Despite the Department of Veterans Affairs' (VA) expansion of mental health services into primary care clinics to reach larger numbers of Veterans with PTSD, many do not receive sufficient treatment to clinically benefit. This study explored whether the odds of premature mental health treatment termination varies by patient race/ethnicity and, if so, whether such variation is associated with differential access to services or beliefs about mental health treatments. MethodsProspective national cohort study of VA patients who were recently diagnosed with PTSD (n = 6,788). Self-administered surveys and electronic VA databases were utilized to examine mental health treatment retention across racial/ethnic groups in the 6 months following the PTSD diagnosis controlling for treatment need, access factors, age, gender, treatment beliefs, and facility factors. ResultsAfrican American and Latino Veterans were less likely to receive a minimal trial of pharmacotherapy and African American Veterans were less likely to receive a minimal trial of any treatment in the 6 months after being diagnosed with PTSD. Controlling for beliefs about mental health treatments diminished the lower odds of pharmacotherapy retention among Latino but not African American Veterans. Access factors did not contribute to treatment retention disparities. ConclusionsEven in safety-net healthcare systems like VA, racial and ethnic disparities in mental health treatment occur. To improve treatment equity, clinicians may need to more directly address patients' treatment beliefs. More understanding is needed to address the treatment disparity for African American Veterans. C1 [Spoont, Michele R.] Univ Minnesota, Sch Med, US Dept Vet Affairs, Natl Ctr PTSD, Minneapolis, MN 55455 USA. [Spoont, Michele R.; Nelson, David B.; Murdoch, Maureen; Sayer, Nina A.; Nugent, Sean; Rector, Thomas; Westermeyer, Joseph] Univ Minnesota, Sch Med, Minneapolis VA Healthcare Syst, CCDOR, Minneapolis, MN 55455 USA. RP Spoont, MR (reprint author), Minneapolis VA Healthcare Syst, CCDOR, 152,Bldg 9,One Vet Dr, Minneapolis, MN 55417 USA. EM michele.spoont@va.gov RI Sayer, Nina/E-3249-2016 FU U.S. Department of Veterans Affairs (VA); Veterans Health Administration; Health Services Research and Development Service [IAC 06-266] FX Contract grant sponsor: U.S. Department of Veterans Affairs (VA); Veterans Health Administration; Health Services Research and Development Service; Contract grant number: IAC 06-266. NR 67 TC 9 Z9 9 U1 5 U2 9 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 JUN PY 2015 VL 32 IS 6 BP 415 EP 425 DI 10.1002/da.22295 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CI2IB UT WOS:000354568500005 PM 25421265 ER PT J AU Zhang, HJ Garcia, JM AF Zhang, Hongjie Garcia, Jose M. TI Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE anamorelin; cancer-anorexia-cachexia syndrome; ghrelin; NSCLC ID GROWTH-HORMONE SECRETAGOGUE; GHRELIN RECEPTOR AGONIST; PLACEBO-CONTROLLED TRIAL; CELL LUNG-CANCER; DOUBLE-BLIND; MESSENGER-RNA; HEALTHY-VOLUNTEERS; ARCUATE NUCLEUS; TUMOR-GROWTH; BODY-WEIGHT AB Introduction: Cancer anorexia-cachexia syndrome (CACS) is associated with increased morbidity and mortality. Anamorelin is a novel, orally active ghrelin receptor agonist in clinical development for the treatment of CACS in NSCLC. The aim of this review is to summarize preclinical and clinical studies evaluating anamorelin as a potential promising treatment for CACS in NSCLC. Areas covered: Pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability of anamorelin for the treatment of CACS in NSCLC were reviewed. Anamorelin administration may lead to increases in food intake, body weight and lean body mass, and a stimulatory effect on growth hormone secretion in NSCLC patients. Anamorelin is well tolerated with no dose-limiting toxicities identified to date. Expert opinion: Targeting ghrelin receptors presents the advantage of potentially addressing multiple mechanisms of CACS simultaneously including appetite, muscle protein balance, adipose tissue metabolism, energy expenditure and inflammation. Clinical data suggest that anamorelin is well tolerated and it effectively increases appetite, body weight and lean mass in patients with advanced NSCLC. Long-term safety remains unknown at this time. The potential synergistic effects of anamorelin with nutritional support or exercise as well as its efficacy/safety in other tumor types are also unknown. C1 [Zhang, Hongjie; Garcia, Jose M.] Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, CTRID, Houston, TX 77030 USA. RP Garcia, JM (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, CTRID, 2002 Holcombe Blvd,Bldg 109,Room 210, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU Department of Veterans Affairs (MERIT) [BX000507, CX000174]; NIA [AG040583]; Aeterna Zentaris Inc.; Helsinn Therapeutics (US), Inc. FX The authors have received funding from Department of Veterans Affairs (MERIT grants: BX000507 and CX000174) and the NIA (AG040583), Aeterna Zentaris Inc., and Helsinn Therapeutics (US), Inc. J Garcia has received consulting or advisory role's fees from Aeterna Zentaris Inc. and Helsinn Therapeutics (US), Inc. 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 73 TC 9 Z9 10 U1 3 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD JUN PY 2015 VL 16 IS 8 BP 1245 EP 1253 DI 10.1517/14656566.2015.1041500 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CH7KI UT WOS:000354214700012 PM 25945893 ER PT J AU Glavey, SV Ghobrial, IM AF Glavey, Siobhan V. Ghobrial, Irene M. TI American Society of Hematology Annual Meeting 2014: highlights in multiple myeloma SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review ID DEXAMETHASONE; LENALIDOMIDE C1 [Glavey, Siobhan V.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Glavey, SV (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM siobhan_glavey@dfci.harvard.edu NR 21 TC 2 Z9 2 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 EI 1747-4094 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD JUN PY 2015 VL 8 IS 3 BP 273 EP 275 DI 10.1586/17474086.2015.1029449 PG 3 WC Hematology SC Hematology GA CH9XD UT WOS:000354389000004 PM 25804827 ER PT J AU Castillo, JJ Chavez, JC Hernandez-Ilizaliturri, FJ Montes-Moreno, S AF Castillo, Jorge J. Chavez, Julio C. Hernandez-Ilizaliturri, Francisco J. Montes-Moreno, Santiago TI CD20-negative diffuse large B-cell lymphomas: biology and emerging therapeutic options SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review DE ALK-positive DLBCL; CD20-negative; multicentric Castleman disease; plasmablastic lymphoma; primary effusion lymphoma ID PRIMARY-EFFUSION-LYMPHOMA; HIV-INFECTED PATIENTS; MULTICENTRIC CASTLEMAN-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKIN-LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; PLASMABLASTIC LYMPHOMA; KAPOSI-SARCOMA; BRENTUXIMAB VEDOTIN; SINGLE-INSTITUTION AB CD20-negative diffuse large B-cell lymphoma (DLBCL) is a rare and heterogeneous group of lymphoproliferative disorders. Known variants of CD20-negative DLBCL include plasmablastic lymphoma, primary effusion lymphoma, large B-cell lymphoma arising in human herpesvirus 8-associated multicentric Castleman disease and anaplastic lymphoma kinase-positive DLBCL. Given the lack of CD20 expression, atypical cellular morphology and aggressive clinical behavior characterized by chemotherapy resistance and inferior survival rates, CD20-negative DLBCL represents a challenge from the diagnostic and therapeutic perspectives. The goals of the present review are to summarize the current knowledge on the biology of the distinct variants of CD20-negative DLBCL, provide future therapeutic directions based on the limited preclinical and clinical data available, and increase awareness concerning these rare malignancies among pathologists and clinicians. C1 [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. [Chavez, Julio C.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Malignant Hematol, Tampa, FL 33682 USA. [Hernandez-Ilizaliturri, Francisco J.] Roswell Pk Canc Inst, Med Oncol & Immunol, Buffalo, NY 14263 USA. [Montes-Moreno, Santiago] Hosp Univ Marques Valdecilla, Dept Pathol, IDIVAL, Santander, Spain. RP Castillo, JJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Montes-Moreno, Santiago/0000-0002-3565-8262; Castillo, Jorge/0000-0001-9490-7532 NR 99 TC 5 Z9 5 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1747-4086 EI 1747-4094 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD JUN PY 2015 VL 8 IS 3 BP 343 EP 354 DI 10.1586/17474086.2015.1007862 PG 12 WC Hematology SC Hematology GA CH9XD UT WOS:000354389000010 PM 25641215 ER PT J AU Im, H Shao, HL Weissleder, R Castro, CM Lee, H AF Im, Hyungsoon Shao, Huilin Weissleder, Ralph Castro, Cesar M. Lee, Hakho TI Nano-plasmonic exosome diagnostics SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE cancer; exosome; extracellular vesicles; molecular diagnosis; surface plasmon resonance ID TUMOR-DERIVED EXOSOMES; CIRCULATING EXOSOMES; MICROVESICLES; RESONANCE; CELLS; THERAPY; ARRAYS; QUANTIFICATION; TRANSMISSION; BIOGENESIS AB Exosomes have emerged as a promising biomarker. These vesicles abound in biofluids and harbor molecular constituents from their parent cells, thereby offering a minimally-invasive avenue for molecular analyses. Despite such clinical potential, routine exosomal analysis, particularly the protein assay, remains challenging, due to requirements for large sample volumes and extensive processing. We have been developing miniaturized systems to facilitate clinical exosome studies. These systems can be categorized into two components: microfluidics for sample preparation and analytical tools for protein analyses. In this report, we review a new assay platform, nano-plasmonic exosome, in which sensing is based on surface plasmon resonance to achieve label-free exosome detection. Looking forward, we also discuss some potential challenges and improvements in exosome studies. C1 [Im, Hyungsoon; Shao, Huilin; Weissleder, Ralph; Castro, Cesar M.; Lee, Hakho] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Shao, Huilin] Agcy Sci Technol & Res, Inst Mol & Cell Biol, Singapore 138673, Singapore. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Castro, Cesar M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Castro, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM cmcastro@mgh.harvard.edu; hlee@mgh.harvard.edu RI ASTAR, IMCB/E-2320-2012; Im, Hyungsoon/A-3178-2009 OI Im, Hyungsoon/0000-0002-0626-1346 FU NIH [R01 HL113156, P01 CA069246, U54 CA151884, T32-CA79443]; DoD OCRP [W81XWH-14-1-0279]; B.S.-Ph.D. National Science Scholarship - Agency for Science, Technology and Research, Singapore FX This work was supported in part by NIH grants R01 HL113156 to H Lee; NIH grants P01 CA069246, U54 CA151884 and T32-CA79443 to R. Weissleder; and DoD OCRP Award W81XWH-14-1-0279 to H Lee. H Shao acknowledges financial support from the B.S.-Ph.D. National Science Scholarship awarded by the Agency for Science, Technology and Research, Singapore. 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 49 TC 5 Z9 5 U1 11 U2 54 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 EI 1744-8352 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD JUN PY 2015 VL 15 IS 6 BP 725 EP 733 DI 10.1586/14737159.2015.1041378 PG 9 WC Pathology SC Pathology GA CI6OU UT WOS:000354880700003 PM 25936957 ER PT J AU Cychosz, CC Phisitkul, P Belatti, DA Glazebrook, MA DiGiovanni, CW AF Cychosz, Chris C. Phisitkul, Phinit Belatti, Daniel A. Glazebrook, Mark A. DiGiovanni, Christopher W. TI Gastrocnemius recession for foot and ankle conditions in adults: Evidence-based recommendations SO FOOT AND ANKLE SURGERY LA English DT Review DE Gastrocnemius; Soleus; Recession; Lengthening; Systematic review; Equinus; Achilles tendinopathy; Metatarsalgia; Plantar fasciitis ID NONINSERTIONAL ACHILLES TENDINOPATHY; DIABETES-MELLITUS; EQUINUS DEFORMITY; PLANTAR FASCIITIS; CONTRACTURE; ULCERS; RELEASE AB Background: Gastrocnemius recession is a surgical technique commonly performed on individuals who suffer from symptoms related to the restricted ankle dorsiflexion that results when tight superficial posterior compartment musculature causes an equinus contracture. Numerous variations for muscle-tendon unit release along the length of the calf have been described for this procedure over the past century, although all techniques share at least partial or complete release of the gastrocnemius muscle given its role as the primary plantarflexor of the ankle. There exists strong evidence to support the use of this procedure in pediatric patients suffering from cerebral palsy, and increasingly enthusiastic support-but less science-behind its application in treating adult foot and ankle pathologies perceived to be associated with gastrocnemius tightness. The purpose of this study, therefore, was to evaluate currently available evidence for using gastrocnemius recession in three adult populations for whom it is now commonly employed: Achilles tendinopathy, midfoot-forefoot overload syndrome, and diabetic foot ulcers. Methods: A systematic review of the literature was performed on December 21, 2013 using the PubMed, Scopus, and Cochrane databases along with the search term "(gastrocnemius OR gastrocsoleus) AND (recession OR release OR lengthening).'' This search generated 1141 results; 12 articles found in the references of these papers were also screened for inclusion. In total, 18 articles met our inclusion criteria. These articles were reviewed and assigned a classification (I-V) of Level of Evidence, according to the criteria recommended by the Journal of Bone & Joint Surgery. Based on these classifications, a Grade of Recommendation was assigned for each of the indications of interest. Results: Grade B evidence-based literature ("fair'') exists to support the use of gastrocnemius recession for the treatment of isolated foot pain due to midfoot/forefoot overload syndrome in adults. There are some data in support of utilizing gastrocnemius recession to treat midfoot or forefoot ulcers and non-insertional Achilles tendinopathy in adults, but to date this evidence remains Grade C-f. Insufficient evidence (Grade I) is currently available to make any recommendation either for or against this procedure for the treatment of insertional Achilles tendinopathy. Conclusion: Scientific literature continues to grow in support of using isolated gastrocnemius recession as an effective treatment strategy for a variety of lower limb pathologies, although it remains clear that higher evidence levels and more carefully controlled investigations will be necessary to more convincingly define the true efficacy and ideal applications of gastrocnemius recession in the adult population. Level of evidence: Level IV systematic review. (C) 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved. C1 [Cychosz, Chris C.; Belatti, Daniel A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Phisitkul, Phinit] Univ Iowa Hosp & Clin, Dept Orthopaed & Rehabil, Iowa City, IA 52242 USA. [Glazebrook, Mark A.] Dalhousie Univ, Orthopaed Surg, Halifax, NS, Canada. [DiGiovanni, Christopher W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Phisitkul, P (reprint author), Univ Iowa Hosp & Clin, 0102X JPP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM phinit-phisitkul@uiowa.edu NR 34 TC 7 Z9 8 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1268-7731 EI 1460-9584 J9 FOOT ANKLE SURG JI Foot Ankle Surg. PD JUN PY 2015 VL 21 IS 2 BP 77 EP 85 DI 10.1016/j.fas.2015.02.001 PG 9 WC Orthopedics SC Orthopedics GA CI8HS UT WOS:000355013000007 PM 25937405 ER PT J AU Chan, AT Peterson, K AF Chan, Andrew T. Peterson, Kathryn TI How to Position for the Gastroenterology Fellowship of Your Choice: The Program Director Perspective SO GASTROENTEROLOGY LA English DT Editorial Material C1 [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.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Peterson, Kathryn] Univ Utah, Div Gastroenterol, Salt Lake City, UT USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM achan@mgh.harvard.edu FU NIDDK NIH HHS [K24 DK098311] NR 4 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2015 VL 148 IS 7 BP 1265 EP 1267 DI 10.1053/j.gastro.2015.04.022 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CI8IC UT WOS:000355014700011 PM 25921370 ER PT J AU Hsu, L Jeon, J Brenner, H Gruber, SB Schoen, RE Berndt, SI Chan, AT Chang-Claude, J Du, MM Gong, J Harrison, TA Hayes, RB Hoffmeister, M Hutter, CM Lin, Y Nishihara, R Ogino, S Prentice, RL Schumacher, FR Seminara, D Slattery, ML Thomas, DC Thornquist, M Newcomb, PA Potter, JD Zheng, YY White, E Peters, U AF Hsu, Li Jeon, Jihyoun Brenner, Hermann Gruber, Stephen B. Schoen, Robert E. Berndt, Sonja I. Chan, Andrew T. Chang-Claude, Jenny Du, Mengmeng Gong, Jian Harrison, Tabitha A. Hayes, Richard B. Hoffmeister, Michael Hutter, Carolyn M. Lin, Yi Nishihara, Reiko Ogino, Shuji Prentice, Ross L. Schumacher, Fredrick R. Seminara, Daniela Slattery, Martha L. Thomas, Duncan C. Thornquist, Mark Newcomb, Polly A. Potter, John D. Zheng, Yingye White, Emily Peters, Ulrike CA Colorectal Transdisciplinary Genetics Epidemiology Colorectal TI A Model to Determine Colorectal Cancer Risk Using Common Genetic Susceptibility Loci SO GASTROENTEROLOGY LA English DT Article DE Risk Determination; Genome-Wide Association Study; Colorectal Cancer Screening; Risk Stratification ID GENOME-WIDE ASSOCIATION; MUTATION CARRIERS; AMERICAN-COLLEGE; PROSTATE-CANCER; CHROMOSOME 8Q24; COLON-CANCER; TASK-FORCE; PREDICTION; METAANALYSIS; HEALTH AB BACKGROUND & AIMS: Risk for colorectal cancer (CRC) can be greatly reduced through screening. To aid in the development of screening strategies, we refined models designed to determine risk of CRC by incorporating information from common genetic susceptibility loci. METHODS: By using data collected from more than 12,000 participants in 6 studies performed from 1990 through 2011 in the United States and Germany, we developed risk determination models based on sex, age, family history, genetic risk score (number of risk alleles carried at 27 validated common CRC susceptibility loci), and history of endoscopic examinations. The model was validated using data collected from approximately 1800 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, conducted from 1993 through 2001 in the United States. RESULTS: We identified a CRC genetic risk score that independently predicted which patients in the training set would develop CRC. Compared with determination of risk based only on family history, adding the genetic risk score increased the discriminatory accuracy from 0.51 to 0.59 (P = .0028) for men and from 0.52 to 0.56 (P = .14) for women. We calculated age-and sex-specific 10-year CRC absolute risk estimates based on the number of risk alleles, family history, and history of endoscopic examinations. A model that included a genetic risk score better determined the recommended starting age for screening in subjects with and without family histories of CRC. The starting age for high-risk men (family history of CRC and genetic risk score, 90%) was 42 years, and for low-risk men (no family history of CRC and genetic risk score, 10%) was 52 years. For men with no family history and a high genetic risk score (90%), the starting age would be 47 years; this is an intermediate value that is 5 years earlier than it would be for men with a genetic risk score of 10%. Similar trends were observed in women. CONCLUSIONS: By incorporating information on CRC risk alleles, we created a model to determine the risk for CRC more accurately. This model might be used to develop screening and prevention strategies. C1 [Hsu, Li; Jeon, Jihyoun; Du, Mengmeng; Gong, Jian; Harrison, Tabitha A.; Lin, Yi; Prentice, Ross L.; Thornquist, Mark; Newcomb, Polly A.; Potter, John D.; Zheng, Yingye; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Brenner, Hermann] German Canc Consortium, Heidelberg, Germany. [Gruber, Stephen B.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hutter, Carolyn M.; Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. [Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA. [Nishihara, Reiko] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nishihara, Reiko] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Schumacher, Fredrick R.; Thomas, Duncan C.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. RP Hsu, L (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,M2-B500, Seattle, WA 98109 USA. EM lih@fhcrc.org; upeters@fhcrc.org RI Hoffmeister, Michael/B-5745-2012; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X FU National Institutes of Health [P01 CA53996, R01AG14358, R25CA094880, U01 HG004446, GEI U01 HG 004438]; Genetics and Epidemiology of Colorectal Cancer Consortium: National Cancer Institute; Genetics and Epidemiology of Colorectal Cancer Consortium: National Institutes of Health; Genetics and Epidemiology of Colorectal Cancer Consortium: US Department of Health and Human Services [U01 CA137088, R01 CA059045]; Colorectal Transdisciplinary Study: National Cancer Institute, National Institutes of Health under Requests for Applications [CA-09-002 (U19 CA148107)]; Genes, Environment and Health Initiative [Z01 CP 010200] FX This work was supported by the National Institutes of Health (P01 CA53996, R01AG14358, and R25CA094880). The grant support for individual studies was as follows: Genetics and Epidemiology of Colorectal Cancer Consortium: National Cancer Institute, National Institutes of Health, and US Department of Health and Human Services (U01 CA137088 and R01 CA059045); Colorectal Transdisciplinary Study: National Cancer Institute, National Institutes of Health under Requests for Applications #CA-09-002 (U19 CA148107). 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 the Colorectal Transdisciplinary Study, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Colorectal Transdisciplinary Study; Darmkrebs: Chancen der Verhutung durch Screening: 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); Diet, Activity and Lifestyle Study: National Institutes of Health (R01 CA48998 to M.L.S.); Health Professionals Follow-up Study: National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, and P50 CA 127003); Nurses' Health Study: National Institutes of Health (R01 CA137178, P01 CA 087969, and P50 CA 127003); Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. In addition, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility prostate cancer genome-wide association study, Colon Cancer Genetic Markers of Susceptibility pancreatic cancer scan (PanScan), and the Lung Cancer and Smoking study. The prostate and PanScan study data sets were accessed with appropriate approval through the database of Genotypes and Phenotypes online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung data sets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by the National Institutes of Health and the Genes, Environment and Health Initiative Z01 CP 010200, National Institutes of Health U01 HG004446 and GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping; Vitamins And Lifestyle Study: National Institutes of Health (K05 CA154337); Women's Health Initiative: the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 60 TC 10 Z9 10 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2015 VL 148 IS 7 BP 1330 EP + DI 10.1053/j.gastro.2015.02.010 PG 24 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CI8IC UT WOS:000355014700025 PM 25683114 ER PT J AU Tucker-Seeley, RD Mitchell, JA Shires, DA Modlin, CS AF Tucker-Seeley, Reginald D. Mitchell, Jamie A. Shires, Deirdre A. Modlin, Charles S., Jr. TI Financial Hardship, Unmet Medical Need, and Health Self-Efficacy Among African American Men SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE African American men; financial hardship; health self-efficacy; unmet medical need ID PROMOTING LIFE-STYLE; LOW-INCOME; SOCIOECONOMIC-STATUS; STRESS PROCESS; OLDER-ADULTS; BEHAVIORS; INFORMATION; STRAIN; OPPORTUNITIES; PERCEPTIONS AB Background. Health self-efficacy (the confidence to take care of one's health) is a key component in ensuring that individuals are active partners in their health and health care. The purpose of this study was to determine the association between financial hardship and health self-efficacy among African American men and to determine if unmet medical need due to cost potentially mediates this association. Method. Cross-sectional analysis was conducted using data from a convenience sample of African American men who attended a 1-day annual community health fair in Northeast Ohio (N = 279). Modified Poisson regression models were estimated to obtain the relative risk of reporting low health self-efficacy. After adjusting for sociodemographic characteristics, those reporting financial hardship were 2.91 times, RR = 2.91 (confidence interval [1.24, 6.83]; p < .05), more likely to report low health self-efficacy. When unmet medical need due to cost was added to the model, the association between financial hardship and low health self-efficacy was no longer statistically significant. Conclusion. Our results suggest that the association between financial hardship and health self-efficacy can be explained by unmet medical need due to cost. Possible intervention efforts among African American men with low financial resources should consider expanding clinical and community-based health assessments to capture financial hardship and unmet medical need due to cost as potential contributors to low health self-efficacy. C1 [Tucker-Seeley, Reginald D.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Tucker-Seeley, Reginald D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mitchell, Jamie A.; Shires, Deirdre A.] Wayne State Univ, Detroit, MI USA. [Modlin, Charles S., Jr.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Tucker-Seeley, RD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW666A, Boston, MA 02215 USA. EM reginald_tucker-seeley@dfci.harvard.edu FU Michigan Center for Urban African American Aging Research (MCUAAAR) [5P30 AG015281]; National Cancer Institute [CA169041-02] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding from the Michigan Center for Urban African American Aging Research (MCUAAAR, Award 5P30 AG015281) was provided to Dr. Mitchell. Dr. Tucker-Seeley is funded by a K01 career development award (Grant# CA169041-02) from the National Cancer Institute. NR 56 TC 0 Z9 0 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 EI 1552-6127 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD JUN PY 2015 VL 42 IS 3 BP 285 EP 292 DI 10.1177/1090198114557125 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CI8GE UT WOS:000355007600001 PM 25413374 ER PT J AU Loucks, EB Gilman, SE Howe, CJ Kawachi, I Kubzansky, LD Rudd, RE Martin, LT Nandi, A Wilhelm, A Buka, SL AF Loucks, Eric B. Gilman, Stephen E. Howe, Chanelle J. Kawachi, Ichiro Kubzansky, Laura D. Rudd, Rima E. Martin, Laurie T. Nandi, Arijit Wilhelm, Aude Buka, Stephen L. TI Education and Coronary Heart Disease Risk: Potential Mechanisms Such as Literacy, Perceived Constraints, and Depressive Symptoms SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE coronary heart disease; depression; education; literacy; mediation; sense of control ID SOCIOECONOMIC-STATUS; CARDIOVASCULAR-DISEASE; MEDIATION ANALYSIS; ADULT MORTALITY; HEALTH LITERACY; UNITED-STATES; METAANALYSIS; FUTURE; COHORT; LINK AB Objective. Education is inversely associated with coronary heart disease (CHD) risk; however the mechanisms are poorly understood. The study objectives were to evaluate the extent to which rarely measured factors (literacy, time preference, sense of control) and more commonly measured factors (income, depressive symptomatology, body mass index) in the education-CHD literature explain the associations between education and CHD risk. Method. The study sample included 346 participants, aged 38 to 47 years (59.5% women), of the New England Family Study birth cohort. Ten-year CHD risk was calculated using the validated Framingham risk algorithm that utilizes diabetes, smoking, blood pressure, total cholesterol, high-density lipoprotein cholesterol, age, and gender. Multivariable regression and mediation analyses were performed. Results. Regression analyses adjusting for age, race/ethnicity, and childhood confounders (e.g., parental socioeconomic status, intelligence) demonstrated that relative to those with greater than or equal to college education, men and women with less than high school had 73.7% (95% confidence interval [CI; 29.5, 133.0]) and 48.2% (95% CI [17.5, 86.8]) higher 10-year CHD risk, respectively. Mediation analyses demonstrated significant indirect effects for reading comprehension in women (7.2%; 95% CI [0.7, 19.4]) and men (7.2%; 95% CI [0.8, 19.1]), and depressive symptoms (11.8%; 95% CI [2.5, 26.6]) and perceived constraint (6.7%, 95% CI [0.7, 19.1]) in women. Conclusions. Evidence suggested that reading comprehension in women and men, and depressive symptoms and perceived constraint in women, may mediate some of the association between education and CHD risk. If these mediated effects are interpreted causally, interventions targeting reading, depressive symptoms, and perceived constraint could reduce educational inequalities in CHD. C1 [Loucks, Eric B.; Howe, Chanelle J.; Wilhelm, Aude; Buka, Stephen L.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Gilman, Stephen E.; Kawachi, Ichiro; Kubzansky, Laura D.; Rudd, Rima E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martin, Laurie T.] RAND Corp, Arlington, VA USA. [Nandi, Arijit] McGill Univ, Montreal, PQ, Canada. RP Loucks, EB (reprint author), Brown Univ, Sch Publ Hlth, Dept Epidemiol, 121 South Main St, Providence, RI 02912 USA. EM eric.loucks@brown.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU National Institutes of Health (National Institute on Aging) [R01AG023397, R01AG048825] FX This study was supported by National Institutes of Health (National Institute on Aging) grants R01AG023397 and R01AG048825. NR 49 TC 3 Z9 3 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 EI 1552-6127 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD JUN PY 2015 VL 42 IS 3 BP 370 EP 379 DI 10.1177/1090198114560020 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CI8GE UT WOS:000355007600010 PM 25431228 ER PT J AU van der Steen, A Knudsen, AB van Hees, F Walter, GP Berger, FG Daguise, VG Kuntz, KM Zauber, AG van Ballegooijen, M Lansdorp-Vogelaar, I AF van der Steen, Alex Knudsen, Amy B. van Hees, Frank Walter, Gailya P. Berger, Franklin G. Daguise, Virginie G. Kuntz, Karen M. Zauber, Ann G. van Ballegooijen, Marjolein Lansdorp-Vogelaar, Iris TI Optimal Colorectal Cancer Screening in States' Low-Income, Uninsured PopulationsThe Case of South Carolina SO HEALTH SERVICES RESEARCH LA English DT Article DE CRC screening; low-income; uninsured population; budget restriction ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED-TRIAL; SERVICES TASK-FORCE; LARGE-INTESTINE; LARGE-BOWEL; COST-EFFECTIVENESS; AUTOPSY; POLYPS; SIGMOIDOSCOPY; COLONOSCOPY AB ObjectiveTo determine whether, given a limited budget, a state's low-income uninsured population would have greater benefit from a colorectal cancer (CRC) screening program using colonoscopy or fecal immunochemical testing (FIT). Data Sources/Study SettingSouth Carolina's low-income, uninsured population. Study DesignComparative effectiveness analysis using microsimulation modeling to estimate the number of individuals screened, CRC cases prevented, CRC deaths prevented, and life-years gained from a screening program using colonoscopy versus a program using annual FIT in South Carolina's low-income, uninsured population. This analysis assumed an annual budget of $1million and a budget availability of 2years as a base case. Principal FindingsThe annual FIT screening program resulted in nearly eight times more individuals being screened, and more important, approximately four times as many CRC deaths prevented and life-years gained than the colonoscopy screening program. Our results were robust for assumptions concerning economic perspective and the target population, and they may therefore be generalized to other states and populations. ConclusionsA FIT screening program will prevent more CRC deaths than a colonoscopy-based program when a state's budget for CRC screening supports screening of only a fraction of the target population. C1 [van der Steen, Alex; van Hees, Frank; van Ballegooijen, Marjolein; Lansdorp-Vogelaar, Iris] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. [Knudsen, Amy B.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Walter, Gailya P.; Berger, Franklin G.] Univ S Carolina, Ctr Colon Canc Res, Columbia, SC 29208 USA. [Daguise, Virginie G.] Bur Community Hlth & Chron Dis Prevent, South Carolina Dept Hlth & Environm Control, Columbia, SC USA. [Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP van der Steen, A (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM alex.vandersteen@erasmusmc.nl FU National Cancer Institute at the National Institutes of Health; Centers for Disease Control and Prevention [U01CA152959] FX Joint Acknowledgment/Disclosure Statement: This work was supported by the National Cancer Institute at the National Institutes of Health and the Centers for Disease Control and Prevention (U01CA152959). The funding sources had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health, the National Cancer Institute, or the Centers for Disease Control and Prevention. NR 41 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2015 VL 50 IS 3 BP 768 EP 789 DI 10.1111/1475-6773.12246 PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CI6OA UT WOS:000354878300009 PM 25324198 ER PT J AU Upadhyay, GA Chatterjee, NA Kandala, J Friedman, D Park, MY Tabtabai, SR Hung, J Singh, JP AF Upadhyay, Gaurav A. Chatterjee, Neal A. Kandala, Jagdesh Friedman, Daniell Park, Mi-Young Tabtabai, Sara R. Hung, Judy Singh, Jagmeet P. TI Assessing mitral regurgitation in the prediction of clinical outcome after cardiac resynchronization therapy SO HEART RHYTHM LA English DT Article DE Cardiac resynchronization therapy (CRT); Biventricular pacing; LV lead electrical delay; QLV; Mitre regurgitation; Heart failure ID LEFT-VENTRICULAR LEAD; HEART-FAILURE PATIENTS; SYSTOLIC DYSFUNCTION; ELECTRICAL DELAY; TERM; SEVERITY; ECHOCARDIOGRAPHY; RECOMMENDATIONS; MORTALITY; MECHANISM AB BACKGROUND Cardiac resynchronization therapy (CRT) has been shown to reduce mitral regurgitation (MR), although the clinical impact of this improvement remains uncertain. OBJECTIVES We sought to evaluate the impact of MR improvement on clinical outcome after CRT and to assess predictors and mechanism for change in MR. METHODS This was a cohort study of patients undergoing CRT for conventional indications with baseline and follow-up echocardiography (at 6 months). MR severity was classified into 4 grades. The primary end point was time to all-cause death or time to first heart failure (HF) hospitalization assessed at 3 years. RESULTS A total of 439 patients were included: median age was 70.2 years, 90 (20.5%) were women, 255 (58.1%) with ischemic cardiomyopathy, and mean QRS width was 162 ms. Worsening severity of baseline MR was independently predictive of HF or all-cause mortality (hazard ratio 1.33; 95% confidence interval 1.01-1.75; P = .042). Reduction in MR after CRT was significantly associated with lower HF hospitalization and improved survival (hazard ratio 0.65; 95% confidence interval 0.49-0.85; P = .002). Degree of baseline MR and longer surface QRS to left ventricular lead time were significant predictors of MR change. Patients with MR reduction exhibited lower mitral valve tenting area (P < .001) and coaptation height (P < .001) than those with stable or worsening MR, suggestive of improved ventricular geometry as a mechanism for change in MR. CONCLUSION Degree of baseline MR and change in MR after CRT predicted all-cause mortality and HF hospitalization at 3 years. Longer surface ORS to left ventricular lead time at implant may be a means to target MR improvement. C1 [Upadhyay, Gaurav A.; Kandala, Jagdesh; Friedman, Daniell; Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Upadhyay, Gaurav A.] Univ Chicago, Heart Rhythm Ctr, Cardiol Sect, Chicago, IL 60637 USA. [Chatterjee, Neal A.; Tabtabai, Sara R.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Park, Mi-Young; Hung, Judy] Massachusetts Gen Hosp, Echocardiog Lab, Boston, MA 02114 USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM jsingh@partners.org OI Friedman, Daniel /0000-0001-5791-1954 NR 29 TC 8 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD JUN PY 2015 VL 12 IS 6 BP 1201 EP 1208 DI 10.1016/j.hrthm.2015.02.022 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CI5TF UT WOS:000354821900018 PM 25708879 ER PT J AU Murshid, A Gong, JL Ahmad, R Borges, TJ Calderwood, SK AF Murshid, Ayesha Gong, Jianlin Ahmad, Ridwan Borges, Thiago J. Calderwood, Stuart K. TI Scavenger receptor SREC-I promotes double stranded RNA-mediated TLR3 activation in human monocytes SO IMMUNOBIOLOGY LA English DT Article DE TLR3; SREC-I; THP1; Poly I:C; Double stranded RNA; Cytokines ID TOLL-LIKE RECEPTOR-3; ENDOTHELIAL-CELLS-I; HUMAN CORNEAL; PROTEIN; IL-8; RECOGNITION; FIBROBLASTS; INTERFERON; EXPRESSION; PH AB Scavenger receptor associated with endothelial cells (SREC-I) was previously shown to be expressed by immune cells and to play a role in CD8(+)-mediated T cell immunity. SREC-I was also shown to modulate the function of Toll like receptors with essential roles in innate immunity. Here we have shown that SREC-I enhanced double stranded RNA (dsRNA)-mediated Toll like receptor-3 (TLR3) activation. Viral double stranded RNA (dsRNA) was demonstrated to be a pathogen associated molecular pattern (PAMP) signaling viral infection. We found that in human monocyte/macrophage THP1 cells as well as murine bone marrow derived macrophages SREC-I led to elevated responses to the dsRNA-like molecule polyinosine-polycytidylic acid (Poly I:C) and enhanced production of inflammatory cytokines. Our data also showed that intracellular/endocytic TLR3 could directly interact with SREC-I in the presence of Poly I:C. The internalized ligand, along with TLR3 and SREC-I localized in endosomes within macrophages and in HEK293 cells engineered to express TLR3 and SREC-I. SREC-I also stimulated dsRNA-mediated TLR3 activation of signaling through the NF kappa beta, MAP kinase and interferon regulatory factor 3 (IRF3) pathways leading to expression of cytokines, most notably interleukin-8 and interferon-beta. We therefore hypothesized that SREC-I could be a receptor capable of internalizing Poly I:C, boosting TLR3 mediated inflammatory signaling and stimulating cytokine production in macrophages. (C) 2015 Elsevier GmbH. All rights reserved. C1 [Murshid, Ayesha; Ahmad, Ridwan; Borges, Thiago J.; Calderwood, Stuart K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Gong, Jianlin] Boston Univ, Med Ctr, Boston, MA 02215 USA. [Borges, Thiago J.] Pontificia Univ Catolica Rio Grande Sul PUCRS, Sch Biosci, Porto Alegre, RS, Brazil. [Borges, Thiago J.] Pontificia Univ Catolica Rio Grande Sul PUCRS, Biomed Res Inst, Porto Alegre, RS, Brazil. RP Calderwood, SK (reprint author), BIDMC, Ctr Life Sci, 3 Blackfan Circle, Boston, MA 02115 USA. EM scalderw@bidmc.harvard.edu OI Borges, Thiago J/0000-0002-6554-0169 FU US National Institutes of Health [RO-1CA047407, RO-1CA119045, RO-1CA094397]; JCRT; CAPES FX This work was supported by US National Institutes of Health research grants RO-1CA047407, RO-1CA119045 and RO-1CA094397. A.M. is a recipient of JCRT and T.J.B. is a recipient of CAPES fellowship. The authors alone are responsible for the content and writing of the paper. NR 24 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD JUN PY 2015 VL 220 IS 6 BP 823 EP 832 DI 10.1016/j.imbio.2014.12.011 PG 10 WC Immunology SC Immunology GA CI8WX UT WOS:000355053500016 PM 25641411 ER PT J AU Smith, RK Fry, RD Mahmoud, NN Paulson, EC AF Smith, Radhika K. Fry, Robert D. Mahmoud, Najjia N. Paulson, E. Carter TI Surveillance after neoadjuvant therapy in advanced rectal cancer with complete clinical response can have comparable outcomes to total mesorectal excision SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Article DE Complete clinical response; Non-operative management; Neoadjuvant chemoradiation; Rectal cancer ID ABDOMINOPERINEAL RESECTION; NONOPERATIVE MANAGEMENT; CHEMORADIATION THERAPY; MORBIDITY; CHEMORADIOTHERAPY; ADENOCARCINOMA AB While the standard of care for patients with rectal cancer who sustain a complete clinical response (cCR) to chemoradiotherapy (CRT) remains proctectomy with total mesorectal excision, data suggests that non-operative management may be a safe alternative. The purpose of this study is to compare outcomes between patients treated with CRT that attained a cCR and opted for a vigilant surveillance to those of the patients who had a complete pathologic response (cPR) following proctectomy. This is a retrospective review of patients treated for adenocarcinoma of the rectum who achieved either a cCR or a cPR following CRT. Patients with a cCR were enrolled in an active surveillance program which included regularly scheduled exams, proctoscopy, serum carcinoembryonic antigen (CEA), endorectal ultrasound, and cross-sectional imaging. Outcomes were compared to those patients who underwent proctectomy with a cPR. Our primary outcome measures were post-treatment complications, recurrence, and survival. We reviewed 18 patients who opted for surveillance after cCR and 30 patients who underwent proctectomy after a cPR. No non-operative patients had a documented treatment complication, while 17 patients with cPR suffered significant morbidity. There were two recurrences in the active surveillance group, one local and once distant, both treated by salvage resection with no associated mortality at 54 and 62 months. In the cPR group, one patient had a distant recurrence 24 months after surgery which was managed non-operatively. This patient died of unrelated causes 35 months after surgery. Active surveillance can be a safe option that avoids the morbidity associated with proctectomy and preserves oncologic outcomes. C1 [Smith, Radhika K.] Temple Univ Hlth Syst, Dept Gen Surg, Philadelphia, PA 19140 USA. [Fry, Robert D.] Hosp Univ Penn, Div Colon & Rectal Surg, Philadelphia, PA 19106 USA. [Mahmoud, Najjia N.; Paulson, E. Carter] Hosp Univ Penn, Div Colon & Rectal Surg, Philadelphia, PA 19104 USA. [Paulson, E. Carter] Hosp Univ Penn, Dept Surg, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Paulson, EC (reprint author), Hosp Univ Penn, Dept Surg, Philadelphia VA Med Ctr, 3900 Woodland Ave,5th Floor Surg Business Off, Philadelphia, PA 19104 USA. EM paulsone@uphs.upenn.edu NR 19 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-1958 EI 1432-1262 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD JUN PY 2015 VL 30 IS 6 BP 769 EP 774 DI 10.1007/s00384-015-2165-2 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CI4HI UT WOS:000354708800005 PM 25787162 ER PT J AU Liu, K Zhang, CF Li, T Ding, YL Tu, T Zhou, FF Qi, WK Chen, HB Sun, XC AF Liu, Kui Zhang, Chunfu Li, Tao Ding, Yanling Tu, Tao Zhou, Fangfang Qi, Wenkai Chen, Huabiao Sun, Xiaochun TI Let-7a inhibits growth and migration of breast cancer cells by targeting HMGA1 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE breast cancer; miRNA; let-7a; HMGA1 ID HMGI(Y) PROTEIN EXPRESSION; MICRORNA FUNCTIONS; TUMOR-SUPPRESSOR; C-ELEGANS; CARCINOMA; METASTASIS; PROLIFERATION; TUMORIGENESIS; INVASION; MYC AB Let-7 is one of the earliest discovered microRNAs (miRNAs) and has been reported to regulate self renewal and tumorigenicity of breast cancer cells. Let-7a is a member of this family and its function has not been fully characterized in breast cancer. First, total RNAs of breast cancer cells (MDA-MB-231, MCF-7), breast cancer tissues and corresponding adjacent normal tissues were extracted and used to detect let-7a expression by qRT-PCR. Secondly, the effects of let-7a on proliferation, colony formation, migration and invasion of breast cancer cells were assessed by in vitro cell culture experiments. Finally, western blotting was performed to demonstrate how let-7a regulated HMGA1 expression. We found that let-7a expression was significantly lower in breast cancer cells and breast cancer tissues compared to corresponding adjacent normal tissues. Cell proliferation, colony formation, migration and invasion were decreased after overexpression of let-7a in breast cancer cells and vice versa. Furthermore, we identified the high mobility group A1 (HMGA1) as a potential target gene of let-7a. Protein expression of the target gene was significantly downregulated in let-7a mimic transfected breast cancer cells and significantly upregulated in let-7a inhibitor transfected breast cancer cells. Our data suggest that let-7a plays an important role as a tumor suppressor gene by targeting HMGA1, which may open novel perspectives for clinical treatments against breast cancer. C1 [Liu, Kui; Li, Tao; Ding, Yanling; Tu, Tao; Zhou, Fangfang; Qi, Wenkai; Chen, Huabiao; Sun, Xiaochun] Jiangsu Univ, Sch Med, Jiangsu Key Lab Clin Lab Med, Zhenjiang 212013, Jiangsu, Peoples R China. [Zhang, Chunfu] Second Peoples Hosp Kunshan, Kunshan 215300, Jiangsu, Peoples R China. [Chen, Huabiao] Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Boston, MA 02114 USA. [Chen, Huabiao] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sun, XC (reprint author), Jiangsu Univ, Sch Med, Jiangsu Key Lab Clin Lab Med, Zhenjiang 212013, Jiangsu, Peoples R China. EM huabiao.chen@mgh.harvard.edu; xiaochun@ujs.edu.cn FU foundation of the Jiangsu University for senior talented man [11JDG0089]; innovation project of Cultivating Graduate of Jiangsu Province [CXLX13_689]; Science Foundation of Kunshan [KS1331] FX This study was supported by the foundation of the Jiangsu University for senior talented man (Grant no. 11JDG0089), the innovation project of Cultivating Graduate of Jiangsu Province (Grant no. CXLX13_689) and the Science Foundation of Kunshan (Grant no. KS1331). NR 57 TC 14 Z9 15 U1 0 U2 8 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 2015 VL 46 IS 6 BP 2526 EP 2534 DI 10.3892/ijo.2015.2949 PG 9 WC Oncology SC Oncology GA CI3QK UT WOS:000354662300026 PM 25846193 ER PT J AU Ballard, A Parker-Autry, C Lin, CP Markland, AD Ellington, DR Richter, HE AF Ballard, Alicia Parker-Autry, Candace Lin, Chee Paul Markland, Alayne D. Ellington, David R. Richter, Holly E. TI Postoperative bowel function, symptoms, and habits in women after vaginal reconstructive surgery SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Bowel preparation; Postoperative bowel function; Vaginal reconstructive surgery ID RANDOMIZED-CONTROLLED-TRIAL; PELVIC FLOOR DISORDERS; URINARY-INCONTINENCE; PROLAPSE SURGERY; ORGAN PROLAPSE; UNITED-STATES; PREVALENCE; OUTCOMES AB The objective was to characterize postoperative bowel symptoms in women undergoing vaginal prolapse reconstructive surgery randomized to preoperative bowel preparation vs a regular diet. Subjects (N = 121) completed two bowel diaries: a 7-day bowel diary immediately before surgery and a 14-day diary postoperatively. Self-reported bowel diary data and symptoms included the time to first bowel movement (BM), daily number of BMs, Bristol Stool Form Scale score, pain, and urgency associated with BM, episodes of fecal incontinence, and use of laxatives. Antiemetic use was abstracted from medical records. Outcomes of groups were compared using Chi-squared/Fisher's exact test or Student's t test as appropriate. Mean time to first postoperative BM was similar in the bowel preparation (n = 60) and control groups (n = 61), 81.2 +/- 28.9 vs 78.6 +/- 28.2 h, p = 0.85. With the first BM, there were no significant differences between bowel preparation and control groups regarding pain (17.2 vs 27.9 %, p = 0.17), fecal urgency with defecation (56.9 vs 52.5 %, p = 0.63), fecal incontinence (14.0 vs 15.0 %, p = 0.88) and > 1 use of laxatives (93.3 vs 96.7 % p = 0.44) respectively. Antiemetic use was similar in both groups (48.3 vs 55.7 % respectively, p = 0.42). There were no differences in the return of bowel function and other bowel symptoms postoperatively between the randomized groups. Lack of bowel preparation does not have an impact on the risk of painful defecation postoperatively. This information may be used to inform patients regarding expectations for bowel function after vaginal reconstructive surgery. C1 [Ballard, Alicia; Parker-Autry, Candace; Ellington, David R.; Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35249 USA. [Lin, Chee Paul] Univ Alabama Birmingham, Ctr Clin & Translat Sci CCTS, Birmingham, AL 35249 USA. [Markland, Alayne D.] Univ Alabama Birmingham, Dept Med, Birmingham VA Med Ctr, Birmingham, AL 35249 USA. [Ballard, Alicia; Parker-Autry, Candace; Ellington, David R.; Richter, Holly E.] Univ Alabama Birmingham, Div Urogynecol & Pelv Reconstruct Surg, Birmingham, AL 35249 USA. RP Richter, HE (reprint author), Univ Alabama Birmingham, Div Urogynecol & Pelv Reconstruct Surg, 619 19th St South,176F Suite 10832, Birmingham, AL 35249 USA. EM hrichter@uabmc.edu OI Markland, Alayne/0000-0002-6567-6744 FU NIDDK NIH HHS [K24 DK068389, 2K24-DK068389] NR 19 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 EI 1433-3023 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD JUN PY 2015 VL 26 IS 6 BP 817 EP 821 DI 10.1007/s00192-015-2634-8 PG 5 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA CI6RN UT WOS:000354888800006 PM 25672646 ER PT J AU Johnson, AM Pulliam, SJ Foust-Wright, C Bordeianou, L Savitt, L Weinstein, MM AF Johnson, A. M. Pulliam, S. J. Foust-Wright, C. Bordeianou, L. Savitt, L. Weinstein, M. M. TI RELATIONSHIP BETWEEN RADIOGRAPHIC AND CLINICAL RECTOCELES IN WOMEN WITH CONSTIPATION: IS THERE A DISEASE CONTINUUM? SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the International-Urogynecological-Association CY JUN 09-13, 2015 CL Nice, FRANCE SP Int Urogynecol Assoc C1 [Johnson, A. M.; Pulliam, S. J.; Foust-Wright, C.; Weinstein, M. M.] Harvard Univ, Massachusetts Gen Hosp,Ctr Pelv Floor Disorders, Sch Med,Div Female Pelv Med, Dept Vincent Obstet Gynecol & Reprod Biol, Boston, MA USA. [Bordeianou, L.; Savitt, L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Colorectal Surg Program, Ctr Pelv Floor Disorders,Div Gen & Gastrointestin, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 EI 1433-3023 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD JUN PY 2015 VL 26 SU 1 MA OP 103 BP S132 EP S133 PG 2 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA CI3AF UT WOS:000354619100104 ER PT J AU Cleary, JM Reardon, DA Azad, N Gandhi, L Shapiro, GI Chaves, J Pedersen, M Ansell, P Ames, W Xiong, H Munasinghe, W Dudley, M Reilly, EB Holen, K Humerickhouse, R AF Cleary, James M. Reardon, David A. Azad, Nilofer Gandhi, Leena Shapiro, Geoffrey I. Chaves, Jorge Pedersen, Michelle Ansell, Peter Ames, William Xiong, Hao Munasinghe, Wijith Dudley, Matt Reilly, Edward B. Holen, Kyle Humerickhouse, Rod TI A phase 1 study of ABT-806 in subjects with advanced solid tumors SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE EGFR; EGFRvIII; Glioblastoma; Solid tumors ID GROWTH-FACTOR-RECEPTOR; SQUAMOUS-CELL CARCINOMAS; MONOCLONAL-ANTIBODY; HUMAN GLIOBLASTOMAS; COLORECTAL-CANCER; EGFR; THERAPY; CHEMOTHERAPY; COMBINATION; CETUXIMAB AB Purpose ABTaEuro806, a humanized recombinant monoclonal antibody, binds a unique epidermal growth factor receptor (EGFR) epitope exposed in the EGFRde2aEuro7 (EGFRvIII) deletion mutant and other EGFR proteins in the activated state. This phase I study evaluated the safety, pharmacokinetics, and recommended phase two dose (RP2D) of ABT-806 in patients with solid tumors that commonly overexpress activated EGFR or EGFRvlll. Methods Patients with advanced solid tumors, including glioblastoma, were eligible. Following a dose escalation phase, expanded safety cohorts of patients with solid tumors or EGFR-amplified glioblastoma were enrolled. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events v4.0; tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.1. EGFR protein expression was quantified by immunohistochemistry. Results 49 patients were treated. Frequent AEs (a parts per thousand yen10 %) possibly/probably related to ABT-806 were fatigue (18 %), nausea (16 %), dermatitis acneiform (12 %), and vomiting (10 %). Only one dose-limiting toxicity (grade three morbilliform rash) occurred. The RP2D was the pre-specified highest dose (24 mg/kg). Systemic exposures were dose proportional between 2 and 24 mg/kg. Median time to progression was 55 days (95 % confidence interval, 53-57) in all patients and 43 days (22-57) for glioblastoma patients. No objective responses occurred; however, two patients had prolonged stable disease. An EGFR-amplified penile cancer patient has stable disease lasting over 2.5 years. Conclusions ABT-806 has unique pharmacokinetic and safety profiles. Toxicities were infrequent and typically low grade at the RP2D. Linear ABT-806 pharmacokinetics suggest lack of significant binding to wild-type EGFR in normal tissues. C1 [Cleary, James M.; Reardon, David A.; Gandhi, Leena; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cleary, James M.; Reardon, David A.; Gandhi, Leena; Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Azad, Nilofer] Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Chaves, Jorge] Northwest Med Specialties, Tacoma, WA USA. [Pedersen, Michelle; Ansell, Peter; Ames, William; Xiong, Hao; Munasinghe, Wijith; Dudley, Matt; Reilly, Edward B.; Holen, Kyle; Humerickhouse, Rod] AbbVie Inc, N Chicago, IL USA. [Cleary, James M.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02215 USA. RP Cleary, JM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jcleary@partners.org OI Gandhi, Leena/0000-0002-2398-9179 FU AbbVie Inc. FX This study was funded by AbbVie Inc. NR 33 TC 3 Z9 3 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD JUN PY 2015 VL 33 IS 3 BP 671 EP 678 DI 10.1007/s10637-015-0234-6 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CI3AZ UT WOS:000354621100013 PM 25895099 ER PT J AU Henderson, MJ AF Henderson, M. J. TI ARE NURSE PRACTITIONERS BECOMING MORE LIKE PHYSICIANS? SO JNP-JOURNAL FOR NURSE PRACTITIONERS LA English DT Editorial Material C1 [Henderson, M. J.] Massachusetts Gen Hosp, Inst Hlth Profess, Nursing, Boston, MA 02114 USA. [Henderson, M. J.] Massachusetts Gen Hosp, Inst Hlth Profess, Adult Gerontol Nurse Practitioner Specialty, Boston, MA 02114 USA. RP Henderson, MJ (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Nursing, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1555-4155 EI 1878-058X J9 JNP-J NURSE PRACT JI JNP-J. Nurse Pract. PD JUN PY 2015 VL 11 IS 6 BP 607 EP 607 PG 1 WC Nursing SC Nursing GA CI7OO UT WOS:000354953800007 ER PT J AU Papaioannou, G Mirzamohammadi, F Lisse, TS Nishimori, S Wein, MN Kobayashi, T AF Papaioannou, Garyfallia Mirzamohammadi, Fatemeh Lisse, Thomas S. Nishimori, Shigeki Wein, Marc N. Kobayashi, Tatsuya TI MicroRNA-140 Provides Robustness to the Regulation of Hypertrophic Chondrocyte Differentiation by the PTHrP-HDAC4 Pathway SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE GROWTH PLATE; GENETIC ANIMAL MODELS; PTHRP; CELL; TISSUE SIGNALING; PARACRINE PATHWAYS; MOLECULAR PATHWAYS; DEVELOPMENT; BONE MODELING AND REMODELING; EPIGENETICS ID ENDOCHONDRAL BONE-FORMATION; CARTILAGE-SPECIFIC MICRORNA-140; MEF2C TRANSCRIPTION FACTOR; HORMONE-RELATED PEPTIDE; HISTONE DEACETYLASE-4; SKELETAL DEVELOPMENT; PARATHYROID-HORMONE; EXPRESSION; PROLIFERATION; TARGETS AB Growth plate chondrocytes go through multiple differentiation steps and eventually become hypertrophic chondrocytes. The parathyroid hormone (PTH)-related peptide (PTHrP) signaling pathway plays a central role in regulation of hypertrophic differentiation, at least in part, through enhancing activity of histone deacetylase 4 (HDAC4), a negative regulator of MEF2 transcription factors that drive hypertrophy. We have previously shown that loss of the chondrocyte-specific microRNA (miRNA), miR-140, alters chondrocyte differentiation including mild acceleration of hypertrophic differentiation. Here, we provide evidence that miR-140 interacts with the PTHrP-HDAC4 pathway to control chondrocyte differentiation. Heterozygosity of PTHrP or HDAC4 substantially impaired animal growth in miR-140 deficiency, whereas these mutations had no effect in the presence of miR-140. miR-140-deficient chondrocytes showed increased MEF2C expression with normal levels of total and phosphorylated HDAC4, indicating that the miR-140 pathway merges with the PTHrP-HDAC4 pathway at the level of MEF2C. miR-140 negatively regulated p38 mitogen-activated protein kinase (MAPK) signaling, and inhibition of p38 MAPK signaling reduced MEF2C expression. These results demonstrate that miR-140 ensures the robustness of the PTHrP/HDAC4 regulatory system by suppressing MEF2C-inducing stimuli. (c) 2014 American Society for Bone and Mineral Research (c) 2015 American Society for Bone and Mineral Research C1 [Kobayashi, Tatsuya] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kobayashi, T (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM tkobayashi1@mgh.harvard.edu FU National Institutes of Health [AR054500, AR056645]; Harvard Stem Cell Institute [SG-0090-13] FX This work was supported by the National Institutes of Health (AR054500 and AR056645 to TK) and the Harvard Stem Cell Institute (SG-0090-13 to TK). We thank Dr. Arthur Broadus for Col2-PTHrP transgenic and PTHrP knockout mice, Dr. Eric Olson for Hdac4 knockout mice, and Dr. Ernestina Schipani for Col2-caPPR transgenic mice. We thank Dr. Henry Kronenberg for helpful discussion. NR 42 TC 9 Z9 10 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2015 VL 30 IS 6 BP 1044 EP 1052 DI 10.1002/jbmr.2438 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CI3CG UT WOS:000354624500013 PM 25529628 ER PT J AU Awad, AJ Walcott, BP Stapleton, CJ Ding, DL Lee, CC Loeffler, JS AF Awad, Ahmed J. Walcott, Brian P. Stapleton, Christopher J. Ding, Dale Lee, Cheng-Chia Loeffler, Jay S. TI Repeat radiosurgery for cerebral arteriovenous malformations SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Review DE Arteriovenous malformation; Gamma knife; LINAC; Neurosurgery; Retreatment; Stereotactic radiosurgery ID GAMMA-KNIFE RADIOSURGERY; STEREOTACTIC RADIOSURGERY; LINEAR-ACCELERATOR; NATURAL-HISTORY; HIGH-GRADE; BRAIN; OBLITERATION; HEMORRHAGE; RISK; OUTCOMES AB We perform a systematic review of repeat radiosurgery for cerebral arteriovenous malformations (AVM) with an emphasis on lesion obliteration rates and complications. Radiosurgery is an accepted treatment modality for AVM located in eloquent cortex or deep brain structures. For residual or persistent lesions, repeat radiosurgery can be considered if sufficient time has passed to allow for a full appreciation of treatment effects, usually at least 3 years. A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. References for this review were identified by searches of MEDLINE, Web of Science and Google Scholar databases. A total of 14 studies comprising 733 patients met the review criteria and were included. For series that reported target dose at both first and repeat treatments, the weighted means were 19.42 Gy and 19.06 Gy, respectively. The mean and median obliteration rate for the repeat radiosurgery treatments were 61% (95% confidence interval 51.9-71.7%) and 61.5%, respectively. The median follow up following radiosurgery ranged from 19.5 to 80 months. Time to complete obliteration after the repeat treatment ranged from 21 to 40.8 months. The most common complications of repeat radiosurgery for AVM included hemorrhage (7.6%) and radiation-induced changes (7.4%). Repeat radiosurgery can be used to treat incompletely obliterated AVM with an obliteration rate of 61%. Complications are related to treatment effect latency (hemorrhage risk) as well as radiation-induced changes. Repeat radiosurgery can be performed at 3 years following the initial treatment, allowing for full realization of effects from the initial treatment prior to commencing therapy. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.; Stapleton, Christopher J.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Awad, Ahmed J.] An Najah Natl Univ, Fac Med & Hlth Sci, Nablus, Israel. [Ding, Dale] Univ Virginia Hlth Syst, Dept Neurosurg, Charlottesville, VA USA. [Lee, Cheng-Chia] Taipei Vet Gen Hosp, Neurol Inst, Dept Neurosurg, Taipei, Taiwan. [Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Loeffler, Jay S.] Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, White Bldg Room 502,55 Fruit St, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [R25 NS065743] NR 58 TC 12 Z9 12 U1 1 U2 6 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 JUN PY 2015 VL 22 IS 6 BP 945 EP 950 DI 10.1016/j.jocn.2015.01.015 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CI8VR UT WOS:000355050300004 PM 25913746 ER PT J AU Reinshagen, C Ruess, D Molcanyi, M Redjal, N Walcott, BP Goldbrunner, R Rieger, B AF Reinshagen, Clemens Ruess, Daniel Molcanyi, Marek Redjal, Navid Walcott, Brian Patrick Goldbrunner, Roland Rieger, Bernhard TI A novel translaminar crossover approach for pathologies in the lumbar hidden zone SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Disc herniation; Hidden zone; Stenosis; Translaminar approach ID DISC HERNIATIONS; MICROSURGICAL APPROACH; PARS INTERARTICULARIS; NEURAL ARCH; ROOT; SPINE; DIAGNOSIS; ANATOMY AB We report eight patients with disc herniations who underwent sequestrectomy via a crossover translaminar technique. The lateral lumbar spinal canal can be divided into several regions: the subarticular, foraminal and extraforaminal zone. Due to its difficult surgical exposure, some authors refer to part of the subarticular and foraminal region as the hidden zone. Conventional approaches involve partial or total facet joint resection, introducing risk of postoperative instability. Under fluoroscopic gu