FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cooper, DC Ziegler, MG Milic, MS Ancoli-Israel, S Mills, PJ Loredo, JS Von Kanel, R Dimsdale, JE AF Cooper, Denise C. Ziegler, Michael G. Milic, Milos S. Ancoli-Israel, Sonia Mills, Paul J. Loredo, Jose S. Von Kaenel, Roland Dimsdale, Joel E. TI Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE endothelial function; polysomnography; sleep; subjective sleep quality; vasodilation ID CARDIOVASCULAR-DISEASE; BRACHIAL-ARTERY; HEALTHY-MEN; APNEA; INFLAMMATION; DYSFUNCTION; STRESS; ATHEROSCLEROSIS; INTERLEUKIN-6; VASODILATION AB Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e. Pittsburgh Sleep Quality Index scores) and objective (i.e. polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps<0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps<0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease. C1 [Cooper, Denise C.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Ziegler, Michael G.; Milic, Milos S.; Loredo, Jose S.; Dimsdale, Joel E.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Ancoli-Israel, Sonia; Mills, Paul J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Von Kaenel, Roland] Univ Hosp Bern, Inselspital, Dept Gen Internal Med, Div Psychosomat Med, CH-3010 Bern, Switzerland. [Von Kaenel, Roland] Univ Bern, Bern, Switzerland. RP Cooper, DC (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM denise.cooper3@va.gov FU National Institutes of Health [HL36005, RR00827, AG08415, P60 MD00220] FX This study was supported by National Institutes of Health Grants HL36005, RR00827, AG08415 and P60 MD00220. NR 30 TC 7 Z9 7 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD FEB PY 2014 VL 23 IS 1 BP 84 EP 93 DI 10.1111/jsr.12083 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA0QD UT WOS:000330800200011 PM 24033699 ER PT J AU James, ML Grau-Sepulveda, MV Olson, DM Smith, EE Hernandez, AF Peterson, ED Schwamm, LH Bhatt, DL Fonarow, GC AF James, Michael L. Grau-Sepulveda, Maria V. Olson, DaiWai M. Smith, Eric E. Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. Bhatt, Deepak L. Fonarow, Gregg C. TI Insurance Status and Outcome after Intracerebral Hemorrhage: Findings from Get With The Guidelines-Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Stroke; intracerebral hemorrhage; epidemiology; cerebrovascular disorders; risk factors; health care policy ID AMERICAN-HEART-ASSOCIATION; PROSPECTIVE-PAYMENT SYSTEM; INPATIENT REHABILITATION; MEDICARE BENEFICIARIES; VEHICULAR INJURY; CARE; HEALTH; MORTALITY; COVERAGE; PROGRAM AB Backgound: Few studies have examined associations among insurance status, treatment, and outcomes in patients hospitalized for intracerebral hemorrhage (ICH). Methods: Through retrospective analyses of the Get With The Guidelines (GWTG)-Stroke database, a national prospective stroke registry, from April 2003 to April 2011, we identified 95,986 nontransferred subjects hospitalized with ICH. Insurance status was categorized as Private/Other, Medicaid, Medicare, or None/Not Documented (ND). Associations between insurance status and in-hospital outcomes and quality of care measures were analyzed using patient-and hospitalspecific variables as covariates. Results: There were significant differences in age and frequency of comorbid conditions by insurance group. Compliance with evidence-based quality of care indicators varied across all insurance status groups (P < .0001) but was generally high. In adjusted analysis with the Private insurance group as reference, the None/ND group most consistently demonstrated higher odds ratios (ORs) for quality of care measures (Dysphagia Screen: OR 1.10, 95% confidence interval [CI] 1.02-1.17, P = .0096; Stroke Education: OR 1.16, 95% CI 1.05-1.29, P = .0042; and Rehabilitation: OR 1.25, 95% CI 1.08-1.44, P = .0027). In-hospital mortality rates were higher for None/ND, Medicaid, and Medicare patients; after risk adjustment, the None/ND group had the highest mortality risk (OR 1.29, 95% CI 1.21-1.38, P < .0001). Medicare and Medicaid patients had lower adjusted odds for both independent ambulation at discharge and discharge to home when compared with the Private/Other group. Conclusions: GWTG-Stroke ICH patients demonstrated differences in mortality, functional status, discharge destination, and quality of care measures associated with insurance status. C1 [James, Michael L.; Grau-Sepulveda, Maria V.; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RP James, ML (reprint author), DUMC 3094, Durham, NC 27710 USA. EM michael.james@duke.edu RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU Ortho-McNeil; Boeringher-Ingelheim; Merck; Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership; American Heart Association Pharmaceutical Round Table; American Heart Association-Scientist Development Grant FX The GWTG-Stroke program is provided by the American Heart Association/American Stroke Association and is currently supported in part by a charitable contribution from Ortho-McNeil. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim and Merck, Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership, and the American Heart Association Pharmaceutical Round Table. This article was also supported by the American Heart Association-Scientist Development Grant (M.L.J.). NR 36 TC 10 Z9 10 U1 0 U2 3 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 FEB PY 2014 VL 23 IS 2 BP 283 EP 292 DI 10.1016/j.jstrokecerebrovasdis.2013.02.016 PG 10 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 302DT UT WOS:000330582500028 PM 23537567 ER PT J AU Bostic, JQ Thurau, L Potter, M Drury, SS AF Bostic, Jeff Q. Thurau, Lisa Potter, Mona Drury, Stacy S. TI Policing the Teen Brain SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 [Bostic, Jeff Q.; Potter, Mona] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bostic, Jeff Q.; Potter, Mona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Potter, Mona] McLean Hosp, Belmont, MA USA. [Thurau, Lisa; Drury, Stacy S.] Tulane Med Sch, New Orleans, LA USA. RP Bostic, JQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, 2 Faith Rd, Windham, NH 03087 USA. FU NIMH NIH HHS [R21 MH094688] NR 5 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2014 VL 53 IS 2 BP 127 EP 129 DI 10.1016/j.jaac.2013.09.021 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AA0WU UT WOS:000330818900001 PM 24472245 ER PT J AU Contreras, MA Alzate, O Singh, AK Singh, I AF Contreras, Miguel A. Alzate, Oscar Singh, Avtar K. Singh, Inderjit TI PPAR alpha Activation Induces N (epsilon)-Lys-Acetylation of Rat Liver Peroxisomal Multifunctional Enzyme Type 1 SO LIPIDS LA English DT Article DE Peroxisome proliferator-activated receptor alpha (PPAR alpha); Lysine-acetylation; Acetylation; Peroxisomes; Rat peroxisomal multifunctional enzyme type 1 (rpMFE-1); Peroxisome proliferation ID ACYL-COA OXIDASE; YEAST YARROWIA-LIPOLYTICA; MOUSE KIDNEY PEROXISOMES; BETA-OXIDATION ENZYMES; QUANTITATIVE PROTEOMICS; BIOGENESIS DISORDERS; LYSINE ACETYLATION; CRYSTAL-STRUCTURE; RECEPTOR-ALPHA; PROTEIN AB Peroxisomes are ubiquitous subcellular organelles that participate in metabolic and disease processes, with few of its proteins undergoing posttranslational modifications. As the role of lysine-acetylation has expanded into the cellular intermediary metabolism, we used a combination of differential centrifugation, organelle isolation by linear density gradient centrifugation, western blot analysis, and peptide fingerprinting and amino acid sequencing by mass spectrometry to investigate protein acetylation in control and ciprofibrate-treated rat liver peroxisomes. Organelle protein samples isolated by density gradient centrifugation from PPAR alpha-agonist treated rat liver screened with an anti-N (epsilon)-acetyl lysine antibody revealed a single protein band of 75 kDa. Immunoprecipitation with this antibody resulted in the precipitation of a protein from the protein pool of ciprofibrate-induced peroxisomes, but not from the protein pool of non-induced peroxisomes. Peptide mass fingerprinting analysis identified the protein as the peroxisomal multifunctional enzyme type 1. In addition, mass spectrometry-based amino acid sequencing resulted in the identification of unique peptides containing 4 acetylated-Lys residues (K-155, K-173, K-190, and K-583). This is the first report that demonstrates posttranslational acetylation of a peroxisomal enzyme in PPAR alpha-dependent proliferation of peroxisomes in rat liver. C1 [Contreras, Miguel A.; Singh, Avtar K.; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Alzate, Oscar] Univ N Carolina, Dept Cell & Dev Biol, Syst Prote Core Lab, Chapel Hill, NC 27599 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Dept Pathol, Charleston, SC 29401 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, 171 Ashley Ave, Charleston, SC 29425 USA. EM miguel.contreras@nih.gov; oscar.alzate@ttuhsc.edu; singhi@musc.edu FU National Center for Research Resources [C06 RR018823, C06 RR015455]; National Institutes of Health [NS-22576, NS-34741, NS-37766, NS-64195] FX The authors greatly appreciate the technical assistance of Ms. Joyce Bryan and Ms. Desiree Vonkollmar, and the help of Dr. Osamu Morinaga for raising the polyclonal antibodies against very long chain acyl-CoA synthetase. They also thank Antonio Contreras for reading the manuscript. This work was supported by Grants from the Extramural Research Facilities Program of the National Center for Research Resources [C06 RR018823 and C06 RR015455] and from the National Institutes of Health [NS-22576, NS-34741, NS-37766, and NS-64195]. NR 49 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 EI 1558-9307 J9 LIPIDS JI Lipids PD FEB PY 2014 VL 49 IS 2 BP 119 EP 131 DI 10.1007/s11745-013-3843-x PG 13 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 304BS UT WOS:000330721100001 PM 24092543 ER PT J AU Sarracanie, M Armstrong, BD Stockmann, J Rosen, MS AF Sarracanie, Mathieu Armstrong, Brandon D. Stockmann, Jason Rosen, Matthew S. TI High Speed 3D Overhauser-Enhanced MRI Using Combined b-SSFP and Compressed Sensing SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE 3D Overhauser MRI; free radicals; EPR; b-SSFP; compressed sensing ID ELECTRON-PARAMAGNETIC-RESONANCE; FIELD-CYCLED PEDRI; FREE-RADICAL SOLUTIONS; IN-VIVO; NITROXYL RADICALS; SURFACE COIL; IMAGE; MICE; EPR; RECONSTRUCTION AB PurposeOverhauser-enhanced MRI is a promising technique for imaging the distribution and dynamics of free radicals. A key challenge for Overhauser-enhanced MRI is attaining high spatial and temporal resolution while simultaneously limiting resonator and sample heating due to the long, high power radio-frequency pulses needed to saturate the electron resonance. MethodsThe approach presented here embeds EPR pulses within a balanced steady state free precession sequence. Unlike other Overhauser-enhanced MRI methods, no separate Overhauser prepolarization step is required. This steady-state approach also eliminates the problem of time-varying Overhauser-enhanced signal and provides constant polarization in the sample during the acquisition. A further increase in temporal resolution was achieved by incorporating undersampled k-space strategies and compressed sensing reconstruction. ResultsWe demonstrate 1 x 2 x 3.5 mm(3) resolution at 6.5 mT across a 54 x 54 x 110 mm(3) sample in 33 s while sampling 30% of k-space. ConclusionThe work presented here overcomes the main limitations of Overhauser enhanced MRI as previously described in the literature, drastically improving speed and resolution, and enabling new opportunities for the measurement of free radicals in living organisms, and for the study of dynamic processes such as metabolism and flow. Magn Reson Med 71:735-745, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Sarracanie, Mathieu; Armstrong, Brandon D.; Stockmann, Jason; Rosen, Matthew S.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Sarracanie, Mathieu; Armstrong, Brandon D.; Stockmann, Jason; Rosen, Matthew S.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Rosen, Matthew S.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Rosen, MS (reprint author), AA Martinos Ctr Biomed Imaging, Low Field MRI & Hyperpolarized Media Lab, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM mrosen@cfa.harvard.edu FU Department of Defense, Defense Medical Research and Development Program, Applied Research and Advanced Technology Development Award [W81XWH-11-2-0076 (DM09094)] FX Grant sponsor: Department of Defense, Defense Medical Research and Development Program, Applied Research and Advanced Technology Development Award; Grant number: W81XWH-11-2-0076 (DM09094). NR 54 TC 10 Z9 10 U1 4 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2014 VL 71 IS 2 BP 735 EP 745 DI 10.1002/mrm.24705 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AA0FA UT WOS:000330769700029 PM 23475813 ER PT J AU Chase, M Goldstein, JN Selim, MH Pallin, DJ Camacho, MA O'Connor, JL Ngo, L Edlow, JA AF Chase, Maureen Goldstein, Joshua N. Selim, Magdy H. Pallin, Daniel J. Camacho, Marc A. O'Connor, Jennifer L. Ngo, Long Edlow, Jonathan A. TI A Prospective Pilot Study of Predictors of Acute Stroke in Emergency Department Patients With Dizziness SO MAYO CLINIC PROCEEDINGS LA English DT Article ID 1ST-EVER ISCHEMIC-STROKE; CEREBELLAR INFARCTION; VESTIBULAR NEURITIS; VERTIGO; MANAGEMENT; PHYSICIANS; DIAGNOSIS; DIZZY; PRESENTATIONS; BEDSIDE AB Objective: To prospectively examine undifferentiated emergency department (ED) patients with dizziness to identify clinical features associated with acute stroke. Patients and Methods: We conducted a pilot study from November 1, 2009, through October 30, 2010, of adult patients with dizziness presenting to 3 urban academic EDs. Data collected included demographic characteristics, medical history, presenting symptoms, examination findings, clinician pretest probability of stroke, and neuroimaging results. Logistic regression was used to identify variables with a significant association with acute stroke (P <. 05). Results: During the study period, we enrolled 473 patients (mean +/- SD age, 56.7 +/- 19.3 years; 60% female; and 71% white). We found 30 acute, serious diagnoses (6.3%), including 14 ischemic strokes, 2 subarachnoid hemorrhages, 7 mass lesions, 2 demyelinating lesions, 2 severe vertebral artery stenoses, 2 acute coronary syndromes, and 1 case of hydrocephalus and meningitis). We identified 6 clinical variables associated with stroke: age (odds ratio [ OR], 1.04; 95% CI, 1.0-1.07), hyperlipidemia (OR, 3.62; 95% CI, 1.24-10.6), hypertension (OR, 4.91; 95% CI, 1.46-16.5), coronary artery disease (OR, 3.33; 95% CI, 1.0610.5), abnormal tandem gait test result (OR, 3.13; 95% CI, 1.10-8.89), and high or moderate physician pretest probability for acute stroke (OR, 18.8; 95% CI, 4.72-74.5). Conclusions: Most ED patients with dizziness do not have a serious cause of their symptoms. Although the small number of outcomes precluded development of a multivariate model, we identified several individual high-risk variables associated with acute ischemic stroke. Further study will be needed to validate the findings of this pilot investigation. (C) 2014 Mayo Foundation for Medical Education and Research C1 [Chase, Maureen; Selim, Magdy H.; Camacho, Marc A.; O'Connor, Jennifer L.; Ngo, Long; Edlow, Jonathan A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pallin, Daniel J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Chase, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Emergency Med, 1 Deaconess Rd, Boston, MA 02215 USA. EM mchase1@bidmc.harvard.edu RI Pallin, Daniel/H-6382-2013; Goldstein, Joshua/H-8953-2016 OI Pallin, Daniel/0000-0002-8517-9702; FU Harvard Catalyst, The Harvard Clinical and Translational Science Center pilot grant [UL1 RR 025758-02] FX This study was supported by Harvard Catalyst, The Harvard Clinical and Translational Science Center pilot grant, UL1 RR 025758-02. NR 30 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 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD FEB PY 2014 VL 89 IS 2 BP 173 EP 180 DI 10.1016/j.mayocp.2013.10.026 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 302DJ UT WOS:000330581500011 PM 24393411 ER PT J AU Mateen, FJ Miller, SA Aksamit, AJ AF Mateen, Farrah J. Miller, Stephanie A. Aksamit, Allen J., Jr. TI Herpes Simplex Virus 2 Encephalitis in Adults SO MAYO CLINIC PROCEEDINGS LA English DT Letter ID CEREBROSPINAL-FLUID; MENINGITIS; TYPE-2 C1 [Mateen, Farrah J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, Stephanie A.] Sanford Clin, Bismarck, ND USA. [Mateen, Farrah J.; Miller, Stephanie A.; Aksamit, Allen J., Jr.] Mayo Clin, Rochester, MN USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD FEB PY 2014 VL 89 IS 2 BP 274 EP 275 DI 10.1016/j.mayocp.2013.12.003 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 302DJ UT WOS:000330581500021 PM 24485138 ER PT J AU Steensma, DP Shampo, MA Kyle, RA AF Steensma, David P. Shampo, Marc A. Kyle, Robert A. TI Wilberforce J. J. Arnold-"St. Helena's Greatest Friend" SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Steensma, David/0000-0001-5130-9284 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD FEB PY 2014 VL 89 IS 2 BP E15 EP E15 DI 10.1016/j.mayocp.2013.01.032 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 302DJ UT WOS:000330581500003 PM 24485142 ER PT J AU Slattery, MJ Bredella, MA Thakur, H Torriani, M Misra, M AF Slattery, Meghan J. Bredella, Miriam A. Thakur, Hena Torriani, Martin Misra, Madhusmita TI Insulin Resistance and Impaired Mitochondrial Function in Obese Adolescent Girls SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; INTRAMYOCELLULAR LIPID-CONTENT; HOMEOSTASIS MODEL ASSESSMENT; TYPE-2 DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; BODY-MASS INDEX; UNITED-STATES; US CHILDREN; WEIGHT-LOSS; GLUCOSE AB Background: Mitochondrial dysfunction plays a role in the development of muscle insulin resistance (IR) and the accumulation of intramyocellular lipid (IMCL) in skeletal muscle that can, in turn, interfere with insulin signaling. The purpose of this study was to assess mitochondrial function (MF) and IMCL in obese adolescent girls with and without IR to determine whether: (1) Girls with IR have impaired MF, and (2) impaired MF in girls with IR is related to higher IMCL. Methods: We examined 22 obese girls aged 13-21 years old for IR [defined as a homeostasis model assessment of insulin resistance (HOMA-IR) value >4. Phosphorus magnetic resonance spectroscopy (31P-MRS) and proton magnetic resonance spectroscopy (1H-MRS), respectively, were used to determine MF and IMCL of the soleus muscle along with magnetic resonance imaging (MRI) measures of visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) in girls with HOMA-IR >4 (insulin-resistant group) versus HOMA-IR 4 (insulin-sensitive group). Serum lipids and waist-to-hip ratio (W/H) were also measured. Results: Girls with IR (n=8) did not differ from the insulin-sensitive group (n=14) for age, bone age, weight, VAT, SAT, TAT, or IMCL. However, the insulin-resistant group had higher W/H. Additionally the insulin-resistance group had a lower log rate of postexercise phosphocreatine (PCr) recovery (ViPCr) and a higher log PCr recovery constant (tau), indicative of impaired MF. Conclusions: Obese girls with increased IR have impaired mitochondrial function. This association is not mediated by alterations in IMCL or adipose tissue. Further studies are necessary to determine whether there is a causal relation between impaired mitochondrial function and IR in obesity and mediators of such a relationship. C1 [Slattery, Meghan J.; Thakur, Hena; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Slattery, MJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,BUL 457B, Boston, MA 02114 USA. EM mslattery@partners.org FU National Institutes of Health (NIH) [UL1 RR025758, K24 HD071843-01A1]; Genentech, San Francisco, CA [L4716s] FX This study was supported by National Institutes of Health (NIH) grants UL1 RR025758 and K24 HD071843-01A1, and an investigator-initiated grant L4716s from Genentech, San Francisco, CA. NR 37 TC 5 Z9 5 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 EI 1557-8518 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD FEB 1 PY 2014 VL 12 IS 1 BP 56 EP 61 DI 10.1089/met.2013.0100 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AA0SR UT WOS:000330808200008 PM 24251951 ER PT J AU Wienerroither, S Rauch, I Rosebrock, F Jamieson, AM Bradner, J Muhar, M Zuber, J Muller, M Decker, T AF Wienerroither, Sebastian Rauch, Isabella Rosebrock, Felix Jamieson, Amanda M. Bradner, James Muhar, Matthias Zuber, Johannes Mueller, Mathias Decker, Thomas TI Regulation of NO Synthesis, Local Inflammation, and Innate Immunity to Pathogens by BET Family Proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; LISTERIA-MONOCYTOGENES INFECTION; SYNCYTIAL VIRUS-INFECTION; NITRIC-OXIDE SYNTHASE; TRANSCRIPTIONAL ELONGATION; GENE-EXPRESSION; P-TEFB; DEPENDENT TRANSCRIPTION; BROMODOMAIN INHIBITION; BACTERIAL-INFECTION AB Transcriptional activation of the Nos2 gene, encoding inducible nitric oxide synthase (iNOS), during infection or inflammation requires coordinate assembly of an initiation complex by the transcription factors NF-kappa B and type I interferon-activated ISGF3. Here we show that infection of macrophages with the intracellular bacterial pathogen Listeria monocytogenes caused binding of the BET proteins Brd2, Brd3, and, most prominently, Brd4 to the Nos2 promoter and that a profound reduction of Nos2 expression occurred in the presence of the BET inhibitor JQ1. RNA polymerase activity at the Nos2 gene was regulated through Brd-mediated C-terminal domain (CTD) phosphorylation at serine 5. Underscoring the critical importance of Brd for the regulation of immune responses, application of JQ1 reduced NO production in mice infected with L. monocytogenes, as well as innate resistance to L. monocytogenes and influenza virus. In a murine model of inflammatory disease, JQ1 treatment increased the colitogenic activity of dextran sodium sulfate (DSS). The data presented in our study suggest that BET protein inhibition in a clinical setting poses the risk of altering the innate immune response to infectious or inflammatory challenge. C1 [Wienerroither, Sebastian; Rauch, Isabella; Rosebrock, Felix; Jamieson, Amanda M.; Decker, Thomas] Univ Vienna, Max F Perutz Labs, Vienna, Austria. [Bradner, James] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Muhar, Matthias; Zuber, Johannes] Inst Mol Pathol, A-1030 Vienna, Austria. [Mueller, Mathias] Univ Vet Med Vienna, Inst Anim Breeding, Vienna, Austria. RP Decker, T (reprint author), Univ Vienna, Max F Perutz Labs, Vienna, Austria. EM Thomas.decker@univie.ac.at OI Jamieson, Amanda/0000-0002-5781-9231; Muller, Mathias/0000-0002-7879-3552 FU Austrian Science Fund (FWF) [SFB-28, P25235-B13]; FWF FX Funding was provided by the Austrian Science Fund (FWF) through grant SFB-28 to M. Muller and T. Decker and grant P25235-B13 to A. M. Jamieson. S. Wienerroither was supported by the FWF through the doctoral program Molecular Mechanisms of Cell Signaling. NR 77 TC 24 Z9 25 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2014 VL 34 IS 3 BP 415 EP 427 DI 10.1128/MCB.01353-13 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 302DQ UT WOS:000330582200011 PM 24248598 ER PT J AU Li, XL Hara, T Choi, YG Subramanian, M Francis, P Bilke, S Walker, RL Pineda, M Zhu, YL Yang, Y Luo, J Wakefield, LM Brabletz, T Park, B Sharma, S Chowdhury, D Meltzer, PS Lal, A AF Li, Xiao Ling Hara, Toshifumi Choi, Youngeun Subramanian, Murugan Francis, Princy Bilke, Sven Walker, Robert L. Pineda, Marbin Zhu, Yuelin Yang, Yuan Luo, Ji Wakefield, Lalage M. Brabletz, Thomas Park, Ben Ho Sharma, Sudha Chowdhury, Dipanjan Meltzer, Paul S. Lal, Ashish TI A p21-ZEB1 Complex Inhibits Epithelial-Mesenchymal Transition through the MicroRNA 183-96-182 Cluster SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BREAST-CANCER CELLS; GENE-EXPRESSION; MIR-200 FAMILY; C-MYC; TRANSCRIPTION FACTOR; TUMOR-METASTASIS; DOWN-REGULATION; TARGETING ZEB1; TGF-BETA; IN-VIVO AB The tumor suppressor p21 acts as a cell cycle inhibitor and has also been shown to regulate gene expression by functioning as a transcription corepressor. Here, we identified p21-regulated microRNAs (miRNAs) by sequencing small RNAs from isogenic p21(+/+) and p21(-/-) cells. Three abundant miRNA clusters, miR-200b-200a-429, miR-200c-141, and miR-183-96-182, were downregulated in p21-deficient cells. Consistent with the known function of the miR-200 family and p21 in inhibition of the epithelial-mesenchymal transition (EMT), we observed EMT upon loss of p21 in multiple model systems. To explore a role of the miR-183-96-182 cluster in EMT, we identified its genome-wide targets and found that miR-183 and miR-96 repressed common targets, including SLUG, ZEB1, ITGB1, and KLF4. Reintroduction of miR-200, miR-183, or miR-96 in p21(-/-) cells inhibited EMT, cell migration, and invasion. Conversely, antagonizing miR-200 and miR-183-96-182 cluster miRNAs in p21(+/+) cells increased invasion and elevated the levels of VIM, ZEB1, and SLUG mRNAs. Furthermore, we found that p21 forms a complex with ZEB1 at the miR-183-96-182 cluster promoter to inhibit transcriptional repression of this cluster by ZEB1, suggesting a reciprocal feedback loop. C1 [Li, Xiao Ling; Hara, Toshifumi; Choi, Youngeun; Subramanian, Murugan; Francis, Princy; Walker, Robert L.; Pineda, Marbin; Zhu, Yuelin; Meltzer, Paul S.; Lal, Ashish] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Choi, Youngeun; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Yang, Yuan; Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Luo, Ji] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Brabletz, Thomas] Univ Freiburg, Med Ctr, Dept Gen & Visceral Surg, Freiburg, Germany. [Brabletz, Thomas] Univ Freiburg, Med Ctr, Ctr Comprehens Canc, Freiburg, Germany. [Park, Ben Ho] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Breast Canc Res Program, Baltimore, MD USA. [Sharma, Sudha] Howard Univ, Coll Med, Dept Biochem & Mol Biol, Washington, DC USA. RP Lal, A (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. EM ashish.lal@nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; DFG [BR 1399/6-1, SFB 850/B2, SFB992/C6]; Deutsche Krebshilfe [109430]; National Institute of General Medical Sciences of the National Institutes of Health [SC1GM093999] FX Ashish Lal was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Thomas Brabletz was supported by the DFG (BR 1399/6-1, SFB 850/B2, and SFB992/C6) and the Deutsche Krebshilfe (grant no. 109430). Sudha Sharma was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number SC1GM093999. NR 68 TC 37 Z9 38 U1 1 U2 26 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2014 VL 34 IS 3 BP 533 EP 550 DI 10.1128/MCB.01043-13 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 302DQ UT WOS:000330582200021 PM 24277930 ER PT J AU Erbe, RW Sims, KB Goss, KA Martin, DR AF Erbe, Richard W. Sims, Katherine B. Goss, Kendrick A. Martin, Dana R. TI An unremarkable clinical presentation of lysosomal acid lipase deficiency (LALD) in a 5 year old with advanced liver pathology SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 10th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 10-13, 2014 CL San Diego, CA SP Lysosomal Dis Network C1 [Erbe, Richard W.] SUNY Buffalo, Womens & Childrens Hosp, Buffalo, NY 14260 USA. [Sims, Katherine B.; Goss, Kendrick A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martin, Dana R.] Synageva BioPharma, Lexington, MA USA. NR 0 TC 0 Z9 0 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 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2014 VL 111 IS 2 MA 70 BP S42 EP S42 DI 10.1016/j.ymgme.2013.12.082 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 304KO UT WOS:000330746000072 ER PT J AU Boros, E Rybak-Akimova, E Holland, JP Rietz, T Rotile, N Blasi, F Day, H Latifi, R Caravan, P AF Boros, Eszter Rybak-Akimova, Elena Holland, Jason P. Rietz, Tyson Rotile, Nicholas Blasi, Francesco Day, Helen Latifi, Reza Caravan, Peter TI Pycup-A Bifunctional, Cage-like Ligand for Cu-64 Radiolabeling SO MOLECULAR PHARMACEUTICS LA English DT Article DE chelator; copper; positron emission tomography; fibrin ID COPPER RADIOPHARMACEUTICALS; CONTRAST AGENT; VIVO STABILITY; RGD PEPTIDE; COMPLEXATION; CHELATOR; PET; DERIVATIVES; IN-111; 1,4,7-TRIAZACYCLONONANE AB In developing targeted probes for positron emission tomography (PET) based on Cu-64, stable complexation of the radiometal is key, and a flexible handle for bioconjugation is highly advantageous. Here, we present the synthesis and characterization of the chelator pycup and four derivatives. Pycup is a cross-bridged cyclam derivative with a pyridyl donor atom integrated into the cross-bridge resulting in a pentadentate ligand. The pycup platform provides kinetic inertness toward Cu-64 dechelation and offers versatile bioconjugation chemistry. We varied the number and type of additional donor atoms by alkylation of the remaining two secondary amines, providing three model ligands, pycup2A, pycup1A1Bn, and pycup2Bn, in 3-4 synthetic steps from cyclam. All model copper complexes displayed very slow decomplexation in 5 M HCl and 90 degrees C (t(1/2): 1.5 h for pycup1A1Bn, 2.7 h for pycup2A, 20.3 h for pycup2Bn). The single crystal crystal X-ray structure of the [Cu(pycup2Bn)](2+) Complex showed that the copper was coordinated in a trigonal, bipyramidal manner. The corresponding radiochemical complexes were at least 94% stable in rat plasma after 24 h. Biodistribution studies conducted in Balb/c mice at 2 h postinjection of Cu-64 labeled pycup2A revealed low residual activity in kidney, liver, and blood pool with predominantly renal clearance observed. Pycup2A was readily conjugated to a fibrin-targeted peptide and labeled with Cu-64 for successful PET imaging of arterial thrombosis in a rat model, demonstrating the utility of our new chelator in vivo. C1 [Boros, Eszter; Rietz, Tyson; Rotile, Nicholas; Blasi, Francesco; Day, Helen; Caravan, Peter] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Rybak-Akimova, Elena; Latifi, Reza] Tufts Univ, Dept Chem, Medford, MA 02155 USA. [Holland, Jason P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA 02114 USA. [Holland, Jason P.] Australian Nucl Sci & Technol Org, Kirrawee, NSW 2232, Australia. RP Boros, E (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM eboros@nmr.mgh.harvard.edu; caravan@nmr.mgh.harvard.edu RI Blasi, Francesco/G-1055-2015; OI Blasi, Francesco/0000-0002-6616-8418; Holland, Jason/0000-0002-0066-219X FU National Heart, Lung, and Blood Institute (NHLBI) [HL109448]; National Center for Research Resources (NCRR) [RR029495]; Swiss National Science Foundation; Australian National Science and Technology Organization; NSF [MRI: CHE-1229426] FX Dr. Peter Mueller (X-ray diffraction facility, MIT chemistry department) is warmly acknowledged for assistance with elucidation of the solid state crystal structure of [Cu(pycup2Bn)]2+. P.C. acknowledges the National Heart, Lung, and Blood Institute for funding (NHLBI, award HL109448) and an instrumentation grant from the National Center for Research Resources (NCRR, award RR029495) for the micro-PET/SPECT/CT. E.B. and J.P.H. thank the Swiss National Science Foundation and the Australian National Science and Technology Organization for support, respectively. E.R.A. acknowledges the US Department of Energy Office of Basic Energy Science. The X-ray diffractometer at Tufts was funded by the NSF (MRI: CHE-1229426). NR 47 TC 23 Z9 23 U1 2 U2 19 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 FEB PY 2014 VL 11 IS 2 BP 617 EP 629 DI 10.1021/mp400686z PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AA0UI UT WOS:000330812500024 PM 24294970 ER PT J AU Wang, T Hartner, WC Gillespie, JW Praveen, KP Yang, SH Mei, LA Petrenko, VA Torchilin, VP AF Wang, Tao Hartner, William C. Gillespie, James W. Praveen, Kulkarni P. Yang, Shenghong Mei, Leslie A. Petrenko, Valery A. Torchilin, Vladimir P. TI Enhanced tumor delivery and antitumor activity in vivo of liposomal doxorubicin modified with MCF-7-specific phage fusion protein SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Breast cancer targeting; Phage display; Cancer nanomedicines; Liposomes; Drug delivery ID METASTATIC BREAST-CANCER; COAT PROTEIN; CONVENTIONAL DOXORUBICIN; MEMBRANE INSERTION; PEPTIDE LIBRARIES; SOLID TUMORS; CELLS; THERAPY; DISPLAY; BINDING AB A novel strategy to improve the therapeutic index of chemotherapy has been developed by the integration of nanotechnology with phage technique. The objective of this study was to combine phage display, identifying tumor-targeting ligands, with a liposomal nanocarrier for targeted delivery of doxorubicin. Following the proof of concept in cell-based experiments, this study focused on in vivo assessment of antitumor activity and potential side-effects of phage fusion protein-modified liposomal doxorubicin. MCF-7-targeted phage-Doxil treatments led to greater tumor remission and faster onset of antitumor activity than the treatments with non-targeted formulations. The enhanced anticancer effect induced by the targeted phage-Doxil correlated with an improved tumor accumulation of doxorubicin. Tumor sections consistently revealed enhanced apoptosis, reduced proliferation activity and extensive necrosis. Phage-Doxil-treated mice did not show any sign of hepatotoxicity and maintained overall health. Therefore, MCF-7-targeted phage-Doxil seems to be an active and tolerable chemotherapy for breast cancer treatment. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wang, Tao; Hartner, William C.; Torchilin, Vladimir P.] Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, Boston, MA 02115 USA. [Gillespie, James W.; Petrenko, Valery A.] Auburn Univ, Coll Vet Med, Dept Pathobiol, Auburn, AL 36849 USA. [Praveen, Kulkarni P.] Northeastern Univ, Ctr Translat Imaging, Boston, MA 02115 USA. [Yang, Shenghong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mei, Leslie A.] Northeastern Univ, Coll Sci, Dept Biol, Boston, MA 02115 USA. RP Torchilin, VP (reprint author), Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, Boston, MA 02115 USA. EM v.torchilin@neu.edu RI Gillespie, James/H-3496-2013 OI Gillespie, James/0000-0003-3779-1072 FU National Institutes of Health [R01 CA125063-01, 1U54CA151881]; Animal Health and Disease Research; College of Veterinary Medicine; Auburn University FX This work was supported by National Institutes of Health grant #R01 CA125063-01 and the Animal Health and Disease Research grant 2006-9, College of Veterinary Medicine, Auburn University to Valery A. Petrenko and by National Institutes of Health grant #1U54CA151881 to Vladimir P. Torchilin. NR 41 TC 15 Z9 16 U1 2 U2 36 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD FEB PY 2014 VL 10 IS 2 BP 421 EP 430 DI 10.1016/j.nano.2013.08.009 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 304DZ UT WOS:000330728400015 PM 24028893 ER PT J AU Buzon, MJ Sun, H Li, C Shaw, A Seiss, K Ouyang, ZY Martin-Gayo, E Leng, J Henrich, TJ Li, JZ Pereyra, F Zurakowski, R Walker, BD Rosenberg, ES Yu, XG Lichterfeld, M AF Buzon, Maria J. Sun, Hong Li, Chun Shaw, Amy Seiss, Katherine Ouyang, Zhengyu Martin-Gayo, Enrique Leng, Jin Henrich, Timothy J. Li, Jonathan Z. Pereyra, Florencia Zurakowski, Ryan Walker, Bruce D. Rosenberg, Eric S. Yu, Xu G. Lichterfeld, Mathias TI HIV-1 persistence in CD4(+) T cells with stem cell like properties SO NATURE MEDICINE LA English DT Article ID MEMORY; DIFFERENTIATION; PRECURSORS; INFECTION; CURE AB Cellular HIV-1 reservoirs that persist despite antiretroviral treatment are incompletely defined. We show that during suppressive antiretroviral therapy, CD4(+) T memory stem cells (T-SCM cells) harbor high per-cell levels of HIV-1 DNA and make increasing contributions to the total viral CD4(+) T cell reservoir over time. Moreover, we conducted phylogenetic studies that suggested long-term persistence of viral quasispecies in CD4(+) T-SCM cells. Thus, HIV-1 may exploit the stem cell characteristics of cellular immune memory to promote long-term viral persistence. C1 [Buzon, Maria J.; Rosenberg, Eric S.; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Buzon, Maria J.; Sun, Hong; Li, Chun; Shaw, Amy; Seiss, Katherine; Ouyang, Zhengyu; Martin-Gayo, Enrique; Leng, Jin; Pereyra, Florencia; Walker, Bruce D.; Yu, Xu G.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Sun, Hong] China Med Univ, Affiliated Hosp 1, Key Lab AIDS Immunol, Dept Lab Med, Shenyang, Peoples R China. [Henrich, Timothy J.; Li, Jonathan Z.; Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Zurakowski, Ryan] Univ Delaware, Dept Elect & Comp Engn, Newark, DE USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Lichterfeld, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM mlichterfeld@partners.org RI Ouyang, Zhengyu/P-3576-2014; Buzon, Maria J/G-8286-2015 OI Buzon, Maria J/0000-0003-4427-9413 FU American Foundation for AIDS Research [108302-51-RGRL]; US National Institutes of Health [AI098487, AI106468, AI089339, AI098480, AI100699, AI074415]; Clinical Scientist Development Award from the Doris Duke Charitable Foundation [2009034]; European Molecular Biology Laboratory; Tosteson postdoctoral fellowship award from Massachusetts General Hospital; Mark and Lisa Schwartz Foundation; Bill & Melinda Gates Foundation FX This work was supported by the American Foundation for AIDS Research (grant 108302-51-RGRL to M.L.) and by the US National Institutes of Health (grants AI098487 and AI106468 to M.L., AI089339 to X.G.Y., AI098480 to T.J.H. and AI100699 to J.Z.L.). M.L. is a recipient of the Clinical Scientist Development Award from the Doris Duke Charitable Foundation (grant number 2009034). M.J.B. is supported by a fellowship award from the European Molecular Biology Laboratory and by the Tosteson postdoctoral fellowship award from Massachusetts General Hospital. Patient blood sample collection was supported by the US National Institutes of Health (grant AI074415), by the Mark and Lisa Schwartz Foundation and by the Bill & Melinda Gates Foundation. Chronically infected 293T cells were kindly provided by F. Bushman (University of Pennsylvania). HIV-1 isolates were kindly provided by D. Littman (New York University). NR 18 TC 102 Z9 104 U1 3 U2 25 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 FEB PY 2014 VL 20 IS 2 BP 139 EP 142 DI 10.1038/nm.3445 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AA2HF UT WOS:000330915000014 PM 24412925 ER PT J AU Haris, M Singh, A Cai, KJ Kogan, F McGarvey, J DeBrosse, C Zsido, GA Witschey, WRT Koomalsingh, K Pilla, JJ Chirinos, JA Ferrari, VA Gorman, JH Hariharan, H Gorman, RC Reddy, R AF Haris, Mohammad Singh, Anup Cai, Kejia Kogan, Feliks McGarvey, Jeremy DeBrosse, Catherine Zsido, Gerald A. Witschey, Walter R. T. Koomalsingh, Kevin Pilla, James J. Chirinos, Julio A. Ferrari, Victor A. Gorman, Joseph H. Hariharan, Hari Gorman, Robert C. Reddy, Ravinder TI A technique for in vivo mapping of myocardial creatine kinase metabolism SO NATURE MEDICINE LA English DT Article ID CARDIOVASCULAR MAGNETIC-RESONANCE; ENERGY PHOSPHATE METABOLITES; FAILING HUMAN MYOCARDIUM; CONTRAST; VIABILITY; EXCHANGE; MRI; SPECTROSCOPY; INFARCTION; QUANTIFICATION AB ATP derived from the conversion of phosphocreatine to creatine by creatine kinase provides an essential chemical energy source that governs myocardial contraction. Here, we demonstrate that the exchange of amine protons from creatine with protons in bulk water can be exploited to image creatine through chemical exchange saturation transfer (CrEST) in myocardial tissue. We show that CrEST provides about two orders of magnitude higher sensitivity compared to H-1 magnetic resonance spectroscopy. Results of CrEST studies from ex vivo myocardial tissue strongly correlate with results from 1H and P-31 magnetic resonance spectroscopy and biochemical analysis. We demonstrate the feasibility of CrEST measurement in healthy and infarcted myocardium in animal models in vivo on a 3-T clinical scanner. As proof of principle, we show the conversion of phosphocreatine to creatine by spatiotemporal mapping of creatine changes in the exercised human calf muscle. We also discuss the potential utility of CrEST in studying myocardial disorders. C1 [Haris, Mohammad; Singh, Anup; Cai, Kejia; Kogan, Feliks; DeBrosse, Catherine; Witschey, Walter R. T.; Hariharan, Hari; Reddy, Ravinder] Univ Penn, Dept Radiol, Ctr Magnet Resonance & Opt Imaging, Philadelphia, PA 19104 USA. [McGarvey, Jeremy; Zsido, Gerald A.; Witschey, Walter R. T.; Koomalsingh, Kevin; Pilla, James J.; Gorman, Joseph H.; Gorman, Robert C.] Univ Penn, Dept Surg, Gorman Cardiovasc Res Grp, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Chirinos, Julio A.; Ferrari, Victor A.] Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. RP Reddy, R (reprint author), Univ Penn, Dept Radiol, Ctr Magnet Resonance & Opt Imaging, Philadelphia, PA 19104 USA. EM krr@mail.med.upenn.edu OI Reddy, Ravinder/0000-0003-4580-2392; Hariharan, Hari/0000-0002-7032-6968 FU National Institutes of Health [P41 EB015893, P41 E5015893S1, R21DA032256-01]; Translational Biomedical Imaging Center of the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania FX This work was supported by National Institutes of Health grants P41 EB015893, P41 E5015893S1 and R21DA032256-01 and a pilot grant from the Translational Biomedical Imaging Center of the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania. The authors acknowledge W Liu and S. Pickup for technical assistance in using the 9.4-T NMR spectrometer, K. Nath for assistance with biochemical analysis and D. Reddy for help with regulatory protocol. NR 40 TC 26 Z9 27 U1 1 U2 20 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 FEB PY 2014 VL 20 IS 2 BP 209 EP 214 DI 10.1038/nm.3436 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AA2HF UT WOS:000330915000023 PM 24412924 ER PT J AU Tahara, N Mukherjee, J de Haas, HJ Petrov, AD Tawakol, A Haider, N Tahara, A Constantinescu, CC Zhou, J Boersma, HH Imaizumi, T Nakano, M Finn, A Fayad, Z Virmani, R Fuster, V Bosca, L Narula, J AF Tahara, Nobuhiro Mukherjee, Jogeshwar de Haas, Hans J. Petrov, Artiom D. Tawakol, Ahmed Haider, Nezam Tahara, Atsuko Constantinescu, Cristian C. Zhou, Jun Boersma, Hendrikus H. Imaizumi, Tsutomu Nakano, Masataka Finn, Aloke Fayad, Zahi Virmani, Renu Fuster, Valentin Bosca, Lisardo Narula, Jagat TI 2-deoxy-2[F-18]fluoro-D-mannose positron emission tomography imaging in atherosclerosis SO NATURE MEDICINE LA English DT Article ID NONINVASIVE DETECTION; GLUCOSE TRANSPORTERS; ADHESION MOLECULE-1; PLAQUE INFLAMMATION; VULNERABLE PLAQUES; DISEASE; FLUORODEOXYGLUCOSE; MACROPHAGES; MECHANISMS AB Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2[F-18]fluoro-D-glucose ([F-18]FDG) has been proposed for identification of patients at higher risk for acute vascular events. Because mannose is an isomer of glucose that is taken up by macrophages through glucose transporters and because mannose receptors are expressed on a subset of the macrophage population in high-risk plaques, we applied F-18-labeled mannose (2-deoxy-2[F-18]fluoro-D-mannose, [F-18]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [F-18]FDM and [F-18]FDG in atherosclerotic lesions in a rabbit model; [F-18]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[C-14]carbon-D-glucose ([C-14]2DG) support at least 35% higher [F-18]FDM uptake by macrophages in cell experiments. We also demonstrate that FDM restricts binding of anti mannose receptor antibody to macrophages by approximately 35% and that mannose receptor targeting may provide an additional avenue for imaging of plaque inflammation. C1 [Tahara, Nobuhiro; Tahara, Atsuko; Imaizumi, Tsutomu] Kurume Univ, Sch Med, Kurume, Fukuoka 830, Japan. [Mukherjee, Jogeshwar; Constantinescu, Cristian C.; Zhou, Jun] Univ Calif Irvine, Irvine, CA USA. [de Haas, Hans J.; Petrov, Artiom D.; Haider, Nezam; Fayad, Zahi; Fuster, Valentin; Narula, Jagat] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [de Haas, Hans J.; Boersma, Hendrikus H.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nakano, Masataka; Virmani, Renu] CVPath Inst, Gaithersburg, MD USA. [Finn, Aloke] Emory Univ, Sch Med, Atlanta, GA USA. [Fuster, Valentin] Ctr Nacl Invest Cardiovasc Carlos III, Madrid, Spain. [Bosca, Lisardo] Univ Autonoma Madrid, Inst Invest Biomed Alberto Sols, Ctr Mixto, Consejo Super Invest Cient, Madrid, Spain. RP Narula, J (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. EM narula@mountsinai.org RI Bosca, Lisardo/A-2059-2008; Fuster, Valentin/H-4319-2015; Mukherjee, Jogeshwar/O-1320-2013 OI Bosca, Lisardo/0000-0002-0253-5469; Fuster, Valentin/0000-0002-9043-9986; Mukherjee, Jogeshwar/0000-0003-1009-877X FU International Research Fund for Subsidy of Kyusyu University School of Medicine Alumni; Banyu Fellowship Program; Banyu Life Science Foundation International; foundation De Drie Lichten; Dutch Heart Association; Spanish Government [BFU2011-24760, RD12/0042/0019]; US National Institutes of Health from the US National Center for Research Resources [S10RR019269]; US National Institute of Biomedical Imaging and Bioengineering [R01 EB006110]; US National Institutes of Health [1RO1-HL68657] FX We thank E. Lopez-Collazo for help in the preparation of human macrophages. Additionally, we thank T. Yamald, D.S. Mohar, S. Pandey, M. Pan, R. Kant and R. Coleman for their help in development of tracer labeling and [18F]FDM imaging. Finally, we thank C. Minh and J. Song for their valuable help with analyzing PET images. This research was supported by a research grant from the International Research Fund for Subsidy of Kyusyu University School of Medicine Alumni and the Banyu Fellowship Program sponsored by Banyu Life Science Foundation International to N.T., research grants from the foundation De Drie Lichten and the Dutch Heart Association (Dr. E. Dekker student grant) to H.J.d.H., grants BFU2011-24760 and RD12/0042/0019 from the Spanish Government to L.B., US National Institutes of Health grant S10RR019269 from the US National Center for Research Resources and grant R01 EB006110 from the US National Institute of Biomedical Imaging and Bioengineering to J.M. and US National Institutes of Health grant 1RO1-HL68657 to J.N. NR 20 TC 48 Z9 49 U1 7 U2 33 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 FEB PY 2014 VL 20 IS 2 BP 215 EP 219 DI 10.1038/nm.3437 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AA2HF UT WOS:000330915000024 PM 24412923 ER PT J AU Simon, SS Chee, YE Haddadin, RI Veldman, PB Borboli-Gerogiannis, S Brauner, SC Chang, KK Chen, SH Gardiner, MF Greenstein, SH Kloek, CE Chen, TC AF Simon, Shira S. Chee, Yewlin E. Haddadin, Ramez I. Veldman, Peter B. Borboli-Gerogiannis, Sheila Brauner, Stacey C. Chang, Kenneth K. Chen, Sherleen H. Gardiner, Matthew F. Greenstein, Scott H. Kloek, Carolyn E. Chen, Teresa C. TI Achieving Target Refraction after Cataract Surgery SO OPHTHALMOLOGY LA English DT Article ID PARTIAL COHERENCE INTERFEROMETRY; LENS POWER CALCULATION; QUALITY-OF-LIFE; ULTRASOUND BIOMETRY; ZEISS IOLMASTER; OPTICAL BIOMETRY; OUTCOMES; PERFORMANCE; ERROR; EXTRACTION AB Purpose: To evaluate the difference between target and actual refraction after phacoemulsification and intraocular lens implantation at an academic teaching institution's Comprehensive Ophthalmology Service. Design: Retrospective study. Participants: We examined 1275 eye surgeries for this study. Methods: All consecutive cataract surgeries were included if they were performed by an attending or resident surgeon from January through December 2010. Postoperative refractions were compared with preoperative target refractions. Patients were excluded if they did not have a preoperative target refraction documented or if they did not have a recorded postoperative manifest refraction within 90 days. Main Outcome Measures: The main outcome measure was percentage of cases achieving a postoperative spherical equivalent +/- 1.0 diopter (D) of target spherical equivalent. Results: We performed 1368 cataract surgeries from January through December of 2010. Of these, 1275 (93%) had sufficient information for analysis. Of the included cases, 94% (1196 of 1275) achieved +/- 1.0 D of target refraction by 90 days after cataract surgery. Conclusions: This paper establishes a new benchmark for a teaching hospital, where 94% of patients achieved within 1.0 D of target refraction after cataract surgery. The refractive outcomes after cataract surgery at this academic teaching institution were higher than average international benchmarks. (C) 2014 by the American Academy of Ophthalmology. C1 [Simon, Shira S.; Chee, Yewlin E.; Haddadin, Ramez I.; Veldman, Peter B.; Borboli-Gerogiannis, Sheila; Brauner, Stacey C.; Chang, Kenneth K.; Chen, Sherleen H.; Gardiner, Matthew F.; Greenstein, Scott H.; Kloek, Carolyn E.; Chen, Teresa C.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu OI Gardiner, Matthew/0000-0002-8864-2379 NR 32 TC 5 Z9 6 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2014 VL 121 IS 2 BP 440 EP 444 DI 10.1016/j.ophtha.2013.09.022 PG 5 WC Ophthalmology SC Ophthalmology GA 302CO UT WOS:000330579200007 PM 24289919 ER PT J AU Loomis, SJ Kang, JH Weinreb, RN Yaspan, BL Bailey, JNC Gaasterland, D Gaasterland, T Lee, RK Lichter, PR Budenz, DL Liu, Y Realini, T Friedman, DS McCarty, CA Moroi, SE Olson, L Schuman, JS Singh, K Vollrath, D Wollstein, G Zack, DJ Brilliant, M Sit, AJ Christen, WG Fingert, J Kraft, P Zhang, K Allingham, RR Pericak-Vance, MA Richards, JE Hauser, MA Haines, JL Pasquale, LR Wiggs, JL AF Loomis, Stephanie J. Kang, Jae H. Weinreb, Robert N. Yaspan, Brian L. Bailey, Jessica N. Cooke Gaasterland, Douglas Gaasterland, Terry Lee, Richard K. Lichter, Paul R. Budenz, Donald L. Liu, Yutao Realini, Tony Friedman, David S. McCarty, Catherine A. Moroi, Sayoko E. Olson, Lana Schuman, Joel S. Singh, Kuldev Vollrath, Douglas Wollstein, Gadi Zack, Donald J. Brilliant, Murray Sit, Arthur J. Christen, William G. Fingert, John Kraft, Peter Zhang, Kang Allingham, R. Rand Pericak-Vance, Margaret A. Richards, Julia E. Hauser, Michael A. Haines, Jonathan L. Pasquale, Louis R. Wiggs, Janey L. TI Association of CAV1/CAV2 Genomic Variants with Primary Open-Angle Glaucoma Overall and by Gender and Pattern of Visual Field Loss SO OPHTHALMOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; NORMAL-TENSION GLAUCOMA; WIDE ASSOCIATION; COMMON VARIANTS; GENE VARIANTS; DEFECTS; HYPERTENSION; PERFORMANCE; EXPRESSION; RECEPTORS AB Purpose: The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. Design: Case-control study. Participants: We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). Methods: We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were metaanalyzed, and a Bonferroni-corrected significance level of 7.7 x 10(-4) was used to account for multiple comparisons. Main Outcome Measures: Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. Results: We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 x 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 x 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 x 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. Conclusions: CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects. (C) 2014 by the American Academy of Ophthalmology. C1 [Loomis, Stephanie J.; Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. [Kang, Jae H.; Christen, William G.; Pasquale, Louis R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Weinreb, Robert N.; Zhang, Kang] Univ Calif San Diego, Dept Ophthalmol, San Diego, CA 92103 USA. [Weinreb, Robert N.; Zhang, Kang] Univ Calif San Diego, Hamilton Glaucoma Ctr, San Diego, CA 92103 USA. [Yaspan, Brian L.] Genentech Inc, San Francisco, CA USA. [Bailey, Jessica N. Cooke; Olson, Lana; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. [Gaasterland, Douglas] Eye Doctors Washington, Chevy Chase, MD USA. [Gaasterland, Terry] Univ Calif San Diego, Scripps Genome Ctr, La Jolla, CA 92093 USA. [Lee, Richard K.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst & Human Genom, Miami, FL 33136 USA. [Lichter, Paul R.; Moroi, Sayoko E.; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Budenz, Donald L.] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. [Liu, Yutao; Allingham, R. Rand; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Liu, Yutao; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Realini, Tony] West Virginia Univ Eye Inst, Dept Ophthalmol, Morgantown, WV USA. [Friedman, David S.; Zack, Donald J.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21205 USA. [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN USA. [Schuman, Joel S.; Wollstein, Gadi] Univ Pittsburgh, UPMC Eye Ctr, Dept Ophthalmol, Pittsburgh, PA USA. [Singh, Kuldev] Stanford Univ, Dept Ophthalmol, Palo Alto, CA 94304 USA. [Vollrath, Douglas] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA. [Brilliant, Murray] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Sit, Arthur J.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA. [Fingert, John] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Anat Cell Biol, Iowa City, IA USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02115 USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. EM janey_wiggs@meei.harvard.edu OI Sit, Arthur/0000-0002-3904-2625; Zack, Don/0000-0002-7966-1973 FU National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, Maryland [HG005259-01]; National Institutes of Health [HHSN268200782096C]; GENEVA project [HG004728]; NIH [CA87969, CA49449, UM1 CA167552, EY009149, HG004608, EY008208, EY015473, EY012118, EY015682, EY011671, EY09580, EY013178, RR015574, EY015872, EY010886, EY009847, EY022766, EY011008, EY144428, EY144448, EY18660]; NEI [3R01EY015872-05S1, P30 EY014104, 3R01EY019126-02S1]; Harvard Glaucoma Center for Excellence, Boston, Massachusetts; Margolis Fund, Waltham, Massachusetts; Research to Prevent Blindness, Inc., New York, New York; Glaucoma Research Foundation, San Francisco, California; Glaucoma Foundation, New York, New York; Bright Focus, Gaithersburg, Maryland; [U01-HG004424]; [U01 HG004446]; [EY015543]; [EY006827]; [HL73042]; [HL073389]; [EY13315] FX Genotyping services for the NEIGHBOR study were provided by the Center for Inherited Disease Research (CIDR), Baltimore, Maryland, and were supported by the National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, Maryland (grant no.: HG005259-01 [J.L.W.]). Additionally, the CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract no.: HHSN268200782096C). Genotyping for the GLAUGEN dataset at the Broad Institute was supported by the GENEVA project (grant no.: HG004728 [L.R.P.]) and the NIH (grant no.: U01-HG004424 [Broad Institute]). Genotype data cleaning and analysis for the GLAUGEN study was supported by the NIH (grant no.: U01 HG004446 [C. Laurie]). Collecting and processing samples for the NEIGHBOR dataset were supported by the NEI (grant nos.: 3R01EY015872-05S1 and P30 EY014104 [J.L.W.] and 3R01EY019126-02S1 [M. A. H.]). Funding for the collection of cases and controls was provided by the NIH (grant nos.: EY015543 [R. R. A.]; EY006827 [D. G.]; P30 EY014104 [J.L.W.] HL73042, HL073389, and EY13315 [M. A. H.; CA87969, CA49449, and UM1 CA167552 J. H. K.]; EY009149 [P. R. L.]; HG004608 [CM]; EY008208 [FAM]; EY015473 [L.R.P.]; EY012118 [M. P-V.]; EY015682 [A. R.]; EY011671 and EY09580 [J. E. R.]; EY013178 [J. S. S.]; RR015574, EY015872, EY010886, EY009847, and EY022766 [J.L.W.]; and EY011008, EY144428, EY144448, and EY18660 [K.Z.]). Drs. Wiggs and Pasquale are supported by the Harvard Glaucoma Center for Excellence, Boston, Massachusetts, and the Margolis Fund, Waltham, Massachusetts. Drs. Wiggs, Pasquale, and Richards are supported by Research to Prevent Blindness, Inc., New York, New York. Dr. Liu is supported by the Glaucoma Research Foundation, San Francisco, California; The Glaucoma Foundation, New York, New York; and American Health Assistance Foundation (now Bright Focus), Gaithersburg, Maryland. The sponsors or funding organizations had no role in the design or conduct of this research. NR 42 TC 27 Z9 27 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2014 VL 121 IS 2 BP 508 EP 516 DI 10.1016/j.ophtha.2013.09.012 PG 9 WC Ophthalmology SC Ophthalmology GA 302CO UT WOS:000330579200016 PM 24572674 ER PT J AU Christen, WG Glynn, RJ Manson, JE MacFadyen, J Bubes, V Schvartz, M Buring, JE Sesso, HD Gaziano, JM AF Christen, William G. Glynn, Robert J. Manson, Joann E. MacFadyen, Jean Bubes, Vadim Schvartz, Miriam Buring, Julie E. Sesso, Howard D. Gaziano, J. Michael TI Effects of Multivitamin Supplement on Cataract and Age-Related Macular Degeneration in a Randomized Trial of Male Physicians SO OPHTHALMOLOGY LA English DT Article ID VITAMIN-E SUPPLEMENTATION; HIGH-DOSE SUPPLEMENTATION; BETA-CAROTENE; CLINICAL-TRIAL; EYE DISEASE; CARDIOVASCULAR-DISEASE; VISUAL FUNCTION; ALPHA-TOCOPHEROL; US PHYSICIANS; VISION LOSS AB Purpose: To test whether long-term multivitamin supplementation affects the incidence of cataract or agerelated macular degeneration (AMD) in a large cohort of men. Design: Randomized, double-blind, placebo-controlled trial. Participants: A total of 14 641 US male physicians aged <= 50 years. Intervention: Daily multivitamin or placebo. Main Outcome Measures: Incident cataract and visually significant AMD responsible for a reduction in bestcorrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Results: During an average of 11.2 years of treatment and follow-up, a total of 1817 cases of cataract and 281 cases of visually significant AMD were confirmed. There were 872 cataracts in the multivitamin group and 945 cataracts in the placebo group (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.83-0.99; P 0.04). For visually significant AMD, there were 152 cases in the multivitamin group and 129 cases in the placebo group (HR, 1.19; 95% CI, 0.94-1.50; P = 0.15). Conclusions: These randomized trial data from a large cohort of middle-aged and older US male physicians indicate that long-term daily multivitamin use modestly and significantly decreased the risk of cataract but had no significant effect on visually significant AMD. (C) 2014 by the American Academy of Ophthalmology. C1 [Christen, William G.; Glynn, Robert J.; Manson, Joann E.; MacFadyen, Jean; Bubes, Vadim; Schvartz, Miriam; Buring, Julie E.; Sesso, Howard D.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Christen, William G.; Glynn, Robert J.; Manson, Joann E.; MacFadyen, Jean; Bubes, Vadim; Schvartz, Miriam; Buring, Julie E.; Sesso, Howard D.; Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Buring, Julie E.; Sesso, Howard D.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Glynn, Robert J.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Dis, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Manson, Joann E.; Buring, Julie E.; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Glynn, Robert J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Christen, WG (reprint author), 900 Commonwealth Ave East, Boston, MA 02215 USA. EM wchristen@rics.bwh.harvard.edu FU National Institutes of Health; DSM Nutritional Products Inc.; Bristol-Meyers Squibb; AstraZeneca; Novartis; nonprofit Aurora Foundation; Tomato Products Wellness Council; Cambridge Theranostics, Ltd.; Veterans Administration; BASF Corporation; Pfizer Inc.; Nutritional Products Inc.; National Eye Institute [CA 097193]; National Institutes of Health (Bethesda, MD) [CA 34944, CA 40360, HL 26490, HL 34595]; BASF Corporation (Florham Park, NJ) FX The author(s) have made the following disclosure(s): W. G. C. received research funding support from the National Institutes of Health and DSM Nutritional Products Inc. (formerly Roche Vitamins). R. J. G. received investigator-initiated research funding from the National Institutes of Health, Bristol-Meyers Squibb, AstraZeneca, and Novartis, and signed a consulting agreement with Merck to give an invited talk. J. E. M. received investigator-initiated research funding from the National Institutes of Health and assistance with study pills and packaging from BASF and Cognis Corporations for the WAFACS and from Pronova BioPharma and Pharmavite for the VITamin D and OmegA-3 TriaL, and funding from the nonprofit Aurora Foundation. J. E. B. received investigator-initiated research funding from the National Institutes of Health and assistance with study pills and packaging from Natural Source Vitamin E Association and Bayer Healthcare for the Women's Health Study. H. D. S. received investigator-initiated research funding from the National Institutes of Health, the Tomato Products Wellness Council, and Cambridge Theranostics, Ltd. J. M. G. received investigator-initiated research funding from the National Institutes of Health, the Veterans Administration, and the BASF Corporation; assistance with study agents and packaging from BASF Corporation and Pfizer Inc. (formerly Wyeth, American Home Products, and Lederle); and assistance with study packaging provided by D. S. M. Nutritional Products Inc. (formerly Roche Vitamins). No other authors reported financial disclosures. Supported by Grants CA 097193 (which included funding from the National Eye Institute and the National Institute on Aging), CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health (Bethesda, MD), and an investigator-initiated grant from BASF Corporation (Florham Park, NJ). Study agents and packaging were provided by BASF Corporation and Pfizer Inc. (formerly Wyeth, American Home Products, and Lederle) (New York, NY), and study packaging was provided by DSM Nutritional Products, Inc. (formerly Roche Vitamins) (Parsippany, NJ). The National Institutes of Health, BASF, Pfizer Inc., and DSM Nutritional Products Inc., had no role in the study design; conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 57 TC 19 Z9 19 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2014 VL 121 IS 2 BP 525 EP 534 DI 10.1016/j.ophtha.2013.09.038 PG 10 WC Ophthalmology SC Ophthalmology GA 302CO UT WOS:000330579200018 PM 24268861 ER PT J AU Levin, MH Pistilli, M Daniel, E Gangaputra, SS Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Jabs, DA Levy-Clarke, GA Kempen, JH AF Levin, Marc H. Pistilli, Maxwell Daniel, Ebenezer Gangaputra, Sapna S. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Jabs, Douglas A. Levy-Clarke, Grace A. Kempen, John H. CA Systemic Immunosuppressive Therapy TI Incidence of Visual Improvement in Uveitis Cases with Visual Impairment Caused by Macular Edema SO OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR INFLAMMATORY DISEASE; OPTICAL COHERENCE TOMOGRAPHY; OCULAR INFLAMMATION; EYE DISEASES; RISK; ACUITY; COMPLICATIONS; INTERMEDIATE; THERAPY; SMOKING AB Purpose: Among cases of visually significant uveitic macular edema (ME), to estimate the incidence of visual improvement and identify predictive factors. Design: Retrospective cohort study. Participants: Eyes with uveitis, seen at 5 academic ocular inflammation centers in the United States, for which ME was documented to be currently present and the principal cause of reduced visual acuity (<20/40). Methods: Data were obtained by standardized chart review. Main Outcome Measures: Decrease of >= 0.2 base 10 logarithm of visual acuity decimal fraction-equivalent; risk factors for such visual improvement. Results: We identified 1510 eyes (of 1077 patients) with visual impairment to a level <20/40 attributed to ME. Most patients were female (67%) and white (76%), and had bilateral uveitis (82%). The estimated 6-month incidence of >= 2 lines of visual acuity improvement in affected eyes was 52% (95% confidence interval [CI], 49%-55%). Vision reduced by ME was more likely to improve by 2 lines in eyes initially with poor visual acuity (<= 20/200; adjusted hazard ratio [HR] 1.5; 95% CI, 1.3-1.7), active uveitis (HR, 1.3; 95% CI, 1.1-1.5), and anterior uveitis as opposed to intermediate (HR, 1.2), posterior (HR, 1.3), or panuveitis (HR, 1.4; overall P 0.02). During follow-up, reductions in anterior chamber or vitreous cellular activity or in vitreous haze each led to significant improvements in visual outcome (P < 0.001 for each). Conversely, snowbanking (HR, 0.7; 95% CI, 0.4-0.99), posterior synechiae (HR, 0.8; 95% CI, 0.6-0.9), and hypotony (HR, 0.2; 95% CI, 0.06-0.5) each were associated with lower incidence of visual improvement with respect to eyes lacking each of these attributes at a given visit. Conclusions: These results suggest that many, but not all, patients with ME causing low vision in a tertiary care setting will enjoy meaningful visual recovery in response to treatment. Evidence of significant ocular damage from inflammation (posterior synechiae and hypotony) portends a lower incidence of visual recovery. Better control of anterior chamber or vitreous activity is associated with a greater incidence of visual improvement, supporting an aggressive anti-inflammatory treatment approach for ME cases with active inflammation. (C) 2014 by the American Academy of Ophthalmology. C1 [Levin, Marc H.; Pistilli, Maxwell; Daniel, Ebenezer; Kempen, John H.] Univ Penn, Perelman Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gangaputra, Sapna S.] Univ Wisconsin, Sch Med, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. [Nussenblatt, Robert B.; Levy-Clarke, Grace A.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Preventat Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Pistilli, Maxwell/0000-0002-4266-4150 FU National Eye Institute [EY014943]; Research to Prevent Blindness; Paul and Evanina Mackall Foundation; Veteran's Affairs Administration; intramural funds of the National Eye Institute FX Supported primarily by National Eye Institute Grant EY014943 (Dr. Kempen). Additional support was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. During part of the conduct of this project, Dr. Levin was a Heed Ophthalmic Society Fellowship recipient, Dr. Kempenwas a Research to Prevent Blindness James S. Adams Special Scholar Award recipient, Dr. Thorne was a Research to Prevent Blindness Harrington Special Scholar Award recipient, and Drs. Jabs and Rosenbaumwere Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr. Suhler receives support from the Veteran's Affairs Administration. Dr. LevyClarke was previously supported by and Dr. Nussenblatt continues to be supported by intramural funds of the National Eye Institute. The funding organizations had no role in the design or conduct of this research. NR 31 TC 14 Z9 15 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2014 VL 121 IS 2 BP 588 EP + DI 10.1016/j.ophtha.2013.09.023 PG 9 WC Ophthalmology SC Ophthalmology GA 302CO UT WOS:000330579200026 PM 24332536 ER PT J AU Avery, CL Sitlani, CM Arking, DE Arnett, DK Bis, JC Boerwinkle, E Buckley, BM Chen, YDI de Craen, AJM Eijgelsheim, M Enquobahrie, D Evans, DS Ford, I Garcia, ME Gudnason, V Harris, TB Heckbert, SR Hochner, H Hofman, A Hsueh, WC Isaacs, A Jukema, JW Knekt, P Kors, JA Krijthe, BP Kristiansson, K Laaksonen, M Liu, Y Li, X MacFarlane, PW Newton-Cheh, C Nieminen, MS Oostra, BA Peloso, GM Porthan, K Rice, K Rivadeneira, FF Rotter, JI Salomaa, V Sattar, N Siscovick, DS Slagboom, PE Smith, AV Sotoodehnia, N Stott, DJ Stricker, BH Sturmer, T Trompet, S Uitterlinden, AG van Duijn, C Westendorp, RGJ Witteman, JC Whitsel, EA Psaty, BM AF Avery, C. L. Sitlani, C. M. Arking, D. E. Arnett, D. K. Bis, J. C. Boerwinkle, E. Buckley, B. M. Chen, Y-D Ida de Craen, A. J. M. Eijgelsheim, M. Enquobahrie, D. Evans, D. S. Ford, I. Garcia, M. E. Gudnason, V. Harris, T. B. Heckbert, S. R. Hochner, H. Hofman, A. Hsueh, W-C Isaacs, A. Jukema, J. W. Knekt, P. Kors, J. A. Krijthe, B. P. Kristiansson, K. Laaksonen, M. Liu, Y. Li, X. MacFarlane, P. W. Newton-Cheh, C. Nieminen, M. S. Oostra, B. A. Peloso, G. M. Porthan, K. Rice, K. Rivadeneira, F. F. Rotter, J. I. Salomaa, V. Sattar, N. Siscovick, D. S. Slagboom, P. E. Smith, A. V. Sotoodehnia, N. Stott, D. J. Stricker, B. H. Stuermer, T. Trompet, S. Uitterlinden, A. G. van Duijn, C. Westendorp, R. G. J. Witteman, J. C. Whitsel, E. A. Psaty, B. M. TI Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval SO PHARMACOGENOMICS JOURNAL LA English DT Article DE gene-environment interaction; genetic epidemiology; QT interval ID GENOME-WIDE ASSOCIATION; CHRONIC HEPATITIS-C; TORSADE-DE-POINTES; HEART-RATE; CARDIAC REPOLARIZATION; COMMON VARIANTS; OLDER-ADULTS; PROLONGATION; MORTALITY; DURATION AB Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the ` missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use = 13.0%), tri/tetracyclic antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction > 5.0 x 10(-8)). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects. C1 [Avery, C. L.; Arnett, D. K.; Stuermer, T.; Whitsel, E. A.] Univ N Carolina, Dept Epidemiol, Bank Amer Ctr, Chapel Hill, NC 27514 USA. [Sitlani, C. M.; Bis, J. C.; Enquobahrie, D.; Heckbert, S. R.; Hochner, H.; Siscovick, D. S.; Psaty, B. M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Arking, D. E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Arking, D. E.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Arnett, D. K.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Boerwinkle, E.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Houston, TX 77030 USA. [Boerwinkle, E.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Buckley, B. M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. [Chen, Y-D Ida; Li, X.; Rotter, J. I.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [de Craen, A. J. M.; Westendorp, R. G. J.] Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands. [Eijgelsheim, M.; Hofman, A.; Kors, J. A.; Krijthe, B. P.; Rivadeneira, F. F.; Stricker, B. H.; Uitterlinden, A. G.; Witteman, J. C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Evans, D. S.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Ford, I.] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Garcia, M. E.; Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Gudnason, V.; Smith, A. V.] Iceland Heart Assoc, Kopavogur, Iceland. [Heckbert, S. R.; Siscovick, D. S.; Psaty, B. M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Hofman, A.; Krijthe, B. P.; Rivadeneira, F. F.; Stricker, B. H.; Uitterlinden, A. G.; Witteman, J. C.] Netherlands Consortium Hlth Aging NCHA, Leiden, Netherlands. [Hsueh, W-C] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Isaacs, A.; Oostra, B. A.; van Duijn, C.] Erasmus Univ, Dept Epidemiol, Genet Epidemiol Unit, Med Ctr, Rotterdam, Netherlands. [Isaacs, A.; Oostra, B. A.; van Duijn, C.] Ctr Med Syst Biol, Leiden, Netherlands. [Jukema, J. W.; Trompet, S.] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Knekt, P.; Kristiansson, K.; Laaksonen, M.; Salomaa, V.] THL Natl Inst Hlth & Welf, Helsinki, Finland. [Kors, J. A.; Stricker, B. H.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Liu, Y.] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [MacFarlane, P. W.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Newton-Cheh, C.] Broad Inst Harvard, 4Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, C.] MIT, Cambridge, MA 02139 USA. [Newton-Cheh, C.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA USA. [Newton-Cheh, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nieminen, M. S.; Porthan, K.] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland. [Peloso, G. M.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Peloso, G. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rice, K.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Rivadeneira, F. F.; Stricker, B. H.; Uitterlinden, A. G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Sattar, N.] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland. [Slagboom, P. E.] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Sotoodehnia, N.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Stott, D. J.] Univ Glasgow, Inst Cardiovasc & Med Sci, Acad Sect Geriatr Med, Glasgow, Lanark, Scotland. [Whitsel, E. A.] Univ N Carolina, Dept Med, Chapel Hill, NC 27514 USA. [Psaty, B. M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Avery, CL (reprint author), Univ N Carolina, Dept Epidemiol, Bank Amer Ctr, 137 East Franklin St,Suite 306, Chapel Hill, NC 27514 USA. EM christy_avery@unc.edu RI Gudnason, Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015; Slagboom, P. Eline/R-4790-2016; OI Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Slagboom, P. Eline/0000-0002-2875-4723; Kristiansson, Kati/0000-0003-4688-107X; Rivadeneira, Fernando/0000-0001-9435-9441 FU National Heart, Lung and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Institutes of Health and NIH Roadmap for Medical Research. Cardiovascular Health Study (CHS) [UL1RR025005]; National Heart, Lung and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079-N01-HC-85086, N01-HC35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C]; NHLBI [HL080295, HL075366, HL087652, HL105756, N02-HL-6-4278]; NINDS [HL080295, HL075366, HL087652, HL105756]; NIA [AG-023629, AG-15928, AG-20098, AG-027058, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; National Center for Research Resources CTSI [DK063491]; National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine [N01-HC-25195]; SNP Health Association Resource (SHARe) project [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Doris Duke Charitable Foundation and the Burroughs Wellcome Fund (Newton-Cheh); NIH [HL080025]; Orion-Farmos Research Foundation; Finnish Foundation for Cardiovascular Research; Academy of Finland [29494, 139635]; National Institutes of Health to The Johns Hopkins University [HHSN268200782096C]; Intramural Research Program of the NIH, National Institute on Aging; National Heart, Lung and Blood Institute (NHLBI) in collaboration with MESA investigators; Clinical Translational Science Institute [UL1RR033176]; Cedars-Sinai General Clinical Research Center Grant [RR00425]; Established Clinical Investigator of the Netherlands Heart Foundation [2001 D 032]; seventh framework program of the European commission [223004]; Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging Grant) [050-060-810]; Erasmus Medical Center and Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly; Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; and the Municipality of Rotterdam; Netherlands Organization for Scientific Research (NWO) [175.010.2005.011, 911.03.012]; Research Institute for Diseases in the Elderly (RIDE); Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) [050-060-810]; National Heart, Lung, and Blood Institute; [N01 HC-95159-N01-HC-95169]; [RR-024156] FX Atherosclerosis Risk in Communities Study (ARIC): The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung and Blood Institute Contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute Contract U01HG004402; and National Institutes of Health Contract HHSN268200625226C. We thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant No. UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Cardiovascular Health Study (CHS): This CHS research was supported by National Heart, Lung and Blood Institute (NHLBI) Contracts N01-HC-85239, N01-HC-85079-N01-HC-85086; N01-HC35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C and NHLBI Grants HL080295, HL075366, HL087652 and HL105756, with additional contribution from NINDS. Additional support was provided through AG-023629, AG-15928, AG-20098 and AG-027058 from the NIA. See also http://www. chs-nhlbi. org/pi. htm. DNA handling and genotyping was supported in part by National Center for Research Resources CTSI Grant UL 1RR033176, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK063491 to the Southern California Diabetes Endocrinology Research Center and the Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR). Framingham Heart Study (FHS): FHS work was supported by the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine (Contract No. N01-HC-25195), its contract with Affymetrix for genotyping services (Contract No. N02-HL-6-4278), based on analyses by FHS investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II), funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Measurement of the Gen 3 ECGs was supported by grants from the Doris Duke Charitable Foundation and the Burroughs Wellcome Fund (Newton-Cheh) and the NIH (HL080025, Newton-Cheh). Health 2000: Supported by the Orion-Farmos Research Foundation (KK and KP), the Finnish Foundation for Cardiovascular Research (KK, KP) and the Academy of Finland (Grant Nos. 129494 and 139635 to VS). Health Aging, Body and Composition (Health ABC): This research was supported by NIA Contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study was funded by NIA Grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract No. HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Multi-Ethnic Study of Atherosclerosis (MESA): MESA and MESA SNP Health Association Resource (SHARe) are conducted and supported by the National Heart, Lung and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by Grants and Contracts N01 HC-95159-N01-HC-95169 and RR-024156.; Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. Additional funding was supported in part by the Clinical Translational Science Institute Grant UL1RR033176 and the Cedars-Sinai General Clinical Research Center Grant RR00425. We also thank the other investigators, the staff and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www. mesa-nhlbi. org. Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): The PROSPER study was supported by an investigator initiated grant obtained from Bristol-Myers Squibb. Professor Dr J W Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (Grant No. 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (Grant No. 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging Grant 050-060-810). Rotterdam Study (RS): The RS is supported by the Erasmus Medical Center and Erasmus University Rotterdam; The Netherlands Organization for Scientific Research; The Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; The Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Support for genotyping was provided by The Netherlands Organization for Scientific Research (NWO) (175.010.2005.011, 911.03.012) and Research Institute for Diseases in the Elderly (RIDE). This study was supported by The Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Project No. 050-060-810. This collaborative effort was supported by an award from the National Heart, Lung and Blood Institute (R01-HL-103612, PI BMP). CLA was supported in part by Grant R00-HL-098458 from the National Heart, Lung, and Blood Institute. NR 62 TC 6 Z9 6 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD FEB PY 2014 VL 14 IS 1 BP 6 EP 13 DI 10.1038/tpj.2013.4 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 302TL UT WOS:000330627700002 PM 23459443 ER PT J AU Sonnenberg, L Gelsomin, E Levy, DE Riis, J Barraclough, S Thorndike, AN AF Sonnenberg, Lillian Gelsomin, Emily Levy, Douglas E. Riis, Jason Barraclough, Susan Thorndike, Anne N. TI A traffic light food labeling intervention increases consumer awareness of health and healthy choices at the point-of-purchase (vol 57, pg 253, 2013) SO PREVENTIVE MEDICINE LA English DT Correction C1 [Sonnenberg, Lillian; Gelsomin, Emily; Barraclough, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Levy, Douglas E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Riis, Jason] Harvard Univ, Sch Business, Boston, MA 02163 USA. [Thorndike, Anne N.] Harvard Univ, Sch Med, Div Gen Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sonnenberg, L (reprint author), Massachusetts Gen Hosp, Ambulatory Nutr Serv, 165 Cambridge St,Suite 402, Boston, MA 02114 USA. EM lsonnenberg@partners.org; egelsomin@partners.org; Dlevy3@partners.org; jriis@hbs.edu; sbarraclough@partners.org; athorndike@partners.org NR 1 TC 0 Z9 0 U1 2 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD FEB PY 2014 VL 59 BP 86 EP 86 DI 10.1016/j.ypmed.2013.11.014 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 303NW UT WOS:000330682200017 ER PT J AU Kugel, S Mostoslavsky, R AF Kugel, Site Mostoslavsky, Raul TI Chromatin and beyond: the multitasking roles for SIRT6 SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID HISTONE DEACETYLASE SIRT6; SILENCING PROTEIN SIR2; STRAND BREAK REPAIR; DNA END RESECTION; LIFE-SPAN; SACCHAROMYCES-CEREVISIAE; HEPATIC GLUCONEOGENESIS; CALORIE RESTRICTION; GENOMIC INSTABILITY; SIR2-LIKE PROTEINS AB In recent years there has been a large expansion in our understanding of SIRT6 biology including its structure, regulation, biochemical activity, and biological roles. SIRT6 functions as an ADP-ribosylase and NAD(+)-dependent deacylase of both acetyl groups and long-chain fatty-acyl groups. Through these functions SIRT6 impacts upon cellular homeostasis by regulating DNA repair, telomere maintenance, and glucose and lipid metabolism, thus affecting diseases such diabetes, obesity, heart disease, and cancer. Such roles may contribute to the overall longevity and health of the organism. Until recently, the known functions of SIRT6 were largely restricted to the chromatin. In this article we seek to describe and expand this knowledge with recent advances in understanding the mechanisms of SIRT6 action and their implications for human biology and disease. C1 [Kugel, Site; Mostoslavsky, Raul] Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mostoslavsky, Raul] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Mostoslavsky, R (reprint author), Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rmostoslavsky@mgh.harvard.edu FU National Institutes of Health (NIH) [GM093072-01, DK088190-01A1]; National Pancreatic Foundation; Canadian Institutes of Health FX Work in the laboratory of R.M. is supported in part by National Institutes of Health (NIH) grants GM093072-01 and DK088190-01A1 and by the National Pancreatic Foundation. S.K. is supported by a Canadian Institutes of Health postdoctoral fellowship. R.M. is a Kristine and Bob Higgins Massachusetts General Hospital Research Scholar and a Howard Goodman Awardee. NR 76 TC 62 Z9 68 U1 1 U2 21 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 2014 VL 39 IS 2 BP 72 EP 81 DI 10.1016/j.tibs.2013.12.002 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA2KG UT WOS:000330922900004 PM 24438746 ER PT J AU Bryant, KL Mancias, JD Kimmelman, AC Der, CJ AF Bryant, Kirsten L. Mancias, Joseph D. Kimmelman, Alec C. Der, Channing J. TI KRAS: feeding pancreatic cancer proliferation SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID RAS-TRANSFORMED CELLS; K-RAS; ONCOGENIC KRAS; DUCTAL ADENOCARCINOMA; GLUTAMINE-METABOLISM; AEROBIC GLYCOLYSIS; ENERGY-METABOLISM; OXIDATIVE STRESS; TUMOR-CELLS; H-RAS AB Oncogenic KRAS mutation is the signature genetic event in the progression and growth of pancreatic ductal adenocarcinoma (PDAC), an almost universally fatal disease. Although it has been appreciated for some time that nearly 95% of PDAC harbor mutationally activated KRAS, to date no effective treatments that target this mutant protein have reached the clinic. A number of studies have shown that oncogenic KRAS plays a central role in controlling tumor metabolism by orchestrating multiple metabolic changes including stimulation of glucose uptake, differential channeling of glucose intermediates, reprogrammed glutamine metabolism, increased autophagy, and macropinocytosis. We review these recent findings and address how they may be applied to develop new PDAC treatments. C1 [Bryant, Kirsten L.; Der, Channing J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Mancias, Joseph D.; Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02215 USA. [Mancias, Joseph D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. [Mancias, Joseph D.; Kimmelman, Alec C.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Der, CJ (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM cjder@med.unc.edu FU National Institutes of Health (NIH); Pancreatic Cancer Action Network-American Association for Cancer Research (AACR); Lustgarten Pancreatic Cancer Foundation; NIH; American Cancer Society (ACS); Department of Defense (DOD); American Society of Radiation Oncology (ASTRO) Junior Faculty Career Research Training Award; [T32 CA71341] FX We apologize to colleagues whose studies we did not cite due to space limitations. C.J.D. is supported by grants from the National Institutes of Health (NIH), Pancreatic Cancer Action Network-American Association for Cancer Research (AACR), and the Lustgarten Pancreatic Cancer Foundation. K.L.B. is supported by a T32 CA71341 training grant. A.C.K. is supported by grants from the NIH, American Cancer Society (ACS), Department of Defense (DOD), and the Lustgarten Pancreatic Cancer Foundation. J.D.M. is supported by an American Society of Radiation Oncology (ASTRO) Junior Faculty Career Research Training Award. NR 79 TC 92 Z9 95 U1 9 U2 39 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 2014 VL 39 IS 2 BP 91 EP 100 DI 10.1016/j.tibs.2013.12.004 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA2KG UT WOS:000330922900006 PM 24388967 ER PT J AU Ankerst, DP Boeck, A Freedland, SJ Jones, JS Cronin, AM Roobol, MJ Hugosson, J Kattan, MW Klein, EA Hamdy, F Neal, D Donovan, J Parekh, DJ Klocker, H Horninger, W Benchikh, A Salama, G Villers, A Moreira, DM Schroder, FH Lilja, H Vickers, AJ Thompson, IM AF Ankerst, Donna P. Boeck, Andreas Freedland, Stephen J. Jones, J. Stephen Cronin, Angel M. Roobol, Monique J. Hugosson, Jonas Kattan, Michael W. Klein, Eric A. Hamdy, Freddie Neal, David Donovan, Jenny Parekh, Dipen J. Klocker, Helmut Horninger, Wolfgang Benchikh, Amine Salama, Gilles Villers, Arnauld Moreira, Daniel M. Schroder, Fritz H. Lilja, Hans Vickers, Andrew J. Thompson, Ian M. TI Evaluating the Prostate Cancer Prevention Trial High Grade prostate cancer risk calculator in 10 international biopsy cohorts: results from the prostate biopsy collaborative group SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Calibration; Discrimination; Net benefit; High-grade prostate cancer; Risk ID PREDICTION MODELS; IMPROVES; ANTIGEN AB To assess the applicability of the Prostate Cancer Prevention Trial High Grade (Gleason grade a parts per thousand yen 7) Risk Calculator (PCPTHG) in ten international cohorts, representing a range of populations. A total of 25,512 biopsies from 10 cohorts (6 European, 1 UK and 3 US) were included; 4 implemented 6-core biopsies, and the remaining had 10 or higher schemes; 8 were screening cohorts, and 2 were clinical. PCPTHG risks were calculated using prostate-specific antigen, digital rectal examination, age, African origin and history of prior biopsy and evaluated in terms of calibration plots, areas underneath the receiver operating characteristic curve (AUC) and net benefit curves. The median AUC of the PCPTHG for high-grade disease detection in the 10- and higher-core cohorts was 73.5 % (range, 63.9-76.7 %) compared with a median of 78.1 % (range, 72.0-87.6 %) among the four 6-core cohorts. Only the 10-core Cleveland Clinic cohort showed clear evidence of under-prediction by the PCPTHG, and this was restricted to risk ranges less than 15 %. The PCPTHG demonstrated higher clinical net benefit in higher-core compared with 6-core biopsy cohorts, and among the former, there were no notable differences observed between clinical and screening cohorts, nor between European and US cohorts. The PCPTHG requires minimal patient information and can be applied across a range of populations. PCPTHG risk thresholds ranging from 5 to 20 %, depending on patient risk averseness, are recommended for clinical prostate biopsy decision-making. C1 [Ankerst, Donna P.; Parekh, Dipen J.; Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Ankerst, Donna P.; Boeck, Andreas] Tech Univ Munich, Garching, Germany. [Freedland, Stephen J.; Moreira, Daniel M.] Durham VA Med Ctr, Durham, NC USA. [Freedland, Stephen J.; Moreira, Daniel M.] Duke Univ, Durham, NC USA. [Jones, J. Stephen; Kattan, Michael W.; Klein, Eric A.] Cleveland Clin, Cleveland, OH 44106 USA. [Cronin, Angel M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Roobol, Monique J.; Schroder, Fritz H.] Erasmus MC, Rotterdam, Netherlands. [Hugosson, Jonas] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Hamdy, Freddie] Univ Oxford, Oxford, England. [Neal, David] Univ Cambridge, Cambridge, England. [Donovan, Jenny] Univ Bristol, Bristol, Avon, England. [Klocker, Helmut; Horninger, Wolfgang] Med Univ Innsbruck, A-6020 Innsbruck, Austria. [Benchikh, Amine] Hop Bichat Claude Bernard, F-75877 Paris 18, France. [Salama, Gilles] Ctr Hosp Intercommunal Castres Mazamet, Castres, France. [Villers, Arnauld] Univ Lille Nord, Dept Urol, CHU Lille, Lille, France. [Lilja, Hans; Vickers, Andrew J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Ankerst, DP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ankerst@uthscsa.edu RI Arnauld, VILLERS/K-6629-2016; OI Arnauld, VILLERS/0000-0002-6298-7758; Lilja, Hans/0000-0001-5871-7846; Neal, David/0000-0002-6033-5086; Moreira, Daniel/0000-0003-4517-244X; Vickers, Andrew/0000-0003-1525-6503 FU National Cancer Institute Cancer Center Support Grant for the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio [P30-CA054174]; European Union [SOC 95 35109, SOC 96 201869 05F022, SOC 97 201329, SOC 98 32241]; EU [PMark:LSHC-CT-2004-503011]; Dutch Cancer Society [KWF 94-869, 98-1657, 2002-277, 2006-3518]; Netherlands Organisation for Health Research and Development [ZonMW-002822820, 22000106, 50-50110-98-311]; Prostate Cancer Research Foundation of Rotterdam (SWOP); Institut National du Cancer [12-2008, 07/3D1616/SPC-111-13/NG-NC, PRE08/AV-CONV]; DRC [2009/119]; Beckman-Coulter-Hybritech Inc; Abbott Pharmaceuticals, Sweden; Af Jochnick's foundation; Catarina and Sven Hagstroms family foundation; Gunvor and Ivan Svensson's foundation; Johanniterorden, King Gustav V Jubilee Clinic Cancer Research Foundation; Sahlgrenska University Hospital; Schering Plough, Sweden; Swedish Cancer Society [09 0107, 080315, 083455]; Wallac Oy, Turkku, Finland; International Agency for Research on Cancer, Lyon; Tyrolean Prostate Cancer Early Detection Group; San Antonio Center of Biomarkers of Risk for Prostate Cancer [CA086402]; UK NIHR Health Technology Assessment Programme [96/20/06, 96/20/99] FX Statistics supported by a National Cancer Institute Cancer Center Support Grant for the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio [P30-CA054174]. Grants to support the work of the ERSPC include: European Union Grants SOC 95 35109, SOC 96 201869 05F022, SOC 97 201329, SOC 98 32241, the 6th Framework Program of the EU: PMark:LSHC-CT-2004-503011; The Dutch Cancer Society (KWF 94-869, 98-1657, 2002-277, 2006-3518); The Netherlands Organisation for Health Research and Development (ZonMW-002822820, 22000106, 50-50110-98-311); The Prostate Cancer Research Foundation of Rotterdam (SWOP); Institut National du Cancer convention 12-2008 Convention : 07/3D1616/SPC-111-13/NG-NC Appel a projets 2007 : Sante publique et Cancers Ligue Nationale Contre le cancer PROJET No. PRE08/AV-CONV. DRC 2009/119 (Tarn); Beckman-Coulter-Hybritech Inc; Abbott Pharmaceuticals, Sweden; Af Jochnick's foundation; Catarina and Sven Hagstroms family foundation; Gunvor and Ivan Svensson's foundation; Johanniterorden, King Gustav V Jubilee Clinic Cancer Research Foundation; Sahlgrenska University Hospital; Schering Plough, Sweden, Swedish Cancer Society (Contract numbers 09 0107, 080315 and 083455); Wallac Oy, Turkku, Finland. The Tyrol study is supported by the International Agency for Research on Cancer, Lyon and the Tyrolean Prostate Cancer Early Detection Group. The SABOR project is supported by the San Antonio Center of Biomarkers of Risk for Prostate Cancer CA086402. The ProtecT study is funded by the UK NIHR Health Technology Assessment Programme (projects 96/20/06, 96/20/99). NR 13 TC 13 Z9 13 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD FEB PY 2014 VL 32 IS 1 BP 185 EP 191 DI 10.1007/s00345-012-0869-2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AA0EO UT WOS:000330768300026 PM 22527674 ER PT J AU Hanson, JT Pierce, RG Dhaliwal, G AF Hanson, Joshua T. Pierce, Read G. Dhaliwal, Gurpreet TI The New Education Frontier: Clinical Teaching at Night SO ACADEMIC MEDICINE LA English DT Article ID REDESIGNING RESIDENCY EDUCATION; PATIENT-CARE; WORK HOURS; INTERNAL-MEDICINE; SUPERVISION; SLEEP; FLOAT; ASSOCIATION; PHYSICIANS; IMPACT AB Regulations that restrict resident work hours and call for increased resident supervision have increased attending physician presence in the hospital during the nighttime. The resulting increased interactions between attendings and trainees provide an important opportunity and obligation to enhance the quality of learning that takes place in the hospital between 6 pm and 8 am. Nighttime education should be transformed in a way that maintains clinical productivity for both attending and resident physicians, integrates high-quality teaching and curricula, and achieves a balance between patient safety and resident autonomy. Direct observation of trainees, instruction in communication, and modeling of cost-efficient medical practice may be more feasible during the night than during daytime hours. To realize the potential of this educational opportunity, training programs should develop skilled nighttime educators and establish metrics to define success. C1 [Hanson, Joshua T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Hanson, Joshua T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Pierce, Read G.] Univ Colorado, Dept Med, Denver, CO USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. RP Hanson, JT (reprint author), 7703 Floyd Curl Dr MC 7982, San Antonio, TX 78229 USA. EM hansonj4@uthscsa.edu NR 33 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD FEB PY 2014 VL 89 IS 2 BP 215 EP 218 DI 10.1097/ACM.0000000000000096 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 298EC UT WOS:000330305900012 PM 24362386 ER PT J AU Thier, SO Kelley, WN Pardes, H Knight, AW Wietecha, M AF Thier, Samuel O. Kelley, William N. Pardes, Herbert Knight, Amy Wimpey Wietecha, Mark TI Success Factors in Merging Teaching Hospitals SO ACADEMIC MEDICINE LA English DT Article ID YORK-UNIVERSITY HOSPITALS; MOUNT-SINAI; MERGER; SYSTEMS; FAILURE AB Merger has served as a major strategy for the leaders of academic medical centers (i.e., teaching hospitals) who are pursuing health system development for their institutions. Applying hindsight to their personal experience, the authors explore common themes in several mergers that have survived the test of time. Although many elements influence merger outcomes, experience suggests several of unique importance. These include effective leadership in the areas of creating trust, managing uncertainty, ensuring medical staff stability, and bridging cultural divides across the organizations. While a quantitative business case should support any merger, the authors' experiences underscore the importance of successfully assessing and managing organizational and individual dynamics when bringing together major teaching hospitals. C1 [Thier, Samuel O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thier, Samuel O.] Partners Healthcare, Boston, MA USA. [Kelley, William N.] Univ Penn, Philadelphia, PA 19104 USA. [Kelley, William N.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Kelley, William N.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kelley, William N.] Univ Pennsylvania Hlth Syst, Philadelphia, PA USA. [Pardes, Herbert] Columbia Univ, Coll Phys & Surg, Fac Med, New York, NY USA. [Pardes, Herbert] New York Presbyterian Hosp, New York, NY USA. [Knight, Amy Wimpey; Wietecha, Mark] Childrens Hosp Assoc, Alexandria, VA 22314 USA. RP Wietecha, M (reprint author), Childrens Hosp Assoc, 401 Wythe St, Alexandria, VA 22314 USA. EM mark.wietecha@childrenshospitals.org NR 20 TC 3 Z9 3 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD FEB PY 2014 VL 89 IS 2 BP 219 EP 223 DI 10.1097/ACM.0000000000000094 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 298EC UT WOS:000330305900013 PM 24362373 ER PT J AU Shunk, R Dulay, M Chou, CL Janson, S O'Brien, BC AF Shunk, Rebecca Dulay, Maya Chou, Calvin L. Janson, Susan O'Brien, Bridget C. TI Huddle-Coaching: A Dynamic Intervention for Trainees and Staff to Support Team-Based Care SO ACADEMIC MEDICINE LA English DT Article ID CENTERED MEDICAL HOME; GUIDE AB Many outpatient clinics where health professionals train will transition to a team-based medical home model over the next several years. Therefore, training programs need innovative approaches to prepare and incorporate trainees into team-based delivery systems. To address this need, educators at the San Francisco Veterans Affairs (VA) Medical Center included trainees in preclinic team huddles, or briefing meetings to facilitate care coordination, and developed an interprofessional huddle-coaching program for nurse practitioner students and internal medicine residents who function as primary providers for patient panels in VA outpatient primary care clinics. The program aimed to support trainees' partnerships with staff and full participation in the VA's Patient Aligned Care Teams. The huddle-coaching program focuses on structuring the huddle process via scheduling, checklists, and designated huddle coaches; building relationships among team members through team-building activities; and teaching core skills to support collaborative practice. A multifaceted evaluation of the program showed positive results. Participants rated training sessions and team-building activities favorably. In interviews, trainees valued their team members and identified improvements in efficiency and quality of patient care as a result of the team-based approach. Huddle checklists and scores on the Team Development Measure indicated progress in team processes and relationships as the year progressed. These findings suggest that the huddle-coaching program was a worthwhile investment in trainee development that also supported the clinic's larger mission to deliver team-based, patient-aligned care. As more training sites shift to team-based care, the huddle-coaching program offers a strategy for successfully incorporating trainees. C1 [Shunk, Rebecca; Dulay, Maya; Chou, Calvin L.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Shunk, Rebecca; Dulay, Maya; Chou, Calvin L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Janson, Susan] Univ Calif San Francisco, Sch Nursing, Dept Community Hlth Syst, San Francisco, CA 94143 USA. [Janson, Susan; O'Brien, Bridget C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [O'Brien, Bridget C.] Univ Calif San Francisco, Off Res & Dev Med Educ, San Francisco, CA 94143 USA. RP Shunk, R (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM rebecca.shunk@va.gov FU Centers of Excellence in Primary Care Education of the Office of Academic Affiliations, U.S. Department of Veterans Affairs Office of Academic Affiliations; San Francisco Veterans Affairs Medical Center; University of California, San Francisco (UCSF) FX The Centers of Excellence in Primary Care Education of the Office of Academic Affiliations, U.S. Department of Veterans Affairs Office of Academic Affiliations; San Francisco Veterans Affairs Medical Center; University of California, San Francisco (UCSF). NR 17 TC 10 Z9 10 U1 1 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD FEB PY 2014 VL 89 IS 2 BP 244 EP 250 DI 10.1097/ACM.0000000000000104 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 298EC UT WOS:000330305900018 PM 24362383 ER PT J AU Oldenburg, CE Barnighausen, T Harling, G Mimiaga, MJ Mayer, KH AF Oldenburg, Catherine E. Baernighausen, Till Harling, Guy Mimiaga, Matthew J. Mayer, Kenneth H. TI Adherence to Post-Exposure Prophylaxis for Non-forcible Sexual Exposure to HIV: A Systematic Review and Meta-Analysis SO AIDS AND BEHAVIOR LA English DT Review DE Post-exposure prophylaxis; Meta-analysis; HIV; Medication adherence ID ANTIRETROVIRAL PREEXPOSURE PROPHYLAXIS; HUMAN-IMMUNODEFICIENCY-VIRUS; RETROSPECTIVE ANALYSIS; PUBLICATION BIAS; TENOFOVIR DF; MEN; PREVENTION; TRANSMISSION; EMTRICITABINE; INFECTION AB To characterize adherence to post-exposure prophylaxis after non-forcible sexual exposure to HIV, we conducted a review of the literature and meta-analysis. Articles were considered if they contained primary adherence data following non-forcible sexual exposure. Random-effects meta-analysis was used to create pooled point estimates for adherence. Of 1,257 abstracts identified through our search algorithm, 17 were eligible for inclusion in this review, representing 3,634 patients enrolled in 3 randomized controlled trials (RCTs), 9 prospective and 5 retrospective observational studies. Pooled adherence, primarily assessed by self-report, was 77 % [95 % confidence interval (CI) 68-87] in prospective observational studies, 81 % (95 % CI 65-96) in retrospective studies, 78 % (95 % CI 65-91) in RCTs, and 78 % (95 % CI 72-85) overall. Overall adherence was moderately high, with high variability between studies. Assessment of adherence could be enhanced by the use of objective measurements. C1 [Oldenburg, Catherine E.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Baernighausen, Till] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Harling, Guy] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Oldenburg, CE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM ceo242@mail.harvard.edu RI Harling, Guy/R-6442-2016; OI Harling, Guy/0000-0001-6604-491X FU NIAID NIH HHS [T32 AI007535, T32AI007535]; NICHD NIH HHS [R01 HD058482]; Wellcome Trust [097410] NR 49 TC 11 Z9 12 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD FEB PY 2014 VL 18 IS 2 BP 217 EP 225 DI 10.1007/s10461-013-0567-0 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 298QR UT WOS:000330339900002 PM 23877791 ER PT J AU Bergman, BG Greene, MC Hoeppner, BB Slaymaker, V Kelly, JF AF Bergman, Brandon G. Greene, M. Claire Hoeppner, Bettina B. Slaymaker, Valerie Kelly, John F. TI Psychiatric Comorbidity and 12-Step Participation: A Longitudinal Investigation of Treated Young Adults SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Dual Diagnosis; 12-Step Participation; Young Adults; Co-Occurring Disorders ID SUBSTANCE USE DISORDERS; LEEDS-DEPENDENCE-QUESTIONNAIRE; NATIONAL EPIDEMIOLOGIC SURVEY; MUTUAL-HELP; EMERGING ADULTHOOD; MAJOR DEPRESSION; CLINICAL-SAMPLE; DRUG-TREATMENT; USE OUTCOMES; ALCOHOL AB BackgroundEvidence indicates that 12-step mutual-help organizations (MHOs), such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA), can play an important role in extending and potentiating the recovery benefits of professionally delivered addiction treatment among young adults with substance use disorders (SUD). However, concerns have lingered regarding the suitability of 12-step organizations for certain clinical subgroups, such as those with dual diagnosis (DD). This study examined the influence of diagnostic status (DD vs. SUD-only) on both attendance and active involvement (e.g., having a sponsor, verbal participation during meetings) in, and derived benefits from, 12-step MHOs following residential treatment. MethodsYoung adults (N=296; 18 to 24years old; 26% female; 95% Caucasian; 47% DD [based on structured diagnostic interview]), enrolled in a prospective naturalistic study of SUD treatment effectiveness, were assessed at intake and 3, 6, and 12months posttreatment on 12-step attendance/active involvement and percent days abstinent (PDA). t-Tests and lagged, hierarchical linear models (HLM) examined the extent to which diagnostic status influenced 12-step participation and any derived benefits, respectively. ResultsFor DD and SUD-only patients, posttreatment attendance and active involvement in 12-step organizations were similarly high. Overall, DD patients had significantly lower PDA relative to SUD-only patients. All patients appeared to benefit significantly from attendance and active involvement on a combined 8-item index. Regarding the primary effects of interest, significant differences did not emerge in derived benefit between DD and SUD-only patients for either attendance (p=0.436) or active involvement (p=0.062). Subsidiary analyses showed, however, that DD patients experienced significantly greater abstinence-related benefit from having a 12-step sponsor. ConclusionsDespite concerns regarding the clinical utility of 12-step MHOs for DD patients, findings indicate that DD young adults participate and benefit as much as SUD-only patients, and may benefit more from high levels of active involvement, particularly having a 12-step sponsor. Future work is needed to clarify how active 12-step involvement might offset the additional recovery burden of a comorbid mental illness on substance use outcomes. C1 [Bergman, Brandon G.; Greene, M. Claire; Hoeppner, Bettina B.; Kelly, John F.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Slaymaker, Valerie] Hazelden Fdn, Center City, MN USA. RP Bergman, BG (reprint author), MGH Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM bgbergman@partners.org FU NIDA [K01DA027097]; NIAAA [1R21AA018185-01A2] FX This work was funded by 1R21AA018185-01A2 and by an anonymous donation for youth research to the Hazelden Foundation. BBH's participation is supported by NIDA grant No. K01DA027097. JFK's participation is supported by NIAAA grant No. 1R21AA018185-01A2. NR 57 TC 4 Z9 4 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2014 VL 38 IS 2 BP 501 EP 510 DI 10.1111/acer.12249 PG 10 WC Substance Abuse SC Substance Abuse GA 297PC UT WOS:000330266400025 PM 24033550 ER PT J AU Lapham, GT Rubinsky, AD Heagerty, PJ Achtmeyer, C Williams, EC Hawkins, EJ Maynard, C Kivlahan, DR Au, D Bradley, KA AF Lapham, Gwen T. Rubinsky, Anna D. Heagerty, Patrick J. Achtmeyer, Carol Williams, Emily C. Hawkins, Eric J. Maynard, Charles Kivlahan, Daniel R. Au, David Bradley, Katharine A. TI Probability and Predictors of Patients Converting from Negative to Positive Screens for Alcohol Misuse SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholism and Addictive Behaviors; Screening; Decision Making ID PRIMARY-CARE; VETERANS-AFFAIRS; AUDIT-C; HEALTH-CARE; PREVENTIVE SERVICES; RISK DRINKING; USE DISORDERS; SCORES; TRAJECTORIES; CONSUMPTION AB BackgroundMedicare reimburses providers for annual alcohol screening. However, the benefit of rescreening patients a year after a negative screen for alcohol misuse is unknown. We hypothesized that some subgroups of patients who screen negative would have a very low probability of converting to a positive subsequent screen (e.g., <0.1%), calling into question the value of annual alcohol screening for some patient subgroups. MethodsThis retrospective cohort study estimated the probability of converting to a positive screen for alcohol misuse a year after a negative screen among outpatients from 30 Veterans Health Administration (VA) medical centers. Alcohol Use Disorders Identification TestConsumption (AUDIT-C) alcohol screening scores (range 0 to 12 points) from 2004 to 2008 were obtained from electronic health record data. Eligible patients screened negative on their initial screen (AUDIT-C scores 0 to 3 for men; 0 to 2 for women). The main outcome was a positive subsequent screen (AUDIT-C scores 4 men; 3 women). ResultsAmong 21,081 women and 323,913 men who screened negative on an initial screen, 5.4% and 6.0%, respectively, screened positive a year later. The adjusted probability of converting to a positive subsequent screen varied from 2.1 to 38.9% depending on age, gender, and initial negative screen score. Women, older patients, and those with initial AUDIT-C scores of 0 were least likely to a convert to a positive subsequent screen, while younger men with AUDIT-C scores of 3 were most likely to a convert to a positive subsequent screen. ConclusionsThe probability of a positive subsequent screen varied depending on age, gender, and initial negative screen score but exceeded 2% in all patient subgroups. Annual rescreening appears reasonable for all VA patients who had a negative screen the year prior. C1 [Lapham, Gwen T.; Rubinsky, Anna D.; Achtmeyer, Carol; Williams, Emily C.; Hawkins, Eric J.; Maynard, Charles; Kivlahan, Daniel R.; Au, David; Bradley, Katharine A.] Hlth Serv Res & Dev HSR&D Northwest Ctr Excellenc, Seattle, WA USA. [Lapham, Gwen T.; Rubinsky, Anna D.; Heagerty, Patrick J.; Williams, Emily C.; Maynard, Charles; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Achtmeyer, Carol; Hawkins, Eric J.; Bradley, Katharine A.] CESATE, Seattle, WA USA. [Achtmeyer, Carol; Au, David] Vet Affairs VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA USA. [Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Au, David; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. RP Lapham, GT (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM gwendolyn.lap-ham@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Department of Veterans Affairs, Veteran Health Administration, Health Services Research and Development Service; Veterans Affairs Substance Use Disorders Quality Enhancement Research Initiative [RRP 11-021] FX The study reported here was supported by the Department of Veterans Affairs, Veteran Health Administration, Health Services Research and Development Service. The manuscript was specifically produced with support from the Veterans Affairs Substance Use Disorders Quality Enhancement Research Initiative (RRP 11-021). Preliminary results of this study were presented at the 35th Annual Research Society on Alcoholism Scientific Meeting, June 2012 in San Francisco, CA. NR 51 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2014 VL 38 IS 2 BP 564 EP 571 DI 10.1111/acer.12260 PG 8 WC Substance Abuse SC Substance Abuse GA 297PC UT WOS:000330266400033 PM 24118025 ER PT J AU Della Torre, E Mattoo, H Mahajan, VS Carruthers, M Pillai, S Stone, JH AF Della Torre, E. Mattoo, H. Mahajan, V. S. Carruthers, M. Pillai, S. Stone, J. H. TI Prevalence of atopy, eosinophilia, and IgE elevation in IgG4-related disease SO ALLERGY LA English DT Article DE allergy; atopy; eosinophilia; IgG4-related disease; Th2 response ID REGULATORY IMMUNE-REACTIONS; PANCREATITIS; MECHANISMS; ALLERGY; TH2 AB IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that can affect virtually every organ system. T-helper type 2 responses have been presumed to be pathogenic in this disease, and a high proportion of patients with IgG4-RD are reported to have longstanding allergies, peripheral blood eosinophilia, and serum IgE elevation. It has therefore been proposed that allergic mechanisms drive IgG4-RD. However, no epidemiological assessment of atopy, peripheral blood eosinophilia, and serum IgE concentrations has ever been undertaken in patients with IgG4-RD. In this study, we evaluated these parameters in a large cohort of patients with IgG4-RD in whom a wide range of organs were affected by disease. Our results demonstrate that the majority of patients with IgG4-RD are nonatopic. Nevertheless, a subset of nonatopic subjects exhibit peripheral blood eosinophilia and elevated IgE, suggesting that processes inherent to IgG4-RD itself rather than atopy per se contribute to the eosinophilia and IgE elevation observed in the absence of atopy. C1 [Della Torre, E.; Mattoo, H.; Mahajan, V. S.; Pillai, S.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Della Torre, E.] Univ Vita Salute San Raffaele, Sch Med, Unit Med & Clin Immunol, Milan, Italy. [Carruthers, M.; Stone, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM pillai@helix.mgh.harvard.edu; jhstone@partners.org OI Della Torre, Emanuel/0000-0002-9192-4270 FU NIH [AI 064930, AI 076505] FX This study was funded by Grants AI 064930 and AI 076505 from the NIH to SP. NR 8 TC 37 Z9 38 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD FEB PY 2014 VL 69 IS 2 BP 269 EP 272 DI 10.1111/all.12320 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 295VX UT WOS:000330145600017 PM 24266692 ER PT J AU Tirumani, SH Shinagare, AB Hargreaves, J Jagannathan, JP Hornick, JL Wagner, AJ Ramaiya, NH AF Tirumani, Sree Harsha Shinagare, Atul B. Hargreaves, Jonathan Jagannathan, Jyothi P. Hornick, Jason L. Wagner, Andrew J. Ramaiya, Nikhil H. TI Imaging Features of Primary and Metastatic Malignant Perivascular Epithelioid Cell Tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; malignant PEComa; malignant perivascular epithelioid tumors; MRI; ultrasound ID OF-THE-LITERATURE; MTOR INHIBITION; SOFT-TISSUE; PECOMA; NEOPLASMS; SARCOMA; PATIENT; UTERUS AB OBJECTIVE. The objective of our study was to describe the imaging features of primary and metastatic malignant perivascular epithelioid cell tumors (PEComas). MATERIALS AND METHODS. In this retrospective study, 36 patients (26 women, 10 men; mean age, 53.1 years; age range, 35-77 years) with a histopathologically confirmed diagnosis of malignant PEComa who were seen at our institute between January 2007 and December 2012 were included. Pretreatment imaging of the primary tumor in 17 patients (CT, n = 13; MRI, n = 9; ultrasound, n = 5) and follow-up imaging in all 36 patients (CT, n = 36; MRI, n = 7) were reviewed by three radiologists in consensus. RESULTS. The most common site of presentation of malignant PEComas was the retroperitoneum (38.9%) followed by the female genital tract (27.8%). Kidneys (8/36) and uterus (8/36) were the organs most frequently involved. The mean largest dimension was 11.01 cm (range, 4.5-25 cm). Primary tumors were well-circumscribed masses (16/17), were heteroechoic on ultrasound (5/5), were hypodense (2/6) to isodense (4/6) enhanced significantly (11/12) and compared with the paraspinal muscles on CT, were hypointense to isointense compared with skeletal muscle on T1-weighted imaging (8/9), were heterogeneously hyperintense compared with skeletal muscle on T2-weighted imaging (9/9), and showed significant post-gadolinium enhancement (7/7) on MRI. Of the 17 primary tumors, necrosis was seen in seven tumors, hemorrhage in three tumors, and calcification in three tumors. Twenty-six of 36 (72%) patients developed metastases, most commonly to the lung (21.6%), liver (17.6%), and peritoneum (10.8%). CONCLUSION. Malignant PEComas in our study were large tumors that most often arise in the kidneys and uterus and metastasize to lungs, liver, or peritoneum. In our experience malignant PEComas should be considered in the differential diagnosis of large well-circumscribed renal and uterine tumors. C1 [Tirumani, Sree Harsha; Shinagare, Atul B.; Hargreaves, Jonathan; 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.; Hargreaves, Jonathan; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Hornick, Jason L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Wagner, Andrew J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wagner, Andrew J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, 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 31 TC 9 Z9 10 U1 0 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2014 VL 202 IS 2 BP 252 EP 258 DI 10.2214/AJR.13.10909 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 299ZN UT WOS:000330434300013 PM 24450662 ER PT J AU Rafferty, EA Park, JM Philpotts, LE Poplack, SP Sumkin, JH Halpern, EF Niklason, LT AF Rafferty, Elizabeth A. Park, Jeong Mi Philpotts, Liane E. Poplack, Steven P. Sumkin, Jules H. Halpern, Elkan F. Niklason, Loren T. TI Diagnostic Accuracy and Recall Rates for Digital Mammography and Digital Mammography Combined With One-View and Two-View Tomosynthesis: Results of an Enriched Reader Study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast cancer; cancer detection; digital mammography; imaging technology; tomosynthesis ID BREAST-CANCER RISK; SCREENING MAMMOGRAPHY; OBSERVER PERFORMANCE; 3 DECADES; DENSITY; POPULATION; COMBINATION; MORTALITY; IMPACT; TRIAL AB OBJECTIVE. The purpose of this study was to compare two methods of combining tomosynthesis with digital mammography by assessing diagnostic accuracy and recall rates for digital mammography alone and digital mammography combined with one-view tomosynthesis and two-view tomosynthesis. SUBJECTS AND METHODS. Three hundred ten cases including biopsy-proven malignancies (51), biopsy-proven benign findings (47), recalled screening cases (138), and negative screening cases (74) were reviewed by 15 radiologists sequentially using digital mammography, adding one-view tomosynthesis, and then two-view tomosynthesis. Cases were assessed for recall and assigned a BI-RADS score and probability of malignancy for each imaging method. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. Screening recall rates were compared using pooled logistical regression analysis. A p value of < 0.0167 was considered significant. RESULTS. The area under the ROC curve (AUC) for digital mammography (DM), DM plus one-view tomosynthesis, and DM plus two-view tomosynthesis was 0.828, 0.864, and 0.895, respectively. Both one-view and two-view tomosynthesis plus DM were significantly better than DM alone (Delta AUCs 0.036 [p = 0.009] and 0.068 [p < 0.001]). Average noncancer recall rates for digital mammography, DM plus one-view tomosynthesis, and DM plus two-view tomosynthesis were 44.2%, 27.2%, and 24.0%, respectively. Combined with DM, one-view and two-view tomosynthesis both showed significantly lower noncancer recall rates than digital mammography alone (p < 0.001). Digital mammography with two-view tomosynthesis showed a significantly lower recall rate than digital mammography with one-view tomosynthesis (p < 0.001). Diagnostic accuracy for dense (Delta AUC, 0.091%; p < 0.001) and nondense (Delta AUC, 0.035%; p = 0.001) breasts improved with DM plus two-view tomosynthesis compared with digital mammography alone. Compared with digital mammography, diagnostic sensitivity for invasive cancers increased with the addition of both one-view (Delta 12.0%, p < 0.001) and two-view (Delta 21.7%, p < 0.001) tomosynthesis. CONCLUSION. The addition of one-view tomosynthesis to conventional digital mammography improved diagnostic accuracy and reduced the recall rate; however, the addition of two-view tomosynthesis provided twice the performance gain in diagnostic accuracy while further reducing the recall rate. C1 [Rafferty, Elizabeth A.; Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Park, Jeong Mi] Univ Iowa Hosp, Dept Radiol, Iowa City, IA USA. [Philpotts, Liane E.] Yale Univ, Sch Med, Dept Radiol, Yale New Haven Hosp, New Haven, CT 06510 USA. [Poplack, Steven P.] Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03766 USA. [Sumkin, Jules H.] Magee Womens Hosp, Dept Radiol, Pittsburgh, PA USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Niklason, Loren T.] Hologic Inc, Bedford, MA USA. RP Rafferty, EA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM erafferty@partners.org FU Hologic FX A grant for image collection and equipment was provided to each of the five participating sites by Hologic. NR 25 TC 25 Z9 25 U1 0 U2 11 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2014 VL 202 IS 2 BP 273 EP 281 DI 10.2214/AJR.13.11240 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 299ZN UT WOS:000330434300016 PM 24450665 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Digital Breast Tomosynthesis From Concept to Clinical Care SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE breast; breast cancer; digital breast tomosynthesis; mammography; screening ID SWEDISH 2-COUNTY TRIAL; CANCER MORTALITY; SCREENING MAMMOGRAPHY; CARCINOMA MORTALITY; OVERDIAGNOSIS; WOMEN; RISK; PERFORMANCE; EXPERIENCE; REDUCTION AB OBJECTIVE. The purpose of this article is to describe the development of digital breast tomosynthesis (DBT) and to describe its advantages over 2D mammography for breast cancer screening. CONCLUSION. Mammographic screening has dramatically reduced breast cancer deaths, but it does not depict all cancer early enough to result in a cure. In addition, because of the recall rates associated with mammography, efforts are underway to reduce access to screening. Use of DBT improves sensitivity and specificity, and there is no longer a need to obtain full-exposure 2D mammograms. DBT will replace standard 2D mammography for breast cancer screening. C1 [Kopans, Daniel B.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Kopans, Daniel B.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Sch Med, Dept Radiol, ACC Ste 240,15 Parkman St, Boston, MA 02114 USA. EM dkopans@partners.org NR 59 TC 25 Z9 25 U1 1 U2 15 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2014 VL 202 IS 2 BP 299 EP 308 DI 10.2214/AJR.13.11520 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 299ZN UT WOS:000330434300020 PM 24450669 ER PT J AU Eisenberg, JD Lewin, SO Pandharipande, PV AF Eisenberg, Jonathan D. Lewin, Sarah O. Pandharipande, Pari V. TI The Fisherman's Cards: How to Address Past and Future Radiation Exposures in Clinical Decision Making SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE clinical decision making; CT; radiation exposure history; radiation risks ID IONIZING-RADIATION; QUALITY-ASSURANCE; PATIENT SAFETY; HISTORIES; CHILDHOOD; SCANS; RISK AB OBJECTIVE. The purpose of this article is to describe how to address patients' past-and future potential-radiation exposures when making an imaging decision in a given situation. CONCLUSION. The Biologic Effects of Ionizing Radiation committee has endorsed a linear no-threshold model to explain the relationship between radiation exposure and cancer risk. This model implies that past and future potential exposures should not impact current decisions. We present an analogy that deconstructs these counterintuitive conclusions and facilitates translation of key radiation risk principles to practice. C1 [Eisenberg, Jonathan D.; Lewin, Sarah O.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Eisenberg, Jonathan D.; Lewin, Sarah O.; Pandharipande, Pari V.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Eisenberg, Jonathan D.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Lewin, Sarah O.] Brown Univ, Providence, RI 02912 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Fl, Boston, MA 02114 USA. EM pari@mgh-ita.org FU NCI NIH HHS [K07CA133097, K07 CA133097] NR 18 TC 5 Z9 5 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2014 VL 202 IS 2 BP 362 EP 367 DI 10.2214/AJR.13.10896 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 299ZN UT WOS:000330434300029 PM 24450678 ER PT J AU Kumar, V Tallaj, JA AF Kumar, V. Tallaj, J. A. TI To Transplant a Kidney With the Heart or Not-That Is the Real Question SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID MULTIORGAN; OUTCOMES AB This editorial addresses the indication for combined heart-kidney transplantation, challenging Schaffer et al's (page 384) recommendations of giving higher priority status exemptions to patients listed for multiple organs. C1 [Kumar, V.] Univ Alabama Birmingham, Div Nephrol Transplant Nephrol, Birmingham, AL USA. [Tallaj, J. A.] Univ Alabama Birmingham, Dept Med, Div Cardiol, Sect Adv Heart Failure Heart Transplantat, Birmingham, AL 35294 USA. [Tallaj, J. A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. RP Tallaj, JA (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiol, Sect Adv Heart Failure Heart Transplantat, Birmingham, AL 35294 USA. EM jtallaj@uab.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2014 VL 14 IS 2 BP 253 EP 254 DI 10.1111/ajt.12523 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 297OT UT WOS:000330265500006 PM 24620374 ER PT J AU Djamali, A Kaufman, DB Ellis, TM Zhong, W Matas, A Samaniego, M AF Djamali, A. Kaufman, D. B. Ellis, T. M. Zhong, W. Matas, A. Samaniego, M. TI Diagnosis and Management of Antibody-Mediated Rejection: Current Status and Novel Approaches SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE Antibody-mediated rejection; complement C4d; donor-specific antibodies; phenotype ID DONOR-SPECIFIC ANTIBODIES; RENAL-ALLOGRAFT REJECTION; KIDNEY-TRANSPLANT RECIPIENTS; HIGHLY SENSITIZED PATIENTS; POSITIVE CROSS-MATCH; SOLID-ORGAN TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; ACUTE HUMORAL REJECTION; HIGH-DOSE IVIG; HLA ANTIBODIES AB Advances in multimodal immunotherapy have significantly reduced acute rejection rates and substantially improved 1-year graft survival following renal transplantation. However, long-term (10-year) survival rates have stagnated over the past decade. Recent studies indicate that antibody-mediated rejection (ABMR) is among the most important barriers to improving long-term outcomes. Improved understanding of the roles of acute and chronic ABMR has evolved in recent years following major progress in the technical ability to detect and quantify recipient anti-HLA antibody production. Additionally, new knowledge of the immunobiology of B cells and plasma cells that pertains to allograft rejection and tolerance has emerged. Still, questions regarding the classification of ABMR, the precision of diagnostic approaches, and the efficacy of various strategies for managing affected patients abound. This review article provides an overview of current thinking and research surrounding the pathophysiology and diagnosis of ABMR, ABMR-related outcomes, ABMR prevention and treatment, as well as possible future directions in treatment. C1 [Djamali, A.] Univ Wisconsin, Dept Med, Div Nephrol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Djamali, A.; Kaufman, D. B.] Univ Wisconsin, Dept Surg, Div Transplantat, Sch Med & Publ Hlth, Madison, WI USA. [Ellis, T. M.; Zhong, W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA. [Zhong, W.] William S Middleton Mem Vet Adm Med Ctr, Pathol Serv, Madison, WI USA. [Zhong, W.] William S Middleton Mem Vet Adm Med Ctr, Lab Serv, Madison, WI USA. [Matas, A.] Univ Minnesota, Dept Surg, Div Transplantat, Minneapolis, MN 55455 USA. [Samaniego, M.] Univ Michigan, Dept Med, Div Nephrol, Ann Arbor, MI 48109 USA. RP Djamali, A (reprint author), Univ Wisconsin, Dept Med, Div Nephrol, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM axd@medicine.wisc.edu FU Bristol-Myers Squibb FX The authors would like to acknowledge CodonMedical (A Division of KnowledgePoint360 Group) for their assistance in conducting literature searches and coordinating the writing and editing of the manuscript, funded by Bristol-Myers Squibb. NR 149 TC 65 Z9 70 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2014 VL 14 IS 2 BP 255 EP 271 DI 10.1111/ajt.12589 PG 17 WC Surgery; Transplantation SC Surgery; Transplantation GA 297OT UT WOS:000330265500007 PM 24401076 ER PT J AU Haas, M Sis, B Racusen, LC Solez, K Glotz, D Colvin, RB Castro, MCR David, DSR David-Neto, E Bagnasco, SM Cendales, LC Cornell, LD Demetris, AJ Drachenberg, CB Farver, CF Farris, AB Gibson, IW Kraus, E Liapis, H Loupy, A Nickeleit, V Randhawa, P Rodriguez, ER Rush, D Smith, RN Tan, CD Wallace, WD Mengel, M AF Haas, M. Sis, B. Racusen, L. C. Solez, K. Glotz, D. Colvin, R. B. Castro, M. C. R. David, D. S. R. David-Neto, E. Bagnasco, S. M. Cendales, L. C. Cornell, L. D. Demetris, A. J. Drachenberg, C. B. Farver, C. F. Farris, A. B., III Gibson, I. W. Kraus, E. Liapis, H. Loupy, A. Nickeleit, V. Randhawa, P. Rodriguez, E. R. Rush, D. Smith, R. N. Tan, C. D. Wallace, W. D. Mengel, M. CA Banff Meeting Report Writing Comm TI Banff 2013 Meeting Report: Inclusion of C4d-Negative Antibody-Mediated Rejection and Antibody-Associated Arterial Lesions SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Acute allograft rejection; antibody-mediated rejection; Banff schema; cardiac allograft; chronic allograft rejection; complement C4d; composite tissue allograft; donor-specific antibodies; liver allograft; lung transplantation; pancreas allograft; renal transplantation; transplant biopsy; transplant glomerulopathy; transplant pathology ID DONOR-SPECIFIC ANTIBODIES; KIDNEY-TRANSPLANT RECIPIENTS; RENAL-ALLOGRAFT BIOPSIES; LUNG TRANSPLANTATION; PROTOCOL BIOPSIES; C4D; INFLAMMATION; PATHOLOGY; CLASSIFICATION; GLOMERULOPATHY AB The 12th Banff Conference on Allograft Pathology was held in Comandatuba, Brazil, from August 19-23, 2013, and was preceded by a 2-day Latin American Symposium on Transplant Immunobiology and Immunopathology. The meeting was highlighted by the presentation of the findings of several working groups formed at the 2009 and 2011 Banff meetings to: (1) establish consensus criteria for diagnosing antibody-mediated rejection (ABMR) in the presence and absence of detectable C4d deposition; (2) develop consensus definitions and thresholds for glomerulitis (g score) and chronic glomerulopathy (cg score), associated with improved inter-observer agreement and correlation with clinical, molecular and serological data; (3) determine whether isolated lesions of intimal arteritis (isolated v) represent acute rejection similar to intimal arteritis in the presence of tubulointerstitial inflammation; (4) compare different methodologies for evaluating interstitial fibrosis and for performing/evaluating implantation biopsies of renal allografts with regard to reproducibility and prediction of subsequent graft function; and (5) define clinically and prognostically significant morphologic criteria for subclassifying polyoma virus nephropathy. The key outcome of the 2013 conference is defining criteria for diagnosis of C4d-negative ABMR and respective modification of the Banff classification. In addition, three new Banff Working Groups were initiated. C1 [Haas, M.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Sis, B.; Solez, K.; Mengel, M.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Racusen, L. C.; Bagnasco, S. M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Glotz, D.] Hop St Louis, Nephrol & Transplantat Serv, Paris, France. [Colvin, R. B.; Smith, R. N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Castro, M. C. R.; David-Neto, E.] Univ Sao Paolo, Fac Med, Renal Transplantat Serv, Div Urol, Sao Paulo, Brazil. [David, D. S. R.] Univ Sao Paolo, Fac Med, Div Pathol, Sao Paulo, Brazil. [Cendales, L. C.] Emory Univ, Sch Med, Emory Transplant Ctr, Atlanta, GA USA. [Cendales, L. C.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Cornell, L. D.] Mayo Clin, Dept Pathol & Lab Med, Rochester, MN USA. [Demetris, A. J.; Randhawa, P.] Univ Pittsburgh, Dept Pathol, Div Transplantat Pathol, Pittasburgh, PA USA. [Drachenberg, C. B.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Farver, C. F.; Rodriguez, E. R.; Rush, D.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA. [Farris, A. B., III] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Gibson, I. W.] Univ Manitoba, Hlth Sci Ctr, Dept Pathol, Winnipeg, MB, Canada. [Kraus, E.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Liapis, H.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Loupy, A.] Hop Necker Enfants Malad, Dept Kidney Transplantat, Paris, France. [Nickeleit, V.] Univ N Carolina, Dept Pathol & Lab Med, Div Nephropathol, Chapel Hill, NC USA. [Rush, D.] Univ Manitoba, Hlth Sci Ctr, Dept Internal Med, Winnipeg, MB, Canada. [Wallace, W. D.] Univ Calif Los Angeles, Dept Lab Med & Pathol, Los Angeles, CA USA. RP Haas, M (reprint author), Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. EM mark.haas@cshs.org RI David-Neto, Elias/C-9112-2012; de Kort, Hanneke/N-3898-2014; David, Daisa/G-6272-2012; Rangel, Erika/H-3066-2013; OI Neil, Desley/0000-0001-9800-6811; de Kort, Hanneke/0000-0003-3601-532X; Rush, David/0000-0002-3451-9447; Roufosse, Candice/0000-0002-6490-4290 FU Alexion; Thermo Fisher; Libbs; Astellas; Baxter; Sanofi; American Society of Transplantation; Associacao Brasileira de Histocompatibilidade; Associacao Brasileira de Transplante de Orgaos; Banff Foundation for Allograft Pathology; Canadian Society of Transplantation; CNPQ-Brasil; Kajoma; Sociedad de Transplante de Latinoamerica y Caribe; Transplantation Society; Transpath, Inc.; University of Alberta; Roche Organ Transplant Research Foundation FX The participants of the 12th Banff Conference gratefully acknowledge the financial support of the following companies and institutions: Alexion, Thermo Fisher (formerly One Lambda), Libbs, Astellas, Baxter, Sanofi, American Society of Transplantation, Associacao Brasileira de Histocompatibilidade, Associacao Brasileira de Transplante de Orgaos, Banff Foundation for Allograft Pathology, Canadian Society of Transplantation, CNPQ-Brasil, Kajoma, Sociedad de Transplante de Latinoamerica y Caribe, The Transplantation Society, Transpath, Inc. and University of Alberta. We also thank the Roche Organ Transplant Research Foundation for a grant to support the establishment of the Banff Foundation for Allograft Pathology. The content of much of this manuscript was presented by M. Haas as an American Society of Transplantation (AST) webinar as part of the AST Timely Topics in Transplantation series on October 15, 2013. NR 38 TC 326 Z9 347 U1 5 U2 39 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2014 VL 14 IS 2 BP 272 EP 283 DI 10.1111/ajt.12590 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 297OT UT WOS:000330265500008 PM 24472190 ER PT J AU Barbon, CM Davies, JK Voskertchian, A Kelner, RH Brennan, LL Nadler, LM Guinan, EC AF Barbon, C. M. Davies, J. K. Voskertchian, A. Kelner, R. H. Brennan, L. L. Nadler, L. M. Guinan, E. C. TI Alloanergization of Human T Cells Results in Expansion of Alloantigen-Specific CD8(+)CD28(-) Suppressor Cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Alloantigen-specific; alloresponse; anergy; regulatory T cell (Treg); CD8 suppresser cell; costimulatory molecule blockade; immune tolerance ID VERSUS-HOST-DISEASE; EXPERIMENTAL AUTOIMMUNE NEURITIS; LIVER-TRANSPLANT RECIPIENTS; IMMUNE REGULATORY CELLS; COSTIMULATORY BLOCKADE; INDUCTION; LYMPHOCYTES; TOLERANCE; ACTIVATION; ANERGY AB Allostimulation with concurrent costimulatory blockade induces alloantigen-specific hyporesponsiveness in responder T cells (alloanergization). Alloanergized responder cells also acquire alloantigen-specific suppressive activity, suggesting this strategy induces active immune tolerance. While this acquired suppressive activity is mediated primarily by CD4(+)FOXP3(+) cells, other cells, most notably CD8(+) suppressor cells, have also been shown to ameliorate human alloresponses. To determine whether alloanergization expands CD8(+) cells with allosuppressive phenotype and function, we used mixed lymphocyte cultures in which costimulatory blockade was provided by belatacept, an FDA-approved, second-generation CTLA-4-immunoglobulin fusion protein that blocks CD28-mediated costimulation, as an in vitro model of HLA-mismatched transplantation. This strategy resulted in an eightfold expansion of CD8(+)CD28(-) T cells which potently and specifically suppressed alloresponses of both CD4(+) and CD8(+) T cells without reducing the frequency of a range of functional pathogen-specific T cells. This CD8-mediated allosuppression primarily required cell-cell contact. In addition, we observed expansion of CD8(+)CD28(-) T cells in vivo in patients undergoing alloanergized HLA-mismatched bone marrow transplantation. Use of costimulatory blockade-mediated alloanergization to expand allospecific CD8(+)CD28(-) suppressor cells merits exploration as an approach to inducing or supporting immune tolerance to alloantigens after allogeneic transplantation. C1 [Barbon, C. M.; Davies, J. K.; Voskertchian, A.; Nadler, L. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Davies, J. K.] Queen Mary Univ London, Barts Canc Inst, Ctr Haematooncol, London, England. [Kelner, R. H.; Brennan, L. L.; Guinan, E. C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nadler, L. M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Nadler, L. M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Guinan, E. C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Guinan, E. C.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM eva_guinan@dfci.harvard.edu FU ASBMT New Investigator Award; MRC Clinician Scientist Award; NCI [U19 CA100265, 1R21 CA137645-01A1] FX We thank Larry Turka for thoughtful comments on the manuscript. JKD was funded by an ASBMT New Investigator Award and an MRC Clinician Scientist Award. ECG, JKD, LMN and LLB were funded by NCI U19 CA100265 and NCI 1R21 CA137645-01A1. NR 43 TC 10 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2014 VL 14 IS 2 BP 305 EP 318 DI 10.1111/ajt.12575 PG 14 WC Surgery; Transplantation SC Surgery; Transplantation GA 297OT UT WOS:000330265500011 PM 24410845 ER PT J AU Leonard, DA Kurtz, JM Mallard, C Albritton, A Duran-Struuck, R Farkash, EA Crepeau, R Matar, A Horner, BM Randolph, MA Sachs, DH Huang, CA Cetrulo, CL AF Leonard, D. A. Kurtz, J. M. Mallard, C. Albritton, A. Duran-Struuck, R. Farkash, E. A. Crepeau, R. Matar, A. Horner, B. M. Randolph, M. A. Sachs, D. H. Huang, C. A. Cetrulo, C. L., Jr. TI Vascularized Composite Allograft Tolerance Across MHC Barriers in a Large Animal Model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Miniature swine; mixed chimerism; skin transplant tolerance; vascularized composite allograft ID HEMATOPOIETIC-CELL TRANSPLANTATION; REGULATORY T-CELLS; MINIATURE SWINE; MIXED CHIMERISM; FOLLOW-UP; FACE TRANSPLANTATION; SKIN HOMOGRAFTS; STEM-CELLS; IN-VITRO; HAND AB Vascularized composite allograft (VCA) transplantation can restore form and function following severe craniofacial injuries, extremity amputations or massive tissue loss. The induction of transplant tolerance would eliminate the need for long-term immunosuppression, realigning the risk-benefit ratio for these life-enhancing procedures. Skin, a critical component of VCA, has consistently presented the most stringent challenge to transplant tolerance. Here, we demonstrate, in a clinically relevant miniature swine model, induction of immunologic tolerance of VCAs across MHC barriers by induction of stable hematopoietic mixed chimerism. Recipient conditioning consisted of T cell depletion with CD3-immunotoxin, and 100cGy total body irradiation prior to hematopoietic cell transplantation (HCT) and a 45-day course of cyclosporine A. VCA transplantation was performed either simultaneously to induction of mixed chimerism or into established mixed chimeras 85-150 days later. Following withdrawal of immunosuppression both VCAs transplanted into stable chimeras (n=4), and those transplanted at the time of HCT (n=2) accepted all components, including skin, without evidence of rejection to the experimental end point 115-504 days posttransplant. These data demonstrate that tolerance across MHC mismatches can be induced in a clinically relevant VCA model, providing proof of concept for long-term immunosuppression-free survival. C1 [Leonard, D. A.; Kurtz, J. M.; Mallard, C.; Albritton, A.; Duran-Struuck, R.; Crepeau, R.; Matar, A.; Horner, B. M.; Sachs, D. H.; Huang, C. A.; Cetrulo, C. L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. [Leonard, D. A.; Horner, B. M.; Randolph, M. A.; Cetrulo, C. L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. [Leonard, D. A.] Univ Manchester, Dept Plast & Reconstruct Surg Res, Manchester, Lancs, England. [Kurtz, J. M.] Univ Cambridge Emmanuel Coll, Dept Biol, Boston, MA USA. [Farkash, E. A.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Cetrulo, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM huangc@helix.mgh.harvard.edu; ccetrulo@partners.org FU NIH NCI [P01CA111519]; NIH NIAID [RO1A1084657]; Musculoskeletal Transplant Foundation; Melina Nakos Foundation; AST-Genentech Basic Science Research Fellowship Award FX The authors wish to thank Jim Winter, Betsy Neylon and Taylor Glor for anesthesia and operating room support; Edward Harrington, Ashley Gusha and Eric Batista for expert animal care and laboratory technical assistance; Nicole Brousaides for histology assistance; Dr. Robert Hawley, Dr. Isabel Hanekamp and Dr. Larry Turka for internal review of the manuscript and Rebecca A. Wark for administrative support. We acknowledge support from CO6RR020135-01 for construction of the facility utilized for production and maintenance of miniature swine. Experimental funding was provided by NIH NCI P01CA111519, NIH NIAID RO1A1084657, the Musculoskeletal Transplant Foundation and Melina Nakos Foundation. DAL received funding from an AST-Genentech Basic Science Research Fellowship Award. NR 46 TC 24 Z9 24 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2014 VL 14 IS 2 BP 343 EP 355 DI 10.1111/ajt.12560 PG 13 WC Surgery; Transplantation SC Surgery; Transplantation GA 297OT UT WOS:000330265500014 PM 24405666 ER PT J AU Irwin, KE Henderson, DC Knight, HP Pirl, WF AF Irwin, Kelly E. Henderson, David C. Knight, Helen P. Pirl, William F. TI Cancer Care for Individuals With Schizophrenia SO CANCER LA English DT Review DE schizophrenia; health care disparities; cancer; treatment; outcomes ID SERIOUS MENTAL-ILLNESS; OF-LIFE CARE; HEALTH-CARE; PSYCHIATRIC-PATIENTS; BIPOLAR DISORDER; RANDOMIZED-TRIAL; CLINICAL-TRIALS; MEDICAL-CARE; MORTALITY; COHORT AB Individuals with schizophrenia are a vulnerable population that has been relatively neglected in health disparities research. Despite having an equivalent risk of developing most cancers, patients with schizophrenia are more likely to die of cancer than the general population. Cancer care disparities are likely the result of patient-, provider-, and systems-level factors and influenced by the pervasive stigma of mental illness. Individuals with schizophrenia have higher rates of health behaviors linked with cancer mortality including cigarette smoking. They also have significant medical comorbidity, are less likely to have up-to-date cancer screening, and may present at more advanced stages of illness. Patients with schizophrenia may be less likely to receive chemotherapy or radiotherapy, have more postoperative complications, and have less access to palliative care. However, opportunities exist for the interdisciplinary team, including medical, surgical, and radiation oncologists; psychiatrists; and primary care physicians, to intervene throughout the continuum of cancer care to promote survival and quality of life. This review summarizes data on overall and cancer-specific mortality for individuals with schizophrenia and reviews specific disparities across the cancer care continuum of screening, diagnosis, treatment, and end-of-life care. Using a case, the authors illustrate clinical challenges for this population including communication, informed consent, and risk of suicide, and provide suggestions for care. Finally, recommendations for research to address the disparities in cancer care for individuals with schizophrenia are discussed. Despite significant challenges, with collaboration between oncology and mental health teams, individuals with schizophrenia can receive high-quality cancer care. Cancer 2014; 120: 323-34. (C) 2013 American Cancer Society. C1 [Irwin, Kelly E.; Knight, Helen P.; Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Irwin, Kelly E.; Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Irwin, KE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, 55 Fruit St, Boston, MA 02114 USA. EM kedwards2@partners.org NR 74 TC 15 Z9 15 U1 6 U2 24 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 FEB 1 PY 2014 VL 120 IS 3 BP 323 EP 334 DI 10.1002/cncr.28431 PG 12 WC Oncology SC Oncology GA 297PP UT WOS:000330267700005 PM 24151022 ER PT J AU Wang, XS Zhao, FM Fisch, MJ O'Mara, AM Cella, D Mendoza, TR Cleeland, CS AF Wang, Xin Shelley Zhao, Fengmin Fisch, Michael J. O'Mara, Ann M. Cella, David Mendoza, Tito R. Cleeland, Charles S. TI Prevalence and Characteristics of Moderate To Severe Fatigue SO CANCER LA English DT Article DE fatigue; patient-reported outcome; practice guidelines; M. D. Anderson Symptom Inventory (MDASI); survivorship ID CANCER-RELATED FATIGUE; CUT-POINTS; DOUBLE-BLIND; PAIN; SURVIVORS; SYMPTOMS; MILD; INTERFERENCE; INVENTORY; IMPACT AB BACKGROUNDThe effective management of fatigue in patients with cancer requires a clear delineation of what constitutes nontrivial fatigue. The authors defined numeric cutpoints for fatigue severity based on functional interference and described the prevalence and characteristics of fatigue in patients with cancer and survivors. METHODSIn a multicenter study, outpatients with breast, prostate, colorectal, or lung cancer rated their fatigue severity and symptom interference with functioning on the M. D. Anderson Symptom Inventory numeric scale of 0 to 10. Ratings of symptom interference guided the selection of numeric rating cutpoints between mild, moderate, and severe fatigue levels. Regression analysis identified significant factors related to reporting moderate/severe fatigue. RESULTSThe statistically optimal cutpoints were 4 for moderate fatigue and 7 for severe fatigue. Moderate/severe fatigue was reported by 983 of 2177 patients (45%) undergoing active treatment and was more likely to occur in patients receiving treatment with strong opioids (odds ratio [OR], 3.00), those with a poor Eastern Cooperative Oncology Group performance status (OR, 2.00), those who had >5% weight loss within 6 months (OR, 1.60), those who were receiving >10 medications (OR, 1.58), those with lung cancer (OR, 1.55), and those with a history of depression (OR, 1.42). Among survivors (patients with complete remission or no evidence of disease, and not currently receiving cancer treatment), 29% of patients (150 of 515 patients) had moderate/severe fatigue that was associated with poor performance status (OR, 3.48) and a history of depression (OR, 2.21). CONCLUSIONSThe current study statistically defined fatigue severity categories related to significantly increased symptom interference. The high prevalence of moderate/severe fatigue in both actively treated patients with cancer and survivors warrants the promoting of the routine assessment and management of patient-reported fatigue. Cancer 2014;120:425-432. (c) 2013 American Cancer Society. C1 [Wang, Xin Shelley; Mendoza, Tito R.; Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. [O'Mara, Ann M.] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Cella, David] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA. RP Wang, XS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1515 Holcombe Blvd,Unit 1450, Houston, TX 77030 USA. EM xswang@mdanderson.org FU National Cancer Institute of the National Institutes of Health [U10 CA37403, U10 CA17145]; Eastern Cooperative Oncology Group [R01 CA026582]; University of Texas MD Anderson Cancer Center Support [P30 CA016672] FX Supported in part by grants from the National Cancer Institute of the National Institutes of Health, including U10 CA37403 and U10 CA17145 to the Eastern Cooperative Oncology Group; R01 CA026582 to Dr. Cleeland ( Principal Investigator); and The University of Texas MD Anderson Cancer Center Support Grant P30 CA016672 to R.A. DePinho ( Principal Investigator). NR 29 TC 33 Z9 33 U1 0 U2 15 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 FEB 1 PY 2014 VL 120 IS 3 BP 425 EP 432 DI 10.1002/cncr.28434 PG 8 WC Oncology SC Oncology GA 297PP UT WOS:000330267700016 PM 24436136 ER PT J AU Fisch, MJ Zhao, F O'Mara, AM Wang, XS Cella, D Cleeland, CS AF Fisch, Michael J. Zhao, Fengmin O'Mara, Ann M. Wang, Xin Shelley Cella, David Cleeland, Charles S. TI Predictors of Significant Worsening of Patient-Reported Fatigue Over a 1-Month Timeframe in Ambulatory Patients With Common Solid Tumors SO CANCER LA English DT Article DE cancer fatigue; symptom management; medical oncology; ambulatory care ID CANCER-RELATED FATIGUE; PLACEBO-CONTROLLED TRIAL; CLINICALLY SIGNIFICANT FATIGUE; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; BREAST-CANCER; DOUBLE-BLIND; RADIATION-THERAPY; ADJUVANT THERAPY; WOMEN AB BACKGROUNDUnderstanding the determinants of fatigue worsening may help distinguish between different fatigue phenotypes and inform clinical trial designs. METHODSPatients with invasive cancer of the breast, prostate, colon/rectum, or lung were enrolled from multiple sites. At enrollment during an outpatient visit and 4 or 5 weeks later, patients rated their symptoms on a numerical rating scale from zero to 10. A 2-point change on that scale was considered clinically significant for a change in fatigue. Effects of demographic and clinical factors on patient-reported fatigue were examined using logistic regression models. RESULTSIn total, 3123 patients were enrolled at baseline, and 3032 patients could be analyzed for fatigue change. At baseline, 23% of patients had no fatigue, 35% had mild fatigue, 25% had moderate fatigue, and 17% had severe fatigue. Key parameters in a model of fatigue worsening included fatigue at baseline (odds ratio [OR], 0.75), disease status (OR, 1.99), performance status (OR, 1.38), history of depression (OR, 1.28), patient perception of bother because of comorbidity (OR, 1.26), and treatment exposures, including recent cancer treatment (OR, 1.77) and receipt of corticosteroids (OR, 1.37). The impact of sex was examined only in patients with colorectal and lung cancer, and it was a significant factor, with men most likely to experience worsening of fatigue (OR, 1.46). CONCLUSIONSPredictors of fatigue worsening included multiple factors that were difficult to modify, including the baseline fatigue level, sex, disease status, performance status, recent cancer treatment, bother because of comorbidity, and history of depression. Future fatigue prevention and treatment trial designs should account for key predictors of worsening fatigue. Cancer 2014;120:442-450 (c) 2013 American Cancer Society. C1 [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Mara, Ann M.] NCI, Bethesda, MD 20892 USA. [Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Wang, Xin Shelley; Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Fisch, MJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Unit 410,1515 Holcombe Blvd, Houston, TX 77030 USA. EM mfisch@mdanderson.org FU National Cancer Institute of the National Institutes of Health [U10 CA37403, U10 CA17145, R01 CA026582] FX This study was supported in part by grants from the National Cancer Institute of the National Institutes of Health, including grants U10 CA37403 and U10 CA17145 to the Eastern Cooperative Oncology Group and grant R01 CA026582 to C.S.C. NR 47 TC 4 Z9 4 U1 2 U2 14 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 FEB 1 PY 2014 VL 120 IS 3 BP 442 EP 450 DI 10.1002/cncr.28437 PG 9 WC Oncology SC Oncology GA 297PP UT WOS:000330267700018 PM 24151111 ER PT J AU Huber, RJ AF Huber, Robert J. TI The cyclin-dependent kinase family in the social amoebozoan Dictyostelium discoideum SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Cyclin-dependent kinase; Mitosis; Growth; Development; Cell cycle; Dictyostelium ID PUROMYCIN-SENSITIVE AMINOPEPTIDASE; CALMODULIN-BINDING PROTEINS; SPORE CELL-DIFFERENTIATION; CDK5; ROSCOVITINE; INHIBITOR; PHOSPHORYLATION; EXPRESSION; NUCLEAR; CANCER AB Cyclin-dependent kinases (Cdk) are a family of serine/threonine protein kinases that regulate eukaryotic cell cycle progression. Their ability to modulate the cell cycle has made them an attractive target for anti-cancer therapies. Cdk protein function has been studied in a variety of Eukaryotes ranging from yeast to humans. In the social amoebozoan Dictyostelium discoideum, several homologues of mammalian Cdks have been identified and characterized. The life cycle of this model organism is comprised of a feeding stage where single cells grow and divide mitotically as they feed on their bacterial food source and a multicellular developmental stage that is induced by starvation. Thus it is a valuable system for studying a variety of cellular and developmental processes. In this review I summarize the current knowledge of the Cdk protein family in Dictyostelium by highlighting the research efforts focused on the characterization of Cdk1, Cdk5, and Cdk8 in this model Eukaryote. Accumulated evidence indicates that each protein performs distinct functions during the Dictyostelium life cycle with Cdk1 being required for growth and Cdk5 and Cdk8 being required for processes that occur during development. Recent studies have shown that Dictyostelium Cdk5 shares attributes with mammalian Cdk5 and that the mammalian Cdk inhibitor roscovitine can be used to inhibit Cdk5 activity in Dictyostelium. Together, these results show that Dictyostelium can be used as a model system for studying Cdk protein function. C1 Harvard Univ, Richard B Simches Res Ctr, Ctr Human Genet Res, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Huber, RJ (reprint author), Harvard Univ, Richard B Simches Res Ctr, Ctr Human Genet Res, Sch Med,Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM rhuber@chgr.mgh.harvard.edu FU Canadian Institutes of Health Research FX The author would like to thank the anonymous reviewers who provided insightful and helpful feedback during the submission process. This review was supported by a Postdoctoral Fellowship from the Canadian Institutes of Health Research (R.J.H.). NR 85 TC 3 Z9 3 U1 2 U2 17 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD FEB PY 2014 VL 71 IS 4 BP 629 EP 639 DI 10.1007/s00018-013-1449-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 302FC UT WOS:000330586500006 PM 23974243 ER PT J AU Restrepo, MI Aliberti, S AF Restrepo, Marcos I. Aliberti, Stefano TI Healthcare-Associated Pneumonia: Where Do We Go Next? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID MULTIDRUG-RESISTANT PATHOGENS; HOSPITALIZED-PATIENTS; COMMUNITY; INFECTIONS; ADULTS C1 [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, ALMD, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Aliberti, Stefano] Univ Milano Bicocca, UO Clin Pneumol, Monza, Italy. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst, ALMD, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; Aliberti, Stefano/K-9115-2016 OI Aliberti, Stefano/0000-0002-0090-4531 FU NCATS NIH HHS [KL2 TR001118, UL1 TR001120]; NHLBI NIH HHS [K23 HL096054, K23HL096054] NR 10 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2014 VL 58 IS 3 BP 340 EP 341 DI 10.1093/cid/cit738 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 300AD UT WOS:000330435900006 PM 24270052 ER PT J AU Youngster, I Sharma, TS Duncan, CN McAdam, AJ AF Youngster, Ilan Sharma, Tanvi S. Duncan, Christine N. McAdam, Alexander J. TI Yield of Fungal Surveillance Cultures in Pediatric Hematopoietic Stem Cell Transplant Patients: A Retrospective Analysis and Survey of Current Practice SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE surveillance cultures; fungal infection; pediatric hematopoietic stem cell transplant; fungal colonization ID BONE-MARROW-TRANSPLANTATION; HEMATOLOGICAL MALIGNANCIES; RECIPIENTS; INFECTIONS; EPIDEMIOLOGY; SPECTRUM; COMPLICATIONS; VORICONAZOLE; ADOLESCENTS; CANDIDIASIS AB Background. Fungal surveillance cultures (FSCs) have been proposed as predictors for development of invasive fungal disease (IFD) and identifiers of the causative organism, although data supporting these are limited and predate universal initiation of antifungal prophylaxis. We aimed to define the epidemiology of fungal colonization and investigate the utility of FSCs for predicting IFD in recipients of pediatric hematopoietic stem cell transplantation (HSCT). Methods. FSCs performed from 2007 to 2011 on HSCT patients and laboratory and clinical data were reviewed, and incidence of IFD was determined. Descriptive analyses of culture results were performed to determine the yield of FSCs and their utility. A Web-based survey of national pediatric HSCT providers was undertaken to evaluate current practice and the relevance of our results. Results. Five thousand six hundred eighteen FSCs from nares, throat, and stool from 360 patients were processed. Of these, 14.8% were positive: 30.3% from stool, 13.2% from throat, and 0.9% from nares; 64.4% of patients had > 1 positive FSCs. Thirty (8.3%) patients had IFD. IFD occurred in 7.9% and 10.1% of patients with positive and negative FSCs, respectively (P = .25). Antifungal coverage was changed in 69 patients (29.9%) after positive FSC; 8.6% developed IFD (n = 2 of 6 pathogen concordance with FSC) compared with 6.7% (P = .59) who had no treatment change (n = 3 of 11 concordance). The response rate to the survey was 70.8%; 40% of institutions reported performing routine FSC. Twenty-five percent of providers would not change management based on FSC results; overall rating of usefulness of FSCs was low. Conclusions. Although FSCs are commonly performed for pediatric HSCT patients, they have limited utility for predicting IFD. C1 [Youngster, Ilan; Sharma, Tanvi S.] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02445 USA. [McAdam, Alexander J.] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02445 USA. [Youngster, Ilan; Sharma, Tanvi S.; Duncan, Christine N.; McAdam, Alexander J.] Harvard Univ, Sch Med, Boston, MA USA. [Duncan, Christine N.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Youngster, I (reprint author), Boston Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02445 USA. EM ilan.youngster@childrens.harvard.edu RI Youngster, Ilan/J-5047-2014 OI Youngster, Ilan/0000-0001-5233-1213 NR 24 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2014 VL 58 IS 3 BP 365 EP 371 DI 10.1093/cid/cit728 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 300AD UT WOS:000330435900011 PM 24192388 ER PT J AU Strle, K Stupica, D Drouin, EE Steere, AC Strle, F AF Strle, Klemen Stupica, Dasa Drouin, Elise E. Steere, Allen C. Strle, Franc TI Elevated Levels of IL-23 in a Subset of Patients With Post-Lyme Disease Symptoms Following Erythema Migrans SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Lyme disease; post-Lyme disease symptoms; inflammation; IL-23; T(H)17 ID BORRELIA-BURGDORFERI; PERSISTENT SYMPTOMS; ARTHRITIS; INFLAMMATION; INTERLEUKIN-23; CHEMOKINES; RESPONSES; THERAPY; HISTORY; CELLS AB Background. The causes of post-Lyme disease symptoms are unclear. Herein, we investigated whether specific immune responses were correlated with such symptoms. Methods. The levels of 23 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in sera from 86 antibiotic-treated European patients with erythema migrans, 45 with post-Lyme symptoms and 41 without symptoms, who were evaluated prior to treatment and 2, 6, and 12 months thereafter. Results. At study entry, significant differences between groups were observed for the type 1 helper T cell (T(H)1)-associated chemokines CXCL9 and CXCL10, which were associated with negative Borrelia cultures, and the type 17 helper T cell (T(H)17)-associated cytokine interleukin 23 (IL-23), which was associated with positive cultures and the development of post-Lyme symptoms (P < .02). Moreover, of the 41 patients with detectable IL-23 levels, 25 (61%) developed post-Lyme symptoms, and all 7 with IL-23 levels >= 230 ng/mL had such symptoms. Furthermore, antibody responses to the ECGF autoantigen were more common in patients with post-Lyme symptoms (P = .07) and were correlated directly with IL-23 levels (P = .02). Despite the presence of post-Lyme symptoms, all posttreatment culture results were negative, antiborrelial antibody responses declined, and there were no objective signs of disseminated disease, suggesting that spirochetal eradication had occurred with treatment in all patients. Conclusions. High T(H)1-associated responses correlated with more effective immune-mediated spirochetal killing, whereas high T(H)17-associated immune responses, often accompanied by autoantibodies, correlated with post-Lyme symptoms, providing a new paradigm for the study of postinfectious symptoms in a subset of patients with Lyme disease. C1 [Strle, Klemen; Drouin, Elise E.; Steere, Allen C.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Strle, Klemen; Drouin, Elise E.; Steere, Allen C.] Harvard Univ, Sch Med, Boston, MA USA. [Stupica, Dasa; Strle, Franc] Univ Med Ctr Ljubljana, Dept Infect Dis, Ljubljana, Slovenia. RP Strle, K (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 55 Fruit St,CNY149-8301, Boston, MA 02114 USA. EM kstrle@partners.org FU National Institutes of Health [AI-101175, K01AR062098]; English, Bonter, Mitchell Foundation; Mathers Foundation; Eshe Fund; Ministry of Science and Technology of the Republic of Slovenia [P3 0296, J3 3636]; Arthritis Foundation FX This work was supported by the National Institutes of Health (AI-101175), the English, Bonter, Mitchell Foundation, the Mathers Foundation, and the Eshe Fund to A. C. S; the Ministry of Science and Technology of the Republic of Slovenia (P3 0296 and J3 3636) to F. S.; and the Arthritis Foundation and the National Institutes of Health (K01AR062098) to K. S. NR 30 TC 22 Z9 23 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2014 VL 58 IS 3 BP 372 EP 380 DI 10.1093/cid/cit735 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 300AD UT WOS:000330435900012 PM 24218102 ER PT J AU Cheng, JM Tirumani, SH Shinagare, AB Jagannathan, JP Hornick, JL Raut, CP Ramaiya, NH AF Cheng, J. M. Tirumani, S. H. Shinagare, A. B. Jagannathan, J. P. Hornick, J. L. Raut, C. P. Ramaiya, N. H. TI MDCT of primary, locally recurrent, and metastatic duodenal gastrointestinal stromal tumours (GISTs): A single institution study of 25 patients with review of literature SO CLINICAL RADIOLOGY LA English DT Article ID SMALL-BOWEL NEOPLASMS; DIFFERENTIAL-DIAGNOSIS; DIFFERENT SITES; PROGNOSIS; FEATURES; CT; SPECTRUM; KIT AB AIM: To describe the multidetector computed tomography (MDCT) features of primary, locally recurrent, and metastatic duodenal gastrointestinal stromal tumours (GISTs). MATERIALS AND METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant, retrospective study, 25 patients [13 men, 12 women; mean age 56 years (34-74 years)] with histopathologically confirmed duodenal GISTs seen at Dana Farber Cancer Institute and Brigham and Women's Hospital from December 1999 to October 2009 were identified. The MDCT of primary tumours in six patients and follow-up imaging in all the 25 patients was reviewed by two radiologists in consensus. Electronic medical records were reviewed to document the clinical characteristics and management. RESULTS: The mean size of the primary tumour was 3.7 cm (range 2.5-5.6 cm). Three of six primary tumours were in the second and third portions of the duodenum, one in the third portion, one in the third and fourth portions, and one in the fourth portion. Three of six of the tumours were exophytic, two were both exophytic and intraluminal, and one was intramural. The tumours were well-circumscribed, round or oval masses, with few lobulations, and were either homogeneously hyper-enhancing or heterogeneously isodense at MDCT. None of the tumours had necrosis, haemorrhage, calcification, or loco regional lymphadenopathy on imaging. Sixteen of 25 (64%) patients developed metastatic disease, the most common sites being liver (14/16; 87.5%) and peritoneum (5/16; 31%). CONCLUSION: Duodenal GISTs are well-circumscribed, round or oval masses, and occur in the second through fourth portions of the duodenum, without lymphadenopathy or duodenal obstruction. Duodenal GISTS metastasize frequently to the liver and peritoneum. (C) 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Cheng, J. M.; Tirumani, S. H.; Shinagare, A. B.; Jagannathan, J. P.; Ramaiya, N. H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Cheng, J. M.; Tirumani, S. H.; Shinagare, A. B.; Jagannathan, J. P.; Ramaiya, N. H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Hornick, J. L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Raut, C. P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Div Surg Oncol, Boston, MA 02215 USA. [Raut, C. P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 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 18 TC 4 Z9 6 U1 0 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 EI 1365-229X J9 CLIN RADIOL JI Clin. Radiol. PD FEB PY 2014 VL 69 IS 2 BP 137 EP 144 DI 10.1016/j.crad.2013.09.002 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 300ZD UT WOS:000330501600004 PM 24161459 ER PT J AU Piris, A Peng, Y Boussahmain, C Essary, LR Gudewicz, TM Hoang, MP AF Piris, Adriano Peng, Yan Boussahmain, Chakib Essary, Lydia R. Gudewicz, Thomas M. Hoang, Mai P. TI Cutaneous and mammary apocrine carcinomas have different immunoprofiles SO HUMAN PATHOLOGY LA English DT Article DE Adipophilin; Cytokeratin 5/6; p63; GATA3; Mammaglobin; Androgen receptor; Estrogen receptor; Progesterone receptor; HER2/neu ID BREAST-CANCER; ADNEXAL NEOPLASMS; METASTATIC ADENOCARCINOMA; ADIPOPHILIN EXPRESSION; DIAGNOSTIC UTILITY; ANDROGEN RECEPTOR; IN-SITU; TUMORS; SKIN; P63 AB Often the distinction of cutaneous apocrine carcinoma from metastatic mammary apocrine carcinoma to the skin can be a diagnostic dilemma because both tumors share similar histologic features and have overlapping immunohistochemical profile. We compared the expression of adipophilin, cytokeratin 5/6, p63, GATA3, mammaglobin, androgen receptor, estrogen receptor, progesterone receptor, and HER2 by immunohistochemistry in 14 cutaneous apocrine carcinomas (11 primary tumors, 3 metastases) and 26 primary apocrine carcinomas of the breast. Whereas focal adipophilin staining was seen in 36% (5/14) of cutaneous apocrine carcinoma, strong and diffuse adipophilin staining was seen in 88% (22/25) of mammary apocrine carcinoma (P = .0013). Differences in estrogen receptor and progesterone receptor expression were also statistically significant (P = .018 and .043). Androgen receptor was strongly positive in all cutaneous and mammary cases. Although there was no significant difference in the frequency of expression of cytokeratin 5/6, p63, HER2, GATA3, and mammaglobin in cutaneous apocrine carcinoma versus mammary apocrine carcinoma, strong and diffuse cytokeratin 5/6 and/or mammaglobin expression were seen only in cutaneous apocrine carcinoma. In conclusion, cutaneous apocrine carcinoma is likely adipophilin- ER+ PR+/- HER2- and can exhibit strong and diffuse cytokeratin 5/6 and/or mammaglobin expression. On the contrary, a mammary apocrine carcinoma is likely alipophilin+ ER- PR- and often exhibit 3+ HER2 with corresponding HER2 gene amplification. A panel of adipophilin, ER, PR, HER2, cytokeratin 5/6, and mammaglobin may be helpful in distinguishing cutaneous apocrine carcinoma from mammary apocrine carcinoma. (C) 2014 Elsevier Inc. All rights reserved. C1 [Piris, Adriano; Boussahmain, Chakib; Gudewicz, Thomas M.; Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Piris, Adriano; Gudewicz, Thomas M.; Hoang, Mai P.] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02114 USA. [Peng, Yan] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75235 USA. [Essary, Lydia R.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75235 USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org NR 29 TC 7 Z9 7 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2014 VL 45 IS 2 BP 320 EP 326 DI 10.1016/j.humpath.2013.09.007 PG 7 WC Pathology SC Pathology GA 301SB UT WOS:000330551300016 PM 24342430 ER PT J AU Nishino, M Mathai, SK Schoenfeld, D Digumarthy, SR Kradin, RL AF Nishino, Michiya Mathai, Susan K. Schoenfeld, David Digumarthy, Subba R. Kradin, Richard L. TI Clinicopathologic features associated with relapse in cryptogenic organizing pneumonia SO HUMAN PATHOLOGY LA English DT Article DE Lung; Cryptogenic organizing pneumonia; Fibrin; Acute fibrinous and organizing pneumonia ID III PROCOLLAGEN PEPTIDE; ACUTE LUNG INJURY; CLINICAL PRESENTATION; SERIES AB Organizing pneumonia (OP) is a histopathologic pattern of response to lung injury. Fibrin is a marker of acute microvascular injury, and variable amounts of intraalveolar fibrin are seen in OP; however, its relevance to clinical outcomes is unclear. We examined lung wedge biopsies of 26 patients with cryptogenic organizing pneumonia (COP), assessed the amount of fibrin associated with airspace organization, and correlated fibrin levels with other histologic, clinical, and radiographic findings. Seven patients with COP had disease relapse. Patients with multifocal fibrin deposits or acute fibrinous and organizing pneumonia (collectively, "high fibrin") showed a higher rate of OP relapse compared to those with no or focal fibrin (60% versus 6%, P < .05). Patients with radiographic evidence of disease involving all three lung zones (upper, middle, and lower) also showed higher rates of relapse compared to those in whom disease was limited to one or two zones (41% versus 0%, P = .055). In patients with both pathologic evidence of high fibrin and radiographic evidence of three-zone disease, OP relapse could be predicted with a sensitivity of 86% and specificity of 84% (positive predictive value of 67% and negative predictive value of 94%). The presence of high levels of intraalveolar fibrin in lung biopsies and radiographic evidence of disease involving all three lung zones is associated with increased risk of relapse in patients with COP, and these features may help identify patients who may benefit from more intensive steroid therapy. (C) 2014 Elsevier Inc. All rights reserved. C1 [Nishino, Michiya; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mathai, Susan K.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Digumarthy, Subba R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM rkradin@partners.org FU Harvard Catalyst; The Harvard Clinical and Translational Science Center (National Center for Research Resources); National Institutes of Health [8UL1TR000170-05]; Harvard University and its affiliated academic health care centers; National Center for Advancing Translational Sciences 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 health care centers). NR 17 TC 8 Z9 9 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2014 VL 45 IS 2 BP 342 EP 351 DI 10.1016/j.humpath.2013.09.010 PG 10 WC Pathology SC Pathology GA 301SB UT WOS:000330551300019 PM 24342432 ER PT J AU Lauwers, GY AF Lauwers, Gregory Y. TI TP53 mutations of intestinal metaplasia-reply SO HUMAN PATHOLOGY LA English DT Letter ID INDEFINITE; NEOPLASIA; LESIONS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Lauwers, GY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM glauwers@partners.org NR 4 TC 0 Z9 0 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 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2014 VL 45 IS 2 BP 431 EP 432 DI 10.1016/j.humpath.2013.08.022 PG 2 WC Pathology SC Pathology GA 301SB UT WOS:000330551300032 PM 24439231 ER PT J AU Abdeldaim, A Bunyavanich, S Rifas-Shiman, S Platts-Mills, TAE Gold, DR Camargo, C Oken, E Gillman, M Litonjua, AA AF Abdeldaim, Amina Bunyavanich, Supinda Rifas-Shiman, Sheryl Platts-Mills, Thomas A. E. Gold, Diane R. Camargo, Carlos, Jr. Oken, Emily Gillman, Matthew Litonjua, Augusto A. TI Race/Ethnicity and SES Are Predictors Of Allergic Sensitization To Environmental and Food Allergens SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Abdeldaim, Amina; Litonjua, Augusto A.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Bunyavanich, Supinda] Icahn Sch Med Mt Sinai, Dept Pediat, Div Pediat Allergy & Immunol, New York, NY USA. [Rifas-Shiman, Sheryl; Oken, Emily; Gillman, Matthew] Harvard Univ, Sch Med, Boston, MA USA. [Platts-Mills, Thomas A. E.] Univ Virginia Hlth Syst, Div Asthma Allergy & Immunol, Charlottesville, VA USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 262 BP AB74 EP AB74 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300260 ER PT J AU Ahluwalia, SK Peng, R Aloe, C Shreffler, WG Krevans, M Hagberg, KA Thorne, PS Walsh, K Matsui, E AF Ahluwalia, Sharon K. Peng, Roger Aloe, Charles Shreffler, Wayne G. Krevans, Mary Hagberg, Karol A. Thorne, Peter S. Walsh, Kenneth Matsui, Elizabeth TI Endotoxin Exposure May Protect Against The Development Of Rhinoconjunctivitis and Respiratory Symptoms In Non-Atopic Individuals With Occupational Exposure To Mice SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Ahluwalia, Sharon K.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Ahluwalia, Sharon K.; Aloe, Charles; Matsui, Elizabeth] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Peng, Roger] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shreffler, Wayne G.] Harvard Univ, Sch Med, Boston, MA USA. [Krevans, Mary; Hagberg, Karol A.] Jackson Lab, Bar Harbor, ME 04609 USA. [Thorne, Peter S.] Univ Iowa, Iowa City, IA USA. [Walsh, Kenneth] Jackson Labs, Bar Harbor, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 529 BP AB151 EP AB151 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300526 ER PT J AU Biagtan, M Babler, B Kakumanu, S Mathur, SK AF Biagtan, Mark Babler, Bryan Kakumanu, Sujani Mathur, Sameer K. TI Effect Of Penicillin Allergy On Outpatient Antibiotic Prescriptions At VA Hospital SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Biagtan, Mark; Kakumanu, Sujani; Mathur, Sameer K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Biagtan, Mark; Babler, Bryan; Kakumanu, Sujani; Mathur, Sameer K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 918 BP AB266 EP AB266 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301234 ER PT J AU Blumenthal, K Shenoy, E Varughese, C Hooper, D Banerji, A AF Blumenthal, Kimberly Shenoy, Erica Varughese, Christy Hooper, David Banerji, Aleena TI Outcomes After Implementation Of An Inpatient Antibiotic Prescribing Pathway For Patients With Penicillin Or Cephalosporin Allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Blumenthal, Kimberly; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Shenoy, Erica] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis,Dept Med, Boston, MA USA. [Shenoy, Erica] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Control Unit,Dept Med, Boston, MA USA. [Varughese, Christy] Massachusetts Gen Hosp, Dept Pharm, Infect Control Unit, Boston, MA 02114 USA. [Hooper, David] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Hooper, David] Massachusetts Gen Hosp, Dept Med, Infect Control Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 745 BP AB215 EP AB215 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301061 ER PT J AU Bunyavanich, S Rifas-Shiman, S Platts-Mills, TAE Workman, LJ Sordillo, J Camargo, C Gillman, M Gold, DR Litonjua, AA AF Bunyavanich, Supinda Rifas-Shiman, Sheryl Platts-Mills, Thomas A. E. Workman, Lisa J. Sordillo, Joanne Camargo, Carlos, Jr. Gillman, Matthew Gold, Diane R. Litonjua, Augusto A. TI Peanut, Milk, and Wheat Intake During Pregnancy Is Associated With Reduced Allergy and Asthma In Children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Bunyavanich, Supinda] Icahn Sch Med Mt Sinai, Dept Pediat, Div Pediat Allergy & Immunol, New York, NY USA. [Rifas-Shiman, Sheryl; Gillman, Matthew] Harvard Univ, Sch Med, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Platts-Mills, Thomas A. E.; Workman, Lisa J.] Univ Virginia Hlth Syst, Div Asthma Allergy & Immunol, Charlottesville, VA USA. [Sordillo, Joanne; Litonjua, Augusto A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 FEB PY 2014 VL 133 IS 2 SU S MA 693 BP AB200 EP AB200 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301009 ER PT J AU Delmonte, OM Meng, FL Alt, F Notarangelo, LD Walter, JE AF Delmonte, Ottavia M. Meng, Feilong Alt, Frederick Notarangelo, Luigi D. Walter, Jolan E. TI Evaluation of a Novel Missense Activation-Induced Deaminase AID Mutation in a Child with Hyper IgM Syndrome: Is it a Pathogenic Mutation? SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Delmonte, Ottavia M.] Harvard Univ, Sch Med, Boston Childrens Hosp, Pediat Residency Program, Boston, MA USA. [Meng, Feilong; Alt, Frederick] Harvard Univ, Sch Med, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Meng, Feilong] Harvard Univ, Sch Med, Immune Dis Inst, Boston Childrens Hosp,Dept Genetcis, Boston, MA USA. [Alt, Frederick] Harvard Univ, Sch Med, Dept Genet, Immune Dis Inst,Boston Childrens Hosp, Boston, MA USA. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Div Immunol, Boston Childrens Hosp, Boston, MA USA. [Notarangelo, Luigi D.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Walter, Jolan E.] Harvard Univ, Sch Med, Div Allergy Immunol, Massachusetts Gen Hosp Children, Boston, MA USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 248 BP AB70 EP AB70 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300246 ER PT J AU Faustman, DL Wang, LM Okubo, Y AF Faustman, Denise L. Wang, Limei Okubo, Yoshiaki TI Human TNFR2 Exhibits Bi-Directional Control over Regulatory T Cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Faustman, Denise L.; Wang, Limei; Okubo, Yoshiaki] Harvard Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA L1 BP AB398 EP AB398 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241302001 ER PT J AU Fleming, E Ruiter, B Hurlburt, BK Maleki, SJ Shreffler, WG AF Fleming, Elizabeth Ruiter, Bert Hurlburt, Barry K. Maleki, Soheila J. Shreffler, Wayne G. TI Monocytes From Peanut-Allergic Patients Express Higher Levels Of RALDH2 In Response To Peanut Protein Than Monocytes From Tolerant Subjects SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Fleming, Elizabeth; Ruiter, Bert; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hurlburt, Barry K.; Maleki, Soheila J.] USDA ARS, So Reg Res Ctr, New Orleans, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 321 BP AB92 EP AB92 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300319 ER PT J AU Hasegawa, K Sullivan, A Turner, S Massaro, S Camargo, C AF Hasegawa, Kohei Sullivan, Ashley Turner, Stuart Massaro, Susan Camargo, Carlos, Jr. TI Asthma Exacerbation In US Adults: Who Are The Frequent Utilizers Of The Emergency Department? SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Hasegawa, Kohei; Sullivan, Ashley; Camargo, Carlos, Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hasegawa, Kohei; Camargo, Carlos, Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Turner, Stuart] Novartis Pharmaceut, E Hanover, NJ USA. [Massaro, Susan] Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 FEB PY 2014 VL 133 IS 2 SU S MA 597 BP AB173 EP AB173 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300594 ER PT J AU He, WJ Harper, N Carrillo, A Andrews, C Rather, C Ramirez, D Jacobs, RL Ahuja, SK AF He, Weijing Harper, Nathan Carrillo, Andrew Andrews, Charles Rather, Cynthia Ramirez, Daniel Jacobs, Robert L. Ahuja, Sunil K. TI Atopic and Non-Atopic Individuals Manifest Partly Concordant Clinical and Leukocyte Responses Following Exposure To House Dust Mite In An Antigen Challenge Chamber (ACC) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [He, Weijing; Harper, Nathan; Carrillo, Andrew; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [He, Weijing; Harper, Nathan; Carrillo, Andrew; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [Andrews, Charles; Rather, Cynthia; Ramirez, Daniel; Jacobs, Robert L.] Biogen Res Chamber, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 773 BP AB223 EP AB223 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301089 ER PT J AU Iammatteo, M Guyer, AC Saff, R Holbrook, E Gray, S Long, AD Banerji, A AF Iammatteo, Melissa Guyer, Autumn Chandler Saff, Rebecca Holbrook, Eric Gray, Stacey Long, Aidan Banerji, Aleena TI Assessing Quality Of Life In Patients With AERD After Aspirin Desensitization SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Iammatteo, Melissa; Saff, Rebecca] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guyer, Autumn Chandler] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Holbrook, Eric; Gray, Stacey] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Long, Aidan; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 10 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 FEB PY 2014 VL 133 IS 2 SU S MA 751 BP AB217 EP AB217 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301067 ER PT J AU Jacobs, RL Rather, C Jimenez, F Martinez, H He, WJ Ramirez, D Andrews, C Ahuja, SK AF Jacobs, Robert L. Rather, Cynthia Jimenez, Fabio Martinez, Hernan He, Weijing Ramirez, Daniel Andrews, Charles Ahuja, Sunil K. TI Validation Of Biogenics Research Chamber For Elicitation Of Symptoms To Dust Mite Antigen (Der p1) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Jacobs, Robert L.; Rather, Cynthia; Ramirez, Daniel; Andrews, Charles] Biogen Res Chamber, San Antonio, TX USA. [Jimenez, Fabio; Martinez, Hernan; He, Weijing; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Jimenez, Fabio; Martinez, Hernan; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 766 BP AB221 EP AB221 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301082 ER PT J AU Kanchongkittiphon, W Gaffin, JM Kopel, LS Sheehan, WJ Baxi, SN Permaul, P Gold, DR Phipatanakul, W AF Kanchongkittiphon, Watcharoot Gaffin, Jonathan M. Kopel, Lianne S. Sheehan, William J. Baxi, Sachin N. Permaul, Perdita Gold, Diane R. Phipatanakul, Wanda TI The Association Of Spirometry With Asthma Control and Asthma Morbidity In Inner City Schoolchildren With Asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Kanchongkittiphon, Watcharoot; Gaffin, Jonathan M.; Kopel, Lianne S.; Sheehan, William J.; Baxi, Sachin N.; Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA. [Kanchongkittiphon, Watcharoot] Mahidol Univ, Ramathibodi Hosp, Bangkok 10700, Thailand. [Gaffin, Jonathan M.; Kopel, Lianne S.; Sheehan, William J.; Baxi, Sachin N.; Permaul, Perdita; Gold, Diane R.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy Immunol, Boston, MA 02114 USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 837 BP AB242 EP AB242 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301153 ER PT J AU Lax, TP Banerji, A Wong, JT Wilson, MT Long, A AF Lax, Timothy P. Banerji, Aleena Wong, Johnson T. Wilson, Michael T. Long, Aidan TI Risk Stratification For Paclitaxel-Induced Hypersensitivity Reactions Improves Quality Of Care SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Lax, Timothy P.; Banerji, Aleena; Wong, Johnson T.; Wilson, Michael T.; Long, Aidan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 534 BP AB152 EP AB152 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300531 ER PT J AU Lee, JXW Wojtczak, H Wachter, AM Lee, M Burns, L Chen, D Yusin, JS AF Lee, Joyce Xiang Wu Wojtczak, Henry Wachter, Allan M. Lee, Martin Burns, Lisa Chen, Diana Yusin, Joseph S. TI Understanding Asthma Medical Nonadherence In Adult and Pediatric Populations SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Lee, Joyce Xiang Wu] VA Greater Los Angeles Hlth Care Syst, Allergy Immunol, Los Angeles, CA USA. [Wojtczak, Henry] Naval Med Ctr San Diego, San Diego, CA USA. [Wachter, Allan M.; Burns, Lisa; Chen, Diana] Fdn Asthma Res & Intervent, Phoenix, AZ USA. [Lee, Martin] UCLA Sch Publ Hlth, Los Angeles, CA USA. [Yusin, Joseph S.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 543 BP AB155 EP AB155 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300540 ER PT J AU Lee, MJ Wickner, PG Schlossman, R Richardson, P Laubach, J Castells, MC AF Lee, Min Jung Wickner, Paige G. Schlossman, Robert Richardson, Paul Laubach, Jacob Castells, Mariana C. TI Oupatient Lenalidomide Desensitization For Delayed Hypersensitivity Reactions In 5 Patients With Multiple Myeloma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Lee, Min Jung] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wickner, Paige G.] Brigham & Womens Hosp, Chestnut Hill, MA USA. [Schlossman, Robert; Richardson, Paul; Laubach, Jacob] Dana Farber Canc Inst, Boston, MA 02115 USA. [Castells, Mariana C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 952 BP AB276 EP AB276 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301268 ER PT J AU Ling, M Islam, S Leung, J Shreffler, WG Luster, AD AF Ling, Morris Islam, Sabina Leung, John Shreffler, Wayne G. Luster, Andrew D. TI CCR8 Is a Receptor For CCL18 On Human Th2 Cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Ling, Morris; Islam, Sabina; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Islam, Sabina; Shreffler, Wayne G.] Harvard Univ, Sch Med, Boston, MA USA. [Leung, John] Tufts Med Ctr, Boston, MA USA. [Luster, Andrew D.] Massachusetts Gen Hosp, Charlestown, MA USA. [Luster, Andrew D.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 8 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 FEB PY 2014 VL 133 IS 2 SU S MA 588 BP AB170 EP AB170 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300585 ER PT J AU McLaurin, EB Marsico, NP Ciolino, JB Villanueva, L Williams, JM Hollander, DA AF McLaurin, Eugene B. Marsico, Nicholas P. Ciolino, Joseph B. Villanueva, Linda Williams, Julia M. Hollander, David A. TI Alcaftadine 0.25% Versus Olopatadine 0.2% In Prevention Of Ocular Itching In Allergic Conjunctivitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [McLaurin, Eugene B.] Total Eye Care PA, Memphis, TN USA. [Marsico, Nicholas P.] East West Eye Inst, Los Angeles, CA USA. [Ciolino, Joseph B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Villanueva, Linda; Williams, Julia M.; Hollander, David A.] Allergan Pharmaceut Inc, Irvine, CA 92715 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 961 BP AB278 EP AB278 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301276 ER PT J AU Parikh, N Yusin, JS AF Parikh, Neil Yusin, Joseph S. TI An Adult With Disseminated Herpes Zoster Infection Found To Have Rare Combined CD4, CD8 T-Cell and NK-Cell Deficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Parikh, Neil] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Yusin, Joseph S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 335 BP AB97 EP AB97 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300333 ER PT J AU Patel, B Karls, J Tompkins, S Nyland, D Clough, JA Ludwig, J Mathur, SK AF Patel, Bhavisha Karls, Joseph Tompkins, Sandra Nyland, Dawn Clough, Jo Ann Ludwig, Jane Mathur, Sameer K. TI Aspirin Allergy In a High Risk VA Population and Potential Benefit From Aspirin Desensitization SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Patel, Bhavisha; Mathur, Sameer K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Patel, Bhavisha; Karls, Joseph; Tompkins, Sandra; Nyland, Dawn; Clough, Jo Ann; Ludwig, Jane; Mathur, Sameer K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 8 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 FEB PY 2014 VL 133 IS 2 SU S MA 915 BP AB265 EP AB265 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301231 ER PT J AU Patil, SU Ogunniyi, A Ma, A Brennan, AK Swenson, T Calatroni, A Moon, J Love, JC Shreffler, WG AF Patil, Sarita U. Ogunniyi, Adebola Ma, Alex Brennan, Alisa K. Swenson, Theadora Calatroni, Agustin Moon, James Love, J. Christopher Shreffler, Wayne G. TI Induction Of Arah2-Specific Memory B Cells Identified Using a Novel Tetramer-Based Approach Occurs Early and Transiently During Peanut Oral Immunotherapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Patil, Sarita U.; Shreffler, Wayne G.] Harvard Univ, Sch Med, Boston, MA USA. [Patil, Sarita U.; Swenson, Theadora; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ogunniyi, Adebola; Love, J. Christopher] MIT, Cambridge, MA 02139 USA. [Ma, Alex] Massachusetts Gen Hosp, Charlestown, MA USA. [Brennan, Alisa K.] Rush Med Coll, Chicago, IL 60612 USA. [Calatroni, Agustin] Rho Inc, Chapel Hill, NC USA. [Moon, James] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 169 BP AB47 EP AB47 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300167 ER PT J AU Permaul, P Sheehan, WJ Petty, C Baxi, SN Gaffin, JM Kopel, LS Kanchongkittiphon, W Fu, CX Gold, DR Phipatanakul, W AF Permaul, Perdita Sheehan, William J. Petty, Carter Baxi, Sachin N. Gaffin, Jonathan M. Kopel, Lianne S. Kanchongkittiphon, Watcharoot Fu, Chunxia Gold, Diane R. Phipatanakul, Wanda TI Allergic Inflammation and Health Outcomes Of Comorbid Asthma and Obesity In Inner-City Black and Hispanic Schoolchildren SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy Immunol, Boston, MA 02114 USA. [Permaul, Perdita; Sheehan, William J.; Baxi, Sachin N.; Gaffin, Jonathan M.; Kopel, Lianne S.; Gold, Diane R.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Sheehan, William J.; Petty, Carter; Baxi, Sachin N.; Gaffin, Jonathan M.; Kopel, Lianne S.; Kanchongkittiphon, Watcharoot; Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA. [Fu, Chunxia; Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 53 BP AB14 EP AB14 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300052 ER PT J AU Ramirez, D Jacobs, RL Rather, C Carrillo, A He, WJ Harper, N Andrews, C Ahuja, SK AF Ramirez, Daniel Jacobs, Robert L. Rather, Cynthia Carrillo, Andrew He, Weijing Harper, Nathan Andrews, Charles Ahuja, Sunil K. TI Baseline Predictors Of Symptom Severity Following Exposure To House Dust Mite In An Antigen Challenge Chamber (ACC) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Ramirez, Daniel; Jacobs, Robert L.; Rather, Cynthia; Andrews, Charles] Biogen Res Chamber, San Antonio, TX USA. [Carrillo, Andrew; He, Weijing; Harper, Nathan; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Carrillo, Andrew; He, Weijing; Harper, Nathan; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 765 BP AB221 EP AB221 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301081 ER PT J AU Riedl, MA Gower, RG Banerji, A AF Riedl, Marc A. Gower, Richard G. Banerji, Aleena TI Current Medical Management Of Hereditary Angioedema (HAE): Follow-Up To a Large Survey Of US Physicians SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Riedl, Marc A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Gower, Richard G.] Marycliff Allergy Specialists, Spokane, WA USA. [Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 113 BP AB31 EP AB31 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300112 ER PT J AU Ruiter, B Fleming, E Hurlburt, BK Maleki, SJ Shreffler, WG AF Ruiter, Bert Fleming, Elizabeth Hurlburt, Barry K. Maleki, Soheila J. Shreffler, Wayne G. TI Peanut Protein Induces Expression Of RALDH2 In Human Dendritic Cells In a TLR2-Dependent Manner SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Ruiter, Bert; Fleming, Elizabeth; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hurlburt, Barry K.; Maleki, Soheila J.] USDA ARS, So Reg Res Ctr, New Orleans, LA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 FEB PY 2014 VL 133 IS 2 SU S MA 322 BP AB92 EP AB92 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300320 ER PT J AU Saff, R Camargo, C Rudders, SA Clark, S Long, AD Banerji, A AF Saff, Rebecca Camargo, Carlos, Jr. Rudders, Susan A. Clark, Sunday Long, Aidan Banerji, Aleena TI Utility Of ICD-9-CM Codes For Identification Of Allergic Drug Reactions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Saff, Rebecca; Camargo, Carlos, Jr.; Long, Aidan; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Rudders, Susan A.] Brown Univ, Rhode Isl Hosp, Div Asthma & Allergy, Dept Pediat,Alpert Sch Med, Providence, RI 02903 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 934 BP AB271 EP AB271 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301250 ER PT J AU Wang, AL Patil, SU Long, A Banerji, A AF Wang, Alberta L. Patil, Sarita U. Long, Aidan Banerji, Aleena TI Risk Stratification Protocol For Carboplatin and Oxaliplatin Hypersensitivity Reactions With Repeat Skin Testing Improves Care SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Wang, Alberta L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Patil, Sarita U.; Long, Aidan; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 532 BP AB152 EP AB152 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300529 ER PT J AU Wong, JT Banerji, A Lax, TP Long, AD Wilson, MT Sokol, C AF Wong, Johnson T. Banerji, Aleena Lax, Timothy P. Long, Aidan Wilson, Michael T. Sokol, Caroline TI Rituxan Hypersensitivity and Management SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Wong, Johnson T.; Banerji, Aleena; Lax, Timothy P.; Long, Aidan; Wilson, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Sokol, Caroline] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2014 VL 133 IS 2 SU S MA 905 BP AB262 EP AB262 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301221 ER PT J AU Pierre, VC Allen, MJ Caravan, P AF Pierre, Valerie C. Allen, Matthew J. Caravan, Peter TI Contrast agents for MRI: 30+years and where are we going? SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Editorial Material DE Magnetic resonance imaging; Contrast agents; Gadolinium; Lanthanides ID NEPHROGENIC SYSTEMIC FIBROSIS; PROTON RELAXATION TIMES; FAST WATER EXCHANGE; HIGH-RELAXIVITY; PARAMAGNETIC SOLUTIONS; FIELD-STRENGTH; GADOLINIUM; COMPLEXES; NMR; STABILITY AB Thirty years ago, Schering filed the first patent application for a contrast agent for magnetic resonance imaging (MRI) covering the forefather of the gadolinium contrast agents and still the most widely used gadolinium probe: gadolinium(III) diethylenetriaminepentaacetate (Magnevist). To date, 11 contrast agents have been approved by the US Food and Drug Administration for intravenous use. Coordination chemists have done a great deal to move the field forward. Our understanding of lanthanide chemistry now makes possible the design of complexes with long rotational correlation times, fast or slow water-exchange rates, high thermodynamic stabilities, and kinetic inertness, leading to sensitive and nontoxic contrast agents. Chemists did not stop there. The last few decades has seen the development of novel classes of probes that yield contrast through different mechanisms, such as paramagnetic chemical exchange saturation transfer agents. Thirty years since the first patent, chemists are still leading the way. The development of high-sensitivity contrast agents for high magnetic fields, safe probes for patients with kidney disorders, and multimodal, targeted, and responsive agents demonstrates that the field of contrast agents for MRI still has much to offer. C1 [Pierre, Valerie C.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Allen, Matthew J.] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA. [Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Pierre, VC (reprint author), Univ Minnesota, Dept Chem, 207 Pleasant St SE, Minneapolis, MN 55455 USA. EM pierre@umn.edu; mallen@chem.wayne.edu; caravan@nmr.mgh.harvard.edu FU NCI NIH HHS [R01 CA161221]; NIBIB NIH HHS [R01 EB009062]; NIGMS NIH HHS [T32 GM008700] NR 50 TC 33 Z9 34 U1 8 U2 84 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0949-8257 EI 1432-1327 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD FEB PY 2014 VL 19 IS 2 BP 127 EP 131 DI 10.1007/s00775-013-1074-5 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 302HB UT WOS:000330593000001 PM 24414380 ER PT J AU Polyzos, SA Mantzoros, CS AF Polyzos, Stergios A. Mantzoros, Christos S. TI Necessity for timely noninvasive diagnosis of nonalcoholic fatty liver disease SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID H-1-MAGNETIC RESONANCE SPECTROSCOPY; NUTRITION EXAMINATION SURVEY; MAGNETIC-RESONANCE; HEPATIC STEATOSIS; METABOLIC SYNDROME; TRANSIENT ELASTOGRAPHY; INSULIN-RESISTANCE; NATIONAL-HEALTH; IN-VIVO; ULTRASOUND C1 [Polyzos, Stergios A.] Aristotle Univ Thessaloniki, Ippokrat Hosp, Med Clin 2, Dept Med, GR-54006 Thessaloniki, Greece. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. RP Polyzos, SA (reprint author), Aristotle Univ Thessaloniki, Ippokrat Hosp, Med Clin 2, Dept Med, GR-54006 Thessaloniki, Greece. EM stergios@endo.gr OI Polyzos, Stergios/0000-0001-9232-4042 NR 66 TC 21 Z9 22 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2014 VL 63 IS 2 BP 161 EP 167 DI 10.1016/j.metabol.2013.10.010 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299SF UT WOS:000330415300001 PM 24290839 ER PT J AU Ko, BJ Park, KH Mantzoros, CS AF Ko, Byung-Joon Park, Kyung Hee Mantzoros, Christos S. TI Diet patterns, adipokines, and metabolism: Where are we and what is next? SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID CARDIOVASCULAR RISK-FACTORS; LOW-CARBOHYDRATE-DIET; PLASMA ADIPONECTIN CONCENTRATIONS; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED FEEDING TRIALS; FRUCTOSE-RICH DIET; LOW-FAT DIETS; SWEETENED BEVERAGE CONSUMPTION; LIFE-STYLE TRAITS; TERM WEIGHT-LOSS C1 [Ko, Byung-Joon; Park, Kyung Hee; Mantzoros, Christos S.] Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Ko, Byung-Joon] Korea Univ, Coll Med, Dept Family Med, Seoul 136705, South Korea. [Park, Kyung Hee] Hallym Univ, Sacred Heart Hosp, Dept Family Med, Gyeonggi Do, South Korea. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Ko, BJ (reprint author), Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. EM beloved920@gmail.com OI Park, Kyung Hee/0000-0001-9806-0076 NR 101 TC 9 Z9 9 U1 2 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2014 VL 63 IS 2 BP 168 EP 177 DI 10.1016/j.metabol.2013.11.004 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299SF UT WOS:000330415300002 PM 24360751 ER PT J AU Bostrom, PA Fernandez-Real, JM Mantzoros, C AF Bostrom, Pontus A. Manuel Fernandez-Real, Jose Mantzoros, Christos TI Irisin in humans: recent advances and questions for future research SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID CIRCULATING LEVELS; ADIPOSE-TISSUE; MESSENGER-RNA; EXERCISE; MUSCLE; EXPRESSION; SERUM; OBESE; FNDC5; RESISTANCE C1 [Bostrom, Pontus A.] Karolinska Inst, Dept Cell & Mol Biol, S-10401 Stockholm, Sweden. [Manuel Fernandez-Real, Jose] Hosp Girona, Sect Diabet Endocrinol & Nutr, Girona, Spain. [Manuel Fernandez-Real, Jose] Hosp Girona, IDIBGI, Girona, Spain. [Manuel Fernandez-Real, Jose] CIBERobn, Madrid, Spain. [Mantzoros, Christos] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Bostrom, PA (reprint author), Karolinska Inst, Dept Cell & Mol Biol, S-10401 Stockholm, Sweden. EM cmantzor@bidmc.harvard.edu OI Fernandez-Real, Jose Manuel/0000-0002-7442-9323 NR 25 TC 33 Z9 34 U1 1 U2 23 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2014 VL 63 IS 2 BP 178 EP 180 DI 10.1016/j.metabol.2013.11.009 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299SF UT WOS:000330415300003 PM 24342075 ER PT J AU Moon, HS Mantzoros, CS AF Moon, Hyun-Seuk Mantzoros, Christos S. TI Regulation of cell proliferation and malignant potential by irisin in endometrial, colon, thyroid and esophageal cancer cell lines SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Irisin; Cell proliferation; Malignant potential; Obesity-related cancer ID PRECURSOR FNDC5; MESSENGER-RNA; WEIGHT-LOSS; EXERCISE; OBESITY; HUMANS; FAT; ADIPONECTIN; MECHANISMS; EXPRESSION AB Objective. Irisin is a novel hormone that has been proposed to mediate the beneficial effects of exercise on metabolism, including body weight regulation and insulin resistance. No previous studies have evaluated whether irisin may regulate cell proliferation and malignant potential of obesity-related cancer cell lines. Materials/Methods. Cell proliferation and malignant potential i.e. cell adhesion and colony formation were studied in vitro using human and mouse obesity-related cancer cell lines i.e. endometrial (FILE and RL95-2), colon (HT29 and MCA38), thyroid (SW579 and BHP7) and esophageal (OE13 and OE33). Results. We observed that, in contrast to metformin, cell proliferation is not regulated by irisin in a dose-dependent manner in human and mouse obesity-related cancer cell lines. Specifically, physiological (5 to 10 nmol/L) and high physiological/pharmacological (50 to 100 nmol/L) concentrations of irisin had no effect on cell proliferation when compared to control in human and mouse endometrial, colon, thyroid and esophageal cancer cell lines. Also, we observed that, in contrast to metformin, neither physiological nor high physiological/ pharmacological concentrations of irisin regulate cell adhesion and/or colony formation in human and mouse endometrial, colon, thyroid and esophageal cancer cell lines. Conclusions. Our data suggest that irisin, in physiological and high physiological/ pharmacological concentrations, has no in vitro effect on cell proliferation and malignant potential of obesity-related cancer cell lines. Future work is needed to determine the regulation of irisin levels and any physiological effects it may have on obesity-related cancers in vivo in animals and humans. (C) 2014 Elsevier Inc. All rights reserved. C1 [Moon, Hyun-Seuk; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Moon, HS (reprint author), Harvard Univ, Sch Med, 330 Brookline Ave,SL Rm 412, Boston, MA 02115 USA. EM oops8976@gmail.com RI Moon, Hyun-Seuk/G-8576-2015 OI Moon, Hyun-Seuk/0000-0002-5216-2090 FU National Institute of Diabetes and Digestive and Kidney Diseases grant [81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX The Mantzoros Laboratory was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant 81913, and by Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NR 25 TC 19 Z9 20 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2014 VL 63 IS 2 BP 188 EP 193 DI 10.1016/j.metabol.2013.10.005 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299SF UT WOS:000330415300005 PM 24268368 ER PT J AU Davis, CR Dearing, E Usher, N Trifiletti, S Zaichenko, L Ollen, E Brinkoetter, MT Crowell-Doom, C Joung, K Park, KH Mantzoros, CS Crowell, JA AF Davis, Cynthia R. Dearing, Eric Usher, Nicole Trifiletti, Sarah Zaichenko, Lesya Ollen, Elizabeth Brinkoetter, Mary T. Crowell-Doom, Cindy Joung, Kyoung Park, Kyung Hee Mantzoros, Christos S. Crowell, Judith A. TI Detailed assessments of childhood adversity enhance prediction of central obesity independent of gender, race, adult psychosocial risk and health behaviors SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Central obesity; Childhood adversity; Psychosocial risk factors; Modifiable risk factors ID METABOLIC SYNDROME; LIFE-COURSE; PSYCHOLOGICAL STRESS; ADIPOSE-TISSUE; US POPULATION; DISEASE; WOMEN; ABUSE; PATHWAYS; SUPPORT AB Objective. This study examined whether a novel indicator of overall childhood adversity, incorporating number of adversities, severity, and chronicity, predicted central obesity beyond contributions of "modifiable" risk factors including psychosocial characteristics and health behaviors in a diverse sample of midlife adults. The study also examined whether the overall adversity score (number of adversities x severity x chronicity) better predicted obesity compared to cumulative adversity (number of adversities), a more traditional assessment of childhood adversity. Materials/Methods. 210 Black/African Americans and White/European Americans, mean age = 45.8; +/- 3.3 years, were studied cross-sectionally. Regression analysis examined overall childhood adversity as a direct, non-modifiable risk factor for central obesity (waist hip ratio) and body mass index (BMI), with and without adjustment for established adult psychosocial risk factors (education, employment, social functioning) and heath behavior risk factors (smoking, drinking, diet, exercise). Results. Overall childhood adversity was an independent significant predictor of central obesity, and the relations between psychosocial and health risk factors and central obesity were not significant when overall adversity was in the model. Overall adversity was not a statistically significant predictor of BMI. Conclusions. Overall childhood adversity, incorporating severity and chronicity and cumulative scores, predicts central obesity beyond more contemporaneous risk factors often considered modifiable. This is consistent with early dysregulation of metabolic functioning. Findings can inform practitioners interested in the impact of childhood adversity and personalizing treatment approaches of obesity within high-risk populations. Prevention/intervention research is necessary to discover and address the underlying causes and impact of childhood adversity on metabolic functioning. (C) 2014 Elsevier Inc. All rights reserved. C1 [Davis, Cynthia R.; Usher, Nicole; Trifiletti, Sarah; Ollen, Elizabeth; Crowell-Doom, Cindy; Crowell, Judith A.] Judge Baker Childrens Ctr, Boston, MA 02120 USA. [Dearing, Eric] Boston Coll, Boston, MA USA. [Zaichenko, Lesya; Brinkoetter, Mary T.; Joung, Kyoung; Park, Kyung Hee; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Brinkoetter, Mary T.; Joung, Kyoung] Boston Childrens Hosp, Div Newborn Med, Boston, MA USA. [Park, Kyung Hee] Hallym Univ, Sacred Heart Hosp, Dept Family Med, Gyeonggi Do, South Korea. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Crowell, Judith A.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Sch Med, Stony Brook, NY 11794 USA. RP Davis, CR (reprint author), Judge Baker Childrens Ctr, 53 Parker Hill Ave, Boston, MA 02120 USA. EM crdavis@jbcc.harvard.edu OI Zaichenko, Lesya/0000-0001-8489-3886; Park, Kyung Hee/0000-0001-9806-0076 FU National Institute of Aging [AG032030]; National Institute of Diabetes and Digestive and Kidney Diseases grant [81913]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources [UL1 RR025758] FX Grant Support: This study was supported by the National Institute of Aging, grant AG032030, and National Institute of Diabetes and Digestive and Kidney Diseases grant 81913. The project described was supported by Grant Number UL1 RR025758 Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 61 TC 13 Z9 13 U1 5 U2 29 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2014 VL 63 IS 2 BP 199 EP 206 DI 10.1016/j.metabol.2013.08.013 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299SF UT WOS:000330415300007 PM 24211017 ER PT J AU Polyzos, SA Kountouras, J Anastasilakis, AD Geladari, EV Mantzoros, CS AF Polyzos, Stergios A. Kountouras, Jannis Anastasilakis, Athanasios D. Geladari, Eleni V. Mantzoros, Christos S. TI Irisin in patients with nonalcoholic fatty liver disease SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Fibronectin type III domain containing 5; Chemerin; Nonalcoholic steatohepatitis; Portal inflammation; Retinol-binding protein-4 ID MOLECULAR-WEIGHT ADIPONECTIN; MESSENGER-RNA EXPRESSION; TYPE-2 DIABETES-MELLITUS; SERUM RETINOL-BINDING-PROTEIN-4; PLASMA ADIPONECTIN; INSULIN-RESISTANCE; CHEMERIN; EXERCISE; HUMANS; PREDICTORS AB Objective. Irisin is a recently discovered myokine proposed to increase thermogenesis-related energy expenditure and improve metabolism. We aimed to comparatively evaluate serum irisin levels in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) vs. controls and study their association with disease severity. Methods. Fifteen and 16 consecutively enrolled patients with biopsy-proven nonalcoholic simple steatosis (NAFL) and steatohepatitis (NASH), respectively, and 24 lean and 28 obese controls without NAFLD were recruited. Irisin, established adipokines and biochemical tests were measured. Results. Serum irisin levels were statistically different in obese controls (33.7 +/- 2.7 ng/mL; p <0.001) and patients with NAFL (30.5 +/- 1.5 ng/mL; p <0.001) and NASH (35.8 +/- 1.9 ng/mL; p = 0.001) compared with lean controls (47.7 +/- 2.0 ng/mL), but were similar among patients with NAFL, NASH and obese controls. This difference remained significant after adjustment for body mass index (or waist circumference), gender, age, insulin resistance (assessed by HOMA-IR or QUICKI), exercise and time since blood collection. Serum leptin and adiponectin, but not irisin, levels were independently from BMI correlated with insulin resistance and cardiometabolic factors. Serum irisin tended to be higher in patients with (36.7 +/- 2.4 ng/mL) than without (30.8 +/- 1.2 ng/mL; p = 0.02) portal inflammation and independently associated with the latter; these data need to be confirmed by future studies. Conclusions. Serum irisin levels differ between lean controls and obese controls or NAFLD patients. Despite similar circulating irisin levels between NAFL and NASH groups, irisin may be independently and positively associated with the presence of portal inflammation. Future clinical and mechanistic studies are needed to confirm and extend these data. (C) 2014 Elsevier Inc. All rights reserved. C1 [Polyzos, Stergios A.; Kountouras, Jannis] Aristotle Univ Thessaloniki, Dept Med, Med Clin 2, Ippokrat Hosp, GR-54006 Thessaloniki, Greece. [Anastasilakis, Athanasios D.] 424 Gen Mil Hosp, Dept Endocrinol, Thessaloniki, Greece. [Geladari, Eleni V.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. [Geladari, Eleni V.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. RP Polyzos, SA (reprint author), 13 Simou Lianidi, Thessaloniki 55134, Greece. EM stergios@endo.gr OI Polyzos, Stergios/0000-0001-9232-4042 FU National Institute of Diabetes and Digestive and Kidney Diseases grant [81913]; BIDMC FX This study was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases grant 81913 and a discretionary grant from BIDMC. NR 50 TC 57 Z9 59 U1 1 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2014 VL 63 IS 2 BP 207 EP 217 DI 10.1016/j.metabol.2013.09.013 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299SF UT WOS:000330415300008 PM 24140091 ER PT J AU Park, KH Zaichenko, L Peter, P Davis, CR Crowell, JA Mantzoros, CS AF Park, Kyung Hee Zaichenko, Lesya Peter, Patricia Davis, Cynthia R. Crowell, Judith A. Mantzoros, Christos S. TI Diet quality is associated with circulating C-reactive protein but not irisin levels in humans SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Irisin; Dietary pattern; Alternate Healthy Eating Index; Mediterranean Diet; C-reactive protein ID MOLECULAR-WEIGHT ADIPONECTIN; MESSENGER-RNA EXPRESSION; HEALTHY EATING INDEX; BODY-MASS INDEX; FAT-FREE MASS; MEDITERRANEAN DIET; METABOLIC SYNDROME; LIFE-STYLE; ENDOTHELIAL DYSFUNCTION; PLASMA-CONCENTRATIONS AB Objective. Adherence to a healthy diet has been shown to decrease the incidence of obesity and associated comorbidities. C-reactive protein (CRP) is an established inflammatory marker and irisin was recently identified as a molecule which may play a role in energy regulation and obesity but whether diet alters irisin levels remains unknown. We aimed to investigate the association between circulating irisin, leptin, and CRP levels and dietary quantity and quality using the Alternate Healthy Eating Index (AHEI) and the Alternate Mediterranean Diet Score (aMED). Materials/Methods. The study evaluated dietary data and biomarker levels of 151 participants between 2009 and 2011 (71 male vs. 80 female, over 35 years old, obese 43.7%). AHEI and aMED scores were calculated based on data derived from self-administered 110-item food-frequency questionnaires estimating usual nutrient intake over the past year. Cross-sectional associations between dietary quantity, quality, body composition by bioelectric impedance, and biomarker levels including irisin, leptin, and CRP after fasting were assessed. Results. CRP, but not irisin, was negatively correlated with AHEI (r = -0.34) and aMED (r = -0.31). Irisin was positively correlated with BMI (r = 0.22), fat mass (r = 0.21), waist circumference (r = 0.24), waist-hip ratio (r = 0.20), leptin (r = 0.32), and CRP (r = 0.25). Participants with the highest AHEI scores tended to have 11.6% lower concentrations of irisin (P for trend = 0.09), but they were not significant after adjustment for potential confounders. Better diet quality was associated with lower CRP concentrations (P for trend = 0.02) in multivariate model. Percentage of energy from carbohydrate was inversely associated with CRP. Conclusions. Unlike CRP, irisin is not associated with dietary quality or quantity. (C) 2014 Elsevier Inc. All rights reserved. C1 [Park, Kyung Hee; Zaichenko, Lesya; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Park, Kyung Hee] Hallym Univ, Sacred Heart Hosp, Dept Family Med, Gyeonggi Do 431796, South Korea. [Peter, Patricia] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02215 USA. [Davis, Cynthia R.; Crowell, Judith A.] Judge Baker Childrens Ctr, Boston, MA USA. [Crowell, Judith A.] SUNY Stony Brook, Sch Med, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Park, KH (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM beloved920@gmail.com OI Zaichenko, Lesya/0000-0001-8489-3886; Park, Kyung Hee/0000-0001-9806-0076 FU National Institute of Aging [R01 AG032030]; National Institute of Diabetes and Digestive and Kidney Diseases [81913]; National Center for Research Resources [UL1 RR025758] FX Source of support: This study was supported by the National Institute of Aging, R01 AG032030, and National Institute of Diabetes and Digestive and Kidney Diseases grant 81913. The project described was supported by Grant Number UL1 RR025758-Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 57 TC 29 Z9 30 U1 1 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2014 VL 63 IS 2 BP 233 EP 241 DI 10.1016/j.metabol.2013.10.011 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299SF UT WOS:000330415300011 PM 24315778 ER PT J AU Beissner, F Schumann, A Brunn, F Eisentrager, D Bar, KJ AF Beissner, Florian Schumann, Andy Brunn, Franziska Eisentraeger, Daniela Baer, Karl-Juergen TI Advances in functional magnetic resonance imaging of the human brainstem SO NEUROIMAGE LA English DT Article DE Brainstem; Functional magnetic resonance imaging; Brainstem nuclei; Resting state; Physiological noise correction; Independent component analysis; Intrinsic connectivity networks ID INDEPENDENT COMPONENT ANALYSIS; PHYSIOLOGICAL NOISE; FMRI DATA; ALGORITHMS; ACTIVATION; DISEASE; CORTEX AB The brainstem is of tremendous importance for our daily survival, and yet the functional relationships between various nuclei, their projection targets, and afferent regulatory areas remain poorly characterized. The main reason for this lies in the sub-optimal performance of standard neuroimaging methods in this area. In particular, fMRI signals are much harder to detect in the brainstem region compared to cortical areas. Here we describe and validate a new approach to measure activation of brainstem nuclei in humans using standard fMRI sequences and widely available tools for statistical image processing. By spatially restricting an independent component analysis to an anatomically defined brainstem mask, we excluded those areas from the analysis that were strongly affected by physiological noise. This allowed us to identify for the first time intrinsic connectivity networks in the human brainstem and to map brainstem-cortical connectivity purely based on functionally defined regions of interest. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved. C1 [Beissner, Florian; Schumann, Andy; Brunn, Franziska; Eisentraeger, Daniela; Baer, Karl-Juergen] Univ Hosp Jena, Dept Psychiat & Psychotherapy, Jena, Germany. [Beissner, Florian] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Beissner, F (reprint author), Univ Hosp Jena, Dept Psychiat & Psychotherapy, Jena, Germany. EM florian.beissner@uni-jena.de FU German Research Foundation [BE4677/1-1]; Horst-Gortz-Foundation FX FBe thanks Vitaly Napadow for helpful discussions. FBe was supported by the German Research Foundation Grant BE4677/1-1. FBr and AS were supported by the Horst-Gortz-Foundation. NR 32 TC 21 Z9 21 U1 2 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2014 VL 86 BP 91 EP 98 DI 10.1016/j.neuroimage.2013.07.081 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 298OZ UT WOS:000330335300011 PM 23933038 ER PT J AU van Dellen, E Douw, L Hillebrand, A Hamer, PCD Baayen, JC Heimans, JJ Reijneveld, JC Stam, CJ AF van Dellen, Edwin Douw, Linda Hillebrand, Arjan Hamer, Philip C. de Witt Baayen, Johannes C. Heimans, Jan J. Reijneveld, Jaap C. Stam, Cornelis J. TI Epilepsy surgery outcome and functional network alterations in longitudinal MEG: A minimum spanning tree analysis SO NEUROIMAGE LA English DT Article DE Lesional epilepsy; Glioma; Resective surgery; Magnetoencephalography; Minimum spanning tree; Network analysis; Functional connectivity ID SIGNAL-SPACE SEPARATION; BRAIN-TUMOR PATIENTS; LOW-GRADE GLIOMAS; TEMPORAL-LOBE EPILEPSY; QUALITY-OF-LIFE; MODULAR ORGANIZATION; UNIFIED SEGMENTATION; CONNECTIVITY; MAGNETOENCEPHALOGRAPHY; LESIONS AB Seizure freedom after resective epilepsy surgery is not obtained in a substantial number of patients with medically intractable epilepsy. Functional neural network analysis is a promising technique for more accurate identification of the target areas for epilepsy surgery, but a better understanding of the correlations between changes in functional network organization due to surgery and postoperative seizure status is required. We explored these correlations in longitudinal magnetoencephalography (MEG) recordings of 20 lesional epilepsy patients. Resting-state MEG recordings were obtained at baseline (preoperatively; TO) and at 3-7 (T1) and 9-15 months after resection (T2). We assessed frequency-specific functional connectivity and performed a minimum spanning tree (MST) network analysis. The MST captures the most important connections in the network. We found a significant positive correlation between functional connectivity in the lower alpha band and seizure frequency at TO, especially in regions where lesions were located. MST leaf fraction, a measure of integration of information in the network, was significantly increased between TO and T2, only for the seizurefree patients. This is in line with previous work, which showed that lower functional network integration in lesional epilepsy patients is related to higher epilepsy burden. Finally, eccentricity and betweenness centrality, which are measures of hub-status, decreased between TO and T2 in seizure free patients, also in regions that were anatomically close to resection cavities. Our results increase insight into functional network changes in successful epilepsy surgery and might eventually be utilized for optimization of neurosurgical approaches. (C) 2013 Elsevier Inc All rights reserved. C1 [van Dellen, Edwin; Douw, Linda; Heimans, Jan J.; Reijneveld, Jaap C.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Canc Ctr Amsterdam, NL-1007 MB Amsterdam, Netherlands. [van Dellen, Edwin; Hillebrand, Arjan; Stam, Cornelis J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Neurophysiol, NL-1007 MB Amsterdam, Netherlands. [van Dellen, Edwin; Hillebrand, Arjan; Stam, Cornelis J.] Vrije Univ Amsterdam Med Ctr, MEG Ctr, NL-1007 MB Amsterdam, Netherlands. [Hamer, Philip C. de Witt; Baayen, Johannes C.] Vrije Univ Amsterdam Med Ctr, Neurosurg Ctr Amsterdam, NL-1007 MB Amsterdam, Netherlands. [Douw, Linda] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Douw, Linda] Harvard Univ, Sch Med, Boston, MA USA. RP van Dellen, E (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Neurol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM E.vanDellen@vumc.nl RI De Witt Hamer, Philip/E-7630-2013 OI De Witt Hamer, Philip/0000-0003-2988-8544 FU Dutch Epilepsy Foundation (NEF) [09-09]; Rubicon grant of the Netherlands Organization for Scientific Research (NWO) FX E. van Dellen was supported by the Dutch Epilepsy Foundation (NEF) grant 09-09. L Douw was supported by the Rubicon grant of the Netherlands Organization for Scientific Research (NWO). Scanning costs were in part funded by the Amsterdam Brain Imaging Platform (ABIP), Amsterdam, The Netherlands. NR 63 TC 26 Z9 26 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2014 VL 86 BP 354 EP 363 DI 10.1016/j.neuroimage.2013.10.010 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 298OZ UT WOS:000330335300037 PM 24128736 ER PT J AU Gramfort, A Luessi, M Larson, E Engemann, DA Strohmeier, D Brodbeck, C Parkkonen, L Hamalainen, MS AF Gramfort, Alexandre Luessi, Martin Larson, Eric Engemann, Denis A. Strohmeier, Daniel Brodbeck, Christian Parkkonen, Lauri Haemaelaeinen, Matti S. TI MNE software for processing MEG and EEG data SO NEUROIMAGE LA English DT Article DE Magnetoencephalography (MEG); Electroencephalography (EEG); Software; Inverse problem; Time-frequency analysis; Connectivity; Non-parametric statistics ID INDEPENDENT COMPONENT ANALYSIS; SPACE SEPARATION METHOD; TEST-DRIVEN DEVELOPMENT; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; CORTICAL OSCILLATIONS; SOURCE LOCALIZATION; INVERSE PROBLEM AB Magnetoencephalography and electroencephalography (M/EEG) measure the weak electromagnetic signals originating from neural currents in the brain. Using these signals to characterize and locate brain activity is a challenging task, as evidenced by several decades of methodological contributions. MNE, whose name stems from its capability to compute conically-constrained minimum-norm current estimates from M/EEG data, is a software package that provides comprehensive analysis tools and workflows including preprocessing, source estimation, time-frequency analysis, statistical analysis, and several methods to estimate functional connectivity between distributed brain regions. The present paper gives detailed information about the MNE package and describes typical use cases while also warning about potential caveats in analysis. The MNE package is a collaborative effort of multiple institutes striving to implement and share best methods and to facilitate distribution of analysis pipelines to advance reproducibility of research. Full documentation is available at http://martinos.org/mne. (C) 2013 Elsevier Inc. All rights reserved. C1 [Gramfort, Alexandre] CNRS LTCI, Telecom ParisTech, Inst Mines Telecom, F-75014 Paris, France. [Gramfort, Alexandre; Luessi, Martin; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gramfort, Alexandre; Luessi, Martin; Haemaelaeinen, Matti S.] Harvard Univ, Sch Med, Charlestown, MA USA. [Gramfort, Alexandre] CEA Saclay, NeuroSpin, F-91191 Gif Sur Yvette, France. [Larson, Eric] Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. [Engemann, Denis A.] Forschungszentrum Julich, Inst Neurosci & Med Cognit Neurosci INM 3, D-52425 Julich, Germany. [Engemann, Denis A.] Univ Hosp Cologne, Dept Psychiat, Brain Imaging Lab, Cologne, Germany. [Strohmeier, Daniel] Ilmenau Univ Technol, Inst Biomed Engn & Informat, Ilmenau, Germany. [Brodbeck, Christian] NYU, Dept Psychol, New York, NY 10003 USA. [Parkkonen, Lauri] Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci, Espoo, Finland. [Parkkonen, Lauri] Aalto Univ, Sch Sci, OV Lounasmaa Lab, Brain Res Unit, Espoo, Finland. RP Gramfort, A (reprint author), CNRS LTCI, Telecom ParisTech, Inst Mines Telecom, 37-39 Rue Dareau, F-75014 Paris, France. EM alexandre.gramfort@telecom-paristech.fr RI Parkkonen, Lauri/G-6755-2012; Hamalainen, Matti/C-8507-2013; OI Parkkonen, Lauri/0000-0002-0130-0801; Gramfort, Alexandre/0000-0001-9791-4404 FU National Institute of Biomedical Imaging and Bioengineering [5R01EB009048, P41RR014075]; National Institute on Deafness and Other Communication Disorders fellowship [F32DC012456]; NSF [0958669, 1042134]; "aivoAALTO" program; Swiss National Science Foundation Early Postdoc. Mobility fellowship [148485]; [ERC-YStG-263584] FX This work was supported by the National Institute of Biomedical Imaging and Bioengineering grants 5R01EB009048 and P41RR014075, National Institute on Deafness and Other Communication Disorders fellowship F32DC012456, and NSF awards 0958669 and 1042134. The work of A.G. was partially supported by ERC-YStG-263584 and LP. was supported by the "aivoAALTO" program. M.L was partially supported by the Swiss National Science Foundation Early Postdoc. Mobility fellowship 148485. NR 103 TC 102 Z9 102 U1 8 U2 27 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2014 VL 86 BP 446 EP 460 DI 10.1016/j.neuroimage.2013.10.027 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 298OZ UT WOS:000330335300046 PM 24161808 ER PT J AU Huang, S Chang, WT Belliveau, JW Hamalainen, M Ahveninen, J AF Huang, Samantha Chang, Wei-Tang Belliveau, John W. Haemaelaeinen, Matti Ahveninen, Jyrki TI Lateralized parietotemporal oscillatory phase synchronization during auditory selective attention SO NEUROIMAGE LA English DT Article ID HUMAN CEREBRAL-CORTEX; RIGHT PARIETAL CORTEX; SOUND LOCALIZATION; BAND OSCILLATIONS; SPATIAL ATTENTION; HUMAN BRAIN; TOP-DOWN; INTERREGIONAL CONNECTIVITY; ALPHA OSCILLATIONS; RIGHT-HEMISPHERE AB Based on the infamous left-lateralized neglect syndrome, one might hypothesize that the dominating right parietal cortex has a bilateral representation of space, whereas the left parietal cortex represents only the contralateral right hemispace. Whether this principle applies to human auditory attention is not yet fully clear. Here, we explicitly tested the differences in cross-hemispheric functional coupling between the intraparietal sulcus (IPS) and auditory cortex (AC) using combined magnetoencephalography (MEG), EEG, and functional MRI (fMRI). Inter-regional pairwise phase consistency (PPC) was analyzed from data obtained during dichotic auditory selective attention task, where subjects were in 10-s trials cued to attend to sounds presented to one ear and to ignore sounds presented in the opposite ear. Using MEG/EEGAIVIRI source modeling, parietotemporal PPC patterns were (a) mapped between all AC locations vs. IPS seeds and (b) analyzed between four anatomically defined AC regions-of-interest (ROI) vs. IPS seeds. Consistent with our hypothesis, stronger cross-hemispheric PPC was observed between the right IPS and left AC for attended right-ear sounds, as compared to PPC between the left IPS and right AC for attended left-ear sounds. In the mapping analyses, these differences emerged at 7-13 Hz, i.e., at the theta to alpha frequency bands, and peaked in Heschl's gyrus and lateral posterior non-primary ACs. The ROI analysis revealed similarly lateralized differences also in the beta and lower theta bands. Taken together, our results support the view that the right parietal cortex dominates auditory spatial attention. (C) 2013 Elsevier Inc. All rights reserved. C1 [Huang, Samantha; Chang, Wei-Tang; Belliveau, John W.; Haemaelaeinen, Matti; Ahveninen, Jyrki] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA USA. [Belliveau, John W.; Haemaelaeinen, Matti] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ahveninen, J (reprint author), MGH MIT HMS Martinos Ctr, Bldg 149 13th St, Charlestown, MA 02129 USA. EM jyrki@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013 FU National Institutes of Health [R01MH083744, R21DC010060, R01HD040712, R01NS037462, 5R01EB009048]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health.; National Center for Research Resources Shared Instrumentation [S10RR014978, S10RR021110, S10RR019307, S10RR014798, S10RR023401] FX We thank An-Yi Hung, Natsuko Mori, Stephanie Rossi, Chinmayi Tengshe, and Nao Suzuki for their help. This work was supported by the National Institutes of Health Awards R01MH083744, R21DC010060, R01HD040712, R01NS037462, and 5R01EB009048. This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. The research environment was additionally supported by the National Center for Research Resources Shared Instrumentation Grants S10RR014978, S10RR021110, S10RR019307, S10RR014798, and S10RR023401. NR 92 TC 4 Z9 7 U1 2 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2014 VL 86 BP 461 EP 469 DI 10.1016/j.neuroimage.2013.10.043 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 298OZ UT WOS:000330335300047 PM 24185023 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Patient-level improvements in pain and activities of daily living after total knee arthroplasty SO RHEUMATOLOGY LA English DT Article DE pain; activity limitation; activities of daily living; function; functional limitation; total knee replacement; arthroplasty; joint replacement; outcomes; patient-reported outcomes; primary ID QUALITY-OF-LIFE; SEVERE FUNCTIONAL LIMITATION; TOTAL HIP-ARTHROPLASTY; PREDICTORS; OUTCOMES; REPLACEMENT; EXPECTATIONS; PARTICIPATION; 5-YEARS; 2-YEARS AB Objective. To study patient-level improvements in pain and limitations of key activities of daily living (ADLs) after primary or revision total knee arthroplasty (TKA). Methods. We analysed prospectively collected data from the Mayo Clinic Total Joint Registry for improvements in index knee pain severity and limitations in three key ADLs (walking, climbing stairs and rising from a chair) from pre-operative to 2 and 5 years post-TKA. Results. The primary TKA cohort consisted of 7229 responders pre-operatively, 7139 at 2 years and 4234 at 5 years post-operatively. The revision TKA cohort consisted of 1206 responders pre-operatively, 1533 at 2 years and 881 at 5 years post-operatively. In the primary TKA cohort, important pain reduction to mild or no knee pain at 2 years was reported by 92% with moderate pre-operative pain and 93% with severe pre-operative pain; respective proportions were 91% and 91% at 5 years follow-up. For revision TKA, respective proportions were 71% and 66% at 2 years and 68% and 74% at 5 years. Three per cent with no/mild pre-operative overall limitation and 19% with moderate/severe pre-operative overall limitation had moderate/severe overall activity limitation 2 years post-operatively; at 5 years the respective proportions were 4% and 22%. Respective proportions for revision TKA were up to 3% and 32% at 2 years and 4% and 34% at 5 years. Conclusion. Our study provides comprehensive data for patient-level improvements in pain and key ADLs. These data can be used to inform patients pre-operatively of expected outcomes, based on pre-operative status, which may further help patients set realistic goals for improvements after TKA. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, 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 Department of Orthopaedic Surgery at the Mayo Clinic FX This study received research funding from the Department of Orthopaedic Surgery at the Mayo Clinic. NR 29 TC 7 Z9 7 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD FEB PY 2014 VL 53 IS 2 BP 313 EP 320 DI 10.1093/rheumatology/ket325 PG 8 WC Rheumatology SC Rheumatology GA 299ZR UT WOS:000330434700017 PM 24162150 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Underlying diagnosis predicts patient-reported outcomes after revision total knee arthroplasty SO RHEUMATOLOGY LA English DT Article DE total knee replacement; risk factor; arthroplasty; joint replacement; patient-reported outcomes; osteoarthritis; rheumatoid arthritis ID TOTAL HIP-ARTHROPLASTY; SEVERE FUNCTIONAL LIMITATION; PAIN; RESPONSIVENESS; TKA; REHABILITATION; FRACTURES; MORBIDITY; 5-YEARS; 2-YEARS AB Objective. To assess the association of underlying diagnosis with outcomes after revision total knee arthroplasty (TKA). Methods. For this cohort study we used prospectively collected data from the Mayo Clinic Total Joint Registry on all revision TKA patients from 1993 to 2005 with 2- or 5-year response to a validated knee questionnaire that assesses pain and function. We used logistic regression to assess the odds of moderate-severe activities of daily living (ADL) limitations and moderate-severe index knee pain 2 and 5 years after revision TKA. Odds ratios (ORs) and 95% CIs are presented. Results. The underlying diagnosis for the 2- and 5-year cohorts was loosening, wear or osteolysis in 73% and 75%; dislocation, bone or prosthesis fracture, instability or non-union in 17% and 15%; and failed prior arthroplasty with components removed or infection in 11% and 11%, respectively. In multivariable adjusted analyses that included preoperative status, compared with patients with loosening/wear/osteolysis, patients with dislocation/fracture/instability/non-union had an OR of 2.1 for moderate-severe ADL limitation (95% CI 1.3, 3.1, P < 0.001) and those with failed prior arthroplasty/infection had an OR of 1.1 (95% CI 0.6, 1.8, P = 0.4). At 5 years, differences were no longer significant. In multivariable adjusted analyses, compared with patients with loosening/wear/osteolysis, patients with dislocation/fracture/instability/non-union had an OR of 2.0 for moderate-severe pain (95% CI 1.3, 3.1, P < 0.01) at 2 years and an OR of 2.1 (95% CI 1.3, 3.8, P = 0.01) at 5 years. Failed prior arthroplasty/infection was not significantly different than the reference category. Conclusion. Underlying diagnosis is independently associated with ADL limitations and pain after revision TKA. This information can help patients have realistic expectations of outcomes. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, 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 Mayo Clinic Orthopaedic Surgery FX This material is the result of work supported by Mayo Clinic Orthopaedic Surgery research funds and the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, AL, USA. NR 29 TC 3 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD FEB PY 2014 VL 53 IS 2 BP 361 EP 366 DI 10.1093/rheumatology/ket357 PG 6 WC Rheumatology SC Rheumatology GA 299ZR UT WOS:000330434700023 PM 24196389 ER PT J AU Roberts, DJ Wilson, ML AF Roberts, Drucilla J. Wilson, Michael L. TI Improving Diagnostic Pathology Capacity for Global Cancer Care Where to Start SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material C1 [Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Roberts, Drucilla J.] Harvard Univ, Sch Med, Boston, MA USA. [Wilson, Michael L.] Denver Hlth, Dept Pathol & Lab Serv, Denver, CO USA. [Wilson, Michael L.] Univ Colorado, Sch Med, Dept Pathol, Aurora, CO USA. RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 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 FEB PY 2014 VL 141 IS 2 BP 150 EP 151 DI 10.1309/AJCPHP7DJQGDAIYW PG 2 WC Pathology SC Pathology GA 296CE UT WOS:000330161900002 PM 24436260 ER PT J AU Hicks, CW Hodin, RA Bordeianou, L AF Hicks, Caitlin W. Hodin, Richard A. Bordeianou, Liliana TI Semi-urgent surgery in hospitalized patients with severe ulcerative colitis does not increase overall J-pouch complications SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Ulcerative colitis; Surgery for IBD; Complications of IBD ID ANAL ANASTOMOSIS; SEPTIC COMPLICATIONS; METAANALYSIS; INFLIXIMAB; COLECTOMY; THERAPY; RISK; COHORT; COLON AB BACKGROUND: Surgeons frequently discourage patients with ulcerative colitis from having surgery in the midst of an acute flare for fear of complications and poor long-term outcomes. METHODS: Outcomes of patients undergoing urgent versus elective surgery for ulcerative colitis were compared via retrospective review. RESULTS: Patients undergoing urgent (n = 80) versus elective (n = 99) surgery were younger, were more malnourished, had more severe active disease, and had higher steroid use (P <= .05). During surgery, hemodynamic stability was similar, but urgent patients underwent more subtotal colectomies (5.1% vs 29%, P < .0001) and fewer laparoscopic procedures (8.8% vs 18%, P = .07). Multivariate regression suggested that short-term complications were increased with higher body mass index and urgency status (P <= .05). Anastomotic leaks and long-term complications were similar between groups. Surgeon inexperience and use of immunomodulators other than infliximab were associated with increased odds of long-term fistula/abscess (odds ratio, 5.56; P = .05] and pouch failure (odds ratio, 13.3; P = .01). CONCLUSIONS: Surgery in patients with acute ulcerative colitis flares is associated with more short-term complications than elective procedures but does not appear to affect risk for anastomotic leak or long-term complications when performed by an expert. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hicks, Caitlin W.; Hodin, Richard A.; Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hicks, Caitlin W.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 27 TC 4 Z9 5 U1 0 U2 3 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 FEB PY 2014 VL 207 IS 2 BP 281 EP 287 DI 10.1016/j.amjsurg.2013.06.006 PG 7 WC Surgery SC Surgery GA 296KM UT WOS:000330183800021 PM 24112682 ER PT J AU Dworkin, SL Grabe, S Lu, T Hatcher, AM Kwena, Z Bukusi, E Mwaura-Muiru, E AF Dworkin, Shari L. Grabe, Shelly Lu, Tiffany Hatcher, Abigail M. Kwena, Zachary Bukusi, Elizabeth Mwaura-Muiru, Esther TI Property Rights Violations as a Structural Driver of Women's HIV Risks: A Qualitative Study in Nyanza and Western Provinces, Kenya (vol 42, pg 703, 2013) SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Correction C1 [Dworkin, Shari L.] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Dworkin, Shari L.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94118 USA. [Grabe, Shelly] Univ Calif Santa Cruz, Dept Psychol, Santa Cruz, CA 95064 USA. [Lu, Tiffany] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hatcher, Abigail M.] Univ Calif San Francisco, Bixby Ctr Reprod Hlth, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94118 USA. [Kwena, Zachary; Bukusi, Elizabeth] Kenya Med Res Inst KEMRI, Ctr Microbiol Res, Kisumu, Kenya. [Mwaura-Muiru, Esther] GROOTS Kenya, Nairobi, Kenya. RP Dworkin, SL (reprint author), Univ Calif San Francisco, 3333 Calif St,LHTS 455, San Francisco, CA 94118 USA. EM shari.dworkin@ucsf.edu RI Hatcher, Abigail/G-9128-2011 OI Hatcher, Abigail/0000-0002-4150-1405 NR 1 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0004-0002 EI 1573-2800 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD FEB PY 2014 VL 43 IS 2 BP 411 EP 411 DI 10.1007/s10508-012-0060-2 PG 1 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 296TI UT WOS:000330207900021 ER PT J AU Spector, M AF Spector, Myron TI The tissue engineer's toolbox manifesto SO BIOMEDICAL MATERIALS LA English DT Editorial Material ID HYDROGELS; MODELS; CELLS; RAT C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD FEB PY 2014 VL 9 IS 1 AR 010201 DI 10.1088/1748-6041/9/1/010201 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 296OU UT WOS:000330195300001 PM 24457154 ER PT J AU Park, JH Tanaka, Y Arango, NA Zhang, LH Benedict, LA Roh, MI Donahoe, PK Teixeira, JM AF Park, Joo Hyun Tanaka, Yoshihiro Arango, Nelson A. Zhang, Lihua Benedict, L. Andrew Roh, Mi In Donahoe, Patricia K. Teixeira, Jose M. TI Induction of WNT inhibitory factor 1 expression by Mullerian inhibiting substance/antiMullerian hormone in the Mullerian duct mesenchyme is linked to Mullerian duct regression SO DEVELOPMENTAL BIOLOGY LA English DT Article DE AntiMullerian hormone; WNT signaling; Reproductive tract development ID FEMALE REPRODUCTIVE-TRACT; TGF-BETA FAMILY; SEXUAL-DIFFERENTIATION; TRANSDUCTION PATHWAY; CONDITIONAL DELETION; TARGETED DISRUPTION; II RECEPTOR; IN-VIVO; SUBSTANCE; CATENIN AB A key event during mammalian sexual development is regression of the Mullerian ducts (MDs) in the bipotential urogenital ridges (UGRs) of fetal males, which is caused by the expression of Mullerian inhibiting substance (MIS) in the Sertoli cells of the differentiating testes. The paracrine signaling mechanisms involved in MD regression are not completely understood, particularly since the receptor for MIS, MISR2, is expressed in the mesenchyme surrounding the MD, but regression occurs in both the epithelium and mesenchyme. Microarray analysis comparing MIS signaling competent and Misr2 knockout embryonic UGRs was performed to identify secreted factors that might be important for MIS-mediated regression of the MD. A seven-fold increase in the expression of Will, an inhibitor of WNT/beta-catenin signaling, was observed in the Misr2-expressing UGRs. Whole mount in situ hybridization of Wif1 revealed a spatial and temporal pattern of expression consistent with Misr2 during the window of MD regression in the mesenchyme surrounding the MD epithelium that was absent in both female UGRs and UGRs knocked out for Misr2. Knockdown of Will expression in male UGRs by Will-specific siRNAs beginning on embryonic day 13.5 resulted in MD retention in an organ culture assay, and exposure of female UGRs to added recombinant human MIS induced Will expression in the MD mesenchyme. Knockdown of Will led to increased expression of beta-catenin and its downstream targets TCF1/LEF1 in the MD mesenchyme and to decreased apoptosis, resulting in partial to complete retention of the MD. These results strongly suggest that WIF1 secretion by the MD mesenchyme plays a role in MD regression in fetal males. (C) 2013 Elsevier Inc. All rights reserved. C1 [Park, Joo Hyun; Tanaka, Yoshihiro; Zhang, Lihua; Teixeira, Jose M.] Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Arango, Nelson A.; Benedict, L. Andrew; Donahoe, Patricia K.] Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA. [Roh, Mi In] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Park, Joo Hyun; Tanaka, Yoshihiro; Arango, Nelson A.; Benedict, L. Andrew; Roh, Mi In; Donahoe, Patricia K.; Teixeira, Jose M.] Harvard Univ, Sch Med, Boston, MA USA. RP Teixeira, JM (reprint author), Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, Grand Rapids, MI 49503 USA. EM jose.teixeira@hc.msu.edu OI Teixeira, Jose/0000-0002-6438-5064 FU NIH [OD012206, CA017393]; DOD grant [W81XWH-12-1-0342] FX We would like to thank Dr. Igor Dawid and Martha Rebbert at NICHD for generously sharing their Wif1-/- mice with us. We are indebted to Dr. Richard Behringer at MD Anderson for providing us with the Misr2-Cre and Misr2-LacZ mice. These studies were supported by NIH grants to JMT (OD012206) and to PKD (CA017393) and by a DOD grant to PKD (W81XWH-12-1-0342). NR 60 TC 1 Z9 1 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD FEB 1 PY 2014 VL 386 IS 1 BP 227 EP 236 DI 10.1016/j.ydbio.2013.12.015 PG 10 WC Developmental Biology SC Developmental Biology GA 297LX UT WOS:000330258000020 PM 24362065 ER PT J AU Branda, JA Rychert, J Burnham, CAD Bythrow, M Garner, OB Ginocchio, CC Jennemann, R Lewinski, MA Manji, R Mochon, AB Procop, GW Richter, SS Sercia, LF Westblade, LF Ferraro, MJ AF Branda, John A. Rychert, Jenna Burnham, Carey-Ann D. Bythrow, Maureen Garner, Omai B. Ginocchio, Christine C. Jennemann, Rebecca Lewinski, Michael A. Manji, Ryhana Mochon, A. Brian Procop, Gary W. Richter, Sandra S. Sercia, Linda F. Westblade, Lars F. Ferraro, Mary Jane TI Multicenter validation of the VITEK MS v2.0 MALDI-TOF mass spectrometry system for the identification of fastidious gram-negative bacteria SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE MALDI-TOF MS; Fastidious; Gram-negative bacilli; Identification; VITEK ID DESORPTION IONIZATION-TIME; NEISSERIA; CARD AB The VITEK MS v2.0 MALDI-TOF mass spectrometry system's performance in identifying fastidious gram-negative bacteria was evaluated in a multicenter study. Compared with the reference method (DNA sequencing), the VITEK MS system provided an accurate, species-level identification for 96% of 226 isolates; an additional 1% were accurately identified to the genus level. (C) 2014 Elsevier Inc. All rights reserved. C1 [Branda, John A.; Rychert, Jenna; Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Branda, John A.; Rychert, Jenna; Ferraro, Mary Jane] Harvard Univ, Sch Med, Boston, MA USA. [Jennemann, Rebecca; Westblade, Lars F.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Burnham, Carey-Ann D.; Westblade, Lars F.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Bythrow, Maureen; Ginocchio, Christine C.; Manji, Ryhana] Dept Pathol & Lab Med, North Shore LIJ Hlth Syst Labs, Lake Success, NY USA. [Ginocchio, Christine C.; Westblade, Lars F.] Hofstra North Shore LIJ Sch Med, Dept Pathol & Lab Med, Hempstead, NY USA. [Lewinski, Michael A.; Mochon, A. Brian] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Procop, Gary W.; Richter, Sandra S.; Sercia, Linda F.] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA. RP Branda, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM jbranda@partners.org OI Burnham, Carey-Ann/0000-0002-1137-840X FU bioMerieux, Inc; bioMerieux; Becton Dickinson; Alere Inc.; Diasorin, Inc.; Accler8; Cepheid; T2 Biosystems; Biofire; Biohelix; Nanosphere; Curetis; Luminex; Bruker; CDC; Forest Laboratories FX This study was performed as part of an FDA trial of the VITEK MS v2.0 system and was funded by the device manufacturer (bioMerieux, Inc). MJF, JAB, and JR have received research funding from bioMerieux and Becton Dickinson. JAB has received research funding from Alere Inc. and Diasorin, Inc. CAB has received research funding from bioMerieux, Accler8, Cepheid, and T2 Biosystems. CCG has received research funding and/or consulting fees from bioMerieux, Becton Dickinson, Biofire, Biohelix, Nanosphere, Curetis, and Luminex. GWP has received research funding from bioMerieux, Bruker, CDC, and Luminex. SSR has received research funding from bioMerieux, Nanosphere, and Forest Laboratories. The findings of this study were presented in abstract form at the 113th General Meeting of the American Society for Microbiology. NR 20 TC 11 Z9 11 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 EI 1879-0070 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD FEB PY 2014 VL 78 IS 2 BP 129 EP 131 DI 10.1016/j.diagmicrobio.2013.08.013 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 295XM UT WOS:000330149700005 PM 24321357 ER PT J AU Kramer, DB Kennedy, KF Spertus, JA Normand, SL Noseworthy, PA Buxton, AE Josephson, ME Zimetbaum, PJ Mitchell, SL Reynolds, MR AF Kramer, Daniel B. Kennedy, Kevin F. Spertus, John A. Normand, Sharon-Lise Noseworthy, Peter A. Buxton, Alfred E. Josephson, Mark E. Zimetbaum, Peter J. Mitchell, Susan L. Reynolds, Matthew R. TI Mortality risk following replacement implantable cardioverter-defibrillator implantation at end of battery life: Results from the NCDR (R) SO HEART RHYTHM LA English DT Article DE Implantable cardioverter-defibrillator; Outcomes research ID PRIMARY PREVENTION; CLINICAL-PRACTICE; PREDICTION; SURVIVAL; SCORE; RECIPIENTS; REGISTRY; THERAPY; BENEFIT; DEATH AB BACKGROUND Implantable cardioverter-defibrillator (ICD) generator replacement at the end of expected battery life accounts for a substantial proportion of all ICD implant procedures. However, little is known about the predictors of mortality following ICD generator replacement. OBJECTIVE The purpose of this study was to identify clinical and procedural factors associated with death following ICD generator replacement. METHODS Patients from the National Cardiovascular Data Registry (NCDR) ICD Registry receiving ICD generator replacements at the end of device battery life between January 1,2005, and March 30, 2010, were eligible. Predictors of mortality were determined using multivariable Cox regression. RESULTS Analysis of 111,826 patients (mean age 70.7 +/- 12.4, 75.5% male) revealed 1-, 3-, and 5-year mortality of 9.8%, 27.0%, and 41.2%, respectively. After adjustment, atrial fibrillation (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.20-1.27) and congestive heart failure (HR 1.21, 95% CI 1.16-1.27) predicted worse survival. In addition to older age (HR 1.43, 95% CI 1.41-1.45), several noncardiac conditions were also associated with poorer survival, including chronic lung disease (HR1.53, 95% CI 1.49-1.57), cerebrovascular disease (HR 1.28, 95% CI 1.24-1.32), diabetes (HR 1.27, 95% CI 1.23-1.30), and lower glomerular filtration rate (HR 1.15 for each 10-unit increment decline, 95% CI 1.14-1.16). In the absence of a non-ICD control group, risk reduction provided by ICD therapy in this cohort is not known. CONCLUSION In addition to age, atrial fibrillation, and congestive heart failure, noncardiac comorbidities are associated with higher mortality following ICD replacement, which should be considered in the decision to undergo this procedure. C1 [Kramer, Daniel B.; Buxton, Alfred E.; Josephson, Mark E.; Zimetbaum, Peter J.; Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kramer, Daniel B.; Normand, Sharon-Lise; Noseworthy, Peter A.; Buxton, Alfred E.; Josephson, Mark E.; Zimetbaum, Peter J.; Mitchell, Susan L.] Harvard Univ, Sch Med, Boston, MA USA. [Kramer, Daniel B.; Mitchell, Susan L.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Kennedy, Kevin F.; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Normand, Sharon-Lise] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Noseworthy, Peter A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reynolds, Matthew R.] Lahey Clin Med Ctr, Burlington, MA 01803 USA. RP Kramer, DB (reprint author), 1200 Ctr St, Boston, MA 02215 USA. EM danielkramer@hsl.harvard.edu FU John A. Hartford Foundation; Harvard Clinical and Translational Science Center; NIH-NIA [K24AG033640]; American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR); Medtronic FX Dr. Kramer is the Lois Green Scholar at the Hebrew SeniorLife Institute for Aging Research and is additionally supported by an award from the John A. Hartford Foundation and a career development award from the Harvard Clinical and Translational Science Center. Dr. Mitchell is supported by NIH-NIA K24AG033640. This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR). The views expressed in this manuscript represent those of the author(s) and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. ICD Registry is an initiative of the American College of Cardiology Foundation and the Heart Rhythm Society. Dr. Spertus reports a contract from the American College of Cardiology Foundation to provide analytic support for the National Cardiovascular Data Registry. Dr. Buxton has received honoraria from St. Jude Medical for serving on DSMB for a clinical trial (unrelated to ICDs); from Medtronic for speaking at educational symposia and serving on Events Committee for a clinical trial (not related to ICDs); and from Boston Scientific for serving on Events Committee for a clinical trial (not related to ICDs). Dr. Josephson has received honoraria from Medtronic for educational courses and small advisory input; and from Biotronik for educational courses. Dr. Reynolds has received research support and consulting income from Medtronic. NR 20 TC 20 Z9 20 U1 0 U2 6 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 FEB PY 2014 VL 11 IS 2 BP 216 EP 221 DI 10.1016/j.hrthm.2013.10.046 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296MR UT WOS:000330189700007 PM 24513917 ER PT J AU Lin, HH Dolmatova, EV Morley, MP Lunetta, KL McManus, DD Magnani, JW Margulies, KB Hakonarson, H del Monte, F Benjamin, EJ Cappola, TP Ellinor, PT AF Lin, Honghuang Dolmatova, Elena V. Morley, Michael P. Lunetta, Kathryn L. McManus, David D. Magnani, Jared W. Margulies, Kenneth B. Hakonarson, Hakon del Monte, Federica Benjamin, Emelia J. Cappola, Thomas P. Ellinor, Patrick T. TI Gene expression and genetic variation in human atria SO HEART RHYTHM LA English DT Article DE Genetics; Expression quantitative trait loci; Gene expression; Atrial tissue ID GENOME-WIDE ASSOCIATION; HEART-FAILURE; FIBRILLATION; DISEASE; OVEREXPRESSION; DYSFUNCTION; DISCOVERY; INTERVAL; BINDING; PROTEIN AB BACKGROUND The human left and right atria have different susceptibilities to develop atrial fibrillation (AF). However, the molecular events related to structural and functional changes that enhance AF susceptibility are still poorly understood. OBJECTIVE The purpose of this study was to characterize gene expression and genetic variation in human atria. METHODS We studied the gene expression profiles and genetic variations in 53 left atrial and 52 right atrial tissue samples collected from the Myocardial Applied Genomics Network (MAGNet) repository. The tissues were collected from heart failure patients undergoing transplantation and from unused organ donor hearts with normal ventricular function. Gene expression was profiled using the Affymetrix GeneChip Human Genome U133A Array. Genetic variation was profiled using the Affymetrix Genome-Wide Human SNP Array 6.0. RESULTS We found that 109 genes were differentially expressed between left and right atrial tissues. A total of 187 and 259 significant cis-associations between transcript levels and genetic variants were identified in left and right atrial tissues, respectively. We also found that a single nucleotide polymorphism at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right atrial tissues. CONCLUSION We found a distinct transcriptional profile between the right and left atrium and extensive cis-associations between atrial transcripts and common genetic variants. Our results implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF. C1 [Lin, Honghuang; Lunetta, Kathryn L.; McManus, David D.; Magnani, Jared W.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst & Boston Univ Framin, Framingham, MA USA. [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Epidemiol, Worcester, MA USA. [Morley, Michael P.; Margulies, Kenneth B.; Hakonarson, Hakon; Cappola, Thomas P.] Univ Penn, Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Dolmatova, Elena V.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [del Monte, Federica] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA. RP Lin, HH (reprint author), Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, 72 East Concord St,B-616, Boston, MA 02118 USA. EM hhlin@bu.edu OI Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health [R01HL092577, 1R01 HL102214, R01HL104156, K24HL105780, R01HL105993, KL2RR031981, 1U01HL105268-01]; American Heart Association [13EIA14220013, 09FTF2190028] FX This work is supported by National Institutes of Health Grant R01HL092577 to Drs. Ellinor and Benjamin, 1R01 HL102214 to Dr. Benjamin, R01HL104156 and K24HL105780 to Dr. Ellinor, R01HL105993 to Dr. Margulies and Cappola, and KL2RR031981 and 1U01HL105268-01 to Dr. McManus; and American Heart Association Award 13EIA14220013 to Dr. Ellinor and 09FTF2190028 to Dr. Magnani. NR 42 TC 12 Z9 12 U1 0 U2 11 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 FEB PY 2014 VL 11 IS 2 BP 266 EP 271 DI 10.1016/j.hrthm.2013.10.051 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296MR UT WOS:000330189700015 PM 24177373 ER PT J AU Hu, W Nevzorova, YA Haas, U Moro, N Sicinski, P Geng, Y Barbacid, M Trautwein, C Liedtke, C AF Hu, Wei Nevzorova, Yulia A. Haas, Ute Moro, Nives Sicinski, Piotr Geng, Yan Barbacid, Mariano Trautwein, Christian Liedtke, Christian TI Concurrent Deletion of Cyclin E1 and Cyclin-Dependent Kinase 2 in Hepatocytes Inhibits DNA Replication and Liver Regeneration in Mice SO HEPATOLOGY LA English DT Article ID MAMMALIAN-CELL-CYCLE; RE-REPLICATION; IN-VIVO; PROGRESSION; COMPLEXES; PHASE; CDK1; EXPRESSION; CHROMATIN; PROTEINS AB The liver has a strong regenerative capacity. After injury, quiescent hepatocytes can reenter the mitotic cell cycle to restore tissue homeostasis. This G(0)/G(1)-S cell-cycle transition of primed hepatocytes is regulated by complexes of cyclin-dependent kinase 2 (Cdk2) with E-type cyclins (CcnE1 or CcnE2). However, single genetic ablation of either E-cyclin or Cdk2 does not affect overall liver regeneration. Here, we systematically investigated the contribution of CcnE1, CcnE2, and Cdk2 for liver regeneration after partial hepatectomy (PH) by generating corresponding double- and triple-knockout (KO) mouse mutants. We demonstrate that conditional deletion of Cdk2 alone in hepatocytes resulted in accelerated induction of CcnE1, but otherwise normal initiation of S phase in vivo and in vitro. Excessive CcnE1 did not contribute to a noncanonical kinase activity, but was located at chromatin together with components of the pre-replication complex (pre-RC), such as the minichromosome maintenance (MCM) helicase. Concomitant ablation of Cdk2 and CcnE1 in hepatocytes caused a defect in pre-RC formation and further led to dramatically impaired S-phase progression by down-regulation of cyclin A2 and cell death in vitro and substantially reduced hepatocyte proliferation and liver regeneration after PH in vivo. Similarly, combined loss of CcnE1 and CcnE2, but also the Cdk2/CcnE1/CcnE2 triple KO in liver, significantly inhibited S-phase initiation and liver mass reconstitution after PH, whereas concomitant ablation of CcnE2 and Cdk2 had no effect. Conclusion: In the absence of Cdk2, CcnE1 performs crucial kinase-independent functions in hepatocytes, which are capable of driving MCM loading on chromatin, cyclin A2 expression, and S-phase progression. Thus, combined inactivation of Cdk2 and CcnE1 is the minimal requirement for blocking S-phase machinery in vivo. C1 [Hu, Wei; Nevzorova, Yulia A.; Haas, Ute; Moro, Nives; Trautwein, Christian; Liedtke, Christian] Rhein Westfal TH Aachen, Univ Hosp Aachen, Dept Med 3, Aachen, Germany. [Sicinski, Piotr; Geng, Yan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Sicinski, Piotr; Geng, Yan] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Barbacid, Mariano] CNIO, Madrid, Spain. RP Liedtke, C (reprint author), Rhein Westfal TH Aachen, Univ Hosp Aachen, Dept Med 3, Pauwelsstr 30, D-52074 Aachen, Germany. EM cliedtke@ukaachen.de FU Deutsche Forschungsgemeinschaft [LI1045/2-4]; European Research Council [ERC-AG/250297-RAS AHEAD] FX This work was supported by a grant of the Deutsche Forschungsgemeinschaft (LI1045/2-4; to C. T. and C. L.). M. B. was supported by a grant from the European Research Council (ERC-AG/250297-RAS AHEAD). NR 27 TC 11 Z9 13 U1 0 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2014 VL 59 IS 2 BP 651 EP 660 DI 10.1002/hep.26584 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298FT UT WOS:000330310300031 PM 23787781 ER PT J AU Zenobia, C Hasturk, H Nguyen, D Van Dyke, TE Kantarci, A Darveau, RP AF Zenobia, Camille Hasturk, Hatice Daniel Nguyen Van Dyke, Thomas E. Kantarci, Alpdogan Darveau, Richard P. TI Porphyromonas gingivalis Lipid A Phosphatase Activity Is Critical for Colonization and Increasing the Commensal Load in the Rabbit Ligature Model SO INFECTION AND IMMUNITY LA English DT Article ID SUBGINGIVAL PLAQUE; LIPOPOLYSACCHARIDE; BACTERIA; HOMEOSTASIS; ACTIVATION; PATHOGEN; INNATE AB Periodontitis is a disease of polymicrobial etiology characterized by inflammation, degradation of host tissue, and bone that irreversibly destroys the supporting apparatus of teeth. Porphyromonas gingivalis contains lipid A with structural heterogeneity that has been postulated to contribute to the initiation of dysbiosis in oral communities by modulating the host response, thereby creating a permissive environment for its growth. We examined two P. gingivalis lipid A phosphatase mutants which contain different "locked" lipid A structures that induce different host cellular responses for their ability to induce dysbiosis and periodontitis in rabbits. Lipopolysaccharide (LPS) preparations obtained from these strains were also examined. After repeated applications of all strains and their respective LPS preparations, P. gingivalis wild type, but not the lipid A mutants, had a significant impact on both the oral commensal microbial load and composition. In contrast, in rabbits exposed to the mutant strains or the LPS preparations, the microbial load did not increase, and yet significant changes in the oral microbial composition were observed. All strains and their respective LPS preparations induced periodontitis. Therefore, the ability to alter the lipid A composition in response to environmental conditions by lipid A phosphatases is required for both colonization of the rabbit and increases in the microbial load. Furthermore, the data demonstrate that multiple dysbiotic oral microbial communities can elicit periodontitis. C1 [Zenobia, Camille; Darveau, Richard P.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Hasturk, Hatice; Daniel Nguyen; Van Dyke, Thomas E.; Kantarci, Alpdogan] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA USA. [Darveau, Richard P.] Univ Washington, Dept Periodont, Seattle, WA 98195 USA. RP Darveau, RP (reprint author), Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. EM rdarveau@u.washington.edu FU U. S. Public Health Service [DE012768, DE020906, DE19938, DE15566]; National Institute of Dental and Craniofacial Research [DE18917] FX This study was supported in part by U. S. Public Health Service grants DE012768 (R.P.D.), DE020906 (A.K.), DE19938, DE15566 (T.E.V.D.), and DE18917 (H.H.) from the National Institute of Dental and Craniofacial Research. NR 22 TC 12 Z9 14 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 FEB PY 2014 VL 82 IS 2 BP 650 EP 659 DI 10.1128/IAI.01136-13 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 298XF UT WOS:000330357100018 PM 24478080 ER PT J AU Lourdault, K Wang, LC Vieira, A Matsunaga, J Melo, R Lewis, MS Haake, DA Gomes-Solecki, M AF Lourdault, Kristel Wang, Long-Chieh Vieira, Ana Matsunaga, James Melo, Rita Lewis, Michael S. Haake, David A. Gomes-Solecki, Maria TI Oral Immunization with Escherichia coli Expressing a Lipidated Form of LigA Protects Hamsters against Challenge with Leptospira interrogans Serovar Copenhageni SO INFECTION AND IMMUNITY LA English DT Article ID IMMUNOGLOBULIN-LIKE PROTEINS; BORRELIA-BURGDORFERI; LETHAL INFECTION; PATHOGENIC LEPTOSPIRA; OUTER-MEMBRANE; LYME-DISEASE; VACCINE; IMMUNITY; MODEL; SPIROCHETE AB Leptospirosis is a potentially fatal zoonosis transmitted by reservoir host animals that harbor leptospires in their renal tubules and shed the bacteria in their urine. Leptospira interrogans serovar Copenhageni transmitted from Rattus norvegicus to humans is the most prevalent cause of urban leptospirosis. We examined L. interrogans LigA, domains 7 to 13 (LigA7-13), as an oral vaccine delivered by Escherichia coli as a lipidated, membrane-associated protein. The efficacy of the vaccine was evaluated in a susceptible hamster model in terms of the humoral immune response and survival from leptospiral challenge. Four weeks of oral administration of live E. coli expressing LigA7-13 improved survival from intraperitoneal (i.p.) and intradermal (i.d.) challenge by L. interrogans serovar Copenhageni strain Fiocruz L1-130 in Golden Syrian hamsters. Immunization with E. coli expressing LigA7-13 resulted in a systemic antibody response, and a significant LigA7-13 IgG level after the first 2 weeks of immunization was completely predictive of survival 28 days after challenge. As in previous LigA vaccine studies, all immunized hamsters that survived infection had renal leptospiral colonization and histopathological changes. In summary, an oral LigA-based vaccine improved survival from leptospiral challenge by either the i.p. or i.d. route. C1 [Lourdault, Kristel; Wang, Long-Chieh; Matsunaga, James; Lewis, Michael S.; Haake, David A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lourdault, Kristel; Matsunaga, James; Haake, David A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. [Vieira, Ana; Melo, Rita; Gomes-Solecki, Maria] Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA. [Gomes-Solecki, Maria] Biopeptides Corp, Memphis, TN USA. RP Haake, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM dhaake@ucla.edu FU National Institutes of Health [R01 AI034431, R43 AI096551]; Centers for Disease Control and Prevention [UO1 CK000107]; VA Merit Research Funds FX This work was supported by grants R01 AI034431 (to D.A.H.) and R43 AI096551 (to M.G.- S.) from the National Institutes of Health, grant UO1 CK000107 (to M.G.- S.) from the Centers for Disease Control and Prevention, and VA Merit Research Funds (to J.M.and D.A.H.). NR 44 TC 13 Z9 13 U1 1 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 FEB PY 2014 VL 82 IS 2 BP 893 EP 902 DI 10.1128/IAI.01533-13 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 298XF UT WOS:000330357100040 PM 24478102 ER PT J AU Han, K Milosevic, M Fyles, A Viswanathan, AN AF Han, Kathy Milosevic, Michael Fyles, Anthony Viswanathan, Akila N. TI Trends in the utilization of brachytherapy in cervical cancer in the United States Reply SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 [Han, Kathy; Milosevic, Michael; Fyles, Anthony] Univ Hlth Network, Princess Margaret Hosp, Radiat Med Program, Toronto, ON, Canada. [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Han, K (reprint author), Univ Hlth Network, Princess Margaret Hosp, Radiat Med Program, Toronto, ON, Canada. NR 5 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2014 VL 88 IS 2 BP 460 EP 461 DI 10.1016/j.ijrobp.2013.10.026 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 296VO UT WOS:000330213700033 PM 24411615 ER PT J AU Mollica, RF Brooks, R Tor, S Lopes-Cardozo, B Silove, D AF Mollica, Richard F. Brooks, Robert Tor, Svang Lopes-Cardozo, Barbara Silove, Derrick TI The enduring mental health impact of mass violence: A community comparison study of Cambodian civilians living in Cambodia and Thailand SO INTERNATIONAL JOURNAL OF SOCIAL PSYCHIATRY LA English DT Article DE Genocide; structural equation modelling; traumatic experience; Cambodian mental health ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; HARVARD TRAUMA QUESTIONNAIRE; ADVERSE CHILDHOOD EXPERIENCES; HOPKINS SYMPTOM CHECKLIST-25; DSM-IV DISORDERS; SURVEY-REPLICATION; BOSNIAN REFUGEES; POSTCONFLICT SETTINGS; PSYCHOLOGICAL TRAUMA AB Background: No population-based studies have directly compared the long-term health and mental health outcomes of conflict- versus non-conflict-affected communities from the same ethnic background. Aims: To identify and compare levels of psychiatric morbidity between a traumatized and non-traumatized civilian community; to investigate the long-term impact of mass violence. Methods: Double-stratified community surveys in Siem Reap and Surin provinces were conducted by highly qualified Cambodian interviewers using culturally validated survey instruments with known psychometric properties. These included Cambodian versions of the Hopkins Symptom Checklist-25, the Harvard Trauma Questionnaire and the Medical Outcome Study Short Form. Results: Siem Reap and Surin respondents experienced 12,266 and 621 major trauma events, respectively; 745 (76.2%) Siem Reap respondents and six (0.6%) Surin respondents reported torture events; 499 (49.5%) Siem Reap respondents and 203 (19.7%) Surin respondents met the clinical threshold for depression (OR 4.01, 95% CI 3.29-4.88); 204 (20.6%) Siem Reap respondents and 23 (2.2%) Surin respondents met the clinical threshold for post-traumatic stress disorder (PTSD) (OR 11.39, 95% CI 7.3-17.7). The MOS physical disability was higher in Siem Reap versus Surin respondents (74 (7.5%) vs 13 (1.3%), (2) = 47.4 df = 1, p < .001). Health status was poorest among Siem Reap respondents when compared with Surin respondents (mean score 1.59 vs 0.59, respectively; t = 19.85 df = 2018, p < .001). Path analysis reveals that recent and past extreme violence are associated with the health and mental health status of the Siem Reap community. Conclusion: After 25 years, the Khmer civilian population that experienced the Pol Pot genocide continues to suffer psychiatric morbidity and poor health. C1 [Mollica, Richard F.; Tor, Svang] Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Dept Psychiat, Cambridge, MA USA. [Brooks, Robert] Australian Aboriginal & Torres Strait Islander He, Kingston, Tas, Australia. [Lopes-Cardozo, Barbara] Ctr Dis Control & Prevent, Atlanta, GA USA. [Silove, Derrick] Univ New S Wales, Psychiat Res & Teaching Unit, Sydney, NSW 2052, Australia. RP Mollica, RF (reprint author), Harvard Program Refugee Trauma, 22 Putnam Ave, Cambridge, MA 02139 USA. EM rmollica@partners.org FU Intramural CDC HHS [CC999999] NR 77 TC 16 Z9 16 U1 3 U2 14 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0020-7640 EI 1741-2854 J9 INT J SOC PSYCHIATR JI Int. J. Soc. Psychiatr. PD FEB PY 2014 VL 60 IS 1 BP 6 EP 20 DI 10.1177/0020764012471597 PG 15 WC Psychiatry SC Psychiatry GA 294CJ UT WOS:000330019700002 PM 23396287 ER PT J AU Bradbury, AR Patrick-Miller, L Egleston, B Schwartz, L Tuchman, L Moore, CW Rauch, P Daly, M AF Bradbury, Angela R. Patrick-Miller, Linda Egleston, Brian Schwartz, Lisa Tuchman, Lisa Moore, Cynthia Wilson Rauch, Paula Daly, Mary TI PERCEPTIONS OF BREAST CANCER RISK, PSYCHOLOGICAL ADJUSTMENT AND BEHAVIORS IN ADOLESCENT GIRLS AT HIGH-RISK AND POPULATION-RISK FOR BREAST CANCER SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 [Bradbury, Angela R.] Univ Penn, Philadelphia, PA 19104 USA. [Patrick-Miller, Linda] Univ Chicago, Chicago, IL 60637 USA. [Egleston, Brian; Daly, Mary] Fox Chase Canc Ctr, Philadelphia, PA USA. [Schwartz, Lisa] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Tuchman, Lisa] Childrens Natl Med Ctr, Washington, DC USA. [Moore, Cynthia Wilson; Rauch, Paula] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2014 VL 54 IS 2 SU S MA 167 BP S87 EP S87 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 298EV UT WOS:000330307800168 ER PT J AU McCauley, HL Silverman, J Broyles, LM Decker, MR Tancredi, D Zelazny, S Miller, E AF McCauley, Heather L. Silverman, Jay Broyles, Lauren M. Decker, Michele R. Tancredi, Daniel Zelazny, Sarah Miller, Elizabeth TI SUBSTANCE USE, INTIMATE PARTNER VIOLENCE AND SEXUAL ASSAULT AMONG ADOLESCENT AND YOUNG ADULT FEMALE FAMILY PLANNING CLIENTS SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 [McCauley, Heather L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Silverman, Jay; Tancredi, Daniel] Univ Calif San Diego, San Diego, CA 92103 USA. [Broyles, Lauren M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Decker, Michele R.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Zelazny, Sarah; Miller, Elizabeth] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. RI Miller, Elizabeth/E-7939-2012 NR 0 TC 1 Z9 1 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2014 VL 54 IS 2 SU S MA 13 BP S7 EP S8 PG 2 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 298EV UT WOS:000330307800014 ER PT J AU Heist, RS Wang, XF Hodgson, L Otterson, GA Stinchcombe, TE Gandhi, L Villalona-Calero, MA Watson, P Vokes, EE Socinski, MA AF Heist, Rebecca S. Wang, Xiaofei Hodgson, Lydia Otterson, Gregory A. Stinchcombe, Thomas E. Gandhi, Leena Villalona-Calero, Miguel A. Watson, Peter Vokes, Everett E. Socinski, Mark A. CA Alliance Clinical Trials Oncology TI CALGB 30704 (Alliance) A Randomized Phase II Study to Assess the Efficacy of Pemetrexed or Sunitinib or Pemetrexed Plus Sunitinib in the Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE CALGB 30704; Lung cancer ID CELL LUNG-CANCER; FUSIONS; RET; ADENOCARCINOMA; BEVACIZUMAB; CARBOPLATIN; PACLITAXEL; TRIAL; ALK AB Background: Second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) improves survival modestly but new strategies are needed. This trial was designed to evaluate an antivascular endothelial growth factor strategy with or without standard chemotherapy in previously treated NSCLC. Methods: Patients with stage IIIB/IV NSCLC with performance status 0 to 1 progressive after first-line chemotherapy were eligible for randomization to pemetrexed, sunitinib, or the combination. Patients were stratified by performance status, stage, and sex. Primary objective was 18-week progression-free survival (PFS) rate; secondary objectives included response, overall survival (OS), and toxicity. Target accrual was 225. The study was terminated early because of decreasing accrual rates. Results: Between April 2008 and September 2011, 130 patients were registered and randomized; of this, 125 patients were treated. Baseline characteristics in the three arms were well balanced. Toxicity was higher in the sunitinib-containing arms. The 18-week PFS rate in the pemetrexed, sunitinib, and combination arms was 54% (95% confidence interval [CI], 40-71), 37% (95% CI, 25-54), and 48% (95% CI, 35-66), respectively (p = 0.25). Median PFS in the pemetrexed, sunitinib, and combination arms in months was 4.9 (2.1-8.8), 3.3 (2.3-4.2), and 3.7 (2.5-5.8), respectively (p = 0.18). There was an overall statistically significant difference in OS between the three arms: median OS in months was 10.5 (8.3-20.2) for pemetrexed, 8.0 (6.8-13.5) for sunitinib, and 6.7 (4.1-10.1) for the combination (p = 0.03). Conclusion: Pemetrexed had a superior toxicity profile to either sunitinib or the combination of pemetrexed and sunitinib. The 18-week PFS rate was not significantly different between the arms. OS was significantly better with pemetrexed alone compared with the two sunitinib-containing arms, with the doublet performing worst for OS. C1 [Heist, Rebecca S.] Massachusetts Gen Hosp, Dept Thorac Oncol, Boston, MA 02114 USA. [Wang, Xiaofei; Hodgson, Lydia] Duke Univ, Dept Oncol, Alliance Stat & Data Ctr, Med Ctr, Durham, NC USA. [Otterson, Gregory A.; Villalona-Calero, Miguel A.] Ohio State Univ, Med Ctr, Dept Oncol, Columbus, OH 43210 USA. [Stinchcombe, Thomas E.] Univ N Carolina, Dept Oncol, Chapel Hill, NC USA. [Gandhi, Leena] Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. [Watson, Peter] Kinston Med Specialists PA, Dept Oncol, Kinston, NC USA. [Vokes, Everett E.] Univ Chicago, Dept Oncol, Chicago, IL 60637 USA. [Socinski, Mark A.] Univ Pittsburgh, Med Ctr, Dept Oncol, Pittsburgh, PA USA. RP Heist, RS (reprint author), Massachusetts Gen Hosp, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM rheist@partners.org OI Gandhi, Leena/0000-0002-2398-9179 FU National Cancer Institute [CA31946]; [CA71323]; [CA45418]; [CA32291]; [CA29165]; [CA114558]; [CA77597]; [CA114558-02]; [CA45564]; [CA11789]; [CA86726]; [CA45808]; [CA77658]; [CA21060]; [CA41287]; [CA47642]; [CA16450]; [CA12046]; [CA77298]; [CA47559]; [CA77406]; [CA047559]; [CA032291] FX The research for CALGB 30704 (Alliance) was supported, in part, by grants from the National Cancer Institute (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chair) and to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD, CA33601). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.; Baptist Cancer Institute CCOP, TN, Lee S. Schwartzberg, MD, supported by CA71323; Christiana Care Health Services, Inc., CCOP, Wilmington, DE, Stephen Grubbs, MD, supported by CA45418; Dana-Farber Cancer Institute, Boston, MA, Harold J. Burstein, MD, PhD, supported by CA32291; Greenville CCOP, Cancer Centers of the Carolinas, Greenville, SC, Jeffrey K. Giguere, MD, supported by CA29165; Heartland Cancer Research CCOP, St. Louis, MO, Alan P. Lyss, MD, supported by CA114558 (Missouri Baptist); Massachusetts General Hospital, Boston, MA, Jeffrey W. Clark, MD, supported by CA32291; Georgetown University Medical Center, Washington, DC, Bruce Cheson, MD, supported by CA77597; Missouri Baptist Medical Center, St. Louis, MO, Alan P. Lyss, MD, supported by CA114558-02; Missouri Valley Consortium CCOP, Omaha, NE, Gamini S. Soori, MD; Mount Sinai Medical Center, Miami, FL, Michael A. Schwartz, MD, supported by CA45564; University of California at San Diego, San Diego, CA, Barbara A. Parker, MD, supported by CA11789; New Hampshire - Oncology-Hematology PA, Concord, NH, Douglas J. Weckstein, MD; Northern Indiana Cancer Research Consortium CCOP, South Bend, IN, Rafat Ansari, MD, supported by CA86726; Southeast Cancer Control Consortium Inc., CCOP, Goldsboro, NC, James N. Atkins, MD, supported by CA45808; The Ohio State University Medical Center, Columbus, OH, Clara D. Bloomfield, MD, supported by CA77658; State University of New York Upstate Medical University, Syracuse, NY, Stephen L. Graziano, MD, supported by CA21060; University of Chicago, Chicago, IL, Hedy L. Kindler, MD, supported by CA41287; University of Iowa, Iowa City, IA, Daniel A. Vaena, MD, supported by CA47642; University of Minnesota, Minneapolis, MN, Bruce A. Peterson, MD, supported by CA16450; University of Missouri/Ellis Fischel Cancer Center, Columbia, MO, Karl E. Freter, MD, supported by CA12046; University of Nebraska Medical Center, Omaha, NE, Apar Ganti, MD, supported by CA77298; University of North Carolina at Chapel Hill, Chapel Hill, NC, Thomas C. Shea, MD, supported by CA47559; University of Vermont, Burlington, VT, Steven M. Grunberg, MD, supported by CA77406; Kinston Medical Specialists, P. A., Kinston, North Carolina; - supported by CA047559; Dana-Farber Cancer Institute, Boston, Massachusetts; supported by CA032291. NR 18 TC 24 Z9 24 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD FEB PY 2014 VL 9 IS 2 BP 214 EP 221 DI 10.1097/JTO.0000000000000071 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 294WH UT WOS:000330078100019 PM 24419419 ER PT J AU de Figueiredo-Pontes, LL Wong, DWS Tin, VPC Chung, LP Yasuda, H Yamaguchi, N Nakayama, S Janne, PA Wong, MP Kobayashi, SS Costa, DB AF de Figueiredo-Pontes, Lorena Lobo Wong, Daisy Wing-Sze Tin, Vicky Pui-Chi Chung, Lap-Ping Yasuda, Hiroyuki Yamaguchi, Norihiro Nakayama, Sohei Jaenne, Pasi Antero Wong, Maria Pik Kobayashi, Susumu Soeda Costa, Daniel Botelho TI Identification and Characterization of ALK Kinase Splicing Isoforms in Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Non-small-cell lung cancer; Tyrosine kinase; Kinase inhibitor; Anaplastic lymphoma kinase; Crizotinib; Alternative splicing; Exon skipping; Exon 27; Exon 23 ID ANAPLASTIC LYMPHOMA KINASE; EML4-ALK FUSION GENE; INHIBITOR CRIZOTINIB; GENOMIC ALTERATIONS; RESISTANCE; NEUROBLASTOMA; MUTATION; EGFR; KIF5B-ALK; ONCOGENE AB Introduction: Anaplastic lymphoma kinase (ALK) rearrangements are present in an important subset of non-small-cell lung cancer (NSCLC) and predict for response to the tyrosine kinase inhibitor crizotinib. In this study, we evaluated the yet unknown frequency and functional role of ALK splicing isoforms in NSCLC. Methods: We analyzed 270 cases of NSCLC for ALK kinase domain splicing aberrations and in addition generated constructs with full-length echinoderm microtubule-associated protein-like 4 (EML4)-ALK (E13;A20) and a splicing isoform. Results: Splicing isoforms of the kinase domain of ALKincluding complete skipping of exon 23 (ALKdel23, ALK p.I1171fs*42) and exon 27 (ALKdel27, ALK p.T1312fs*0)were identified in 11.1% (30 of 270 cases) of NSCLC, and these changes coexisted with ALK rearrangements, KRAS mutations, and EGFR mutations. ALK splicing isoforms were observed with full-length EML4-ALK in crizotinib-naive and treated NSCLCs. ALK T1312fs*0 was unable to render cells solely dependent on ALK signaling. Unlike EML4-ALK and EML4-ALK p.L1196M, EML4-ALK T1312fs*0 did not autophosphorylate ALK or other phosphotyrosine sites. Coexpression of equal amounts of EML4-ALK T1312fs*0 and EML4-ALK did not result in resistance to crizotinib, whereas coexpression of EML4-ALK L1196M with EML4-ALK resulted in resistance to inhibition of ALK by crizotinib. Conclusions:ALK kinase splicing isoforms were present in NSCLC and even if translated seemed to be nonfunctional variants of ALK. C1 [de Figueiredo-Pontes, Lorena Lobo; Yasuda, Hiroyuki; Yamaguchi, Norihiro; Nakayama, Sohei; Kobayashi, Susumu Soeda; Costa, Daniel Botelho] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Wong, Daisy Wing-Sze; Tin, Vicky Pui-Chi; Chung, Lap-Ping; Wong, Maria Pik] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Jaenne, Pasi Antero] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Costa, DB (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM mwpik@hku.hk; skobayas@bidmc.harvard.edu; dbcosta@bidmc.harvard.edu RI Figueiredo-Pontes, Lorena/K-6520-2013; OI Costa, Daniel/0000-0002-0689-395X FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [237730/2012-0]; Pfizer; Roche; AstraZeneca; Boehringer Ingelheim; Sanofi Aventis; Chugai; National Institutes of Health [CA136851, CA090578]; University of Hong Kong [CRCG 104002074]; United Against Lung Cancer; American Cancer Society RSG [11-186]; American Society of Clinical Oncology Conquer Cancer Foundation; [CA126026]; [CA169259] FX Dr. de Figueiredo-Pontes was funded in part through fellowships from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (no. 237730/2012-0). Dr. Janne has received consulting fees from Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Sanofi Aventis, and Chugai. He received grants CA136851 and CA090578 (from the National Institutes of Health). Dr. Wong received support from the University of Hong Kong (CRCG 104002074). Dr. Kobayashi received grants CA126026 and CA169259 and support from the United Against Lung Cancer. Dr. Costa has received consulting fees from Pfizer, Roche, and AstraZeneca. He received grant from American Cancer Society RSG 11-186 and was supported by the American Society of Clinical Oncology Conquer Cancer Foundation and the National Institutes of Health (CA090578). All other authors declare no conflict of interest. NR 29 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD FEB PY 2014 VL 9 IS 2 BP 248 EP 253 DI 10.1097/JTO.0000000000000050 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 294WH UT WOS:000330078100023 PM 24419423 ER PT J AU Fang, R Zheng, C Sun, YH Han, XK Gao, B Li, CG Liu, HY Wong, KK Liu, XY Chen, HQ Ji, HB AF Fang, Rong Zheng, Chao Sun, Yihua Han, Xiangkun Gao, Bin Li, Chenguang Liu, Hongyan Wong, Kwok-Kin Liu, Xin-Yuan Chen, Haiquan Ji, Hongbin TI Integrative Genomic Analysis Reveals a High Frequency of LKB1 Genetic Alteration in Chinese Lung Adenocarcinomas SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Liver kinase B1; Lung cancer; Multiplex ligation-dependent probe amplification ID PEUTZ-JEGHERS-SYNDROME; CANCER PATIENTS; MUTATIONS; SPECTRUM; LKB1/STK11 AB Liver kinase B1 (LKB1) genetic alteration in lung cancer involves not only point mutations and small deletion of several base pairs but also exonic loss. However, most of recent studies in LKB1 gene status only focus on point mutations and small deletion, and thus may underestimate the actual frequency of LKB1 genetic alteration in lung cancer. Thus, an integrative analysis of LKB1 genetic alteration is timely and important for providing a better estimate for the incidence of genetic alterations in this important tumor suppressor gene. One hundred and seven lung adenocarcinomas with more than 70% tumor have been analyzed for mutation of LKB1 as well as LKB1 large deletions detection by using multiplex ligation-dependent probe amplification analysis. These samples were also analyzed for EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET status in stepwise method. Among 107 lung adenocarcinomas analyzed, 29 (27.1%) harbored LKB1 genetic alteration. Twenty-three (21.5%) harbored LKB1 large exonic deletions and eight (7.48%) had LKB1 points mutations, two samples harbored both LKB1 large exonic deletions and point mutations. Eighty-seven samples (81.31%) harbored known driver mutations and 20 samples (18.69%) had no identifiable driver mutations. A high rate of LKB1 genetic alteration in Chinese lung adenocarcinomas is revealed by the integrative analysis of point mutation and exonic deletion. Moreover, LKB1 genetic alterations are concurrent with EGFR, KRAS, HER2, and CD74-ROS fusions. C1 [Fang, Rong] Ningbo Univ, Sch Med, Zhejiang Prov Key Lab Pathophysiol, Ningbo 315211, Zhejiang, Peoples R China. [Zheng, Chao; Han, Xiangkun; Gao, Bin; Liu, Hongyan; Liu, Xin-Yuan; Ji, Hongbin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China. [Sun, Yihua; Li, Chenguang; Chen, Haiquan] Fudan Univ, Shanghai Canc Ctr, Dept Thorac Surg, Shanghai 200433, Peoples R China. [Sun, Yihua; Li, Chenguang; Chen, Haiquan] Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China. [Sun, Yihua; Li, Chenguang; Chen, Haiquan] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wong, Kwok-Kin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ji, HB (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China. EM hbji@sibcb.ac.cn OI wong, kwok kin/0000-0001-6323-235X FU National Basic Research Program of China [2012CB910800, 2010CB912102]; National Natural Science Foundation of China [81101583, 81372509, 31370747, 30971461]; Science and Technology Commission of Shanghai Municipality [12JC1409800]; SA-SIBS scholarship program FX This work was supported by the National Basic Research Program of China (2012CB910800 and 2010CB912102), the National Natural Science Foundation of China (81101583, 81372509, 31370747 and 30971461), the Science and Technology Commission of Shanghai Municipality (12JC1409800), the SA-SIBS scholarship program (HL and HJ). NR 16 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD FEB PY 2014 VL 9 IS 2 BP 254 EP 258 DI 10.1097/JTO.0000000000000056 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 294WH UT WOS:000330078100024 PM 24419424 ER PT J AU Patel, VI Mukhopadhyay, S Guest, JM Conrad, MF Watkins, MT Kwolek, CJ LaMuraglia, GM Cambria, RP AF Patel, Virendra I. Mukhopadhyay, Shankha Guest, Julie M. Conrad, Mark F. Watkins, Michael T. Kwolek, Christopher J. LaMuraglia, Glenn M. Cambria, Richard P. TI Impact of severe chronic kidney disease on outcomes of infrainguinal peripheral arterial intervention SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 21-23, 2012 CL Boston, MA SP New England Soc Vasc Surg ID EXTREMITY BYPASS-SURGERY; CRITICAL LIMB ISCHEMIA; STAGE RENAL-DISEASE; PREVENT-III; REVASCULARIZATION; ANGIOPLASTY; MULTICENTER; STRATIFICATION; THERAPY; FAILURE AB Objective: Patients with severe chronic kidney disease (CKD) and peripheral vascular disease are at increased risk of major adverse limb events (MALEs) and death; however, patients with end-stage renal disease have been excluded in current objective performance goals. We evaluated the effect of severe (class 4 and 5) CKD on outcomes after infrainguinal endovascular arterial interventions. Methods: All primary peripheral vascular interventions (PVIs) performed at a single institution (January 2002 through December 2009) were included. End points were defined by Society for Vascular Surgery objective performance goals for critical limb ischemia (CLI), which include all-cause mortality, reintervention, and composite end points of death or amputation and MALEs (reintervention or amputation). Univariate and multivariable analysis was used to examine the effect of severe CKD on study end points. Results: A total of 879 PVIs were performed, with severe CKD in 125 (14%). Severe CKD patients were significantly (P < .05) more likely to have diabetes (64% vs 46%), CLI (72% vs 11%), and need a multilevel PVI (34% vs 19%) or tibial intervention (35% vs 20%) compared with the remainder of the cohort. Distribution of TransAtlantic Inter-Society Consensus C and D lesions were similar (19% severe CKD vs 15%; P = .2). Severe CKD predicted perioperative (30-day) reintervention (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.5-4; P = .05), amputation or death (OR, 3.1; 95% CI, 1.1-9; P = .04), and MALEs (OR, 2.8; 95% CI, 1.3-6.1; P = .04), which was independent of CLI in multivariable regression analysis. On Kaplan-Meier analysis, severe CKD was significantly (log-rank P < .05) associated with death (31% +/- 4% vs 7% +/- 1%), amputation (14% +/- 3% vs 3% +/- 1%), and MALEs (40% +/- 5% vs 26% +/- 2%) at 1 year. Freedom from reintervention was similar at 1 year (70% +/- 5% severe CKD vs 75% +/- 2%; P = .23). Risk-adjusted (age, CLI, diabetes, coronary artery disease) Cox proportional hazards regression showed that severe CKD increased the risk of late mortality (hazard ratio [HR], 2.4; 95% CI, 1.8-3.2; P < .01), amputation (HR, 2.1; 95% CI, 1.1-3.9; P = .02), and death or amputation (HR, 1.8; 95% CI, 1.3-2.4; P = .04), without increasing the risk of late reinterventions or MALEs. Conclusions: CKD independently predicts early and late adverse events after a PVI, in particular, excessive mortality. CKD should figure prominently in clinical decision making for patients with peripheral vascular disease. C1 [Patel, Virendra I.; Mukhopadhyay, Shankha; Guest, Julie M.; Conrad, Mark F.; Watkins, Michael T.; Kwolek, Christopher J.; LaMuraglia, Glenn M.; Cambria, Richard P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA. RP Patel, VI (reprint author), Massachusetts Gen Hosp, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM vpatel4@partners.org NR 26 TC 18 Z9 18 U1 1 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 FEB PY 2014 VL 59 IS 2 BP 368 EP 375 DI 10.1016/j.jvs.2013.09.006 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 295QA UT WOS:000330129400016 PM 24176634 ER PT J AU Matos, JM Barshes, NR Mccoy, S Pisimisis, G Felkai, D Kougias, P Lin, PH Bechara, CF AF Matos, Jesus M. Barshes, Neal R. Mccoy, Sally Pisimisis, George Felkai, Deborah Kougias, Panos Lin, Peter H. Bechara, Carlos F. TI Validating common carotid stenosis by duplex ultrasound with carotid angiogram or computed tomography scan SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 29-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg ID RADIATION-THERAPY; NECK RADIATION AB Background: No consensus exists for duplex ultrasound criteria in the diagnosis of significant common carotid artery (CCA) stenosis. In general, peak systolic velocity (PSV) >150 cm/s with poststenotic turbulence indicates a stenosis >50%. The purpose of our study is to correlate CCA duplex velocities with angiographic findings of significant stenosis >60%. Methods: We reviewed the carotid duplex records from 2008 to 2011 looking for patients with isolated CCA stenosis and no ipsilateral internal or contralateral carotid artery disease who received either a carotid angiogram or a computed tomography scan. We identified 25 patients who had significant CCA disease >60%. We also selected 74 controls without known CCA stenosis. We performed receiver operating characteristics analysis to correlate PSV and end-diastolic velocity (EDV) with angiographic stenosis >60%. The degree of stenosis was determined by measuring the luminal stenosis in comparison to the proximal normal CCA diameter. Results: Most patients had a carotid angiogram (21/25), four only had a computed tomography angiography and four had both. Eighteen patients had history of neck radiation. The CCA PSV >= 250 cm/s had a sensitivity of 98.7% (81.5%-100%) and a specificity of 95.7% (92.0%-99.9%), CCA PSV >= 300 cm/s had a sensitivity of 90.9% (69.4%-98.4%) and a specificity of 98.7% (92.0%-99.9%). The CCA EDV >= 40 cm/s had a sensitivity of 95.5% (95% confidence interval of 75.1-99.8%) and specificity of 98.7% (92.0%-99.9%), EDV >= 60 cm/s had a sensitivity of 100% (75.1%-99.8%) and specificity of 87% (94.1-100%), and EDV >= 70 cm/s had a sensitivity of 86.4% (64.0%-96.4%) and specificity of 100% (94.1%-100%). The presence of both PSV <250 cm/s and EDV <60 cm/s had a 98.7% negative predictive value, and the presence of both PSV >= 250 cm/s and EDV >= 60 cm/s had 100% positive predictive value. Conclusions: Establishing CCA duplex criteria to screen patients with significant stenosis is crucial to identify those who will need further imaging modality or treatment. In our laboratory, CCA PSV >= 250 cm/s and EDV >= 60 cm/s are thresholds that can be used to identify significant (>60%) CCA stenosis with a high degree of accuracy. C1 [Matos, Jesus M.; Barshes, Neal R.; Pisimisis, George; Kougias, Panos; Lin, Peter H.; Bechara, Carlos F.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc & Endovasc Therapy, Houston, TX 77030 USA. [Barshes, Neal R.; Mccoy, Sally; Pisimisis, George; Felkai, Deborah; Kougias, Panos; Bechara, Carlos F.] Michael E DeBakey VA Med Ctr, Houston, TX USA. RP Bechara, CF (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, 2002 Holcombe Blvd 112, Houston, TX 77030 USA. EM bechara@bcm.edu NR 19 TC 4 Z9 5 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2014 VL 59 IS 2 BP 435 EP 439 DI 10.1016/j.jvs.2013.08.030 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 295QA UT WOS:000330129400024 PM 24080127 ER PT J AU Aebi, S Gelber, S Anderson, SJ Lang, I Robidoux, A Martin, M Nortier, JWR Paterson, AHG Rimawi, MF Canada, JMB Thurlimann, B Murray, E Mamounas, EP Geyer, CE Price, KN Coates, AS Gelber, RD Rastogi, P Wolmark, N Wapnir, IL AF Aebi, Stefan Gelber, Shari Anderson, Stewart J. Lang, Istvan Robidoux, Andre Martin, Miguel Nortier, Johan W. R. Paterson, Alexander H. G. Rimawi, Mothaffar F. Canada, Jose Manuel Baena Thuerlimann, Beat Murray, Elizabeth Mamounas, Eleftherios P. Geyer, Charles E., Jr. Price, Karen N. Coates, Alan S. Gelber, Richard D. Rastogi, Priya Wolmark, Norman Wapnir, Irene L. CA CALOR Investigators TI Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial SO LANCET ONCOLOGY LA English DT Article ID SURGICAL ADJUVANT BREAST; TUMOR RECURRENCE; RADIATION-THERAPY; RECEPTOR CONVERSION; CONSERVING SURGERY; LOCAL RECURRENCE; METASTASES; PROGNOSIS; MASTECTOMY; TAMOXIFEN AB Background Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. Methods The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1: 1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. Findings From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4.9 years (IQR 3.6-6.0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0.59 [95% CI 0.35-0.99]; p=0.046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (p(interaction)=0.046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (p(interaction)=0.43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. Interpretation Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. C1 [Aebi, Stefan] Luzerner Kantonsspital, CH-6000 Paris 16, France. [Aebi, Stefan] Univ Bern, Bern, Switzerland. [Aebi, Stefan; Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Gelber, Shari; Price, Karen N.; Gelber, Richard D.] Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gelber, Shari; Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Anderson, Stewart J.] Univ Pittsburgh, Dept Biostat, Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr,Dept Biostat,Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Rastogi, Priya] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Robidoux, Andre] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Martin, Miguel] Univ Complutense, Inst Invest Sanitaria Gregorio Maranon, E-28040 Madrid, Spain. [Nortier, Johan W. R.] Leids Univ, Ctr Med, Leiden, Netherlands. [Paterson, Alexander H. G.] Tom Baker Canc Clin, Calgary, AB, Canada. [Rimawi, Mothaffar F.] Baylor Coll Med, Houston, TX 77030 USA. [Canada, Jose Manuel Baena] Hosp Puerta Del Mar, Cadiz, Spain. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Murray, Elizabeth] Univ Cape Town, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Mamounas, Eleftherios P.] MD Anderson Canc Ctr, Orlando, FL USA. [Geyer, Charles E., Jr.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. [Wapnir, Irene L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Aebi, S (reprint author), Luzerner Kantonsspital, CH-6000 Paris 16, France. EM stefan.aebi@onkologie.ch RI Aebi, Stefan/F-2004-2010; OI Aebi, Stefan/0000-0002-3383-9449; MARTIN, MIGUEL/0000-0001-9237-3231; Anderson, Stewart/0000-0001-8948-0650 FU US Department of Health and Human Services [U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651, U10-CA-75362]; US Department of Health and Human Services; Swiss Group for Clinical Cancer Research (SAKK); Frontier Science and Technology Research Foundation; Australian and New Zealand Breast Cancer Trials Group; Swedish Cancer Society; Oncosuisse; Cancer Association of South Africa; Foundation for Clinical Research of Eastern Switzerland (OSKK); Grupo Espanol de Investigacion en Cancer de Mama (GEICAM); Dutch Breast Cancer Trialists' Group (BOOG) FX US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Espanol de Investigacion en Cancer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG). NR 28 TC 45 Z9 45 U1 3 U2 15 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 FEB PY 2014 VL 15 IS 2 BP 156 EP 163 DI 10.1016/S1470-2045(13)70589-8 PG 8 WC Oncology SC Oncology GA 297AY UT WOS:000330228700028 PM 24439313 ER PT J AU Haining, WN AF Haining, W. Nicholas TI Strength in numbers: comparing vaccine signatures the modular way SO NATURE IMMUNOLOGY LA English DT News Item ID YELLOW-FEVER VACCINE; SYSTEMS BIOLOGY; RESPONSES; HUMANS AB Gene-expression signatures of the human vaccine response can be complex and noisy. Li et al. develop a new collection of gene-expression modules and use it to compare the response to five different vaccines. C1 [Haining, W. Nicholas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Boston, MA USA. [Haining, W. Nicholas] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Haining, WN (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu NR 14 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 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2014 VL 15 IS 2 BP 139 EP 141 PG 3 WC Immunology SC Immunology GA 295XV UT WOS:000330150600007 PM 24448573 ER PT J AU De Nardo, D Labzin, LI Kono, H Seki, R Schmidt, SV Beyer, M Xu, DK Zimmer, S Lahrmann, C Schildberg, FA Vogelhuber, J Kraut, M Ulas, T Kerksiek, A Krebs, W Bode, N Grebe, A Fitzgerald, ML Hernandez, NJ Williams, BRG Knolle, P Kneilling, M Rocken, M Lutjohann, D Wright, SD Schultze, JL Latz, E AF De Nardo, Dominic Labzin, Larisa I. Kono, Hajime Seki, Reiko Schmidt, Susanne V. Beyer, Marc Xu, Dakang Zimmer, Sebastian Lahrmann, Catharina Schildberg, Frank A. Vogelhuber, Johanna Kraut, Michael Ulas, Thomas Kerksiek, Anja Krebs, Wolfgang Bode, Niklas Grebe, Alena Fitzgerald, Michael L. Hernandez, Nicholas J. Williams, Bryan R. G. Knolle, Percy Kneilling, Manfred Roecken, Martin Luetjohann, Dieter Wright, Samuel D. Schultze, Joachim L. Latz, Eicke TI High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3 SO NATURE IMMUNOLOGY LA English DT Article ID INFLAMMATORY RESPONSE; LIPID RAFTS; ATHEROSCLEROSIS; CHOLESTEROL; MICE; HDL; ACTIVATION; VIVO; TOLL-LIKE-RECEPTOR-4; RECOGNITION AB High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies. C1 [De Nardo, Dominic; Labzin, Larisa I.; Vogelhuber, Johanna; Grebe, Alena; Latz, Eicke] Univ Bonn, Univ Hosp, Inst Innate Immun, Biomed Ctr, Bonn, Germany. [Kono, Hajime] Teikyo Univ, Sch Med, Dept Internal Med, Tokyo 173, Japan. [Seki, Reiko] Teikyo Univ, Fac Med Technol, Dept Clin Lab Sci, Tokyo 173, Japan. [Schmidt, Susanne V.; Beyer, Marc; Kraut, Michael; Ulas, Thomas; Krebs, Wolfgang; Schultze, Joachim L.] Univ Bonn, Life & Med Sci Inst, Bonn, Germany. [Xu, Dakang; Williams, Bryan R. G.] Monash Univ, Monash Inst Med Res, Melbourne, Vic 3004, Australia. [Xu, Dakang] Hangzhou Normal Univ, Sch Med, Inst Ageing Res, Hangzhou, Zhejiang, Peoples R China. [Zimmer, Sebastian; Lahrmann, Catharina; Bode, Niklas] Univ Bonn, Dept Med Cardiol, Bonn, Germany. [Schildberg, Frank A.; Knolle, Percy] Univ Bonn, Inst Mol Med, Bonn, Germany. [Schildberg, Frank A.; Knolle, Percy] Univ Bonn, Inst Expt Immunol, Bonn, Germany. [Kerksiek, Anja] Univ Bonn, Inst Clin Chem & Clin Pharmacol, Bonn, Germany. [Fitzgerald, Michael L.; Hernandez, Nicholas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA USA. [Knolle, Percy] Tech Univ Munich, Inst Mol Immunol, D-80290 Munich, Germany. [Kneilling, Manfred; Roecken, Martin] Univ Tubingen, Dept Dermatol, Tubingen, Germany. [Kneilling, Manfred] Univ Tubingen, Werner Siemens Imaging Ctr, Dept Preclin Imaging & Radiopharm, Tubingen, Germany. [Wright, Samuel D.] CSL Ltd, Cardiovasc Therapeut, Parkville, Vic, Australia. [Latz, Eicke] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA. [Latz, Eicke] German Ctr Neurodegenerat Dis, Bonn, Germany. RP Latz, E (reprint author), Univ Bonn, Univ Hosp, Inst Innate Immun, Biomed Ctr, Bonn, Germany. EM eicke.latz@uni-bonn.de RI Williams, Bryan/A-5021-2009; Schultze, Joachim/D-7794-2011; OI Williams, Bryan/0000-0002-4969-1151; Schultze, Joachim/0000-0003-2812-9853; Labzin, Larisa/0000-0001-9098-4493; Knolle, Percy A./0000-0003-2983-0414; De Nardo, Dominic/0000-0002-7045-4695 FU US National Institutes of Health [1R01HL093262, 1R01HL112661]; German Research foundation [SFB670, SFB685]; Excellence Cluster ImmunoSensation; Australian National Health and Medical Research Council [1006588]; Operational Infrastructure Support Program (Victoria state Government, Australia); Naito Foundation (Japan); Ministry of Health, Labour and Welfare; Ministry of Education, Culture, Sports, Science and Technology of Japan FX We acknowledge C. Thiele (University of Bonn) for helpful discussions and J.-C. Hernandez (University of Medellin) for help with experiments. We thank C.M. De Nardo for critical reading of the manuscript. We thank T. Hai (Ohio State University) for the original Atf3-deficient mice. The work was funded by grants from US National Institutes of Health (1R01HL093262 to E.L., and 1R01HL112661 to E.L. and M.L.F.), the German Research foundation (SFB670 to E.L., SFB685 to M.Kn. and M.R.), the Excellence Cluster ImmunoSensation to E.L. and J.L.S., the Australian National Health and Medical Research Council (1006588), the Operational Infrastructure Support Program (Victoria state Government, Australia) to B.R.G.W. and D.X., and the Naito Foundation (Japan) and the Ministry of Health, Labour and Welfare and Grant-in-Aid for Scientific Research on Innovative Areas for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to H.K. E.L. is a member of the Center for Molecular Inflammation Research at the Norwegian University of Science and Technology. NR 42 TC 86 Z9 86 U1 4 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2014 VL 15 IS 2 BP 152 EP 160 DI 10.1038/ni.2784 PG 9 WC Immunology SC Immunology GA 295XV UT WOS:000330150600009 PM 24317040 ER PT J AU Weissleder, R Nahrendorf, M Pittet, MJ AF Weissleder, Ralph Nahrendorf, Matthias Pittet, Mikael J. TI Imaging macrophages with nanoparticles SO NATURE MATERIALS LA English DT Review ID SUPERPARAMAGNETIC IRON-OXIDE; TUMOR-ASSOCIATED MACROPHAGES; ACUTE MYOCARDIAL-INFARCTION; LYMPH-NODE METASTASES; CARDIOVASCULAR MAGNETIC-RESONANCE; IN-VIVO MRI; CONTRAST AGENT; COMPUTED-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUES; LABELED NANOPARTICLES AB Nanomaterials have much to offer, not only in deciphering innate immune cell biology and tracking cells, but also in advancing personalized clinical care by providing diagnostic and prognostic information, quantifying treatment efficacy and designing better therapeutics. This Review presents different types of nanomaterial, their biological properties and their applications for imaging macrophages in human diseases, including cancer, atherosclerosis, myocardial infarction, aortic aneurysm, diabetes and other conditions. We anticipate that future needs will include the development of nanomaterials that are specific for immune cell subsets and can be used as imaging surrogates for nanotherapeutics. New in vivo imaging clinical tools for noninvasive macrophage quantification are thus ultimately expected to become relevant to predicting patients' clinical outcome, defining treatment options and monitoring responses to therapy. C1 [Weissleder, Ralph; Nahrendorf, Matthias; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Weissleder, Ralph; Nahrendorf, Matthias; Pittet, Mikael J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institutes of Health through the National Cancer Institute Centers of Cancer Nanotechnology Excellence consortia; National Heart Lung and Blood Institute Program of Excellence in Nanotechnology consortia FX We would like to thank the National Institutes of Health for supporting this research through the National Cancer Institute Centers of Cancer Nanotechnology Excellence consortia and the National Heart Lung and Blood Institute Program of Excellence in Nanotechnology consortia. We especially would like to thank our collaborators and members of Chemical Safety Board for many helpful discussions. NR 182 TC 180 Z9 180 U1 44 U2 329 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1476-1122 EI 1476-4660 J9 NAT MATER JI Nat. Mater. PD FEB PY 2014 VL 13 IS 2 BP 125 EP 138 DI 10.1038/nmat3780 PG 14 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA 296KB UT WOS:000330182700018 PM 24452356 ER PT J AU Lai, PS Hang, JQ Zhang, FY Lin, XY Zheng, BY Dai, HL Su, L Cai, TX Christiani, DC AF Lai, Peggy S. Hang, Jing Qing Zhang, Feng Ying Lin, Xinyi Zheng, Bu Yong Dai, Hei Lian Su, Li Cai, Tianxi Christiani, David C. TI Gender differences in the effect of occupational endotoxin exposure on impaired lung function and death: the Shanghai Textile Worker Study SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID COTTON DUST; BACTERIAL-ENDOTOXIN; FOLLOW-UP; MORTALITY; DISEASE; STANDARDIZATION; RESPONSES; OUTCOMES; CHINESE; ASTHMA AB Objective Airborne endotoxin exposure has adverse and protective health effects. Studies show men have augmented acute inflammatory responses to endotoxin. In this longitudinal cohort study we investigated the effect of long-term exposure to endotoxin in cotton dust on health, and determined whether these effects differ by gender. Methods In the Shanghai Textile Worker Study, 447 cotton and 472 control silk textile workers were followed from 1981 to 2011 with repeated measures of occupational endotoxin exposure, spirometry and health questionnaires. Impaired lung function was defined as a decline in forced expiratory volume in one second to less than the 5th centile of population predicted. Death was ascertained by death registries. We used Cox proportional hazards models to assess the effect of endotoxin exposure on the time to development of impaired lung function and death. Results 128 deaths and 164 diagnoses of impaired lung function were ascertained between 1981 and 2011. HRs for the composite end point of impaired lung function or death was 1.47 (95% Cl 1.09 to 1.97) for cotton vs silk workers and 1.04 (95% Cl 1.01 to 1.07) per 10 000 endotoxin units (EU)/m(3)-years increase in exposure. HRs for all-cause mortality was 1.36 (95% Cl 0.93 to 1.99) for cotton vs silk workers and 1.04 (95% Cl 0.99 to 1.08) per 10 000 EU/m(3)-years. The risk associated with occupational endotoxin exposure was elevated only in men. Conclusions Occupational endotoxin exposure is associated with an increase in the risk of impaired lung function and all-cause mortality in men. C1 [Lai, Peggy S.; Christiani, David C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Lai, Peggy S.; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hang, Jing Qing; Zhang, Feng Ying; Zheng, Bu Yong; Dai, Hei Lian] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Lin, Xinyi; Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Lai, PS (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. EM lai.peggy.s@gmail.com OI Lai, Peggy/0000-0001-9501-8606 FU National Institutes of Health (NIH) [ES00002, F32 ES020082, K23ES023700]; National Institute for Occupational Safety and Health (NIOSH) [OH002421] FX This study was supported by National Institutes of Health (NIH) grants ES00002, F32 ES020082, K23ES023700, and National Institute for Occupational Safety and Health (NIOSH) grant OH002421. NR 47 TC 5 Z9 5 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD FEB PY 2014 VL 71 IS 2 BP 118 EP 125 DI 10.1136/oemed-2013-101676 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 295HV UT WOS:000330108100009 PM 24297825 ER PT J AU Pedersen, CG Jensen, SOW Gradus, J Johnsen, SP Mainz, J AF Pedersen, Charlotte Gjorup Jensen, Signe Olrik Wallenstein Gradus, Jaimie Johnsen, Soren Paaske Mainz, Jan TI Systematic Suicide Risk Assessment for Patients With Schizophrenia: A National Population-Based Study SO PSYCHIATRIC SERVICES LA English DT Article ID PRACTICE GUIDELINES; 1ST EPISODE; CARE; DEPRESSION; ADHERENCE; PSYCHOSIS; REGISTER AB Objectives: Systematic suicide risk assessment is recommended for patients with schizophrenia; however, little is known about the implementation of suicide risk assessment in routine clinical practice. The study aimed to determine the use of systematic suicide risk assessment at discharge and predictors of suicide attempt among hospitalized patients with schizophrenia in Denmark. Methods: A one-year follow-up study was conducted of 9,745 patients with schizophrenia who were discharged from psychiatric wards and registered in a national population-based schizophrenia registry between 2005 and 2009. Results: The proportion of patients receiving suicide risk assessment at discharge from a psychiatric ward increased from 72% (95% confidence interval [CI]=71%-74%) in 2005, when the national monitoring began, to 89% (CI.89%-90%) in 2009. Within one year after discharge, 1% of all registered patients had died by suicide and 8% had attempted suicide. One out of three patients who died by suicide had no documented suicide risk assessment before discharge. Conclusions: The use of systematic suicide risk assessment at discharge among patients with schizophrenia increased in Denmark between 2005 and 2009, in accordance with recommendations in national clinical guidelines and monitoring in a national clinical registry. Additional efforts are warranted to ensure a lower risk of suicidal behavior after hospital discharge. C1 [Pedersen, Charlotte Gjorup; Jensen, Signe Olrik Wallenstein] Aalborg Psychiat Hosp, Unit Psychiat Res, Aalborg, Denmark. [Gradus, Jaimie] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Johnsen, Soren Paaske] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. [Mainz, Jan] Aalborg Univ Hosp, Odense, Denmark. [Mainz, Jan] Univ Southern Denmark, Odense, Denmark. RP Pedersen, CG (reprint author), Aalborg Psychiat Hosp, Unit Psychiat Res, Aalborg, Denmark. EM chargo@gmail.com OI Gradus, Jaimie/0000-0003-1459-5327 NR 27 TC 7 Z9 8 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD FEB PY 2014 VL 65 IS 2 BP 226 EP 231 DI 10.1176/appi.ps.201200021 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 297LR UT WOS:000330257400015 PM 24178133 ER PT J AU Hazlett, EA Lamade, RV Graff, FS McClure, MM Kolaitis, JC Goldstein, KE Siever, LJ Godbold, JH Moshier, E AF Hazlett, Erin A. Lamade, Raina V. Graff, Fiona S. McClure, Margaret M. Kolaitis, Jeanine C. Goldstein, Kim E. Siever, Larry J. Godbold, James H. Moshier, Erin TI Visual-spatial working memory performance and temporal gray matter volume predict schizotypal personality disorder group membership SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizotypal; Prefrontal cortex; Temporal lobe volume; Neurocognition; Working memory; Dot Test; CVLT; PASAT; Diagnostic classification ID UNMEDICATED SCHIZOPHRENIA-PATIENTS; PREFRONTAL CORTEX; NEUROPSYCHOLOGICAL PERFORMANCE; MENTAL-DISORDERS; CONTINUED EVIDENCE; NEGATIVE SYMPTOMS; GYRUS VOLUME; SPECTRUM; MRI; DEFICITS AB Background: Prior work shows individuals with schizotypal personality disorder (SPD) evince temporal lobe volume abnormalities similar to schizophrenia but sparing of prefrontal cortex, which may mitigate psychosis and the severe neurocognitive impairments observed in schizophrenia. This study examined the extent to which frontal-temporal gray matter volume and neurocognitive performance predict: (1) SPD group membership in a demographically-balanced sample of 51 patients and 37 healthy controls; and (2) symptom severity in SPD. Methods: Dimensional gray-matter volume (left frontal-temporal regions (Brodmann area (BA) 10, 21, 22)) and neurocognitive performance on key memory tasks (California Verbal Learning Test (CVLT), Dot Test, Paced Auditory Serial Addition Test (PASAT)), all salient to schizophrenia-spectrum disorders were examined in a multi-variable model. Results: Middle temporal gyrus (BA21) volume and spatial-working memory (Dot Test) performance were significant predictors of SPD group membership likelihood, with poorer working-memory performance indicating increased probability of SPD membership. Combining across regional volumes or cognitive measures resulted in fair-to-good discrimination of group membership, but including neurocognitive and non-collinear regional volume measures together resulted in a receiver-operating-characteristic (ROC) curve with improved diagnostic discrimination. Larger BA10 volume in dorsolateral prefrontal cortex (DLPFC) significantly predicted less symptom severity in SPD. Conclusions: These findings suggest that temporal lobe volume and spatial-working memory performance are promising biological/phenotype markers for likelihood of SPD classification, while greater DLPFC volume may serve as a protective factor. Published by Elsevier B.V. C1 [Hazlett, Erin A.; Lamade, Raina V.; Graff, Fiona S.; McClure, Margaret M.; Kolaitis, Jeanine C.; Goldstein, Kim E.; Siever, Larry J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Siever, Larry J.] James J Peter Vet Affairs Med Ctr, Dept Outpatient Psychiat, Bronx, NY USA. [Hazlett, Erin A.; Lamade, Raina V.; Graff, Fiona S.; McClure, Margaret M.; Siever, Larry J.] James J Peter Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN 3, Bronx, NY USA. [Hazlett, Erin A.; Kolaitis, Jeanine C.] James J Peter Vet Affairs Med Ctr, Bronx, NY USA. [Godbold, James H.; Moshier, Erin] Icahn Sch Med Mt Sinai, Dept Biostat, New York, NY USA. RP Hazlett, EA (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN 3, 130 West Kingsbridge Rd,Rm 6A-45, Bronx, NY 10468 USA. EM erin.hazlett@mssm.edu FU VA MERIT grant [I01 CX000261]; Department of Veterans Affairs VISN3 Mental Illness Research, Education, and Clinical Center (MIRECC) at the James J. Peters VA Medical Center FX Support for this work came from a VA MERIT grant (I01 CX000261) to E.A.H. and the Department of Veterans Affairs VISN3 Mental Illness Research, Education, and Clinical Center (MIRECC) at the James J. Peters VA Medical Center. NR 80 TC 5 Z9 5 U1 1 U2 7 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 FEB PY 2014 VL 152 IS 2-3 BP 350 EP 357 DI 10.1016/j.schres.2013.12.006 PG 8 WC Psychiatry SC Psychiatry GA 296MF UT WOS:000330188500005 PM 24398009 ER PT J AU Swerdlow, NR Light, GA Sprock, J Calkins, ME Green, MF Greenwood, TA Gur, RE Gur, RC Lazzeroni, LC Nuechterlein, KH Radant, AD Ray, A Seidman, LJ Siever, LJ Silverman, JM Stone, WS Sugar, CA Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL AF Swerdlow, Neal R. Light, Gregory A. Sprock, Joyce Calkins, Monica E. Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Nuechterlein, Keith H. Radant, Allen D. Ray, Amrita Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Sugar, Catherine A. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. TI Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS SO SCHIZOPHRENIA RESEARCH LA English DT Review DE Endophenotype; Genetics; Multi-site; Prepulse inhibition; Schizophrenia; Startle ID ACOUSTIC STARTLE RESPONSE; SENSORIMOTOR GATING DEFICITS; 1ST-EPISODE SCHIZOPHRENIA; ANTIPSYCHOTIC-NAIVE; JAPANESE PATIENTS; REFLEX; HABITUATION; MEDICATION; PSYCHOSIS; CONSORTIUM AB Background: Startle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site "COGS-2" study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data. Methods: Eyeblink startle was measured in carefully screened HCS and schizophrenia patients (n = 1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures. Results: 884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p = 0.0005) and sex (p < 0.002), and a significant diagnosis x test site interaction. HCS > schizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures. Discussion: The COGS-2multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia "endophenotype" of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses. (C) 2013 Elsevier B.V. All rights reserved. C1 [Swerdlow, Neal R.; Light, Gregory A.; Sprock, Joyce; Greenwood, Tiffany A.; Tsuang, Ming T.; Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Green, Michael F.; Nuechterlein, Keith H.; Sugar, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lazzeroni, Laura C.; Ray, Amrita] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Lazzeroni, Laura C.; Ray, Amrita] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Light, Gregory A.; Sprock, Joyce; Sugar, Catherine A.; Braff, David L.] VA San Diego Healthcare Syst, MIRECC, VISN 22, San Diego, CA USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Swerdlow, NR (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM nswerdlow@ucsd.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Sprock, Joyce/0000-0003-0225-9422; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU National Institute of Mental Health [R01-MH065571, R01-MH065588, R01-MH065562, R01-MH065707, R01-MH065554, R01-MH065578, R01-MH065558, R01 MH86135, K01-MH087889]; National Institutes of Health [HHSN268200782096C] FX This study was supported by grants R01-MH065571, R01-MH065588, R01-MH065562, R01-MH065707, R01-MH065554, R01-MH065578, R01-MH065558, R01 MH86135, and K01-MH087889 from the National Institute of Mental Health. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract Number HHSN268200782096C. NR 69 TC 27 Z9 28 U1 1 U2 11 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 FEB PY 2014 VL 152 IS 2-3 BP 503 EP 512 DI 10.1016/j.schres.2013.12.004 PG 10 WC Psychiatry SC Psychiatry GA 296MF UT WOS:000330188500026 PM 24405980 ER PT J AU Jain, RK AF Jain, Rakesh K. TI An Indirect Way to Tame Cancer SO SCIENTIFIC AMERICAN LA English DT Article C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. NR 0 TC 13 Z9 14 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD FEB PY 2014 VL 310 IS 2 BP 46 EP 53 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296SK UT WOS:000330205500031 PM 24640331 ER PT J AU Depauw, N Dias, MF Rosenfeld, A Seco, JC AF Depauw, Nicolas Dias, Marta F. Rosenfeld, Anatoly Seco, Joao C. TI Ion Radiography as a Tool for Patient Set-up & Image Guided Particle Therapy: A Monte Carlo Study SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article ID PROTON COMPUTED-TOMOGRAPHY; SIMULATIONS; RESOLUTION; DENSITY; KV AB This study investigate the use of ion radiography as a tool for patient set-up and tumor tracking capabilities for image guided particle therapy (IGPT) using Monte Carlo simulations. One pediatric, two lung and one liver cancer patients were considered in this study. For each patient, 230 and 330 MeV proton, and 500 MeV/nucleon carbon ion pencil beams were simulated through their computed tomography (CT) data set using GEANT4.9.0. Energy, position and direction cosines of each particle were recorded in front and behind the patient. Ion radiographs were subsequently reconstructed using a dedicated in-house software. The image quality was assessed by evaluating the contrast-to-noise ratio of the tumor and its surrounding tissue. In the lung and liver cases, each CT phase of the breathing cycle was treated individually and dynamic sequences were later produced to appreciate tumor motion. Reconstructed radiographs show high spatial resolution. This allows for excellent imaging capabilities in pediatric patients, comparable to X-ray imaging at a fraction of the imaging dose. There is clear visualization of the tumor edges in the lung due to the great contrast-to-noise ratio between the tumor and its surrounding tissues; tumor motion is observed and comparable to 4D CT data thus allowing for on-line tumor tracking during ion radiotherapy. Conversely, tumor edge detection is difficult in liver, and fiducial markers are required to attempt indirect tumor tracking for IGPT. Ion radiographs with high spatial resolution can be generated using the PR-creator software resulting in pediatric patient set-up capabilities at a fraction of the current imaging dose, as well as the capacity to track moving targets in order to achieve IGPT. C1 [Depauw, Nicolas; Seco, Joao C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Depauw, Nicolas; Rosenfeld, Anatoly] Univ Wollongong UoW, Ctr Med Radiat Phys, Wollongong, NSW 2522, Australia. [Dias, Marta F.] Univ Lisbon, Fac Sci, Inst Biophys & Biomed Engn, P-1749016 Lisbon, Portugal. RP Depauw, N (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, 55 Fruit St, Boston, MA 02114 USA. EM ndepauw@partners.org RI Rosenfeld, Anatoly/D-1989-2014 NR 16 TC 4 Z9 4 U1 2 U2 6 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 EI 1533-0338 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD FEB PY 2014 VL 13 IS 1 BP 69 EP 76 DI 10.7785/tcrt.2012.500357 PG 8 WC Oncology SC Oncology GA 295VH UT WOS:000330143900008 PM 23819498 ER PT J AU Breyer, BN Cohen, BE Bertenthal, D Rosen, RC Neylan, TC Seal, KH AF Breyer, Benjamin N. Cohen, Beth E. Bertenthal, Daniel Rosen, Raymond C. Neylan, Thomas C. Seal, Karen H. TI Lower Urinary Tract Dysfunction in Male Iraq and Afghanistan War Veterans: Association With Mental Health Disorders: A Population-based Cohort Study SO UROLOGY LA English DT Article ID QUALITY-OF-LIFE; CORTICOTROPIN-RELEASING-FACTOR; OVERACTIVE BLADDER; UNITED-STATES; BACH SURVEY; DEPRESSIVE SYMPTOMS; UROLOGICAL SYMPTOMS; PREVALENCE; WOMEN; INCONTINENCE AB OBJECTIVE To determine the prevalence and correlates of lower urinary tract symptoms (LUTS) among returned Iraq and Afghanistan veterans; in particular its association with mental health diagnoses and medication use. METHODS We performed a retrospective cohort study of Iraq and Afghanistan veterans who were new users of U. S. Department of Veterans Affairs health care. Mental health diagnoses were defined by International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) codes from medical records. LUTS was defined by ICD-9-CM code, use of prescription medication for LUTS, or procedure for LUTS. We determined the independent association of mental health diagnoses and LUTS after adjusting for sociodemographic and military service characteristics, comorbidities, and medications. RESULTS Of 519,189 veterans, 88% were men and the mean age was 31.8 years (standard deviation +/- 9.3). The overall prevalence of LUTS was 2.2% (11,237/519,189). Veterans with post-traumatic stress disorder (PTSD) were significantly more likely to have a LUTS diagnosis, prescription, or related procedure (3.5%) compared with veterans with no mental health diagnoses (1.3%) or a mental health diagnosis other than PTSD (3.1%, P < .001). In adjusted models, LUTS was significantly more common in veterans with PTSD with and without other mental health disorders vs those without mental health disorders (adjusted relative risk [ARR] - 2.04, 95% confidence interval [CI] 1.94-2.15) and in veterans prescribed opioids (ARR = 2.46, 95% CI = 2.36-2.56). CONCLUSION In this study of young returned veterans, mental health diagnoses and prescription for opioids were independently associated with increased risk of receiving a diagnosis, treatment, or procedure for LUTS. Provider awareness may improve the detection and treatment of LUTS, and improve patient care and quality of life. (C) 2014 Published by Elsevier Inc. C1 [Breyer, Benjamin N.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. New England Res Inst, Watertown, MA 02172 USA. RP Breyer, BN (reprint author), Univ Calif San Francisco, Dept Urol, 400 Parnassus Ave,A610, San Francisco, CA 94143 USA. EM bbreyer@urology.ucsf.edu FU National Institute for Health (NIH) [K12DK083021]; Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration FX This research was supported, in part, by grants from the National Institute for Health (NIH) grant K12DK083021 (BNB), the Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration (DB), the Department of Veterans Affairs (VA) Health Services Research and Development (HSR&D) Research Enhancement Award Program at the San Francisco VA Medical Center (KHS), and an NIH/NHLBI grant K23 HL 094765-01 (BEC). This manuscript is the result of work supported with resources and the use of facilities at the Veterans Administration Medical Center, San Francisco, California. NR 30 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD FEB PY 2014 VL 83 IS 2 BP 312 EP 319 DI 10.1016/j.urology.2013.08.047 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 296ZF UT WOS:000330223600018 PM 24149111 ER PT J AU Eisner, BH AF Eisner, Brian H. TI EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. 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 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD FEB PY 2014 VL 83 IS 2 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 296ZF UT WOS:000330223600080 ER PT J AU Vaananen, RM Lilja, H Kauko, L Helo, P Kekki, H Cronin, AM Vickers, AJ Nurmi, M Alanen, K Bjartell, A Pettersson, K AF Vaananen, Riina-Minna Lilja, Hans Kauko, Leni Helo, Pauliina Kekki, Henna Cronin, Angel M. Vickers, Andrew J. Nurmi, Martti Alanen, Kalle Bjartell, Anders Pettersson, Kim TI Cancer-associated Changes in the Expression of TMPRSS2-ERG, PCA3, and SPINK1 in Histologically Benign Tissue From Cancerous vs Noncancerous Prostatectomy Specimens SO UROLOGY LA English DT Article ID MESSENGER-RNAS; GENE; FUSION; HYBRIDIZATION; QUANTIFICATION; PROGNOSIS; DIAGNOSIS; URINE; ASSAY; DD3 AB OBJECTIVE To investigate whether messenger ribonucleic acid (mRNA) expression of TMPRSS2-ERG fusion gene, a suggested prostate cancer (PCa) biomarker, was specific to cancerous lesions alone and to study the expression of SPINK1 and PCA3 mRNAs in the same cohort to also explore the proposed mutual exclusivity of TMPRSS2-ERG and SPINK1 expression. METHODS Levels of 2 TMPRSS2-ERG transcripts, PCA3, and SPINK1 mRNAs were measured with highly standardized reverse transcription quantitative polymerase chain reaction assays in cystoprostatectomy specimens from 19 patients with invasive bladder cancer and 174 radical prostatectomy (RP) samples (88 histologically benign prostate [HBP] tissues and 86 from cancerous lesions) from 87 patients with clinically localized PCa. RESULTS Expression of TMPRSS2-ERG transcripts was detected in 45 of 88 (51%) HBP tissues from RP specimens and more frequently (57 of 86, 66%) found in cancerous lesions. In contrast, TMPRSS2-ERG expression was detected in only 2 of 19 (11%) cystoprostatectomy specimens, both with incidental PCa foci elsewhere in the gland. Similar trends of changes in the expression of PCA3 and SPINK1 were present in HBP tissue from RP compared with cystoprostatectomy specimens. CONCLUSION Although the expression of TMPRSS2-ERG, SPINK1, and PCA3 mRNA is higher or more frequently found in cancerous lesions, HBP tissues from patients with clinically localized PCa manifest molecular, mRNA level changes that are absent in cystoprostatectomy specimens lacking incidental PCa foci or infrequent in cystoprostatectomy specimens containing incidental PCa. If this finding is replicated, these molecular assays could be used to inform men with negative biopsy results about the likelihood of cancerous lesions in unsampled regions and hence the need for repeat biopsy. UROLOGY 83: 511.e1e511.e7, 2014. (C) 2014 Elsevier Inc. C1 [Vaananen, Riina-Minna] Univ Turku, Dept Biotechnol, FIN-20520 Turku, Finland. Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Urol Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med GU Oncol, New York, NY 10021 USA. Univ Oxford, Nuffield Dept Surg Sci, Oxford, England. Univ Tampere, Inst Biomed Technol, FIN-33101 Tampere, Finland. Lund Univ, Skane Univ Hosp, Dept Lab Med, Malmo, Sweden. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Turku Univ Hosp, Dept Surg, FIN-20520 Turku, Finland. Turku Univ Hosp, Dept Pathol, FIN-20520 Turku, Finland. Lund Univ, Dept Clin Sci, Div Urol Canc, Skane Univ Hosp, Malmo, Sweden. RP Vaananen, RM (reprint author), Univ Turku, Dept Biotechnol, Tykistokatu 6A 6th Floor, FIN-20520 Turku, Finland. EM riina-minna.vaananen@utu.fi OI Lilja, Hans/0000-0001-5871-7846; Vickers, Andrew/0000-0003-1525-6503 FU Academy of Finland [206690]; European Union 6th Framework [LSHC-CT-2004-503011]; National Cancer Institute [R33 CA 127768-03, R01 CA160816-02, P50-CA92629]; Swedish Cancer Society [11-0624]; Sidney Kimmel Center for Prostate and Urologic Cancers; Prostate Cancer Foundation; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford; Fundacion Federico SA FX This work was supported by the Academy of Finland (Project 206690), the European Union 6th Framework contract LSHC-CT-2004-503011 (P-Mark), the National Cancer Institute (R33 CA 127768-03, R01 CA160816-02, P50-CA92629), the Swedish Cancer Society (11-0624), the Sidney Kimmel Center for Prostate and Urologic Cancers, David H Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford, and Fundacion Federico SA. NR 29 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 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD FEB PY 2014 VL 83 IS 2 DI 10.1016/j.urology.2013.11.005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 296ZF UT WOS:000330223600082 ER PT J AU Polydoro, M Dzhala, VI Pooler, AM Nicholls, SB McKinney, AP Sanchez, L Pitstick, R Carlson, GA Staley, KJ Spires-Jones, TL Hyman, BT AF Polydoro, Manuela Dzhala, Volodymyr I. Pooler, Amy M. Nicholls, Samantha B. McKinney, A. Patrick Sanchez, Laura Pitstick, Rose Carlson, George A. Staley, Kevin J. Spires-Jones, Tara L. Hyman, Bradley T. TI Soluble pathological tau in the entorhinal cortex leads to presynaptic deficits in an early Alzheimer's disease model SO ACTA NEUROPATHOLOGICA LA English DT Article DE Tau; Arc induction; Synaptic dysfunction; Alzheimer's disease ID PAIRED-PULSE FACILITATION; READILY RELEASABLE POOL; LONG-TERM POTENTIATION; MOSSY FIBER SYNAPSES; NULL MUTANT MICE; MONOCLONAL-ANTIBODY; RAT HIPPOCAMPUS; MOUSE MODEL; POSTTETANIC POTENTIATION; SYNAPTIC PLASTICITY AB Neurofibrillary tangles (NFTs), a hallmark of Alzheimer's disease, are intracellular silver and thioflavin S-staining aggregates that emerge from earlier accumulation of phospho-tau in the soma. Whether soluble misfolded but nonfibrillar tau disrupts neuronal function is unclear. Here we investigate if soluble pathological tau, specifically directed to the entorhinal cortex (EC), can cause behavioral or synaptic deficits. We studied rTgTauEC transgenic mice, in which P301L mutant human tau overexpressed primarily in the EC leads to the development of tau pathology, but only rare NFT at 16 months of age. We show that the early tau lesions are associated with nearly normal performance in contextual fear conditioning, a hippocampal-related behavior task, but more robust changes in neuronal system activation as marked by Arc induction and clear electrophysiological defects in perforant pathway synaptic plasticity. Electrophysiological changes were likely due to a presynaptic deficit and changes in probability of neurotransmitter release. The data presented here support the hypothesis that misfolded and hyperphosphorylated tau can impair neuronal function within the entorhinal-hippocampal network, even prior to frank NFT formation and overt neurodegeneration. C1 [Polydoro, Manuela; Dzhala, Volodymyr I.; Pooler, Amy M.; Nicholls, Samantha B.; Sanchez, Laura; Staley, Kevin J.; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Pooler, Amy M.] Kings Coll London, Inst Psychiat, Dept Neurosci, London SE5 8AF, England. [McKinney, A. Patrick] Harvard NeuroDiscovery Ctr, NeuroBehav Lab Core, Boston, MA 02115 USA. [Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT 59405 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 114 16th St Room 2009, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Spires-Jones, Tara/0000-0003-2530-0598 FU National Institutes of Health [R00AG033670, R21AG03885, R01AG026249-07, 5T32AG00022222]; American Health Assistance Foundation; Glenn Foundation; Alzheimer's Association Zenith Award [ZEN-09-132524]; Alzheimer's Research UK; Harvard NeuroDiscovery Center FX This work was supported by National Institutes of Health grants: R00AG033670, R21AG03885, R01AG026249-07, 5T32AG00022222, American Health Assistance Foundation, the Glenn Foundation, The Alzheimer's Association Zenith Award ZEN-09-132524, Alzheimer's Research UK, and a portion of the behavioral work was supported by the Harvard NeuroDiscovery Center. We thank Mark Mayford for providing neuropsin-tTA mice, and Peter Davies for providing tau antibodies. NR 63 TC 21 Z9 21 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD FEB PY 2014 VL 127 IS 2 BP 257 EP 270 DI 10.1007/s00401-013-1215-5 PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 293SD UT WOS:000329993100008 PM 24271788 ER PT J AU Schopfer, DW Ku, IA Regan, M Whooley, MA AF Schopfer, David W. Ku, Ivy A. Regan, Mathilda Whooley, Mary A. TI Growth differentiation factor 15 and cardiovascular events in patients with stable ischemic heart disease (The Heart and Soul Study) SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROME; RISK STRATIFICATION; MYOCARDIAL-INFARCTION; PROGNOSTIC UTILITY; FAILURE; RECLASSIFICATION; INDIVIDUALS; PREDICTION; BIOMARKERS; SEVERITY AB Background Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts mortality in patients with chronic stable angina or acute coronary syndrome. However, the association of GDF-15 with cardiovascular (CV) events and the mechanisms of this association are not well understood. Methods We measured plasma GDF-15 and cardiac disease severity in 984 patients with stable ischemic heart disease who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent CV events (myocardial infarction, stroke, and CV death), hospitalization for heart failure, and all-cause mortality were determined by chart review during an average of 8.9-year follow-up. Results Each doubling in GDF-15 was associated with a 2.5-fold increased rate of CV events (hazard ratio [HR] 2.53, 95% CI 2.13-3.01, P < .001). This association persisted after extensive adjustment for covariates including comorbid conditions, measures of cardiac disease severity, cardiac function, inflammatory markers, and adipokines (HR 1.44, 95% CI 1.11-1.87, P < .01). Participants who had GDF-15 levels in the highest tertile had higher mortality compared with those in the lowest tertile (HR 2.73, 95% CI 1.80-4.15, P <= .001 adjusted for all covariates). Addition of GDF-15 to existing risk factors resulted in a 50% change in net reclassification of patients' risk for mortality. Conclusions Higher levels of GDF-15 are associated with major CV events in patients with stable ischemic heart disease. This suggests that GDF-15 is capturing an element of risk not explained by other known risk factors. C1 [Schopfer, David W.; Regan, Mathilda; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ku, Ivy A.] Kaiser Permanente San Francisco, Dept Cardiol, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Schopfer, DW (reprint author), 4150 Clement St 111A1, San Francisco, CA 94121 USA. EM david.schopfer@ucsf.edu NR 31 TC 10 Z9 12 U1 1 U2 13 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 FEB PY 2014 VL 167 IS 2 BP 186 EP + DI 10.1016/j.ahj.2013.09.013 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 290MD UT WOS:000329761200010 PM 24439979 ER PT J AU Bello, AK Stenvinkel, P Lin, M Hemmelgarn, B Thadhani, R Klarenbach, S Chan, C Zimmerman, D Cembrowski, G Strippoli, G Carrero, JJ Tonelli, M AF Bello, Aminu K. Stenvinkel, Peter Lin, Meng Hemmelgarn, Brenda Thadhani, Ravi Klarenbach, Scott Chan, Christopher Zimmerman, Deborah Cembrowski, George Strippoli, Giovanni Carrero, Juan-Jesus Tonelli, Marcello TI Serum Testosterone Levels and Clinical Outcomes in Male Hemodialysis Patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Serum testosterone; dialysis; adverse clinical outcomes; health-related quality of life (HRQoL) ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; QUALITY-OF-LIFE; ENDOGENOUS TESTOSTERONE; CARDIOVASCULAR-DISEASE; ANDROGEN DEFICIENCY; OLDER MEN; ENDOTHELIAL DYSFUNCTION; REPLACEMENT THERAPY; SEXUAL DYSFUNCTION AB Background: Studies linking low serum testosterone concentration to adverse clinical outcomes in hemodialysis patients have been relatively small. We investigated the role of testosterone in adverse outcomes and quality of life in an incident cohort of male Canadian hemodialysis patients. Study Design: A prospectively designed multicenter observational study using data from the Canadian Kidney Disease Cohort Study (CKDCS). Setting & Participants: Male patients initiating hemodialysis therapy since February 14, 2005, in 3 Canadian centers serving ethnically diverse populations were studied (N=623). Predictor: Serum testosterone levels using the International Society of Andrology, International Society for the Study of the Aging Male, and European Association of Urology cutoffs (low,,231 ng/dL; borderline, 231-346 ng/dL; normal,>346 ng/dL). Outcomes: All-cause mortality, fatal and nonfatal cardiovascular (CV) events, and Health Utility Index (HUI)-assessed health-related quality of life. Measurements: Participants completed a structured interview on demographics and medical history and an HUI questionnaire (version 3). Routine laboratory test results captured into the study database, and serum testosterone measured within 3 months after initiation of the baseline hemodialysis session. Results: During a median follow-up of 20 (range, 1-81) months, 166 (27%) died and 98 (20%) had a CV event. Mean serum testosterone level was 234.1 +/- 146.1 (SD) ng/dL. Higher serum testosterone levels were associated with significantly decreased unadjusted risk of death (HR per 10-ng/dL increase, 0.58; 95% CI, 0.37-0.90). There was a statistically significant trend for higher all-cause mortality with low serum testosterone levels in adjusted analyses (P < 0.001). Higher levels of log-transformed testosterone were associated with significantly higher HUI scores (P for trend < 0.001), and low levels of serum testosterone were associated significantly with lower HUI scores (P for trend < 0.001). Although there was a significant trend in the unadjusted risk of CV events among participants with low serum testosterone levels (P < 0.001), the risk was no longer significant after adjustment for age. There was no significant interaction with age and serum testosterone level tested as continuous variables (P=0.07). Limitations: A short follow-up period and serum testosterone measured on a single occasion. Conclusions: Lowserumtestosteroneconcentrationmaybe amodifiable risk factor for adverse outcomes and poor quality of life in male hemodialysis patients. This hypothesis should be tested in randomized controlled trials. (C) 2014 by the National Kidney Foundation, Inc. C1 [Bello, Aminu K.; Lin, Meng; Klarenbach, Scott; Cembrowski, George; Tonelli, Marcello] Univ Alberta, Edmonton, AB T6B 2B7, Canada. [Stenvinkel, Peter; Carrero, Juan-Jesus] Karolinska Inst, Stockholm, Sweden. [Hemmelgarn, Brenda] Univ Calgary, Calgary, AB, Canada. [Thadhani, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chan, Christopher] Univ Toronto, Toronto, ON, Canada. [Zimmerman, Deborah] Ottawa Hosp, Ottawa, ON, Canada. [Strippoli, Giovanni] Mario Negri Sud Consortium, Maria Imbaro, Italy. RP Tonelli, M (reprint author), Univ Alberta, 7-129 CSB,8440 112 St NW, Edmonton, AB T6B 2B7, Canada. EM mtonelli-admin@med.ualberta.ca RI Tonelli, Marcello/B-3028-2009; Bello, Aminu/D-2213-2013; OI Stenvinkel, Peter/0000-0002-8785-4820; Carrero, Juan Jesus/0000-0003-4763-2024 FU Canadian Institutes of Health Research; Abbott Laboratories; Alberta Heritage Foundation for Medical Research; Northern Alberta Renal Program; Government of Canada Research Chair; Swedish Research Council; National Institutes of Health [K24 DK094872] FX The CKDCS is funded by the Canadian Institutes of Health Research, Abbott Laboratories, Alberta Heritage Foundation for Medical Research, and the Northern Alberta Renal Program. These sponsors are entitled to view the manuscript prior to submission and may provide comments; the investigators may consider these comments, but are not required to change the manuscript; and the final decision to submit the manuscript rests with the investigators. The authors also acknowledge the support of the Department of Laboratory Medicine, Karolinska University Hospital Stockholm, Sweden( Dr Stenvinkel), for the analysis of total testosterone and sex hormone-binding globulin samples. Dr Tonelli was also supported by a Government of Canada Research Chair. Drs Hemmelgarn, Klarenbach, and Tonelli were all supported by a joint initiative between Alberta Health and Wellness and the Universities of Alberta and Calgary. These funding organizations played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Drs Stenvinkel and Carrero acknowledge grant support from the Swedish Research Council. Dr Thadhani is supported by National Institutes of Health grant K24 DK094872. NR 37 TC 11 Z9 11 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2014 VL 63 IS 2 BP 268 EP 275 DI 10.1053/j.ajkd.2013.06.010 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 293NX UT WOS:000329980100015 PM 23896484 ER PT J AU Batal, I Bijol, V Schlossman, RL Rennke, HG AF Batal, Ibrahim Bijol, Vanesa Schlossman, Robert L. Rennke, Helmut G. TI Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits in a Kidney Allograft SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Paraprotein; proliferative glomerulonephritis; transplant glomerulitis ID LIGHT-CHAIN DEPOSITION; CHRONIC LYMPHOCYTIC-LEUKEMIA; IGG DEPOSITS; NEPHROTIC SYNDROME; MULTIPLE-MYELOMA; RENAL-ALLOGRAFT; CELL LYMPHOMA; HEAVY-CHAIN; DISEASE; GAMMOPATHY AB Paraprotein may accumulate in glomeruli and cause kidney damage associated with variable histopathologic patterns and a characteristic immunofluorescence staining restricted to a single light chain and/or a single heavy chain isotype. Hence, such glomerular injury includes diseases caused by deposition of a monoclonal light chain, heavy chain, or entire immunoglobulin (light and heavy chains), which may manifest as proliferative glomerulonephritis. In this report, we focus on the latter as the least characterized of the 3, particularly in the transplantation setting. We describe a case of late transplant dysfunction associated with glomerular immunoglobulin G1/kappa deposits. We also present our experience with proliferative glomerulonephritis and monoclonal immunoglobulin deposits in transplant and native kidney biopsies, with reference to the literature. (C) 2014 by the National Kidney Foundation, Inc. C1 [Batal, Ibrahim; Bijol, Vanesa; Rennke, Helmut G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Batal, Ibrahim; Bijol, Vanesa; Schlossman, Robert L.; Rennke, Helmut G.] Harvard Univ, Sch Med, Boston, MA USA. [Schlossman, Robert L.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Batal, I (reprint author), Brigham & Womens Hosp, Dept Pathol, Kidney Pathol Serv, 75 Francis St, Boston, MA 02115 USA. EM ibatal@partners.org FU American Society of Transplantation Clinical Fellowship Grant FX Dr Batal was supported by an American Society of Transplantation Clinical Fellowship Grant. NR 32 TC 2 Z9 2 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2014 VL 63 IS 2 BP 318 EP 323 DI 10.1053/j.ajkd.2013.07.015 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 293NX UT WOS:000329980100022 PM 24051081 ER PT J AU Hashim, T Elbaz, S Patel, K Morgan, CJ Fonarow, GC Fleg, JL McGwin, G Cutter, GR Allman, RM Prabhu, SD Zile, MR Bourge, RC Ahmed, A AF Hashim, Taimoor Elbaz, Shereen Patel, Kanan Morgan, Charity J. Fonarow, Gregg C. Fleg, Jerome L. McGwin, Gerald Cutter, Gary R. Allman, Richard M. Prabhu, Sumanth D. Zile, Michael R. Bourge, Robert C. Ahmed, Ali TI Digoxin and 30-day All-cause Hospital Admission in Older Patients with Chronic Diastolic Heart Failure SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Diastolic heart failure; Digoxin; 30-day all-cause hospital admission ID ANGINA-PECTORIS; MORTALITY; TRIAL; HYPERTROPHY; MORBIDITY; PROGRAM AB BACKGROUND: In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients. METHODS: In the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age >= 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin. RESULTS: All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and >= 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, heart failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79). CONCLUSIONS: In older patients with chronic diastolic heart failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in systolic heart failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients. Published by Elsevier Inc. C1 [Hashim, Taimoor; Elbaz, Shereen; Patel, Kanan; Morgan, Charity J.; McGwin, Gerald; Cutter, Gary R.; Allman, Richard M.; Prabhu, Sumanth D.; Bourge, Robert C.; Ahmed, Ali] Univ Alabama Birmingham, Birmingham, AL USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA. [Allman, Richard M.; Prabhu, Sumanth D.; Ahmed, Ali] Vet Affairs Med Ctr, Birmingham, AL USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Ahmed, A (reprint author), UAB Comprehens Ctr Healthy Aging, 1720 2nd Ave South,CH19-219, Birmingham, AL 35294 USA. EM aahmed@uab.edu FU National Heart, Lung, and Blood Institute (NHLBI); Department of Veterans Affairs Cooperative Studies Program; National Institutes of Health from the NHLBI [R01-HL085561, R01-HL085561-S, R01-HL097047] FX The Digitalis Investigation Group (DIG) study was conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) and the Department of Veterans Affairs Cooperative Studies Program, in collaboration with the DIG Investigators. This article was prepared using a limited access dataset obtained from the NHLBI and does not necessarily reflect the opinions or views of the DIG Study or the NHLBI. Dr. Ahmed was in part supported by the National Institutes of Health through grants (R01-HL085561, R01-HL085561-S and R01-HL097047) from the NHLBI. NR 15 TC 8 Z9 11 U1 0 U2 6 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 FEB PY 2014 VL 127 IS 2 BP 132 EP 139 DI 10.1016/j.amjmed.2013.08.006 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 293PQ UT WOS:000329985800018 PM 24067296 ER PT J AU Thorndike, AN Riis, J Sonnenberg, LM Levy, DE AF Thorndike, Anne N. Riis, Jason Sonnenberg, Lillian M. Levy, Douglas E. TI Traffic-Light Labels and Choice Architecture Promoting Healthy Food Choices SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SUGAR-SWEETENED BEVERAGES; PUBLIC-HEALTH; OBESITY; RESTAURANTS; CONSUMPTION; CONSUMERS; BEHAVIOR; INTERVENTION; DISEASE; IMPACT AB Background: Preventing obesity requires maintenance of healthy eating behaviors over time. Food labels and strategies that increase visibility and convenience of healthy foods (choice architecture) promote healthier choices, but long-term effectiveness is unknown. Purpose: Assess effectiveness of traffic-light labeling and choice architecture cafeteria intervention over 24 months. Design: Longitudinal pre-post cohort follow-up study between December 2009 and February 2012. Data were analyzed in 2012. Setting/participants: Large hospital cafeteria with a mean of 6511 transactions daily. Cafeteria sales were analyzed for (1) all cafeteria customers and (2) a longitudinal cohort of 2285 hospital employees who used the cafeteria regularly. Intervention: After a 3-month baseline period, cafeteria items were labeled green (healthy); yellow (less healthy); or red (unhealthy) and rearranged to make healthy items more accessible. Main outcome measures: Proportion of cafeteria sales that were green or red during each 3month period from baseline to 24 months. Changes in 12-and 24-month sales were compared to baseline for all transactions and transactions by the employee cohort. Results: The proportion of sales of red items decreased from 24% at baseline to 20% at 24 months (p<0.001), and green sales increased from 41% to 46% (p<0.001). Red beverages decreased from 26% of beverage sales at baseline to 17% at 24 months (p<0.001); green beverages increased from 52% to 60% (p<0.001). Similar patterns were observed for the cohort of employees, with the largest change for red beverages (23%-14%, p<0.001). Conclusions: A traffic-light and choice architecture cafeteria intervention resulted in sustained healthier choices over 2 years, suggesting that food environment interventions can promote longterm changes in population eating behaviors. C1 [Thorndike, Anne N.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Sonnenberg, Lillian M.] Massachusetts Gen Hosp, Nutr Serv, Boston, MA 02114 USA. [Sonnenberg, Lillian M.] Massachusetts Gen Hosp, Food Serv, Boston, MA 02114 USA. [Levy, Douglas E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Riis, Jason] Harvard Univ, Sch Business, Boston, MA 02163 USA. RP Thorndike, AN (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM athorndike@partners.org FU Robert Wood Johnson Foundation's Pioneer Portfolio; Donaghue Foundation through the grant "Applying Behavioral Economics to Perplexing Health and Health Care Challenges"; NIH/National Heart Lung and Blood institute [K23 HL93221] FX This research is supported by the Robert Wood Johnson Foundation's Pioneer Portfolio and the Donaghue Foundation through the grant "Applying Behavioral Economics to Perplexing Health and Health Care Challenges." Dr. Thorndike is supported by the NIH/National Heart Lung and Blood institute grant K23 HL93221. Neither the NIH nor the Robert Wood Johnson and Donaghue Foundations had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 36 TC 43 Z9 43 U1 9 U2 68 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 2014 VL 46 IS 2 BP 143 EP 149 DI 10.1016/j.amepre.2013.10.002 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 291VM UT WOS:000329859200007 PM 24439347 ER PT J AU Hecht, GA Blaser, MJ Gordon, J Kaplan, LM Knight, R Laine, L Peek, R Sanders, ME Sartor, B Wu, GD Yang, VW AF Hecht, Gail A. Blaser, Martin J. Gordon, Jeffrey Kaplan, Lee M. Knight, Rob Laine, Loren Peek, Richard Sanders, Mary Ellen Sartor, Balfour Wu, Gary D. Yang, Vincent W. TI What Is the Value of a Food and Drug Administration Investigational New Drug Application for Fecal Microbiota Transplantation to Treat Clostridium difficile Infection? SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID GUT MICROBIOTA; OBESITY; DISEASE C1 [Hecht, Gail A.] Loyola Univ, Stritch Sch Med, Dept Med, Div Gastroenterol & Nutr, Chicago, IL 60611 USA. [Blaser, Martin J.] NYU, Dept Med, Langone Med Ctr, Dept Vet Affairs Med Ctr, New York, NY 10016 USA. [Blaser, Martin J.] NYU, Dept Microbiol, Langone Med Ctr, Dept Vet Affairs Med Ctr, New York, NY 10016 USA. [Gordon, Jeffrey] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, BioFrontiers Inst, Dept Chem & Biochem, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Dept Comp Sci, BioFrontiers Inst, Boulder, CO 80309 USA. [Laine, Loren] Yale Univ, Sch Med, Sect Digest Dis, New Haven, CT USA. [Laine, Loren] VA Connecticut Healthcare Syst, West Haven, CT USA. [Peek, Richard] Vanderbilt Univ, Div Gastroenterol, Nashville, TN 37235 USA. [Sanders, Mary Ellen] Int Sci Assoc Probiot & Prebiot, Davis, CA USA. [Sartor, Balfour] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Sartor, Balfour] Univ N Carolina, Dept Microbiol, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Sartor, Balfour] Univ N Carolina, Dept Immunol, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Wu, Gary D.] Univ Penn, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Yang, Vincent W.] SUNY Stony Brook, Sch Med, Dept Med, Stony Brook, NY 11794 USA. RP Hecht, GA (reprint author), Loyola Univ, Stritch Sch Med, Dept Med, Div Gastroenterol & Nutr, Chicago, IL 60611 USA. RI Knight, Rob/D-1299-2010 NR 16 TC 9 Z9 9 U1 0 U2 14 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 FEB PY 2014 VL 12 IS 2 BP 289 EP 291 DI 10.1016/j.cgh.2013.10.009 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 290KK UT WOS:000329754900022 PM 24148361 ER PT J AU Gallagher, MW Naragon-Gainey, K Brown, TA AF Gallagher, Matthew W. Naragon-Gainey, Kristin Brown, Timothy A. TI Perceived Control is a Transdiagnostic Predictor of Cognitive-Behavior Therapy Outcome for Anxiety Disorders SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Perceived control; Anxiety; CBT; Treatment outcome; Transdiagnostic ID OBSESSIVE-COMPULSIVE SYMPTOMS; SOCIAL-INTERACTION ANXIETY; DSM-IV ANXIETY; PANIC DISORDER; EMOTIONAL DISORDERS; POSTTRAUMATIC-STRESS; PHOBIA QUESTIONNAIRE; UNIFIED PROTOCOL; SENSITIVITY; COVARIANCE AB Perceived control has been proposed to be a general psychological vulnerability factor that confers an elevated risk for developing anxiety disorders, but there is limited research examining perceived control during cognitive-behavioral therapies (CBT). The present study examined whether treatment resulted in improvements in perceived control, and the indirect effects of CBT on changes in symptoms of obsessive-compulsive disorder, social phobia, generalized anxiety disorder, and panic disorder via changes in perceived control. Participants (n = 606) were a large clinical sample presenting for treatment at an outpatient anxiety disorders clinic. Participants completed a series of self-report questionnaires and a structured clinical interview at an intake evaluation and at two follow-up assessments 12 and 24 months later, with the majority of participants initiating CBT between the first two assessments. Results of latent growth curve models indicated that individuals initiating CBT subsequently reported large increases in perceived control and significant indirect effects of treatment on intraindividual changes in each of the four anxiety disorders examined via intraindividual changes in perceived control. These results suggest that the promotion of more adaptive perceptions of control is associated with recovery from anxiety disorders. Furthermore, the consistent finding of indirect effects across the four anxiety disorders examined underscores the transdiagnostic importance of perceived control in predicting CBT outcomes. C1 [Gallagher, Matthew W.] VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, Behav Sci Div, Boston, MA 02130 USA. [Gallagher, Matthew W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Naragon-Gainey, Kristin] SUNY Buffalo, Buffalo, NY 14260 USA. [Brown, Timothy A.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Gallagher, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, Behav Sci Div, 150 South Huntington Ave, Boston, MA 02130 USA. EM mwg@bu.edu FU NIMH NIH HHS [R01 MH039096] NR 48 TC 14 Z9 14 U1 6 U2 20 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD FEB PY 2014 VL 38 IS 1 BP 10 EP 22 DI 10.1007/s10608-013-9587-3 PG 13 WC Psychology, Clinical SC Psychology GA 293TZ UT WOS:000329997900002 PM 24563563 ER PT J AU Sylvia, LG Salcedo, S Bianchi, MT Urdahl, AK Nierenberg, AA Deckersbach, T AF Sylvia, Louisa G. Salcedo, Stephanie Bianchi, Matt T. Urdahl, Anna K. Nierenberg, Andrew A. Deckersbach, Thilo TI A Novel Home Sleep Monitoring Device and Brief Sleep Intervention for Bipolar Disorder: Feasibility, Tolerability, and Preliminary Effectiveness SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Brief sleep intervention; Home sleep monitoring; Bipolar disorder; Insomnia; Hypersomnia ID QUALITY INDEX; CIRCADIAN-RHYTHMS; MOOD DISORDERS; INSOMNIA; RELIABILITY; DEPRESSION; SCALE; VALIDITY; MANIA AB Sleep disturbance is common in bipolar disorder and negatively impacts its course of illness. The purpose of this study is to assess the feasibility and tolerability of a novel EKG-based home sleep monitoring device (M1) as well as a brief (two session) psychosocial sleep intervention for individuals with bipolar disorder. The sleep intervention is individually tailored for patients with insomnia or hypersomnia and extends skills designed for non-psychiatric populations as well as includes specific considerations for sleep disturbance in bipolar disorder. We found that both the M1 device and the sleep intervention were feasible and well tolerated. Participants' sleep duration improved after the brief sleep intervention, but their sleep was more unstable as measured by the M1. Self-reported sleepiness, sleep quality, and mood symptoms improved; however, only some measures reached statistical significance (i.e., duration of sleep, dysfunction due to sleepiness). These data suggest that the M1 device is a feasible means to obtain objective sleep quality and quantity data in individuals with bipolar disorder. A brief sleep intervention may be helpful in improving sleep in a bipolar population at risk for substantial sleep disturbance, but larger, longitudinal studies are warranted. C1 [Sylvia, Louisa G.; Salcedo, Stephanie; Bianchi, Matt T.; Urdahl, Anna K.; Nierenberg, Andrew A.; Deckersbach, Thilo] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Sylvia, Louisa G.; Salcedo, Stephanie; Bianchi, Matt T.; Urdahl, Anna K.; Nierenberg, Andrew A.; Deckersbach, Thilo] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Sylvia, Louisa G.; Bianchi, Matt T.; Nierenberg, Andrew A.; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA USA. RP Sylvia, LG (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org FU NIMH NIH HHS [K23 MH091182] NR 25 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD FEB PY 2014 VL 38 IS 1 BP 55 EP 61 DI 10.1007/s10608-013-9575-7 PG 7 WC Psychology, Clinical SC Psychology GA 293TZ UT WOS:000329997900006 PM 24511171 ER PT J AU Aggarwal, S Cavalcanti, BM Pavan-Langston, D AF Aggarwal, Shruti Cavalcanti, Bernardo M. Pavan-Langston, Deborah TI Treatment of Pseudodendrites in Herpes Zoster Ophthalmicus With Topical Ganciclovir 0.15% Gel SO CORNEA LA English DT Article DE herpes zoster ophthalmicus; pseudodendrites; ganciclovir ID KERATITIS; VIRUS; RECURRENT; PENETRATION; MANAGEMENT; MORBIDITY AB Purpose:There is no standard of treatment for epithelial pseudodendrites in herpes zoster ophthalmicus (HZO). The purpose of this study is to report the topical antiviral drug, 0.15% ganciclovir for treatment of these lesions.Methods:This is a retrospective, interventional case series of 4 patients who were diagnosed with HZO epithelial pseudodendrites despite being given oral antiviral treatment and who underwent 0.15% ganciclovir gel topical treatment. Main outcome measures included epithelial healing time, visual acuity, and corneal sensation.Results:All 4 patients were immunocompetent and had epithelial lesions unresponsive to antiviral treatment with oral valacyclovir. Treatment with topical 0.15% ganciclovir gel 5 times a day resulted in the lesions healing successfully within 7 days with improved visual acuity in 3 patients and an increase in corneal sensation in 2 of the 4 patients.Conclusions:Topical 0.15% ganciclovir gel, 5 times a day until pseudodendritic lesion healing and tapering to bid for 2 to 4 weeks thereafter, is an effective treatment for pseudodendrites in HZO-affected cases that are often a challenge to manage with other oral or topical antivirals. C1 [Aggarwal, Shruti; Cavalcanti, Bernardo M.; Pavan-Langston, Deborah] Harvard Univ, Sch Med, Cornea & Refract Surg Serv, Dept Ophthalmol, Boston, MA 02114 USA. [Aggarwal, Shruti; Cavalcanti, Bernardo M.] Harvard Univ, Sch Med, Ocular Surface Imaging Ctr, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pavan-Langston, D (reprint author), Harvard Univ, Sch Med, Cornea & Refract Surg Serv, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM deborah_langston@meei.harvard.edu FU Nancy and Vanderburgh Johnstone Funds; Georgianna Stevens Fund FX Supported by the Nancy and Vanderburgh Johnstone Funds (DPL) and the Georgianna Stevens Fund (DPL). The funding organizations had no role in the design or conduct of this research. NR 26 TC 7 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD FEB PY 2014 VL 33 IS 2 BP 109 EP 113 DI 10.1097/ICO.0000000000000020 PG 5 WC Ophthalmology SC Ophthalmology GA 292LT UT WOS:000329903900001 PM 24322809 ER PT J AU Stevenson, W Sadrai, Z Hua, J Kodati, S Huang, JF Chauhan, SK Dana, R AF Stevenson, William Sadrai, Zahra Hua, Jing Kodati, Shilpa Huang, Jing-Feng Chauhan, Sunil K. Dana, Reza TI Effects of Topical Janus Kinase Inhibition on Ocular Surface Inflammation and Immunity SO CORNEA LA English DT Article DE ocular surface inflammation; corneal thermocautery; dry eye disease; Janus kinase; tofacitinib (CP-690; 550) ID DRY EYE DISEASE; JAK INHIBITOR; TOFACITINIB CP-690,550; DOUBLE-BLIND; ANTAGONIST; ARTHRITIS; MUTATION; PLACEBO; CELLS; GENE AB Purpose:To determine the effects of topical Janus kinase inhibition on ocular surface inflammation and immunity.Methods:Ophthalmic 0.003% tofacitinib (CP-690,550) was administered topically to inhibit Janus kinase activation at the ocular surface. Male BALB/c mice 6 to 8 weeks of age were subjected to corneal thermocautery and randomized to receive tofacitinib, vehicle, or no treatment. Corneas were subsequently excised for fluorescence-activated cell sorting and quantitative real-time reverse transcription polymerase chain reaction. Female C57BL/6 mice 6 to 8 weeks of age were exposed to desiccating stress to induce experimental dry eye disease and randomized to receive tofacitinib, tofacitinib and vehicle, vehicle, or no treatment. Corneal fluorescein staining was performed to evaluate clinical disease severity. The corneas and conjunctivae were harvested for immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction.Results:After corneal thermocautery, it was found that tofacitinib treatment decreased the corneal infiltration of CD45(+), Gr-1(+), and CD11b(+) cells on days 1 and 3. Transcripts encoding interleukin (IL)-1 and IL-6 were significantly decreased by tofacitinib treatment at post-thermocautery day 3. In experimental dry eye disease, tofacitinib treatment twice per day significantly decreased corneal fluorescein staining on days 12 and 15. The corneal infiltration of CD11b(+) cells was significantly decreased by tofacitinib treatment twice per day. Tofacitinib treatment twice per day significantly increased the corneal expression of IL-1RA, and significantly decreased the corneal expression of tumor necrosis factor and IL-23. Further, tofacitinib treatment twice per day significantly decreased the conjunctival expression of IL-17A and significantly increased the conjunctival expression of FoxP3.Conclusions:Topical ophthalmic tofacitinib, a Janus kinase inhibitor, suppressed ocular surface inflammation and immunity in experimental corneal thermocautery and dry eye disease. C1 [Stevenson, William; Sadrai, Zahra; Hua, Jing; Kodati, Shilpa; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. [Huang, Jing-Feng] Pfizer Inc, Med Dev Grp, San Diego, CA USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU NIH [EY-20889]; Pfizer, Inc. FX This research was supported by NIH Grant EY-20889 and Pfizer, Inc. No authors received compensation for the development of this manuscript. J.-F. Huang was an employee of Pfizer, Inc at the time of this study. NR 33 TC 5 Z9 5 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD FEB PY 2014 VL 33 IS 2 BP 177 EP 183 DI 10.1097/ICO.0000000000000019 PG 7 WC Ophthalmology SC Ophthalmology GA 292LT UT WOS:000329903900014 PM 24342887 ER PT J AU Salvador-Culla, B Behlau, I Sayegh, RR Stacy, RC Dohlman, CH Delori, F AF Salvador-Culla, Borja Behlau, Irmgard Sayegh, Rony R. Stacy, Rebecca C. Dohlman, Claes H. Delori, Francois TI Very Low Risk of Light-Induced Retinal Damage During Boston Keratoprosthesis Surgery: A Rabbit Study SO CORNEA LA English DT Article DE Boston keratoprosthesis; light-induced retinal damage; operating microscope; cornea surgery in rabbits ID INTRAOCULAR-LENS IMPLANTATION; OPERATING MICROSCOPE; CATARACT-SURGERY; OCULAR MEDIA; ELECTRORETINOGRAM; EYE; MACULOPATHY; EXTRACTION; RADIATION; EXPOSURES AB Purpose:The aim of this study was to assess the possibility of light damage to the retina by a surgical microscope during implantation of a Boston Keratoprosthesis (B-KPro) in rabbits.Methods:The retinal irradiance from a Zeiss OPMI Lumera S7 operating microscope was measured at the working distance (16.5 cm). Light transmittance through an isolated B-KPro was measured. A B-KPro was implanted into 1 eye of 12 rabbits with the optic covered during the procedure. The operated eyes were then continuously exposed to a fixed light intensity under the microscope for 1 hour. Fluorescein angiography was carried out on days 2 and 9 postsurgery, after which the animals were euthanized. Further, we compared the potential of these retinal exposures to well-accepted light safety guidelines applicable to humans.Results:Light transmittance of B-KPro revealed a blockage of short wavelengths (<390 nm) and of long wavelengths (1660-1750 nm) of light. In addition, the surgical microscope filtered a part of the blue, ultraviolet, and infrared wavelengths. Neither fluorescein angiography nor a histological examination showed any morphological retinal changes in our rabbits. Moreover, the retinal exposures were well below the safety limits.Conclusions:Modern surgical microscopes have filters incorporated in them that block the most damaging wavelengths of light. The B-KPro is made of 100% poly(methyl methacrylate), which makes it in itself a blocker of short wavelengths of light. No damage could be demonstrated in the animal study, and the retinal exposures were well below the safety limits. Together, these results suggest that light exposures during B-KPro surgery present a low risk of photochemical damage to the retina. C1 [Salvador-Culla, Borja; Behlau, Irmgard; Sayegh, Rony R.; Dohlman, Claes H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. [Salvador-Culla, Borja; Behlau, Irmgard; Sayegh, Rony R.; Stacy, Rebecca C.; Dohlman, Claes H.; Delori, Francois] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Stacy, Rebecca C.; Delori, Francois] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Delori, Francois] Schepens Eye Res Inst, Boston, MA USA. RP Salvador-Culla, B (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM borja_salvador@meei.harvard.edu RI Sayegh, Rony/G-8777-2013 OI Sayegh, Rony/0000-0002-0119-4201 FU Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary, Boston, MA FX Supported by Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary, Boston, MA. NR 27 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD FEB PY 2014 VL 33 IS 2 BP 184 EP 190 DI 10.1097/ICO.0000000000000029 PG 7 WC Ophthalmology SC Ophthalmology GA 292LT UT WOS:000329903900015 PM 24322800 ER PT J AU Bittner, EA Schmidt, U AF Bittner, Edward A. Schmidt, Ulrich TI Duration of Delirium and Postintensive Care Functional Outcome: Over the Hill? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE activity of daily living; delirium; outcome ID CAUSATION C1 [Bittner, Edward A.; Schmidt, Ulrich] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Bittner, EA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2014 VL 42 IS 2 BP 466 EP 467 DI 10.1097/01.ccm.0000435679.14177.62 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 291WS UT WOS:000329863400054 PM 24434453 ER PT J AU Hawkins, AT Berger, DL Shellito, PC Sylla, P Bordeianou, L AF Hawkins, Alexander T. Berger, David L. Shellito, Paul C. Sylla, Patrica Bordeianou, Liliana TI Wound Dehiscence After Abdominoperineal Resection for Low Rectal Cancer Is Associated With Decreased Survival SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Abdominoperineal resection; Complication; Dehiscence; Rectal adenocarcinoma; Survival ID PATHOLOGICAL COMPLETE RESPONSE; PREOPERATIVE CHEMORADIATION; FLAP RECONSTRUCTION; SPHINCTER PRESERVATION; PELVIC SPACE; RISK-FACTORS; EXCISION; CARCINOMA; RECURRENCE; MORBIDITY AB BACKGROUND: Abdominoperineal resection for low rectal adenocarcinoma is a common procedure with high morbidity, including perineal wound complications. OBJECTIVE: The purpose of this study was to determine risk factors for perineal wound dehiscence and to investigate the effect of wound dehiscence on survival. DESIGN: This was a retrospective medical chart review. SETTINGS: The study was conducted in a tertiary care university medical center. PATIENTS: Patients included in the study were those with low rectal adenocarcinoma who underwent abdominoperineal resection between January 2001 and June 2012. MAIN OUTCOMES MEASURES: We assessed the incidence of perineal wound dehiscence, as well as survival, after surgery. RESULTS: A total of 249 patients underwent abdominoperineal resection for rectal carcinoma. The mean age was 62.6 years (range, 23.0-98.0 years), 159 (63.8%) were male, and the mean BMI was 27.9 (range, 16.7-58.5). There were 153 patients (61.1%) who survived for 5 years after surgery. Sixty-nine patients (27.7%) developed wound dehiscence. Multivariable analysis revealed the following associations with dehiscence: BMI (OR, 1.09; 95% CI, 1.03-1.15; p = 0.002), IBD (OR, 6.6; 95% CI, 1.4-32.5; p = 0.02), history of other malignant neoplasm (OR, 3.1; 95% CI, 1.5-6.6), and abdominoperineal resection for cancer recurrence (OR, 2.8; 95% CI, 1.2-6.3; p = 0.01). In the survival analysis, wound dehiscence was associated with decreased survival (mean survival time for dehiscence vs no dehiscence, 66.6 months vs 76.6 months; p = 0.01). This relationship persisted in the multivariable analysis (HR, 1.7; 95% CI, 1.1-2.8; p = 0.02). LIMITATIONS: This was a retrospective, observational study from a single center. CONCLUSIONS: The adjusted risk of death was 1.7 times higher in patients who experienced dehiscence than in those who did not. Attention to perineal wound closure with consideration of flap creation should at least be given to patients with a history of malignant neoplasm, those with IBD, those with rectal cancer recurrence, and women undergoing posterior vaginectomy. Preoperative weight loss should also reduce dehiscence risk. C1 [Hawkins, Alexander T.; Berger, David L.; Shellito, Paul C.; Sylla, Patrica; Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WAC 4-460, Boston, MA 02114 USA. EM lbordeianou@partners.org FU Brigham & Women's Center for Surgery and Public Health Arthur Tracy Cabot Fellowship; National Institutes of Health National Heart, Lung, and Blood Institute T32 Harvard/Longwood Vascular Surgery Training Program [HL007734] FX Dr Hawkins was supported by a grant from the Brigham & Women's Center for Surgery and Public Health Arthur Tracy Cabot Fellowship and the National Institutes of Health National Heart, Lung, and Blood Institute T32 (HL007734) Harvard/Longwood Vascular Surgery Training Program. NR 38 TC 14 Z9 15 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD FEB PY 2014 VL 57 IS 2 BP 143 EP 150 DI 10.1097/DCR.0000000000000027 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 292IY UT WOS:000329896600004 PM 24401874 ER PT J AU Ando, M Sunaguchi, N Wu, YL Do, S Sung, YJ Louissaint, A Yuasa, T Ichihara, S Gupta, R AF Ando, Masami Sunaguchi, Naoki Wu, Yanlin Synho Do Sung, Yongjin Louissaint, Abner Yuasa, Tetsuya Ichihara, Shu Gupta, Rajiv TI Crystal analyser-based X-ray phase contrast imaging in the dark field: implementation and evaluation using excised tissue specimens SO EUROPEAN RADIOLOGY LA English DT Article DE Technology; Radiologic; Diagnostic techniques; Cardiovascular; Mammography; Diagnostic imaging; Tomography; X-ray computed ID COMPUTED-TOMOGRAPHY; PENDELLOSUNG FRINGES; DYNAMICAL THEORY; DIFFRACTION; INTERFEROMETER; RECONSTRUCTION; MRI AB We demonstrate the soft tissue discrimination capability of X-ray dark-field imaging (XDFI) using a variety of human tissue specimens. The experimental setup for XDFI comprises an X-ray source, an asymmetrically cut Bragg-type monochromator-collimator (MC), a Laue-case angle analyser (LAA) and a CCD camera. The specimen is placed between the MC and the LAA. For the light source, we used the beamline BL14C on a 2.5-GeV storage ring in the KEK Photon Factory, Tsukuba, Japan. In the eye specimen, phase contrast images from XDFI were able to discriminate soft-tissue structures, such as the iris, separated by aqueous humour on both sides, which have nearly equal absorption. Superiority of XDFI in imaging soft tissue was further demonstrated with a diseased iliac artery containing atherosclerotic plaque and breast samples with benign and malignant tumours. XDFI on breast tumours discriminated between the normal and diseased terminal duct lobular unit and between invasive and in-situ cancer. X-ray phase, as detected by XDFI, has superior contrast over absorption for soft tissue processes such as atherosclerotic plaque and breast cancer. aEuro cent X-ray dark field imaging (XDFI) can dramatically increase sensitivity of phase detection. aEuro cent XDFI can provide enhanced soft tissue discrimination. aEuro cent With XDFI, abnormal anatomy can be visualised with high spatial/contrast resolution. C1 [Ando, Masami] Tokyo Univ Sci, RIST, Noda, Chiba 2788510, Japan. [Sunaguchi, Naoki] Gunma Univ, Grad Sch Engn, Kiryu, Gunma 3768515, Japan. [Wu, Yanlin] Grad Univ Adv Studies, Dept Mat Struct Sci, Sch High Energy Accelerator Sci, Tsukuba, Ibaraki 3050801, Japan. [Synho Do; Sung, Yongjin; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Synho Do; Sung, Yongjin; Louissaint, Abner; Gupta, Rajiv] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Louissaint, Abner] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yuasa, Tetsuya] Yamagata Univ, Fac Engn, Yonezawa, Yamagata 9928510, Japan. [Ichihara, Shu] Nagoya Med Ctr, Dept Pathol, Nagoya, Aichi 460001, Japan. RP Gupta, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St Suite 400B, Boston, MA 02114 USA. EM rgupta1@partners.org RI Yuasa, Tetsuya/F-5006-2013 FU DARPA AXiS program [N66001-11-4204, 1300217190]; Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan [22591353]; National Hospital Organization FX The authors would like to thank Mr. Kazuki Matsui, Ms Megumi Yokoyama and Ms Mayumi Kataoka for their technical assistance, and Dr. Suzuko Moritani and Dr. Masaki Hasegawa for providing clinicopathological data. Valuable help in sample preparation and imaging was provided by Drs. Suzanne Lee, Kazuyuki Hyodo, Qingkai Huo, Ms. Andrea Schmitz and Mr. Yuki Nakao. Computational calculation of the spatial resolution in XDFI was performed using the Takagi-Taupin theory by Dr. Yoshifumi Suzuki, to whom the authors would like to express their thanks. This work was supported, in part, by the DARPA AXiS program, grant no. N66001-11-4204, P.R. no. 1300217190. This research was also supported in part by a Grant-in-Aid for Scientific Research (no. 22591353) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan and in part by a Grant-in-Aid for Clinical Research from the National Hospital Organization. The experiment was performed under the approval of the PF User Association (PF-UA) at KEK under no. 2008S2-002, 2011G-672 for use of the Photon Factory. NR 31 TC 6 Z9 6 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 EI 1432-1084 J9 EUR RADIOL JI Eur. Radiol. PD FEB PY 2014 VL 24 IS 2 BP 423 EP 433 DI 10.1007/s00330-013-3021-9 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 290UI UT WOS:000329783400020 PM 24048725 ER PT J AU Arrillaga-Romany, I Reardon, DA Wen, PY AF Arrillaga-Romany, Isabel Reardon, David A. Wen, Patrick Y. TI Current status of antiangiogenic therapies for glioblastomas SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE angiogenesis; antiangiogenic therapy; bevacizumab; glioblastoma ID ENDOTHELIAL GROWTH-FACTOR; RECURRENT MALIGNANT GLIOMA; RESPONSE ASSESSMENT CRITERIA; II CLINICAL-TRIALS; PHASE-II; TUMOR ANGIOGENESIS; IN-VIVO; PROANGIOGENIC FACTORS; PROGNOSTIC-FACTORS; KINASE INHIBITOR AB Introduction: Glioblastoma (GBM), the most common primary malignant brain tumor in adults, lacks effective long-term treatment. The tumor is dependent on neovascularization for survival, making angiogenesis an attractive target for therapeutic intervention. The exact mechanism underlying the effects of antiangiogenic agents on GBM remains debatable, although it likely involves vascular endothelial growth factor (VEGF), and other proangiogenic growth factors. Early studies in the recurrent GBM setting were promising and prompted two multinational randomized phase three trials (AVAglio and RTOG 0825) investigating the effect of bevacizumab, an anti-VEGF monoclonal antibody, in newly diagnosed GBM. Areas covered: In this article, the authors discuss the basic mechanisms of angiogenesis and antiangiogenic resistance. The authors additionally summarize the current state of clinical research and how it will impact both future research and the development antiangiogenic therapies. Expert opinion: The ultimate utility of antiangiogenic therapy in the management of GBM remains unclear. In an effort to improve outcomes, there remains an urgent need to better understand the biology underlying angiogenesis and tumor survival, as well as mechanisms of antiangiogeneic resistance. Ultimately, combinatorial approaches using antiangiogenic agents, targeted molecular therapy, immunotherapy or cytotoxics may be needed to improve treatment outcomes. C1 [Arrillaga-Romany, Isabel] Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. [Arrillaga-Romany, Isabel] Harvard Univ, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Reardon, David A.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02215 USA. [Reardon, David A.; Wen, Patrick Y.] Harvard Univ, Ctr Neurooncol, Sch Med, Boston, MA 02215 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurooncol, Dept Neurol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org FU Amgen, Inc.; Astra-Zeneca; Boehringer Ingelheim; Esai Pharmaceuticals; Exelixis; Genentech; Geron; MedImmune; Merck Co.; Novartis AG; Sanofi-Aventis; Vascular Biogenics FX P Wen has received research support from Amgen, Inc., Astra-Zeneca, Boehringer Ingelheim, Esai Pharmaceuticals, Exelixis, Genentech, Geron, MedImmune, Merck & Co., Novartis AG, Sanofi-Aventis and Vascular Biogenics. He has also served on advisory boards of Merck & Co., Novartis AG and EMD Serono. They have also had speaker support from Merck & Co., Genentech/Roche and GlaxoSmithKline. Additionally, D Reardon acts as an advisor for Genentech (Roche), Merck & Co. (Schering-Plough) and EMD Serono. NR 99 TC 20 Z9 20 U1 0 U2 24 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD FEB PY 2014 VL 23 IS 2 BP 199 EP 210 DI 10.1517/13543784.2014.856880 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291OI UT WOS:000329837600005 PM 24320142 ER PT J AU Gala, MK Mizukami, Y Le, LP Moriichi, K Austin, T Yamamoto, M Lauwers, GY Bardeesy, N Chung, DC AF Gala, Manish K. Mizukami, Yusuke Le, Long P. Moriichi, Kentaro Austin, Thomas Yamamoto, Masayoshi Lauwers, Gregory Y. Bardeesy, Nabeel Chung, Daniel C. TI Germline Mutations in Oncogene-Induced Senescence Pathways Are Associated With Multiple Sessile Serrated Adenomas SO GASTROENTEROLOGY LA English DT Article DE Serrated Polyposis Syndrome; Hereditary Colon Cancer; Sessile Serrated Polyp; RNF43 ID HYPERPLASTIC POLYPOSIS SYNDROME; OF-FUNCTION VARIANTS; COLORECTAL-CANCER; PANCREATIC-CANCER; 1ST-DEGREE RELATIVES; TUMOR PROGRESSION; COMMON DISEASES; RARE VARIANTS; CARCINOMA; PROTEIN AB BACKGROUND & AIMS: Little is known about the genetic factors that contribute to the development of sessile serrated adenomas (SSAs). SSAs contain somatic mutations in BRAF or KRAS early in development. However, evidence from humans and mouse models indicates that these mutations result in oncogene-induced senescence (OIS) of intestinal crypt cells. Progression to serrated neoplasia requires cells to escape OIS via inactivation of tumor suppressor pathways. We investigated whether subjects with multiple SSAs carry germline loss-of-function mutations (nonsense and splice site) in genes that regulate OIS: the p16-Rb and ATM-ATR DNA damage response pathways. METHODS: Through a bioinformatic analysis of the literature, we identified a set of genes that function at the main nodes of the p16-Rb and ATM-ATR DNA damage response pathways. We performed whole-exome sequencing of 20 unrelated subjects with multiple SSAs; most had features of serrated polyposis. We compared sequences with those from 4300 subjects matched for ethnicity (controls). We also used an integrative genomics approach to identify additional genes involved in senescence mechanisms. RESULTS: We identified mutations in genes that regulate senescence (ATM, PIF1, TELO2, XAF1, and RBL1) in 5 of 20 subjects with multiple SSAs (odds ratio, 3.0; 95% confidence interval, 0.9-8.9; P=.04). In 2 subjects, we found nonsense mutations in RNF43, indicating that it is also associated with multiple serrated polyps (odds ratio, 460; 95% confidence interval, 23.1-16,384; P=6.8 x 10(-5)). In knockdown experiments with pancreatic duct cells exposed to UV light, RNF43 appeared to function as a regulator of ATM-ATR DNA damage response. CONCLUSIONS: We associated germline loss-of-function variants in genes that regulate senescence pathways with the development of multiple SSAs. We identified RNF43 as a regulator of the DNA damage response and associated nonsense variants in this gene with a high risk of developing SSAs. C1 [Gala, Manish K.; Mizukami, Yusuke; Moriichi, Kentaro; Austin, Thomas; Yamamoto, Masayoshi; Chung, Daniel C.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Le, Long P.; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mizukami, Yusuke; Le, Long P.; Lauwers, Gregory Y.; Bardeesy, Nabeel; Chung, Daniel C.] Harvard Univ, Sch Med, Boston, MA USA. [Mizukami, Yusuke; Bardeesy, Nabeel; Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mizukami, Yusuke] Sapporo Higashi Tokushukai Hosp, Ctr Clin & Biomed Res, Sapporo, Hokkaido, Japan. RP Chung, DC (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 704, Boston, MA 02114 USA. EM dchung@partners.org FU American College of Gastroenterology; Ministry of Education, Science, Sports, and Culture of Japan [22590754]; Warshaw Institute for Pancreatic Cancer Research; National Institutes of Health [CA92594]; Kate J. and Dorothy L. Clapp Fund FX Supported by grants from the American College of Gastroenterology (Pilot Clinical Research Award to M. K. G); Ministry of Education, Science, Sports, and Culture of Japan (22590754 to Y.M.), Warshaw Institute for Pancreatic Cancer Research (to Y.M.), National Institutes of Health (CA92594 to D. C. C.), and the Kate J. and Dorothy L. Clapp Fund (to D.C.C.). NR 66 TC 14 Z9 17 U1 0 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2014 VL 146 IS 2 BP 520 EP + DI 10.1053/j.gastro.2013.10.045 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 290LE UT WOS:000329757800032 PM 24512911 ER PT J AU Kroy, DC Ciuffreda, D Cooperrider, JH Tomlinson, M Hauck, GD Aneja, J Berger, C Wolski, D Carrington, M Wherry, EJ Chung, RT Tanabe, KK Elias, N Freeman, GJ de Kruyff, RH Misdraji, J Kim, AY Lauer, GM AF Kroy, Daniela C. Ciuffreda, Donatella Cooperrider, Jennifer H. Tomlinson, Michelle Hauck, Garrett D. Aneja, Jasneet Berger, Christoph Wolski, David Carrington, Mary Wherry, E. John Chung, Raymond T. Tanabe, Kenneth K. Elias, Nahel Freeman, Gordon J. de Kruyff, Rosemarie H. Misdraji, Joseph Kim, Arthur Y. Lauer, Georg M. TI Liver Environment and HCV Replication Affect Human T-Cell Phenotype and Expression of Inhibitory Receptors SO GASTROENTEROLOGY LA English DT Article DE Immune Regulation; Costimulation; T-Cell Exhaustion; Inflammation ID C VIRUS-INFECTION; CHRONIC VIRAL-INFECTION; PD-1 EXPRESSION; CD8(+); EXHAUSTION; LYMPHOCYTES; PERSISTENCE; SUBSETS; ANTIGEN; CD4(+) AB BACKGROUND & AIMS: There is an unclear relationship between inhibitory receptor expression on T cells and their ability to control viral infections. Studies of human immune cells have been mostly limited to T cells from blood, which is often not the site of infection. We investigated the relationship between T-cell location, expression of inhibitory receptors, maturation, and viral control using blood and liver T cells from patients with hepatitis C virus (HCV) and other viral infections. METHODS: We analyzed 36 liver samples from HCV antibody-positive patients (30 from patients with chronic HCV infection, 5 from patients with sustained virological responses to treatment, and 1 from a patient with spontaneous clearance) with 19 paired blood samples and 51 liver samples from HCV-negative patients with 17 paired blood samples. Intrahepatic and circulating lymphocytes were extracted; T-cell markers and inhibitory receptors were quantified for total and virus-specific T cells by flow cytometry. RESULTS: Levels of the markers PD-1 and 2B4 (but not CD160, TIM-3, or LAG-3) were increased on intrahepatic T cells from healthy and diseased liver tissues compared with T cells from blood. HCV-specific intrahepatic CD8(+) T cells from patients with chronic HCV infection were distinct in that they expressed TIM-3 along with PD-1 and 2B4. In comparison, HCV-specific CD8(+) T cells from patients with sustained virological responses and T cells that recognized cytomegalovirus lacked TIM-3 but expressed higher levels of LAG-3; these cells also had different memory phenotypes and proliferative capacity. CONCLUSIONS: T cells from liver express different inhibitory receptors than T cells from blood, independent of liver disease. HCV-specific and cytomegalovirus-specific CD8(+) T cells can be differentiated based on their expression of inhibitory receptors; these correlate with their memory phenotype and levels of proliferation and viral control. C1 [Kroy, Daniela C.; Ciuffreda, Donatella; Cooperrider, Jennifer H.; Tomlinson, Michelle; Hauck, Garrett D.; Aneja, Jasneet; Wolski, David; Chung, Raymond T.; Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Tomlinson, Michelle; Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Elias, Nahel] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Berger, Christoph; Carrington, Mary; Freeman, Gordon J.; de Kruyff, Rosemarie H.; Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Berger, Christoph; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Carrington, Mary] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. [Wherry, E. John] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wherry, E. John] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [de Kruyff, Rosemarie H.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. RP Lauer, GM (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM glauer@mgh.harvard.edu FU Deutsche Forschungsgemeinschaft [Kr3839/1-1]; National Institutes of Health (NIH) [U19 AI082630]; NIH [U19 AI066345, R01 AI105035, P01 AI054456, R01 A1089955]; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; NIH, Frederick National Laboratory, Center for Cancer Research FX Supported by Deutsche Forschungsgemeinschaft (Kr3839/1-1 to D. C. K.), National Institutes of Health (NIH) grant U19 AI082630 (to G. M. L., E.J.W., R. T. C., G.J.F., and J.M.), NIH grant U19 AI066345 (to G. M. L., A.Y.K.), NIH grant R01 AI105035 (to G. M. L.), NIH grant P01 AI054456 (to R. D. K. and G.J.F.), and NIH grant R01 A1089955 (to R. D. K. and G.J.F.). This project was funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. This research was also supported in part by the Intramural Research Program of the NIH, Frederick National Laboratory, Center for Cancer Research. NR 25 TC 26 Z9 30 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 FEB PY 2014 VL 146 IS 2 BP 550 EP 561 DI 10.1053/j.gastro.2013.10.022 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 290LE UT WOS:000329757800035 PM 24148617 ER PT J AU Canto, MI Anandasabapathy, S Brugge, W Falk, GW Dunbar, KB Zhang, Z Woods, K Almario, JA Schell, U Goldblum, J Maitra, A Montgomery, E Kiesslich, R AF Canto, Marcia Irene Anandasabapathy, Sharmila Brugge, William Falk, Gary W. Dunbar, Kerry B. Zhang, Zhe Woods, Kevin Almario, Jose Antonio Schell, Ursula Goldblum, John Maitra, Anirban Montgomery, Elizabeth Kiesslich, Ralf CA Confocal Endomicroscopy Barrett's TI In vivo endomicroscopy improves detection of Barrett's esophagus-related neoplasia: a multicenter international randomized controlled trial (with video) SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CONFOCAL LASER ENDOMICROSCOPY; HIGH-GRADE DYSPLASIA; SURGICAL-TREATMENT; ENDOSCOPY; MANAGEMENT; ADENOCARCINOMA; CLASSIFICATION; SURVEILLANCE; EFFICACY; BIOPSY AB Background: Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the GI tract mucosa. However, there are limited data on endoscope-based CLE (eCLE) for imaging Barrett's esophagus (BE). Objective: To compare high-definition white-light endoscopy (HDWLE) alone with random biopsy (RB) and HDWLE + eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia. Design: Multicenter, randomized, controlled trial. Setting: Academic medical centers. Patients: Adult patients with BE undergoing routine surveillance or referred for early neoplasia. Intervention: Patients were randomized to HDWLE + RB (group 1) or HDWLE + eCLE + TB (group 2). Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2. Blinded expert pathology diagnosis was the reference standard. Main Outcome Measurements: Diagnostic yield, performance characteristics, clinical impact. Results: A total of 192 patients with BE were studied. HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia (34% vs 7%; < .0001), compared with HDWLE + RB but with comparable accuracy. HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia (22% vs 6%; P = .002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (P < .0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients. Limitations: Tertiary-care referral centers and expert endoscopists limit generalizability. Conclusion: Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy. (Clinical trial registration number: NCT01124214.) (Gastrointest Endosc 2014; 79:211-21.) C1 [Canto, Marcia Irene; Almario, Jose Antonio] Johns Hopkins Med Inst, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA. [Anandasabapathy, Sharmila] Mt Sinai Med Ctr, New York, NY 10029 USA. [Brugge, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Falk, Gary W.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dunbar, Kerry B.] Univ Texas SW Med Ctr Dallas, Dallas Vet Affairs Med Ctr, Dallas, TX 75390 USA. [Zhang, Zhe] Johns Hopkins Med Inst, Dept Oncol, Div Biostat & Bioinformat, Baltimore, MD 21205 USA. [Woods, Kevin] Emory Univ, Sch Med, Emory Univ Hosp, Atlanta, GA USA. [Schell, Ursula; Kiesslich, Ralf] Johannes Gutenberg Univ Mainz, D-55122 Mainz, Germany. [Goldblum, John] Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA. [Maitra, Anirban; Montgomery, Elizabeth] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Canto, MI (reprint author), Johns Hopkins Univ, Div Gastroenterol, Johns Hopkins Hosp, 1800 Orleans St,Blalock 407, Baltimore, MD 21287 USA. EM mcanto@jhmi.edu OI Falk, Gary/0000-0002-7143-1436 FU Pentax Medical Corporation; American Society for Gastrointestinal Endoscopy Takeda Research Endowment Fund FX M. Canto received grant support from Pentax Medical Corporation for this trial. Pentax Medical Corporation provided a research grant to help support this investigator-initiated trial but had no influence on the study design, conduct of the study, analysis of the results, or preparation of the manuscript. American Society for Gastrointestinal Endoscopy Takeda Research Endowment Fund. No other financial relationships relevant to this publication were disclosed. NR 31 TC 52 Z9 53 U1 1 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2014 VL 79 IS 2 BP 211 EP 221 DI 10.1016/j.gie.2013.09.020 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 290LO UT WOS:000329759200008 PM 24219822 ER PT J AU Varamini, B Sikalidis, AK Bradford, KL AF Varamini, Behzad Sikalidis, Angelos K. Bradford, Kathryn L. TI Resveratrol increases cerebral glycogen synthase kinase phosphorylation as well as protein levels of drebrin and transthyretin in mice: an exploratory study SO INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION LA English DT Article DE beta-amyloid; Alzheimer's disease; drebrin; glycogen synthase kinase 3-beta; neurodegeneration; resveratrol; tau; transthyretin ID MILD COGNITIVE IMPAIRMENT; APPSWE/PS1DE9 MOUSE MODEL; AMYLOID-BETA PEPTIDES; ALZHEIMERS-DISEASE; METABOLIC DISEASE; INDUCED APOPTOSIS; SIRTUINS; TAU; INHIBITORS; EXPRESSION AB Alzheimer's disease (AD) is characterized by intraneuronal beta-amyloid plaques and hyperphosphorylated tau, leading to neuronal cell death and progressive memory losses. This exploratory work investigates if dietary resveratrol, previously shown to have broad antiaging effects and improve AD pathology in vivo, leads to neuroprotective changes in specific protein targets in the mouse brain. Both wild-type and APP/PS1 mice, a transgenic AD mouse model, received control AIN-93G diet or AIN-93G supplemented with resveratrol. Pathology parameters and AD risk were assessed via measurements on plaque burden, levels of phosphorylated glycogen synthase kinase 3-beta (GSK3-beta), tau, transthyretin and drebrin. Dietary resveratrol treatment did not decrease plaque burden in APP/PS1 mice. However, resveratrol-fed mice demonstrated increases in GSK3-beta phosphorylation, a 3.8-fold increase in protein levels of transthyretin, and a 2.2-fold increase in drebrin. This study broadens our understanding of specific mechanisms and targets whereby resveratrol provides neuroprotection. C1 [Varamini, Behzad; Sikalidis, Angelos K.; Bradford, Kathryn L.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Sikalidis, Angelos K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Inst Med, Boston, MA 02115 USA. RP Varamini, B (reprint author), Cornell Univ, Div Nutr Sci, B40 Savage Hall, Ithaca, NY 14853 USA. EM bv29@cornell.edu OI Varamini, Behzad/0000-0001-8076-6628 FU NIH [DK07158] FX BV was supported by NIH grant DK07158. NR 67 TC 9 Z9 9 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0963-7486 EI 1465-3478 J9 INT J FOOD SCI NUTR JI Int. J. Food Sci. Nutr. PD FEB PY 2014 VL 65 IS 1 BP 89 EP 96 DI 10.3109/09637486.2013.832171 PG 8 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 291TE UT WOS:000329851900013 PM 24020380 ER PT J AU Meng, R Wang, XY Hussain, M Dornbos, D Meng, L Liu, Y Wu, Y Ning, MM Ferdinando, B Lo, EH Ding, YC Ji, XM AF Meng, Ran Wang, Xiaoying Hussain, Mohammed Dornbos, David, III Meng, Lu Liu, Yu Wu, Yan Ning, Mingming Ferdinando S, Buonanno Lo, Eng H. Ding, Yuchuan Ji, Xunming TI Evaluation of plasma D-dimer plus fibrinogen in predicting acute CVST SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE acute; cerebral venous sinus thrombosis; d-dimer; fibrinogen ID CEREBRAL-VENOUS-THROMBOSIS; SINUS THROMBOSIS; PULMONARY-EMBOLISM; DIAGNOSIS; THROMBOEMBOLISM; METAANALYSIS; ASSAY; VENOGRAPHY; INFARCTION; DISEASE AB Background Prompt diagnosis of cerebral venous sinus thrombosis is a challenge owing in part to its complex and non-specific early clinical symptoms. Objective This study aims to evaluate the value of clinically useful biomarkers (d-dimer and fibrinogen) for cerebral venous sinus thrombosis prediction. Methods Two-hundred and thirty-three suspected cerebral venous sinus thrombosis patients were enrolled in this prospective study. Thirty-four cases confirmed as cerebral venous sinus thrombosis using imaging modalities, whereas the other 199 cases served as mimic controls. Plasma samples of 34 healthy controls were further collected from age- and gender-matched volunteers. D-dimer and fibrinogen levels of all patients and controls were measured before imaging and treatment. The dynamic D-dimer and fibrinogen levels in cerebral venous sinus thrombosis cases after anticoagulation were monitored for up to 180 consecutive days. Results At admission before treatment the average D-dimer and fibrinogen levels in cerebral venous sinus thrombosis group were 968.9 +/- 160.1 mu g/l and 6.9 +/- 1.3 g/l, both of which were significantly elevated when compared with that of the controls. In cerebral venous sinus thrombosis patients, 94.1% had D-dimer elevation, 73.5% had fibrinogen elevation, and 67.6% had both elevated D-dimer and fibrinogen. During acute phase, the sensitivity and specificity of predicting cerebral venous sinus thrombosis using only d-dimer were 94.1% and 97.5%, whereas that of D-dimer in combination with fibrinogen were 67.6% and 98.9%. After administering anticoagulation, D-dimer levels gradually recovered; however, fibrinogen levels fluctuated with 33.3% of the patients still exhibiting elevated values up until 180 days. Conclusions D-dimer may serve as an important screening tool to determine the urgency of obtaining magnetic resonance imaging/magnetic resonance venography or digital subtraction angiography in patients presenting with clinical symptoms that are suspected of cerebral venous sinus thrombosis. Furthermore, d-dimer in combination with fibrinogen may increase the predictive value of acute cerebral venous sinus thrombosis. C1 [Meng, Ran; Liu, Yu; Wu, Yan; Ji, Xunming] Capital Med Univ, Key Lab Neurodegenerat Dis, China Amer Inst Neurosci, Cerebral Vasc Dis Res Inst,Xuanwu Hosp,Minist Edu, Beijing 100053, Peoples R China. [Meng, Ran; Liu, Yu; Wu, Yan; Ji, Xunming] Capital Med Univ, Dept Neurol, Xuanwu Hosp, Key Lab Neurodegenerat Dis,Minist Educ, Beijing 100053, Peoples R China. [Meng, Ran; Wang, Xiaoying; Ning, Mingming; Ferdinando S, Buonanno; Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hussain, Mohammed; Dornbos, David, III; Ding, Yuchuan] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. [Meng, Lu] Univ Georgia, Complex Carbohydrate Res Ctr, Dept Biochem & Mol Biol, Athens, GA 30602 USA. RP Ji, XM (reprint author), Capital Med Univ, Xuan Wu Hosp, China Amer Inst Neurosci, Cerebrovasc Dis Res Inst, Beijing 100053, Peoples R China. EM jixm70@ccmu.edu.cn FU China National Natural Science Foundation [30770741]; Talented Technical Personnel Program of Beijing High Level Health Systems [2009-03-02] FX This work was supported in part by the China National Natural Science Foundation (30770741) and the Talented Technical Personnel Program of Beijing High Level Health Systems (2009-03-02). We thank Ms. Jessica L. Poppe for language editorial assistance. NR 38 TC 5 Z9 11 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD FEB PY 2014 VL 9 IS 2 BP 166 EP 173 DI 10.1111/ijs.12034 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 291LH UT WOS:000329829700007 PM 23506130 ER PT J AU Nebenzahl-Guimaraes, H Jacobson, KR Farhat, MR Murray, MB AF Nebenzahl-Guimaraes, Hanna Jacobson, Karen R. Farhat, Maha R. Murray, Megan B. TI Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Review DE M; tuberculosis; microbial susceptibility tests; genetics; SNPs; in vitro resistance ID GENOTYPE MTBDR ASSAY; EMBB CODON 306; DNA GYRASE; ISONIAZID RESISTANCE; ETHAMBUTOL RESISTANCE; IN-VITRO; FLUOROQUINOLONE RESISTANCE; NUCLEOTIDE POLYMORPHISMS; PULMONARY TUBERCULOSIS; QUINOLONE RESISTANCE AB Improving our understanding of the relationship between the genotype and the drug resistance phenotype of Mycobacterium tuberculosis will aid the development of more accurate molecular diagnostics for drug-resistant tuberculosis. Studies that use direct genetic manipulation to identify the mutations that cause M. tuberculosis drug resistance are superior to associational studies in elucidating an individual mutations contribution to the drug resistance phenotype. We systematically reviewed the literature for publications reporting allelic exchange experiments in any of the resistance-associated M. tuberculosis genes. We included studies that introduced single point mutations using specialized linkage transduction or site-directed/in vitro mutagenesis and documented a change in the resistance phenotype. We summarize evidence supporting the causal relationship of 54 different mutations in eight genes (katG, inhA, kasA, embB, embC, rpoB, gyrA and gyrB) and one intergenic region (furA-katG) with resistance to isoniazid, the rifamycins, ethambutol and fluoroquinolones. We observed a significant role for the strain genomic background in modulating the resistance phenotype of 21 of these mutations and found examples of where the same drug resistance mutations caused varying levels of resistance to different members of the same drug class. This systematic review highlights those mutations that have been shown to causally change phenotypic resistance in M. tuberculosis and brings attention to a notable lack of allelic exchange data for several of the genes known to be associated with drug resistance. C1 [Nebenzahl-Guimaraes, Hanna; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nebenzahl-Guimaraes, Hanna] Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands. [Nebenzahl-Guimaraes, Hanna] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal. [Nebenzahl-Guimaraes, Hanna] PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal. [Jacobson, Karen R.] Boston Univ, Sch Med, Infect Dis Sect, Boston, MA 02118 USA. [Jacobson, Karen R.] Boston Med Ctr, Boston, MA 02118 USA. [Jacobson, Karen R.] Univ Stellenbosch, DST NRF Ctr Excellence Biomed TB Res, MRC Ctr Mol Cellular Biol, Div Mol Biol & Human Genet,Fac Med & Hlth Sci, Cape Town, South Africa. [Farhat, Maha R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care, Boston, MA 02114 USA. [Murray, Megan B.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. RP Nebenzahl-Guimaraes, H (reprint author), Natl Inst Publ Hlth & Environm RIVM, POB 1, NL-3720 BA Bilthoven, Netherlands. EM hanna.guimaraes@gmail.com OI Jacobson, Karen/0000-0003-4239-3685 FU Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/33902/2009]; National Institutes of Health/Fogarty International Center [1K01 TW009213]; departmental funds of the pulmonary division of Massachusetts General Hospital; National Institutes of Health/NIAID [U19 A1076217] FX This work was supported by the Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/33902/2009 to H. N.-G.), the National Institutes of Health/Fogarty International Center (1K01 TW009213 to K.R.J.), departmental funds of the pulmonary division of Massachusetts General Hospital to M. R. F. and the National Institutes of Health/NIAID (U19 A1076217 to M.B.M.). NR 59 TC 25 Z9 25 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD FEB PY 2014 VL 69 IS 2 BP 331 EP 342 DI 10.1093/jac/dkt358 PG 12 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 292RY UT WOS:000329921100006 PM 24055765 ER PT J AU Makanji, HS Becker, SJE Mudgal, CS Jupiter, JB Ring, D AF Makanji, H. S. Becker, S. J. E. Mudgal, C. S. Jupiter, J. B. Ring, D. TI Evaluation of the scratch collapse test for the diagnosis of carpal tunnel syndrome SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Article DE Carpal tunnel syndrome; scratch collapse test; diagnosis; electrophysiology ID GENERAL-POPULATION; ELECTROMYOGRAPHY; SENSITIVITY; PREVALENCE AB This prospective study measured and compared the diagnostic performance characteristics of various clinical signs and physical examination manoeuvres for carpal tunnel syndrome (CTS), including the scratch collapse test. Eighty-eight adult patients that were prescribed electrophysiological testing to diagnose CTS were enrolled in the study. Attending surgeons documented symptoms and results of standard clinical manoeuvres. The scratch collapse test had a sensitivity of 31%, which was significantly lower than the sensitivity of Phalen's test (67%), Durkan's test (77%), Tinel's test (43%), CTS-6 lax (88%), and CTS-6 stringent (54%). The scratch test had a specificity of 61%, which was significantly lower than the specificity of thenar atrophy (96%) and significantly higher than the specificity of Durkan's test (18%) and CTS-6 lax (13%). The sensitivity of the scratch collapse test was not superior to other clinical signs and physical examination manoeuvers for CTS, and the specificity of the scratch collapse test was superior to that of Durkan's test and CTS-6 lax. Further studies should seek to limit the influence of a patient's clinical presentation on scratch test performance and assess the scratch test's inter-rater reliability. C1 [Makanji, H. S.; Becker, S. J. E.; Mudgal, C. S.; Jupiter, J. B.; Ring, D.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Becker, Stephanie/N-5761-2014 NR 20 TC 1 Z9 1 U1 0 U2 5 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 FEB PY 2014 VL 39 IS 2 BP 181 EP 186 DI 10.1177/1753193413497191 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 292RB UT WOS:000329918800012 PM 23855039 ER PT J AU Becker, SJE Makanji, HS Ring, D AF Becker, S. J. E. Makanji, H. S. Ring, D. TI Changes in treatment plan for carpal tunnel syndrome based on electrodiagnostic test results SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Article DE Carpal tunnel syndrome; change; electrodiagnostic test; results; treatment plan ID RELEASE; DIAGNOSIS; VALIDATION; SYMPTOMS; SURGERY; HYPOCHONDRIASIS; CRITERIA; OUTCOMES AB This study evaluated how often the treatment plan for carpal tunnel syndrome (CTS) changed based on electrodiagnostic test results. Secondly, we assessed factors associated with a change in the treatment plan for CTS. One-hundred-and-thirty English-speaking adult patients underwent electrodiagnostic testing in a prospective cohort study. Treatment plan was recorded before and after testing. Treatment plan changed in 25 patients (19%) based on electrodiagnostic test results. The plan for operative treatment before testing decreased significantly after testing (83% versus 72%). The best logistic regression model for no change in treatment plan included a prolonged or non-recordable median distal sensory latency (normal, prolonged, or non-recordable), and explained 24% of the variation. For surgeons that manage CTS on the basis of objective pathophysiology rather than symptoms, electrodiagnostic test results often lead to changes in recommended treatment. C1 [Becker, S. J. E.; Makanji, H. S.; Ring, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Becker, Stephanie/N-5761-2014 FU Anna Foundation NOREF; Genootschap Noorthey; Stichting Vreedefonds, the Netherlands FX S. J. E. Becker was supported by the Anna Foundation NOREF, Genootschap Noorthey, and Stichting Vreedefonds, the Netherlands, for Scientific Research. NR 38 TC 3 Z9 3 U1 2 U2 9 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 FEB PY 2014 VL 39 IS 2 BP 187 EP 193 DI 10.1177/1753193413497903 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 292RB UT WOS:000329918800013 PM 23906785 ER PT J AU Wojcik, G Latanich, R Mosbruger, T Astemborski, J Kirk, GD Mehta, SH Goedert, JJ Kim, AY Seaberg, EC Busch, M Thomas, DL Duggal, P Thio, CL AF Wojcik, Genevieve Latanich, Rachel Mosbruger, Tim Astemborski, Jacquie Kirk, Gregory D. Mehta, Shruti H. Goedert, James J. Kim, Arthur Y. Seaberg, Eric C. Busch, Michael Thomas, David L. Duggal, Priya Thio, Chloe L. TI Variants in HAVCR1 Gene Region Contribute to Hepatitis C Persistence in African Americans SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE human genetics; Tim 1; hepatitis C virus ID GENOME-WIDE ASSOCIATION; SPONTANEOUS CLEARANCE; VIRUS-INFECTION; IMPUTATION; GENOTYPES; OUTCOMES AB To confirm previously identified polymorphisms in HAVCR1 that were associated with persistent hepatitis C virus (HCV) infection in individuals of African and of European descent, we studied 165 subjects of African descent and 635 subjects of European descent. Because the association was only confirmed in subjects of African descent (rs6880859; odds ratio, 2.42; P = .01), we then used 379 subjects of African descent (142 with spontaneous HCV clearance) to fine-map HAVCR1. rs111511318 was strongly associated with HCV persistence after adjusting for IL28B and HLA (adjusted P = 8.8 x 10(-4)), as was one 81-kb haplotype (adjusted P = .0006). The HAVCR1 genomic region is an independent genetic determinant of HCV persistence in individuals of African descent. C1 [Wojcik, Genevieve; Kirk, Gregory D.; Mehta, Shruti H.; Seaberg, Eric C.; Thomas, David L.; Duggal, Priya] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Latanich, Rachel; Mosbruger, Tim; Astemborski, Jacquie; Kirk, Gregory D.; Thomas, David L.; Thio, Chloe L.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kim, Arthur Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA USA. [Busch, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Busch, Michael] Blood Syst Res Inst, Viral Reference Lab & Repository Core, San Francisco, CA USA. RP Thio, CL (reprint author), Johns Hopkins Univ, Sch Med, 855 N Wolfe St, Baltimore, MD 21205 USA. EM cthio@jhmi.edu FU National Institutes of Health (NIH) [R01 DA013324, RO1-HL-076902, DA04334, DA12568, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; Intramural Research Program of the National Cancer Institute; NIH [U19-AI-066345, R01-DA031056, R01-DA-033541] FX This project was supported by the National Institutes of Health (NIH; grant number R01 DA013324 to D. L. T.). REVELL is funded by the NIH (grant number RO1-HL-076902). ALIVE is funded by the NIH (grant numbers DA04334 to G. D. K., DA12568 to S. H. M.). The WIHS is funded by the NIH (grant numbers UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant number UO1-HD-32632). WIHS is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, the National Institute on Deafness and Other Communication Disorders, and the National Center for Research Resources (UCSF-CTSI grant number UL1 RR024131). MHCS II is supported in part by the Intramural Research Program of the National Cancer Institute. A. Y. K. is funded by the NIH (grant numbers U19-AI-066345, R01-DA031056, and R01-DA-033541). NR 14 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2014 VL 209 IS 3 BP 355 EP 359 DI 10.1093/infdis/jit444 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 292SE UT WOS:000329921700009 PM 23964107 ER PT J AU Han, JH Maslow, J Han, XY Xie, SX Tolomeo, P Santana, E Carson, L Lautenbach, E AF Han, Jennifer H. Maslow, Joel Han, Xiaoyan Xie, Sharon X. Tolomeo, Pam Santana, Evelyn Carson, Lesley Lautenbach, Ebbing TI Risk Factors for the Development of Gastrointestinal Colonization With Fluoroquinolone-Resistant Escherichia coli in Residents of Long-Term Care Facilities SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Escherichia coli; fluoroquinolones; resistance; long-term care; risk factors ID GRAM-NEGATIVE BACILLI; ANTIBIOTIC-RESISTANCE; ANTIMICROBIAL USE; NURSING-HOMES; MUTATIONS; INFECTIONS; EMERGENCE; IMPACT AB Background. The objective of this study was to assess risk factors for the development of fluoroquinolone (FQ)-resistant Escherichia coli gastrointestinal tract colonization in long-term care facility (LTCF) residents. Methods. A prospective cohort study was conducted from 2006 to 2008 at 3 LTCFs. Residents initially colonized with FQ-susceptible E. coli were followed by means of serial fecal sampling for new FQ-resistant E. coli colonization for up to 12 months or until discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQ-resistant E. coli colonization, with antibiotic and device exposures modeled as time-varying covariates. Results. Fifty-seven (47.5%) of 120 residents became newly colonized with FQ-resistant E. coli, with a median time to colonization of 57 days. Fecal incontinence (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.04-3.06; P = .04) was significantly associated with FQ-resistant E. coli acquisition. Receipt of amoxicillin-clavulanate (HR, 6.48; 95% CI, 1.43-29.4; P = .02) and the presence of a urinary catheter (HR, 3.81; 95% CI, 1.06-13.8; P = .04) during LTCF stay increased the risk of new FQ-resistant E. coli colonization. Conclusions. Acquisition of FQ-resistant E. coli was common, with nearly half of LTCF residents developing new FQ-resistant E. coli colonization. Further studies are needed on interventions to limit the emergence of FQ-resistant E. coli in LTCFs. C1 [Han, Jennifer H.; Lautenbach, Ebbing] Univ Penn, Perelman Sch Med, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. [Han, Jennifer H.; Han, Xiaoyan; Xie, Sharon X.; Tolomeo, Pam; Lautenbach, Ebbing] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Han, Jennifer H.; Han, Xiaoyan; Xie, Sharon X.; Tolomeo, Pam; Lautenbach, Ebbing] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Carson, Lesley] Univ Penn, Perelman Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. [Santana, Evelyn] Philadelphia Vet Affairs Med Ctr, Sect Infect Dis, Philadelphia, PA USA. [Maslow, Joel] Morristown Mem Hosp, Div Infect Dis, Morristown, NJ USA. RP Han, JH (reprint author), Hosp Univ Penn, Div Infect Dis, Dept Med, 811 Blockely Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jennifer.han@uphs.upenn.edu FU National Institutes of Health [R01-AG023792, K24-AI080942]; Pennsylvania State Department of Health (Commonwealth Universal Research Enhancement Program grant); Centers for Disease Control and Prevention Epicenters Program [U54-CK000163] FX This work was supported by the National Institutes of Health (grants R01-AG023792 and K24-AI080942 to E. L.), the Pennsylvania State Department of Health (Commonwealth Universal Research Enhancement Program grant to E. L.), and the Centers for Disease Control and Prevention Epicenters Program (grant U54-CK000163 to E. L.). NR 24 TC 9 Z9 10 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2014 VL 209 IS 3 BP 420 EP 425 DI 10.1093/infdis/jit471 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 292SE UT WOS:000329921700016 PM 23986544 ER PT J AU Bell, RE Khaled, M Netanely, D Schubert, S Golan, T Buxbaum, A Janas, MM Postolsky, B Goldberg, MS Shamir, R Levy, C AF Bell, Rachel E. Khaled, Mehdi Netanely, Dvir Schubert, Steffen Golan, Tamar Buxbaum, Amir Janas, Maja M. Postolsky, Benny Goldberg, Michael S. Shamir, Ron Levy, Carmit TI Transcription Factor/microRNA Axis Blocks Melanoma Invasion Program by miR-211 Targeting NUAK1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID TUMOR-SUPPRESSOR LKB1; CANCER STEM-CELLS; MALIGNANT-MELANOMA; IN-VIVO; EXPRESSION; MICRORNAS; MITF; KINASE; ARK5; GENE AB Melanoma is one of the deadliest human cancers, responsible for approximately 80% of skin cancer mortalities. The aggressiveness of melanoma is due to its capacity to proliferate and rapidly invade surrounding tissues, leading to metastases. A recent model suggests melanoma progresses by reversibly switching between proliferation and invasion transcriptional signatures. Recent studies show that cancer cells are more sensitive to microRNA (miRNA) perturbation than are non-cancer cells; however, the roles of miRNAs in melanoma plasticity remain unexplored. Here, we use the gene expression profiles of melanoma and normal melanocytes to characterize the transcription factor miRNA relationship that modulates the proliferative and invasive programs of melanoma. We identified two sets of miRNAs that likely regulate these programs. Interestingly, one of the miRNAs involved in melanoma invasion is miR-211, a known target of the master regulator microphthalmia-associated transcription factor (MITF). We demonstrate that miR-211 contributes to melanoma adhesion by directly targeting a gene, NUAK1. Inhibition of miR-211 increases NUAK1 expression and decreases melanoma adhesion, whereas upregulation of miR-211 restores adhesion through NUAK1 repression. This study defines the MITF/miR-211 axis that inhibits the invasive program by blocking adhesion. Furthermore, we have identified NUAK1 as a potential target for the treatment of metastatic melanoma. C1 [Bell, Rachel E.; Golan, Tamar; Buxbaum, Amir; Postolsky, Benny; Levy, Carmit] Tel Aviv Univ, Dept Human Genet & Biochem, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Khaled, Mehdi] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Khaled, Mehdi; Schubert, Steffen; Janas, Maja M.; Goldberg, Michael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Khaled, Mehdi; Schubert, Steffen; Janas, Maja M.; Goldberg, Michael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Netanely, Dvir] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. RP Levy, C (reprint author), Tel Aviv Univ, IL-69978 Tel Aviv, Israel. EM carmitlevy@post.tau.ac.il RI khaled, mehdi/C-4854-2012 FU The Israeli Centers for Research Excellence (I-CORE); Israel Cancer Association (ICA); Israel Cancer Research Fund (ICRF); US-Israel Binational Science Fund (BSF); Fritz Thyssen Stiftung; Marie Curie Career Integration Grants (CIG); Dalya Gridinger Fund; Fingerhot Carol; Lionara Fund; Shtacher Family Award; Israel Cancer Research Fund; Raymond and Beverly Sackler Chair in Bioinformatics; Edmond J. Safra Center for Bioinformatics at Tel Aviv University FX We gratefully acknowledge the help received from Dr David Fisher in numerous aspects of this work; Dr Carl Novina and Dr Hanah Margalit are thanked for useful discussions. We would like to extend our gratitude to Dr Meenhard Herlyn and Dr Levi Garraway for supplying melanoma short-term cultures for these studies. CL gratefully acknowledges grants from The Israeli Centers for Research Excellence (I-CORE), Israel Cancer Association (ICA), Israel Cancer Research Fund (ICRF), US-Israel Binational Science Fund (BSF), Fritz Thyssen Stiftung, Marie Curie Career Integration Grants (CIG), Dalya Gridinger Fund, Fingerhot Carol, and Lionara Fund, and the Shtacher Family Award. RS was supported in part by a grant from the Israel Cancer Research Fund and by the Raymond and Beverly Sackler Chair in Bioinformatics. ON was supported in part by a fellowship from the Edmond J. Safra Center for Bioinformatics at Tel Aviv University. NR 64 TC 32 Z9 34 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2014 VL 134 IS 2 BP 441 EP 451 DI 10.1038/jid.2013.340 PG 11 WC Dermatology SC Dermatology GA 292IS UT WOS:000329896000023 PM 23934065 ER PT J AU Breuer, J Gutierrez, J Latchaw, R Lehr, R Sorensen, AG AF Breuer, Josy Gutierrez, Juan Latchaw, Richard Lehr, Robert Sorensen, A. Gregory TI Gadobutrol in the Central Nervous System at Three Doses: Results From a Phase II, Randomized, Multicenter Trial SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE central nervous system; contrast-enhanced magnetic resonance imaging; gadobutrol ID ENHANCED MR-ANGIOGRAPHY; BRAIN-METASTASES; CONTRAST AGENTS; CEREBRAL METASTASES; SAFETY AB PurposeTo investigate the efficacy and safety of three doses of gadobutrol and determine the minimum effective dose for contrast-enhanced MRI of the central nervous system (CNS). Materials and MethodsThis was a Phase II, multicenter, double-blind, parallel-group controlled study in subjects referred for contrast-enhanced MRI of the CNS. Subjects were randomized to receive gadobutrol 0.03, 0.1, or 0.3mmol/kg body weight, and underwent unenhanced, gadobutrol-enhanced, and comparator-enhanced MRI scans. Three blinded readers assessed the images. Primary efficacy variables were number of lesions detected, border delineation, contrast enhancement, and internal morphology. ResultsOf the 229 randomized subjects, 173 were evaluated for efficacy. Clinically meaningful improvements in lesion border delineation, contrast enhancement, and internal morphology were observed for 0.1mmol/kg gadobutrol. Pair-wise comparisons of a composite score of the four primary variables showed the 0.1mmol/kg dose to be statistically superior to the 0.03mmol/kg dose (P=0.003). The 0.3mmol/kg dose showed no statistically significant difference with the 0.1mmol/kg dose. Twenty-two (9.8%) subjects reported at least one treatment-emergent adverse event (TEAE). No TEAE was reported at an incidence >3.5%. ConclusionThe 0.1mmol/kg dose of gadobutrol was effective and well tolerated for contrast-enhanced MRI of the CNS. J. Magn. Reson. Imaging 2014;39:410-418. (c) 2013 Wiley Periodicals, Inc. C1 [Breuer, Josy; Lehr, Robert] Bayer Healthcare Pharmaceut, Berlin, Germany. [Gutierrez, Juan] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Latchaw, Richard] Univ Calif Davis, Davis Med Ctr, Sacramento, CA 95817 USA. [Sorensen, A. Gregory] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. RP Breuer, J (reprint author), Bayer Healthcare Pharmaceut Pharma AG, Muellerstr 178, D-13352 Berlin, Germany. EM josy.breuer@bayer.com FU Bayer Healthcare Pharmaceuticals; ACRIN; NIH/NCI; Siemens; AstraZeneca; Breakaway Imaging; Eli Lilly; Genentech; EPIX Pharmaceuticals; General Electric Healthcare; Mitsubishi Pharma; Thermal Technologies; Novartis FX Clinical trial registration number: NCT00862459: Dose finding study of gadavist in central nervous system (CNS) magnetic resonance imaging (MRI). Registry: ClinicalTrials.gov. Author Disclosures: Josy Breuer and Robert Lehr are full-time employees of Bayer Healthcare Pharmaceuticals. Juan Gutierrez has received speaker bureau fees from Bayer Healthcare Pharmaceuticals. Richard Latchaw has no disclosure. Gregory Sorensen has a salary from ACRIN, royalties from General Electric and Olea Medical, has contracted research with NIH/NCI and Siemens, received consultancy fees and grant support from AstraZeneca, and received consultancy fees from Bayer Healthcare Pharmaceuticals, Breakaway Imaging, Eli Lilly, Genentech, EPIX Pharmaceuticals, General Electric Healthcare, Mitsubishi Pharma, Thermal Technologies, and Novartis. NR 25 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD FEB PY 2014 VL 39 IS 2 BP 410 EP 418 DI 10.1002/jmri.24180 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 290KA UT WOS:000329753400020 PM 23681501 ER PT J AU Peacock, ZS Aghaloo, T Bouloux, GF Cillo, JE Hale, RG Le, AD Lee, JS Kademani, D AF Peacock, Zachary S. Aghaloo, Tara Bouloux, Gary F. Cillo, Joseph E., Jr. Hale, Robert G. Le, Anh D. Lee, Janice S. Kademani, Deepak TI Proceedings From the 2013 American Association of Oral and Maxillofacial Surgeons Research Summit SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID BISPHOSPHONATE-RELATED OSTEONECROSIS; TRANSORAL ROBOTIC SURGERY; ADVANCED OROPHARYNX CANCER; SQUAMOUS-CELL CARCINOMA; JAW-LIKE DISEASE; RISK-FACTORS; MULTIPLE-MYELOMA; HUMAN-PAPILLOMAVIRUS; SURGICAL-MANAGEMENT; PARATHYROID-HORMONE AB The American Association of Oral and Maxillofacial Surgeons, the Oral and Maxillofacial Surgery Foundation, and the International Association of Oral and Maxillofacial Surgeons sponsored the fifth research summit, which convened on May 2 and 3 in Rosemont, Illinois. The Research Summits are convened biennially to facilitate the discussion and collaboration of oral and maxillofacial surgeons with clinical and basic science researchers in fields affecting the specialty. The goal is to advance the field of oral and maxillofacial surgery through exposure and education in topics that ultimately benefit the oral and maxillofacial surgical patient. This edition of the research summit included the topics of robotic surgery and antiresorptive-related osteonecrosis of the jaws (ARONJ). Most importantly, this research summit saw the development of research interest groups (RIGs) in the fields of anesthesia, maxillofacial oncology and reconstructive surgery, obstructive sleep apnea and orthognathic surgery, temporomandibular joint surgery, and trauma. These RIGs developed specific research goals with a plan to continue working on potential projects at the AAOMS Clinical Trials Course on May 7 to 9, 2013 at the University of Michigan in Ann Arbor. The summit program was developed by the AAOMS Committee on Research Planning and Technology Assessment. The charge of the committee is to encourage and promote research within the specialty and to encourage interdisciplinary collaboration. The research summit serves as a platform for oral and maxillofacial surgeons to lead the goal of advancement of research relevant to the specialty. This article provides an overview of the presentations that were made in the sessions on robotic surgery and ARONJ. The research summit keynote address and two additional presentations on patient registries are summarized and updates from the RIGs that were formed at the 2013 research summit are highlighted. (C) 2014 American Association of Oral and Maxillofacial Surgeons C1 [Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Aghaloo, Tara] Univ Calif Los Angeles, Div Oral & Maxillofacial Surg, Los Angeles, CA USA. [Bouloux, Gary F.] Emory Univ, Sch Med, Dept Surg, Div Oral & Maxillofacial Surg, Atlanta, GA 30322 USA. [Cillo, Joseph E., Jr.] Allegheny Gen Hosp, Div Oral & Maxillofacial Surg, Pittsburgh, PA 15212 USA. [Hale, Robert G.] US Army, Inst Surg Res, Ft Sam Houston, TX 78234 USA. [Le, Anh D.] Univ Penn, Dept Oral & Maxillofacial Surg Pharmacol, Philadelphia, PA 19104 USA. [Lee, Janice S.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Kademani, Deepak] Univ Minnesota, Div Oral & Maxillofacial Surg, Minneapolis, MN USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM zpeacock@partners.org NR 95 TC 1 Z9 1 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2014 VL 72 IS 2 BP 241 EP 253 DI 10.1016/j.joms.2013.09.037 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 290KV UT WOS:000329756500005 PM 24438595 ER PT J AU Susarla, SM Peacock, ZS Williams, WB Rabinov, JD Keith, DA Kaban, LB AF Susarla, Srinivas M. Peacock, Zachary S. Williams, W. Bradford Rabinov, James D. Keith, David A. Kaban, Leonard B. TI Role of Computed Tomographic Angiography in Treatment of Patients With Temporomandibular Joint Ankylosis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INTERNAL MAXILLARY ARTERY; LEFORT-I OSTEOTOMY; DIRECT-PUNCTURE; ARTERIOVENOUS-MALFORMATIONS; COIL EMBOLIZATION; MANAGEMENT; PSEUDOANEURYSM; HEMORRHAGE; PROTOCOL; SURGERY AB Purpose: To evaluate the use of preoperative computed tomographic angiography (CTA) and selective embolization as an ancillary tool for the treatment of patients with temporomandibular joint (TMJ) ankylosis. Materials and Methods: The present study was a case series of subjects with bilateral TMJ ankylosis who had undergone preoperative CTA and surgical release with immediate reconstruction. The indications for CTA were either an intimate association between the vessels and the ankylotic mass on the facial computed tomography (CT) scan or a history of multiple previous TMJ operations. In cases in which intimate anatomic association was present between the branches of the maxillary artery and the ankylotic masses, preoperative selective embolization was performed. All subjects underwent a standard approach to ankylosis release with immediate reconstruction and were followed up for up to 6 months postoperatively. The demographic and operative variables were recorded for each subject. Results: Five subjects (mean age, 36.4 years; 3 females) with bilateral TMJ ankylosis underwent release and had undergone preoperative CTA for vascular assessment. Three subjects underwent preoperative embolization. The total operating time ranged from 5.9 to 10.3 hours. The intraoperative blood loss ranged from 150 to 3,750 mL. One patient who had undergone unilateral embolization required an intraoperative transfusion because of bleeding on the nonembolized side. No adverse cardiac, renal, or neurologic events developed secondary to the blood loss. In all 5 subjects, the preoperative maximal incisor opening was less than 15 mm, increased to more than 35 mm intraoperatively, and was 30 mm or more at 6 months or longer of follow-up. Conclusions: In select cases, CTA can be a useful adjunct in the treatment of patients with TMJ ankylosis. (C) 2014 American Association of Oral and Maxillofacial Surgeons C1 [Susarla, Srinivas M.] Johns Hopkins Univ, Johns Hopkins Hosp, Sch Med, Dept Plast & Reconstruct Surg, Baltimore, MD USA. [Susarla, Srinivas M.; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Peacock, Zachary S.; Keith, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med & Attending Oral & Maxillofacial Sur, Boston, MA 02115 USA. [Williams, W. Bradford] Santa Clara Med Ctr, Dept Plast Surg, Santa Clara, CA USA. [Rabinov, James D.] Harvard Univ, Sch Med, Boston, MA USA. [Rabinov, James D.] Dept Radiol, Div Intervent Neuroradiol, Boston, MA USA. [Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Susarla, SM (reprint author), Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, 204 E Joppa Rd,1203, Towson, MD 21286 USA. EM ssusarl1@jhmi.edu OI Susarla, Srinivas/0000-0003-0155-8260 FU Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation FX This study was supported by the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (SMS, ZSP) and the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation (SMS). NR 25 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2014 VL 72 IS 2 BP 267 EP 276 DI 10.1016/j.joms.2013.09.024 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 290KV UT WOS:000329756500009 PM 24268963 ER PT J AU Cooper, JA Tucker, VL Papakostas, GI AF Cooper, James A. Tucker, Vivian L. Papakostas, George I. TI Resolution of sleepiness and fatigue: A comparison of bupropion and selective serotonin reuptake inhibitors in subjects with major depressive disorder achieving remission at doses approved in the European Union SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE Bupropion; major depressive disorder; fatigue; remission; sleepiness ID DOUBLE-BLIND; RESIDUAL SYMPTOMS; MODAFINIL AUGMENTATION; SUSTAINED-RELEASE; ANTIDEPRESSANT EFFICACY; FLUOXETINE; OUTPATIENTS; DISABILITY; MANAGEMENT; SERTRALINE AB Unlike selective serotonin reuptake inhibitors (SSRIs), bupropion may be classified as a dual noradrenaline and dopamine reuptake inhibitor, a difference with potential implications for the treatment of residual sleepiness and fatigue in major depressive disorder (MDD). Post-hoc analysis of subjects with remitted MDD was performed on data pooled from six double-blind, randomized trials comparing the European Union (EU)-approved dose of 300 mg/day bupropion with SSRIs (sertraline, paroxetine or escitalopram) for the resolution of sleepiness and fatigue. Hypersomnia score was defined as the sum of scores of the Hamilton Depression Rating Scale (HDRS) items 22, 23, and 24; fatigue score as HDRS item 13 score; and remission as HDRS-177. Similar proportions of bupropion- and SSRI-treated subjects achieved remission at study endpoint (169/343, 49.3% vs 324/656, 49.4%; last observation carried forward (LOCF), p=0.45). Fewer bupropion-treated remitters had residual symptoms of sleepiness (32/169, 18.9% vs 104/324, 32.1%; p<0.01) and fatigue (33/169, 19.5% vs 98/324, 30.2%; p<0.05). Bupropion-treated remitters also showed greater improvement (mean change from baseline) in sleepiness (p<0.05) and fatigue scores (p<0.01) at endpoint: benefits were evident from week 2 for sleepiness (p<0.01) and week 4 for fatigue (p<0.01). Bupropion treatment at the EU-approved dose of 300 mg/day may offer advantages over SSRIs in the resolution of sleepiness and fatigue in remitted MDD patients. C1 [Cooper, James A.] GlaxoSmithKline, Brentford TW8 9GS, Middx, England. [Tucker, Vivian L.] GlaxoSmithKline, Res Triangle Pk, NC USA. [Papakostas, George I.] Massachusetts Gen Hosp, Depress Clin Res Program, Boston, MA 02114 USA. RP Cooper, JA (reprint author), GlaxoSmithKline, 980 Great West Rd, Brentford TW8 9GS, Middx, England. EM james.5.cooper@gsk.com FU GlaxoSmithKline FX All listed authors met the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors wish to acknowledge the following individuals for their assistance with study management and critical review during the development of the manuscript: Alok Krishen, Kalpesh Joshi, Leigh Ragone and Nathalie Richard, all of whom are employees of GlaxoSmithKline. Editorial support, in the form of development, assembling tables and figures, collating author comments, copyediting, fact checking and referencing, was provided by Annirudha Chillar of Cactus Communications Inc., and funded by GlaxoSmithKline. NR 47 TC 12 Z9 13 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 EI 1461-7285 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD FEB PY 2014 VL 28 IS 2 BP 118 EP 124 DI 10.1177/0269881113514878 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 292JB UT WOS:000329896900004 PM 24352716 ER PT J AU Keung, EZ Hornick, JL Bertagnolli, MM Baldini, EH Raut, CP AF Keung, Emily Z. Hornick, Jason L. Bertagnolli, Monica M. Baldini, Elizabeth H. Raut, Chandrajit P. TI Predictors of Outcomes in Patients with Primary Retroperitoneal Dedifferentiated Liposarcoma Undergoing Surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PREOPERATIVE RADIATION-THERAPY; SOFT-TISSUE SARCOMA; LOCOREGIONAL RECURRENCE; HISTOLOGIC SUBTYPE; SINGLE INSTITUTION; DOSE-ESCALATION; MANAGEMENT; RESECTION; SURVIVAL; PATTERN AB BACKGROUND: Although sarcoma histology is recognized as a prognostic factor, most studies of retroperitoneal sarcomas report results combining multiple histologies and are inadequately powered to identify prognostic factors specific to a particular histology. We reviewed our experience with retroperitoneal dedifferentiated liposarcoma (RP DDLPS) to identify factors predictive of outcomes. STUDY DESIGN: All patients with RP DDLPS treated at our institution between 1998 and 2008 were reviewed. Multivariable Cox regression analyses were performed to identify factors predictive of progression-free survival (PFS), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and overall survival (OS). RESULTS: We identified 119 patients with primary DDLPS. Median tumor size was 20.5 cm; 21% were multifocal. French Federation of Cancer Centers Sarcoma Group tumor grades were intermediate in 53% of patients and high in 28% (unknown 19%). Resections were complete (R0/R1) in 80% of patients and incomplete (R2) in 11% (unknown 9%). Tumors were removed intact in 72% of patients and fragmented in 16% (unknown 12%). Median follow-up was 74.1 months. One hundred patients (84%) experienced recurrence or progression, with 92% occurring in the retroperitoneum. Median PFS, LRFS, DRFS, and OS were 21.1, 21.5, 45.8, and 59.0 months, respectively, and were significantly worse with R2 resection. On multivariate analysis, tumor integrity (intact vs fragmented) was predictive of PFS, multifocality predicted LRFS, and extent of resection (R0/R1 vs R2), grade, and tumor integrity predicted OS. CONCLUSIONS: In this cohort of primary RP DDLPS, factors under surgeon control (tumor integrity, extent of resection) and reflective of tumor biology (grade, multifocality) impact patient outcomes. (JAmColl Surg 2014; 218: 206-217. (C) 2014 by the American College of Surgeons) C1 [Keung, Emily Z.; Bertagnolli, Monica M.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Baldini, Elizabeth H.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Keung, Emily Z.; Hornick, Jason L.; Bertagnolli, Monica M.; Baldini, Elizabeth H.; Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Keung, Emily Z.; Hornick, Jason L.; Bertagnolli, Monica M.; Baldini, Elizabeth H.; Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 27 TC 23 Z9 25 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 2014 VL 218 IS 2 BP 206 EP 217 DI 10.1016/j.jamcollsurg.2013.10.009 PG 12 WC Surgery SC Surgery GA 290NB UT WOS:000329763900010 PM 24315890 ER PT J AU Melis, M Pinna, A Okochi, S Masi, A Rosman, AS Neihaus, D Saunders, JK Newman, E Gouge, TH AF Melis, Marcovalerio Pinna, Antonio Okochi, Shunpei Masi, Antonio Rosman, Alan S. Neihaus, Dena Saunders, John K. Newman, Elliot Gouge, Thomas H. TI Validation of the Surgical Apgar Score in a Veteran Population Undergoing General Surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID MORBIDITY AB BACKGROUND: The Surgical Apgar Score (SAS, a 10-point score calculated using limited intraoperative data) can correlate with postoperative morbidity and mortality after general surgery. We evaluated reliability of SAS in a veteran population. STUDY DESIGN: We prospectively collected demographics, medical history, type of surgery, and postoperative outcomes for any veteran undergoing general surgery at our institution (2006-2011). We categorized patients in 4 SAS groups and compared differences in morbidity and mortality. RESULTS: Our study population included 2,125 patients (SAS <= 4: n = 29; SAS 5 - 6: n = 227; SAS 7 - 8: n = 797; SAS 9 - 10: n = 1,072). Low-SAS patients were likely to have significant preoperative comorbidities and to undergo major surgery, and had increased postoperative morbidity and 30-day mortality. CONCLUSIONS: The SAS is easily calculated from 3 routinely available intraoperative measurements, correlates with fixed preoperative risk (acute conditions, pre-existing comorbidities, operative complexity), and effectively identifies veterans at high risk for postoperative complications. (J Am Coll Surg 2014; 218: 218-225. (C) 2014 by the American College of Surgeons) C1 [Melis, Marcovalerio; Pinna, Antonio; Okochi, Shunpei; Masi, Antonio; Neihaus, Dena; Saunders, John K.; Newman, Elliot; Gouge, Thomas H.] VAMC, New York Harbor Healthcare Syst, Dept Surg, Washington, DC USA. [Melis, Marcovalerio; Pinna, Antonio; Masi, Antonio; Saunders, John K.; Newman, Elliot; Gouge, Thomas H.] NYU, Sch Med, Dept Surg, New York, NY 10010 USA. [Pinna, Antonio] Univ Sassari, Clin Chirurg, Dept Gen Surg, I-07100 Sassari, Italy. [Rosman, Alan S.] Mt Sinai Sch Med, Gastroenterol Sect, New York, NY USA. [Rosman, Alan S.] Mt Sinai Sch Med, Program Med, New York, NY USA. [Rosman, Alan S.] James J Peters VAMC, New York, NY USA. RP Melis, M (reprint author), NYU, Sch Med, 423 East 23rd St,Rm 4153 N, New York, NY 10010 USA. EM marcovalerio.melis@nyumc.org OI Pinna, Antonio/0000-0002-2187-6744; Gouge, Thomas/0000-0001-8381-4146 NR 11 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 2014 VL 218 IS 2 BP 218 EP 225 DI 10.1016/j.jamcollsurg.2013.10.021 PG 8 WC Surgery SC Surgery GA 290NB UT WOS:000329763900011 PM 24315891 ER PT J AU Araki, K Conrad, C Ogiso, S Kuwano, H Gayet, B AF Araki, Kenichiro Conrad, Claudius Ogiso, Satoshi Kuwano, Hiroyuki Gayet, Brice TI Intraoperative Ultrasonography of Laparoscopic Hepatectomy: Key Technique for Safe Liver Transection SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OPEN HEPATIC RESECTION; ULTRASOUND; TUMORS C1 [Araki, Kenichiro; Conrad, Claudius; Ogiso, Satoshi; Gayet, Brice] Paris Descartes Univ, Inst Mutualiste Montsouris, Dept Digest Dis, F-75014 Paris, France. [Araki, Kenichiro; Kuwano, Hiroyuki] Gunma Univ, Grad Sch Med, Dept Gen Surg Sci Surg 1, Gunma, Japan. [Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Gayet, B (reprint author), Paris Descartes Univ, Inst Mutualiste Montsouris, Dept Digest Dis, 42 Brouvard Jourdan, F-75014 Paris, France. EM brice.gayet@imm.fr NR 11 TC 16 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 2014 VL 218 IS 2 BP E37 EP E41 DI 10.1016/j.jamcollsurg.2013.10.022 PG 5 WC Surgery SC Surgery GA 290NB UT WOS:000329763900002 PM 24315651 ER PT J AU Shoag, J Eisner, BH AF Shoag, Jonathan Eisner, Brian H. TI Relationship between C-reactive Protein and Kidney Stone Prevalence SO JOURNAL OF UROLOGY LA English DT Article DE kidney; nephrolithiasis; C-reactive protein; nutrition surveys; age groups ID URINARY-TRACT; UNITED-STATES; NEPHROLITHIASIS; RISK; BIOMARKERS AB Purpose: We evaluated the relationship between serum C-reactive protein and the lifetime kidney stone prevalence. Materials and Methods: We performed a cross-sectional study of participants from the Continuous National Health and Nutrition Examination Survey (NHANES) from 2007 to 2008 and 2008 to 2009. Data were available on 11,033 participants. Results: On univariate analysis we noted a strong correlation between C-reactive protein quintile and kidney stone history. After adjusting for known confounders multivariate logistic regression revealed a significant relationship between C-reactive protein and the lifetime prevalence of kidney stones in younger individuals (age 20 to 39 years, p for trend - 0.002). In individuals 20 to 39 years old the lifetime prevalence of kidney stones increased with increasing C-reactive protein quintile (p 0.002 for trend), specifically, those in the third quintile (OR 3.86, 95% CI 1.07-13.88, p = 0.04) and the fifth quintile (OR 3.85, 95% CI 1.46-10.17, p = 0.009). The fourth quintile of C-reactive protein approached statistical significance (OR 2.56, 95% CI 0.96-6.81, p = 0.059). The relationship between C-reactive protein and kidney stone history was not significant in the older age groups (40 to 59 and 60 years or greater). Conclusions: There exists a significant relationship between serum C-reactive protein and self-reported kidney stones in younger individuals. This may shed light on potential mechanisms of stone formation in this age group and help gain a better understanding of stone risk mediators. Further studies are needed to understand the mechanisms underlying these epidemiological findings. C1 New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Urol, New York, NY USA. [Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Eisner, BH (reprint author), Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 25 TC 1 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD FEB PY 2014 VL 191 IS 2 BP 372 EP 375 DI 10.1016/j.juro.2013.09.033 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 291MM UT WOS:000329832800033 PM 24071479 ER PT J AU Sedaghat, AR Gray, ST Kieff, DA AF Sedaghat, Ahmad R. Gray, Stacey T. Kieff, David A. TI Preapproval of Sinus Computed Tomography for Otolaryngologic Evaluation of Chronic Rhinosinusitis Does Not Save Health Care Costs SO LARYNGOSCOPE LA English DT Article DE Chronic rhinosinusitis; computed tomography; delivery of health care; insurance; health; nasal surgical procedures; endoscopic sinus surgery; health policy; preauthorization; preapproval ID PRIOR-AUTHORIZATION PROGRAMS AB Objectives/HypothesisTo evaluate the cost-effectiveness of preapproval requirements for computed tomography (CT) of the sinuses in the evaluation and management of chronic rhinosinusitis (CRS). Study DesignRetrospective analysis of prospectively collected data. MethodsOver a 6-month period, all sinus CT scans ordered by an otolaryngology practice and requiring preapproval by a third-party payor were tabulated. Characteristics of the preapproval process that were recorded and analyzed included time spent by office administrative staff, need for peer-to-peer review, and time spent by the ordering physician. ResultsAll 111 sinus CT scans ordered during the 6-month time period required preapproval based on insurer requirements38 performed by computer, 71 by telephone, and two required bothcosting an average of 8.1 minutes per scan by administrative staff (range, 2.0-20.0 minutes). Thirteen preapprovals required peer-to-peer telephone interaction by the ordering physician, utilizing an average of 7.7 minutes (range, 5-12 minutes). In no case was the insurance company peer an otolaryngologist. Ultimately, no sinus CT scan request was rejected by a third-party payor. ConclusionsPreapprovals for sinus CTs ordered by otolaryngologists are unlikely to save costs for third-party payors, as sinus CT for the evaluation of CRS is well established and therefore unlikely to be rejected. Preapproval in this context comes at the expense of practice administrative and physicians' time. Based on our results, preapproval for sinus CT scans ordered by an otolaryngologist for evaluation of CRS appears to be an unnecessary and costly requirement. Laryngoscope, 124:373-377, 2014 Level of EvidenceN/A. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 15 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2014 VL 124 IS 2 BP 373 EP 377 DI 10.1002/lary.24269 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 292VE UT WOS:000329929900013 PM 23794515 ER PT J AU Mayerhoff, RM Guzman, M Jackson-Menaldi, C Munoz, D Dowdall, J Maki, A Johns, MM Smith, LJ Rubin, AD AF Mayerhoff, Ross M. Guzman, Marco Jackson-Menaldi, Cristina Munoz, Daniel Dowdall, Jayme Maki, Ahmed Johns, Michael M., III Smith, Libby J. Rubin, Adam D. TI Analysis of Supraglottic Activity During Vocalization in Healthy Singers SO LARYNGOSCOPE LA English DT Article DE Laryngeal hyperfunction; supraglottic hyperfunction; laryngoscopy; videostroboscopy; singing voice; classical singers; dysphonia ID VOCAL HYPERFUNCTION; TENSION DYSPHONIA; VOICE DISORDERS; LARYNGEAL; FEATURES; TRACT AB Objectives/HypothesisThe present study aims to evaluate the degree of anterior-posterior and medial supraglottic laryngeal compression in healthy singers of different voice classifications while singing different pitches, loudness, and phonatory tasks. Study DesignProspective study. MethodsThirty-six classically trained singers (11 sopranos, 11 mezzo-sopranos, six tenors, and eight baritones) with at least 5 years of voice training and absence of any voice pathology within the past year were included. Flexible endoscopic voice evaluations were recorded and edited to include samples of different pitches, levels of loudness, and phonatory tasks. Sound was removed from the video samples. Two blinded laryngologists were asked to assess medial and anterior-posterior supraglottic compression using a visual analog scale for each sample. ResultsMedial compression was significantly greater in male subjects and specifically tenors during loud phonation, during high pitch, and while phonating the vowel /a/. Anterior-posterior compression was also significantly greater in males and specifically baritones during loud voice production and with phonation of the vowel /a/. No difference was noted in relation to pitch. Correlation between anterior-posterior and medial compression was demonstrated. Medial compression was less severe than anterior-posterior compression. ConclusionsSupraglottic hyperfunction is present in healthy singers. Recognizing factors that might affect supraglottic hyperfunction in the healthy voice may help us to understand when hyperfunction is truly contributing to a patient's vocal pathology. Level of Evidence4. Laryngoscope, 124:504-509, 2014 C1 [Mayerhoff, Ross M.; Jackson-Menaldi, Cristina] Wayne State Univ, Dept Otolaryngol Head & Neck Surg, Detroit, MI USA. [Guzman, Marco] Univ Chile, Sch Commun Sci, Santiago, Chile. [Guzman, Marco] Clin Las Condes, Voice Ctr, Santiago, Chile. [Jackson-Menaldi, Cristina; Rubin, Adam D.] Lakeshore Ear Nose & Throat Ctr, Lakeshore Profess Voice Ctr, St Clair Shores, MI USA. [Munoz, Daniel] Barros Luco Trudeau Hosp, Dept Network Management, Santiago, Chile. [Dowdall, Jayme] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Dowdall, Jayme] Brigham & Womens Hosp, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Maki, Ahmed] McLaren Oakland, Pontiac, MI USA. [Maki, Ahmed] Michigan State Univ, E Lansing, MI 48824 USA. [Johns, Michael M., III] Emory Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Atlanta, GA USA. [Johns, Michael M., III] Emory Voice Ctr, Atlanta, GA USA. [Smith, Libby J.] Univ Pittsburgh, Med Ctr, Dept Otolaryngol Head & Neck Surg, Pittsburgh, PA USA. [Rubin, Adam D.] Univ Michigan, Med Ctr, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. RP Rubin, AD (reprint author), 21000 E Twele Mile Rd,Suite 111, St Clair Shores, MI 48081 USA. EM rubinad1968@gmail.com NR 26 TC 4 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2014 VL 124 IS 2 BP 504 EP 509 DI 10.1002/lary.24310 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 292VE UT WOS:000329929900037 PM 23877891 ER PT J AU Rachakonda, T Jeffe, DB Shin, JJ Mankarious, L Fanning, RJ Lesperance, MM Lieu, JEC AF Rachakonda, Tara Jeffe, Donna B. Shin, Jennifer J. Mankarious, Leila Fanning, Robert J. Lesperance, Marci M. Lieu, Judith E. C. TI Validity, Discriminative Ability, and Reliability of the Hearing-Related Quality of Life Questionnaire for Adolescents SO LARYNGOSCOPE LA English DT Article DE Adolescents; quality of life; hearing loss; validation study ID MENTAL-HEALTH; EDUCATIONAL-ATTAINMENT; HANDICAP INVENTORY; CHILDREN; ADULTS; IMPAIRMENTS; PREVALENCE; FORCE; YOUTH; USERS AB Objectives/HypothesisThe prevalence of hearing loss (HL) in adolescents has grown over the past decade, but hearing-related quality of life (QOL) has not been well-measured. We sought to develop a reliable, valid measure of hearing-related QOL for adolescents and the Hearing Environments And Reflection on Quality of Life (HEAR-QL). Study DesignMultisite observational study. MethodsAdolescents with HL and siblings without HL were recruited from five centers. Participants completed the HEAR-QL and validated questionnaires measuring generic pediatric QOL (PedsQL), depression and anxiety (RCADS-25), and hearing-related QOL for adults (HHIA) to determine construct and discriminant validity. Participants completed the HEAR-QL 2 weeks later for test-retest reliability. We used exploratory principal components analysis to determine the HEAR-QL factor structure and measured reliability. Sensitivity and specificity of the HEAR-QL, PedsQL, HHIA, and RCADS-25 were assessed. We compared scores on all surveys between those with normal hearing, unilateral, and bilateral HL. ResultsA total of 233 adolescents (13-18 years old) participated: 179 with HL, 54 without HL. The original 45-item HEAR-QL was shortened to 28 items after determining factor structure. The resulting HEAR-QL-28 demonstrated excellent reliability (Cronbach's alpha=0.95) and construct validity (HHIA: r=.845, PedsQL: r=.587; RCADS-25: r=.433). The HEAR-QL-28 displayed excellent discriminant validity, with higher area under the curve (0.932) than the PedsQL (0.597) or RCADS-25 (0.529). Teens with bilateral HL using hearing devices reported worse QOL on the HEAR-QL and HHIA than peers with HL not using devices. ConclusionsThe HEAR-QL is a sensitive, reliable, and valid measure of hearing-related QOL for adolescents. Level of Evidence2b. Laryngoscope, 124:570-578, 2014 C1 [Rachakonda, Tara; Lieu, Judith E. C.] Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. [Jeffe, Donna B.] Washington Univ, Sch Med, Dept Med Hlth Behav Res, St Louis, MO USA. [Shin, Jennifer J.; Mankarious, Leila] Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. [Fanning, Robert J.] Phoenix Childrens Hosp, Dept Audiol, Barrow Neurol Inst, Phoenix, AZ USA. [Lesperance, Marci M.] Univ Michigan Hlth Syst, Div Pediat Otolaryngol, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI USA. RP Lieu, JEC (reprint author), 660 S Euclid Ave,Campus Box 8115, St Louis, MO 63110 USA. EM lieuj@wustl.edu FU American Hearing Research Foundation (AHRF) Wiley H. Harrison Memorial Research Award; Clinical and Translational Science Award; NIH/National Center for Research Resources (NCRR)/National Center for Advancing Translational Science (NCATS) [UL1RR024992]; National Institutes of Health (NIH) [K23 DC006638]; National Cancer Institute (NCI) Cancer Center [P30 CA091842]; [5T32DC000022-2] FX Funding for this study was obtained from the American Hearing Research Foundation (AHRF) Wiley H. Harrison Memorial Research Award and the Clinical and Translational Science Award to Washington University, funded by NIH/National Center for Research Resources (NCRR)/National Center for Advancing Translational Science (NCATS) grant (UL1RR024992). Dr. Lieu was supported in part by a National Institutes of Health (NIH) grant (K23 DC006638). Dr. Rachakonda also was supported by a training grant (5T32DC000022-2). Dr. Jeffe was supported in part by funding from the National Cancer Institute (NCI) Cancer Center Support Grant (P30 CA091842) to the Siteman Cancer Center for services provided through the Health Behavior, Communication, and Outreach Core. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the AHRF, NCRR, NCATS, NCI, or NIH. The authors have no funding, financial relationships, or conflicts of interest to disclose. NR 27 TC 5 Z9 5 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2014 VL 124 IS 2 BP 570 EP 578 DI 10.1002/lary.24336 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 292VE UT WOS:000329929900049 PM 23900836 ER PT J AU Pies, C Kotelchuck, M AF Pies, Cheri Kotelchuck, Milton TI Bringing the MCH Life Course Perspective to Life SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Editorial Material ID CHRONIC DISEASE EPIDEMIOLOGY; HEALTH-PROMOTION; PREVENTION C1 [Pies, Cheri] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Kotelchuck, Milton] MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Res & Policy, Boston, MA USA. [Kotelchuck, Milton] Harvard Univ, Sch Med, Boston, MA USA. RP Pies, C (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 279 Univ Hall, Berkeley, CA 94720 USA. EM cpies@berkeley.edu; mkotelchuck@partners.org NR 34 TC 4 Z9 4 U1 1 U2 9 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 FEB PY 2014 VL 18 IS 2 SI SI BP 335 EP 338 DI 10.1007/s10995-013-1408-5 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 290XD UT WOS:000329790900001 PM 24352623 ER PT J AU Lartey, FM Ahn, GO Shen, B Cord, KT Smith, T Chua, JY Rosenblum, S Liu, HG James, ML Chernikova, S Lee, SW Pisani, LJ Tirouvanziam, R Chen, JW Palmer, TD Chin, FT Guzman, R Graves, EE Loo, BW AF Lartey, Frederick M. Ahn, G-One Shen, Bin Cord, Keith-Travis Smith, Tenille Chua, Joshua Y. Rosenblum, Sahar Liu, Hongguang James, Michelle L. Chernikova, Sophia Lee, Star W. Pisani, Laura J. Tirouvanziam, Rabindra Chen, John W. Palmer, Theo D. Chin, Frederick T. Guzman, Raphael Graves, Edward E. Loo, Billy W., Jr. TI PET Imaging of Stroke-Induced Neuroinflammation in Mice Using [F-18]PBR06 SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Stroke; Neuroinflammation; Translocator protein 18 kDa (TSPO); Peripheral benzodiazepine receptor (PBR); Positron emission tomography (PET); [F-18]PBR06 ID PROTEIN 18 KDA; PERIPHERAL BENZODIAZEPINE-RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; INFLAMMATORY RESPONSE; CEREBRAL-ISCHEMIA; HUMAN BRAIN; RAT-BRAIN; MICROGLIA; LIGAND AB The purpose of this study is to evaluate the 18 kDa translocator protein (TSPO) radioligand [F-18]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([F-18]PBR06) as a positron emission tomography (PET) imaging biomarker of stroke-induced neuroinflammation in a rodent model. Stroke was induced by transient middle cerebral artery occlusion in Balb/c mice. Dynamic PET/CT imaging with displacement and preblocking using PK111195 was performed 3 days later. PET data were correlated with immunohistochemistry (IHC) for the activated microglial markers TSPO and CD68 and with autoradiography. [F-18]PBR06 accumulation peaked within the first 5 min postinjection, then decreased gradually, remaining significantly higher in infarct compared to noninfarct regions. Displacement or preblocking with PK11195 eliminated the difference in [F-18]PBR06 uptake between infarct and noninfarct regions. Autoradiography and IHC correlated well spatially with uptake on PET. [F-18]PBR06 PET specifically images TSPO in microglial neuroinflammation in a mouse model of stroke and shows promise for imaging and monitoring microglial activation/neuroinflammation in other disease models. C1 [Lartey, Frederick M.; Ahn, G-One; Cord, Keith-Travis; Chernikova, Sophia; Lee, Star W.; Graves, Edward E.; Loo, Billy W., Jr.] Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA. [Graves, Edward E.; Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA. [Shen, Bin; Liu, Hongguang; James, Michelle L.; Pisani, Laura J.; Chin, Frederick T.] Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA. [Smith, Tenille; Chua, Joshua Y.; Rosenblum, Sahar; Lee, Star W.; Guzman, Raphael] Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA. [Tirouvanziam, Rabindra] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Ahn, G-One] Pohang Univ Sci & Technol, Kyungbuk 790784, South Korea. [Chen, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Chen, John W.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lee, Star W.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. [Smith, Tenille; Rosenblum, Sahar; Guzman, Raphael] Univ Basel, Dept Neurosurg, Basel, Switzerland. [Smith, Tenille; Rosenblum, Sahar; Guzman, Raphael] Univ Basel, Dept Biomed, Basel, Switzerland. [Tirouvanziam, Rabindra] Emory Univ, Sch Med, Dept Pediat, Emory Childrens Ctr CF Res, Atlanta, GA USA. [Palmer, Theo D.] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA. RP Graves, EE (reprint author), Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA. EM EGraves@Stanford.edu; BWLoo@Stanford.edu RI Shen, Bin/F-8111-2014 FU Bio-X Interdisciplinary Initiatives Program (IIP) award from Stanford University; Developmental Cancer Research Award (DCRA) in Translational Research from Stanford Cancer Institute; NCI ICMIC [CA114747]; American Heart Association [AHA-0835274]; CIRM [RC1-0134]; National Research Foundation of Korea; Ministry of Education, Science and Technology, Korea [R31-10105, NRF-2012M3A9C6049796]; Department of Radiation Oncology, Stanford University FX The authors thank Dr. Victor W. Pike and the National Institute of Mental Health for providing the [18F]PBR06 precursor and standard, Dr. Makoto Higuchi of the National Institute of Radiological Sciences, Japan, for providing the TSPO antibody and the Stanford Center for Innovation in In Vivo Imaging. The study was supported in part by a Bio-X Interdisciplinary Initiatives Program (IIP) award from Stanford University (to BWL), a Developmental Cancer Research Award (DCRA) in Translational Research from Stanford Cancer Institute (to BWL), a NCI ICMIC P50 award (CA114747 to Dr. Sanjiv Sam Gambhir), an American Heart Association Grant (AHA-0835274 N to RG), a CIRM grant (RC1-0134 to TDP), grants from the National Research Foundation of Korea and the Ministry of Education, Science and Technology, Korea (R31-10105 and NRF-2012M3A9C6049796 to G-OA), and the Department of Radiation Oncology, Stanford University. NR 31 TC 10 Z9 11 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD FEB PY 2014 VL 16 IS 1 BP 109 EP 117 DI 10.1007/s11307-013-0664-5 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 290XZ UT WOS:000329793200014 PM 23836504 ER PT J AU Mizukami, K Abrahamson, EE Mi, ZP Ishikawa, M Watanabe, K Kinoshita, S Asada, T Ikonomovic, MD AF Mizukami, Katsuyoshi Abrahamson, Eric E. Mi, Zhiping Ishikawa, Masanori Watanabe, Kazushi Kinoshita, Setsuo Asada, Takashi Ikonomovic, Milos D. TI Immunohistochemical analysis of ubiquilin-1 in the human hippocampus: Association with neurofibrillary tangle pathology SO NEUROPATHOLOGY LA English DT Article DE Alzheimer; amyloid; Plic-1; tau; ubiquilin ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; UBIQUITIN; BRAINS; PROGRESSION; SUBUNITS; X-34 AB This post mortem immunohistochemical study examined the localization and distribution of ubiquilin-1 (UBL), a shuttle protein which interacts with ubiquitin and the proteasome, in the hippocampus from Alzheimer's disease (AD) dementia cases, and age-matched cases without dementia. In Braak stages 0-I-II cases, UBL immunoreactivity was detected in a dense fiber network in the neuropil, and in the cell cytoplasm and nucleoplasm of neurons in Cornu Ammonis (CA) fields and dentate gyrus granular neurons. In Braak stages III-IV and V-VI cases, UBL immunoreactivity was reduced in the neuropil and in the cytoplasm of the majority of CA1 neurons; some CA1 pyramidal neurons and the majority of CA2/3 pyramidal, CA4 multipolar, and dentate granular neurons had markedly increased UBL immunoreactivity in the nucleoplasm. Dual immunofluorescence analysis of UBL and antibody clone AT8 revealed co-localization most frequently in CA1 pyramidal neurons in Braak stage III-IV and V-VI cases. Further processing using the pan-amyloid marker X-34 revealed prominent UBL/X-34 dual labeling of extracellular NFT confined to the CA1/subiculum in Braak stage V-VI cases. Our results demonstrate that in AD hippocampus, early NFT changes are associated with neuronal up-regulation of UBL in nucleoplasm, or its translocation from the cytoplasm to the nucleus. The perseverance of UBL changes in CA2/3, CA4 and dentate gyrus, generally considered as more resistant to NFT pathology, but not in the CA1, may mark a compensatory, potentially protective response to increased tau phosphorylation in hippocampal neurons; the failure of such a response may contribute to neuronal degeneration in end-stage AD. C1 [Mizukami, Katsuyoshi] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tokyo 1120012, Japan. [Ishikawa, Masanori; Asada, Takashi] Univ Tsukuba, Inst Clin Med, Dept Psychiat, Tsukuba, Ibaraki 305, Japan. [Watanabe, Kazushi; Kinoshita, Setsuo] Proubase Technol Inc, Kawasaki, Kanagawa, Japan. [Abrahamson, Eric E.; Mi, Zhiping; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Abrahamson, Eric E.; Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Mizukami, K (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, Bunkyo Ku, 3-29-1 Otsuka, Tokyo 1120012, Japan. EM kmizukam@taiiku.tsukuba.ac.jp FU NIH [NIA AG05133, AG014449, AG025204]; Snee-Reinhardt Charitable Foundation; Japanese Ministry of Education, Culture, Sports, Science and Technology FX We are indebted to the support of the participants in the ADRC at the University of Pittsburgh. This study was supported by NIH grants NIA AG05133 (University of Pittsburgh ADRC), AG014449 and AG025204 (MDI), The Snee-Reinhardt Charitable Foundation (MDI), and by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (KM). Ms. Suganya Srinivasan, Ms. Lan Shao, Ms. Natsuko Kato and Ms. Megumi Mitani provided expert technical assistance. NR 28 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-6544 EI 1440-1789 J9 NEUROPATHOLOGY JI Neuropathology PD FEB PY 2014 VL 34 IS 1 BP 11 EP 18 DI 10.1111/neup.12055 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 291LB UT WOS:000329829100002 PM 23869942 ER PT J AU McLean, SA Ulirsch, JC Slade, GD Soward, AC Swor, RA Peak, DA Jones, JS Rathlev, NK Lee, DC Domeier, RM Hendry, PL Bortsov, AV Bair, E AF McLean, Samuel A. Ulirsch, Jacob C. Slade, Gary D. Soward, April C. Swor, Robert A. Peak, David A. Jones, Jeffrey S. Rathlev, Niels K. Lee, David C. Domeier, Robert M. Hendry, Phyllis L. Bortsov, Andrey V. Bair, Eric TI Incidence and predictors of neck and widespread pain after motor vehicle collision among US litigants and nonlitigants SO PAIN LA English DT Article DE Jurisprudence; Legislation; Motor vehicle collision; Musculoskeletal pain; Neck pain; Whiplash injuries ID POSTTRAUMATIC-STRESS-DISORDER; WHIPLASH-ASSOCIATED DISORDERS; PERITRAUMATIC DISTRESS INVENTORY; EARLY RISK-ASSESSMENT; PRIMARY-CARE; EMERGENCY-DEPARTMENT; DEPRESSIVE SYMPTOMS; INJURY COMPENSATION; PROGNOSTIC-FACTORS; RATING-SCALE AB Debate continues regarding the influence of litigation on pain outcomes after motor vehicle collision (MVC). In this study we enrolled European Americans presenting to the emergency department (ED) in the hours after MVC (n = 948). Six weeks later, participants were interviewed regarding pain symptoms and asked about their participation in MVC-related litigation. The incidence and predictors of neck pain and widespread pain 6 weeks after MVC were compared among those engaged in litigation (litigants) and those not engaged in litigation (nonlitigants). Among the 859 of 948 (91%) participants completing 6-week follow-up, 711 of 849 (83%) were nonlitigants. Compared to nonlitigants, litigants were less educated and had more severe neck pain and overall pain, and a greater extent of pain at the time of ED evaluation. Among individuals not engaged in litigation, persistent pain 6 weeks after MVC was common: 199 of 711 (28%) had moderate or severe neck pain, 92 of 711 (13%) had widespread pain, and 29 of 711 (4%) had fibromyalgia-like symptoms. Incidence of all 3 outcomes was significantly higher among litigants. Initial pain severity in the ED predicted pain outcomes among both litigants and nonlitigants. Markers of socioeconomic disadvantage predicted worse pain outcomes in litigants but not nonlitigants, and individual pain and psychological symptoms were less predictive of pain outcomes among those engaged in litigation. These data demonstrate that persistent pain after MVC is common among those not engaged in litigation, and provide evidence for bidirectional influences between pain outcomes and litigation after MVC. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [McLean, Samuel A.; Ulirsch, Jacob C.; Soward, April C.; Bortsov, Andrey V.] Univ N Carolina, TRYUMPH Res Program, Chapel Hill, NC 27599 USA. [McLean, Samuel A.; Ulirsch, Jacob C.; Soward, April C.; Bortsov, Andrey V.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC 27599 USA. [McLean, Samuel A.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC 27599 USA. [Slade, Gary D.; Bair, Eric] Univ N Carolina, Sch Dent, Chapel Hill, NC 27599 USA. [Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. [Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jones, Jeffrey S.] Spectrum Hlth Syst, Dept Emergency Med, Grand Rapids, MI USA. [Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY USA. [Domeier, Robert M.] St Joseph Mercy Hlth Syst, Dept Emergency Med, Ypsilanti, MI USA. [Hendry, Phyllis L.] Univ Florida, Dept Emergency Med, Jacksonville, FL USA. RP McLean, SA (reprint author), Univ N Carolina, Med Sch Wing C CB 7010, Chapel Hill, NC 27599 USA. EM smclean@aims.unc.edu OI McLean, Samuel/0000-0001-9482-3582; Bair, Eric/0000-0001-8733-7869 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01AR056328] FX Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01AR056328. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the participants for taking part in this study. Gary Slade, PhD, is a consultant at Algynomics, Inc. NR 72 TC 18 Z9 18 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD FEB PY 2014 VL 155 IS 2 BP 309 EP 321 DI 10.1016/j.pain.2013.10.016 PG 13 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 293PF UT WOS:000329984200014 PM 24145211 ER PT J AU Yang, F Whang, J Derry, WT Vardeh, D Scholz, J AF Yang, Fang Whang, John Derry, William T. Vardeh, Daniel Scholz, Joachim TI Analgesic treatment with pregabalin does not prevent persistent pain after peripheral nerve injury in the rat SO PAIN LA English DT Article DE Postoperative pain; Neuropathic pain; Preventive analgesia; Pregabalin ID CHANNEL ALPHA(2)DELTA-1 SUBUNIT; SPINAL DORSAL-HORN; NEUROPATHIC PAIN; POSTSURGICAL PAIN; DESCENDING FACILITATION; POSTOPERATIVE PAIN; SOMATOTOPIC ORGANIZATION; INTRATHECAL GABAPENTIN; THERMAL HYPERALGESIA; TACTILE ALLODYNIA AB Reducing the risk of chronic postoperative pain through preventive analgesia is an attractive therapeutic concept. Because peripheral nerve lesions are a major cause of chronic pain after surgery, we tested in rats whether analgesic treatment with pregabalin (PGB) has the capacity to mitigate the development of persistent neuropathic pain-like behavior. Starting on the day of spared nerve injury or 1 week later, we treated rats with a continuous intrathecal infusion of PGB (300 or 900 mu g/24 hours) or vehicle for up to 28 days. Rats receiving early PGB treatment had almost normal withdrawal thresholds for punctate mechanical stimuli and were clearly less sensitive to pinprick or cold stimulation. The responses to punctate mechanical and cold stimulation were still reduced for a brief period after the infusion was terminated, but the difference from vehicle-treated rats was minor. Essentially, the analgesic effect of PGB was limited to the duration of the infusion, whether analgesia started at the time of surgery or with a delay of 1 week, independently of the length of the treatment. PGB did not suppress the activation of spinal microglia, indicating that analgesia alone does not eliminate certain pain mechanisms even if they depend, at least partially, on nociceptive input. Unexpectedly, intrathecal infusion of PGB did not inhibit the nerve injury-induced accumulation of its binding target, the voltage-gated calcium channel subunit alpha 2 delta 1, at primary afferent terminals in the spinal cord. Interference with the synaptic trafficking of alpha 2 delta 1 is not required to achieve analgesia with PGB. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Yang, Fang; Whang, John; Scholz, Joachim] Columbia Univ Coll Phys & Surg, Dept Anesthesiol, New York, NY 10032 USA. [Derry, William T.; Vardeh, Daniel] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Derry, William T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Vardeh, Daniel] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scholz, Joachim] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. RP Scholz, J (reprint author), Columbia Univ, Med Ctr, Dept Anesthesiol, 630 West 168th St,P&S Box 46, New York, NY 10032 USA. EM js3932@cumc.columbia.edu FU Pfizer FX We thank Teri A. Herbert and Kaavya Mahajan for assistance with the behavioral testing and the analysis of alpha 2 delta 1 expression in the dorsal horn of the spinal cord. This study was supported by an unrestricted research grant from Pfizer. NR 76 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD FEB PY 2014 VL 155 IS 2 BP 356 EP 366 DI 10.1016/j.pain.2013.10.024 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 293PF UT WOS:000329984200019 PM 24176928 ER PT J AU Dostalova, Z Zhou, XJ Liu, AP Zhang, X Zhang, YH Desai, R Forman, SA Miller, KW AF Dostalova, Zuzana Zhou, Xiaojuan Liu, Aiping Zhang, Xi Zhang, Yinghui Desai, Rooma Forman, Stuart A. Miller, Keith W. TI Human alpha 1 beta 3 gamma 2L gamma-aminobutyric acid type A receptors: High-level production and purification in a functional state SO PROTEIN SCIENCE LA English DT Article DE human 132 GABA(A)R; HEK293 TetR cells; purification; reconstitution ID GATED ION-CHANNEL; MAMMALIAN-CELL LINE; X-RAY-STRUCTURE; GABA(A) RECEPTOR; HIGH-AFFINITY; SUBUNIT; BINDING; EXPRESSION; PHARMACOLOGY; RECONSTITUTION AB Gamma-aminobutyric acid type A receptors (GABA(A)Rs) are the most important inhibitory chloride ion channels in the central nervous system and are major targets for a wide variety of drugs. The subunit compositions of GABA(A)Rs determine their function and pharmacological profile. GABA(A)Rs are heteropentamers of subunits, and (1)(2)(3)(2)(2L)(1) is a common subtype. Biochemical and biophysical studies of GABA(A)Rs require larger quantities of receptors of defined subunit composition than are currently available. We previously reported high-level production of active human 13 GABA(A)R using tetracycline-inducible stable HEK293 cells. Here we extend the strategy to receptors containing three different subunits. We constructed a stable tetracycline-inducible HEK293-TetR cell line expressing human (N)-FLAG-132L-(C)-(GGS)(3)GK-1D4 GABA(A)R. These cells achieved expression levels of 70-90 pmol [H-3]muscimol binding sites/15-cm plate at a specific activity of 15-30 pmol/mg of membrane protein. Incorporation of the 2 subunit was confirmed by the ratio of [H-3]flunitrazepam to [H-3]muscimol binding sites and sensitivity of GABA-induced currents to benzodiazepines and zinc. The 132L GABA(A)Rs were solubilized in dodecyl-d-maltoside, purified by anti-FLAG affinity chromatography and reconstituted in CHAPS/asolectin at an overall yield of approximate to 30%. Typical purifications yielded 1.0-1.5 nmoles of [H-3]muscimol binding sites/60 plates. Receptors with similar properties could be purified by 1D4 affinity chromatography with lower overall yield. The composition of the purified, reconstituted receptors was confirmed by ligand binding, Western blot, and proteomics. Allosteric interactions between etomidate and [H-3]muscimol binding were maintained in the purified state. C1 [Dostalova, Zuzana; Zhou, Xiaojuan; Liu, Aiping; Zhang, Xi; Zhang, Yinghui; Desai, Rooma; Forman, Stuart A.; Miller, Keith W.] Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Dostalova, Zuzana; Zhang, Xi; Zhang, Yinghui; Miller, Keith W.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. EM k_miller@helix.mgh.harvard.edu FU National Institute of General Medical Sciences [GM 58448]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX Grant sponsor: National Institute of General Medical Sciences; Grant number: GM 58448; Grant sponsor: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. NR 35 TC 7 Z9 7 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD FEB PY 2014 VL 23 IS 2 BP 157 EP 166 DI 10.1002/pro.2401 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292YZ UT WOS:000329939900003 PM 24288268 ER PT J AU Moye, J Wachen, JS Mulligan, EA Doherty, K Naik, AD AF Moye, Jennifer Wachen, Jennifer Schuster Mulligan, Elizabeth A. Doherty, Kelly Naik, Aanand D. TI Assessing multidimensional worry in cancer survivors SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; anxiety; worry; posttraumatic stress disorder; fear of recurrence ID RECURRENCE; ANXIETY; SCALE; FEARS C1 [Moye, Jennifer; Wachen, Jennifer Schuster; Mulligan, Elizabeth A.; Doherty, Kelly] VA Boston Hlth Care Syst, Boston, MA USA. [Moye, Jennifer; Mulligan, Elizabeth A.] Harvard Univ, Sch Med, Boston, MA USA. [Wachen, Jennifer Schuster] Boston Univ, Sch Med, Boston, MA 02118 USA. [Naik, Aanand D.] Baylor Coll Med, Michael E DeBakey VAMC, Houston, TX 77030 USA. RP Moye, J (reprint author), VA Boston Hlth Care Syst, Boston, MA USA. EM jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Michael E DeBakey VA Medical Center [HFP90-020]; Boston VA Research Institute (BVARI); Harvard Medical School Milton Fund; Department of Veterans Affairs Rehabilitation Research and Development Service [5I01RX000104-02] FX This material is the result of work supported with resources and the use of facilities at the Boston VA Medical Center and the Houston VA Health Services Research & Development Center of Excellence (HFP90-020) at the Michael E DeBakey VA Medical Center. We thank the members of the Veterans Cancer Rehabilitation Study (Vetcares) Research team. We are indebted to the veterans who have participated in our research studies and allow us to contribute to their healthcare. Funding for part one of this project was provided by the Boston VA Research Institute (BVARI) and the Harvard Medical School Milton Fund. Funding for part two of this project was provided by the Department of Veterans Affairs Rehabilitation Research and Development Service #5I01RX000104-02. NR 10 TC 4 Z9 4 U1 0 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 FEB PY 2014 VL 23 IS 2 BP 237 EP 240 DI 10.1002/pon.3381 PG 4 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 290HZ UT WOS:000329746800015 PM 24105759 ER PT J AU Back, SE Killeen, TK Teer, AP Hartwell, EE Federline, A Beylotte, F Cox, E AF Back, Sudie E. Killeen, Therese K. Teer, Andrew P. Hartwell, Emily E. Federline, Amanda Beylotte, Frank Cox, Elizabeth TI Substance use disorders and PTSD: An exploratory study of treatment preferences among military veterans. SO ADDICTIVE BEHAVIORS LA English DT Article DE Substance use disorders; PTSD; Post traumatic stress disorder; Prolonged exposure; Military ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; COMORBID ALCOHOL DEPENDENCE; COCAINE DEPENDENCE; EXPOSURE THERAPY; PSYCHOLOGICAL TREATMENTS; PROLONGED EXPOSURE; TREATMENT PROGRAMS; SYMPTOM INTERPLAY; SELF-MEDICATION AB Background: Substance use disorders (SUDs) and Post Traumatic Stress Disorder (PTSD) frequently co-occur among Veterans and are associated with poor treatment outcomes. Historically, treatments for SUDs and PTSD have been delivered sequentially and independently. More recently, however, integrated treatments have shown promise. This study investigated Veterans' perceptions of the interrelationship between SUDs and PTSD, as well as treatment preferences. Methods: Participants were 35 Veterans of recent military conflicts in Iraq and Afghanistan, and prior operations, who completed the Treatment Preferences Questionnaire as well as an in-depth interview. Results: The majority (94.3%) perceived a relationship between their SUD and PTSD symptoms. Veterans reported that PTSD symptom exacerbation was typically (85.3%) associated with an increase in substance use, and PTSD symptom improvement was typically (61.8%) followed by a decrease in substance use (p <.01). Approximately 66% preferred an integrated treatment approach. Conclusions: Although preliminary, the findings provide clinically-relevant information that can be used to enhance the development and provision of care for Veterans with SUDs and PTSD. Published by Elsevier Ltd. C1 [Back, Sudie E.; Killeen, Therese K.; Teer, Andrew P.; Hartwell, Emily E.; Federline, Amanda; Beylotte, Frank; Cox, Elizabeth] Med Univ S Carolina, Charleston, SC 29425 USA. [Back, Sudie E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Back, SE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 67 President St,POB 250861, Charleston, SC 29425 USA. EM backs@musc.edu FU NIDA [R01-DA030143] FX Funding for this study was supported by NIDA grant R01-DA030143 (PI: Back, SE). NIDA and NIH had no further role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. NR 48 TC 11 Z9 11 U1 2 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2014 VL 39 IS 2 SI SI BP 369 EP 373 DI 10.1016/j.addbeh.2013.09.017 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 286OU UT WOS:000329479400001 PM 24199930 ER PT J AU Creech, SK Borsari, B AF Creech, Suzannah K. Borsari, Brian TI Alcohol use, military sexual trauma, expectancies, and coping skills in women veterans presenting to primary care SO ADDICTIVE BEHAVIORS LA English DT Article DE Women veterans; Alcohol; Coping; Expectancies; Military sexual trauma ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-GUARD SOLDIERS; MENTAL-HEALTH; IDENTIFICATION TEST; GENDER-DIFFERENCES; COLLEGE-STUDENTS; CIVILIAN TRAUMA; DRINKING; SAMPLE; ABUSE AB Background: Little is known regarding alcohol use and its correlates in women veterans. An understanding of these variables is of utility to providers in primary care at Veterans Affairs (VA) hospitals, who are among the first to identify and intervene for problem drinking. Objective: The objective of this study was to describe and explore the associations between posttraumatic stress disorder symptoms, experience of military sexual trauma (MST), expectancies for alcohol use, and coping skills in predicting drinking behavior. Design: Each month all women veterans attending appointments in primary care were mailed a letter alerting them to the study. Women then received a call asking them to participate, and many were directly recruited at their primary care appointment. Participants then completed a survey of current alcohol use and related variables in a private room. Participants: Participants were 93 women veterans seeking care at VA. Main measures: Measures included the Alcohol Use Disorders Identification Test, a modified version of the VA MST screen, the Davidson Trauma Scale; the Coping Inventory for Stressful Situations, and the Brief Comprehensive Effects of Alcohol Questionnaire. Key results: Positive expectancies and evaluations emerged as significant correlates of AUDIT scores, while PTSD symptoms were not related to AUDIT scores. A hierarchical regression revealed a significant positive interaction between avoidance coping and positive evaluations. Depression, positive evaluations and avoidance coping were significant independent predictors of AUDIT scores in the final model, but MST was not. Conclusions: Findings highlight the importance of considering of the function of alcohol use when delivering clinical interventions and the need for further research on the association between MST and drinking in women veterans. Published by Elsevier Ltd. C1 [Creech, Suzannah K.; Borsari, Brian] Providence VA Med Ctr, Providence, RI 02908 USA. [Creech, Suzannah K.; Borsari, Brian] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Creech, Suzannah K.] VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, Boston, MA 02130 USA. [Borsari, Brian] Brown Univ, Warren Alpert Med Sch, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RP Creech, SK (reprint author), Providence VAMC, Bldg 32,830 Chalkstone Ave, Providence, RI 02908 USA. EM Suzannah.creech@va.gov OI Creech, Suzannah/0000-0002-6582-1673 FU Department of Veterans Affairs VISN 1 Career Development Award [V1 CDA2011-11]; National Institute on Alcohol Abuse and Alcoholism [R01 AA017874] FX This project was supported by a Department of Veterans Affairs VISN 1 Career Development Award V1 CDA2011-11 to Suzannah K. Creech. Brian Borsari's contribution was supported by National Institute on Alcohol Abuse and Alcoholism Grant R01 AA017874. This material is the result of work supported with resources and the use of facilities at the Providence VA Medical Center. Neither the Department of Veterans Affairs nor the National Institute on Alcohol Abuse and Alcoholism had a role in the study design, collection, analysis or interpretation of data, writing the manuscript, or the decision to submit the manuscript for publication. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. NR 46 TC 10 Z9 10 U1 3 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2014 VL 39 IS 2 SI SI BP 379 EP 385 DI 10.1016/j.addbeh.2013.02.006 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 286OU UT WOS:000329479400003 PM 23498717 ER PT J AU Chakravorty, S Grandner, MA Mavandadi, S Perlis, ML Sturgis, EB Oslin, DW AF Chakravorty, Subhajit Grandner, Michael A. Mavandadi, Shahrzad Perlis, Michael L. Sturgis, Elliott B. Oslin, David W. TI Suicidal ideation in Veterans misusing alcohol: Relationships with insomnia symptoms and sleep duration SO ADDICTIVE BEHAVIORS LA English DT Article DE Veterans; Suicidal ideation; Insomnia; Sleep duration; Alcohol ID GENERAL-POPULATION; PSYCHIATRIC-DISORDERS; COMPLETED SUICIDE; PRIMARY-CARE; BEHAVIOR; ADULTS; ASSOCIATION; DEPRESSION; DRINKING; INDIVIDUALS AB Objective: The aim of this investigation was to assess the relationships between suicidal ideation and insomnia symptoms in Veterans misusing alcohol. Method: Data were extracted in this retrospective chart review of Veterans referred from primary care for a behavioral health evaluation (N = 161) based on evidence of heavy drinking, drug use or another behavioral problem. Suicidal ideation (SI) was assessed using the Paykel questionnaire. Insomnia symptoms were assessed with standard diary questions in an interview format and pertained to sleep latency (SL), wake after sleep onset time (WASO), sleep quality (SQ), and habitual sleep duration (HSD). The relations between suicidal ideation and insomnia symptoms were assessed using ordinal regression analyses adjusted for socio-demographic, psychiatric and addiction-related variables. Results: Suicidal ideation was reported in 62 (39%) of the Veterans interviewed. In a multivariable model, only inadequate SQ was associated with suicidal ideation. Short sleepers were more likely to endorse suicidal ideation and have attempted suicide in the past year. In addition, older age, inadequate financial status, and the presence of a psychiatric disorder were also significantly associated with suicidal ideation in most of the adjusted models. Conclusion: Given their association with suicidal ideation, insomnia symptoms in Veterans misusing alcohol should prompt an assessment of underlying psychiatric and social factors. Published by Elsevier Ltd. C1 [Chakravorty, Subhajit; Mavandadi, Shahrzad; Sturgis, Elliott B.; Oslin, David W.] Philadelphia Vet Affairs Med Ctr, MIRECC VISN 4, Philadelphia, PA 19104 USA. [Chakravorty, Subhajit; Grandner, Michael A.; Mavandadi, Shahrzad; Perlis, Michael L.; Oslin, David W.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Chakravorty, S (reprint author), Philadelphia Vet Affairs Med Ctr, MIRECC, 2nd Floor,Postal Code 116,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM SubhajitChakravorty@uphs.upenn.edu FU VISN-4 MIRECC of the Philadelphia Veterans Affairs Medical Center; Department of Veterans Affairs; National Institutes of Health [1K23HL110216-01, 1R21ES022931-01] FX The VISN-4 MIRECC of the Philadelphia Veterans Affairs Medical Center supported this study. The authors (SC, SM, DO) received salary support from the Department of Veterans Affairs. Dr. Grandner received a grant support from the National Institutes of Health ( 1K23HL110216-01, 1R21ES022931-01). NR 49 TC 11 Z9 11 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2014 VL 39 IS 2 SI SI BP 399 EP 405 DI 10.1016/j.addbeh.2013.09.022 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 286OU UT WOS:000329479400006 PM 24169371 ER PT J AU Sartor, CE Kranzler, HR Gelernter, J AF Sartor, Carolyn E. Kranzler, Henry R. Gelernter, Joel TI Rate of progression from first use to dependence on cocaine or opioids: A cross-substance examination of associated demographic, psychiatric, and childhood risk factors SO ADDICTIVE BEHAVIORS LA English DT Article DE Cocaine dependence; Opioid dependence; Transition ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; DRUG-USE DISORDERS; UNITED-STATES; SEMISTRUCTURED ASSESSMENT; GENDER-DIFFERENCES; RAPID PROGRESSION; ALCOHOLISM SSADDA; CONDUCT DISORDER; HEROIN USERS AB Background: A number of demographic factors, psychiatric disorders, and childhood risk factors have been associated with cocaine dependence (CD) and opioid dependence (OD), but little is known about their relevance to the rate at which dependence develops. Identification of the subpopulations at elevated risk for rapid development of dependence and the risk factors that accelerate the course of dependence is an important public health goal. Methods: Data were derived from cocaine dependent (n = 6333) and opioid dependent (n = 3513) participants in a multi-site study of substance dependence. Mean age was approximately 40 and 40% of participants were women; 51.9% of cocaine dependent participants and 29.5% of opioid dependent participants self-identified as Black/African-American. The time from first use to dependence was calculated for each substance and a range of demographic, psychiatric, and childhood risk factors were entered into ordinal logistic regression models to predict the (categorical) transition time to CD and OD. Results: In both the cocaine and opioid models, conduct disorder and childhood physical abuse predicted rapid development of dependence and alcohol and nicotine dependence diagnoses were associated with slower progression to CD or OD. Blacks/African Americans were at greater risk than European Americans to progress rapidly to OD. Conclusions: Only a subset of factors known to be associated with CD and OD predicted the rate at which dependence developed. Nearly all were common to cocaine and opioids, suggesting that sources of influence on the timing of transitions to dependence are shared across the two substances. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Sartor, Carolyn E.; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Kranzler, Henry R.] Univ Penn, Perelman Sch Med, Dept Psychiat, Treatment Res Ctr, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, MIRECC VISN4, Philadelphia, PA 19104 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. RP Sartor, CE (reprint author), Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Healthcare Syst, 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM carolyn.sartor@yale.edu FU National Institutes of Health (NIH) [AA017921, DA12849, DA12690, AA11330, AA13736]; VA CT; Philadelphia VA Mental Illness Research, Education, and Clinical Centers (MIRECCs) FX Funding for this study was provided by the National Institutes of Health (NIH) grants AA017921, DA12849, DA12690, AA11330, and AA13736 and the VA CT and Philadelphia VA Mental Illness Research, Education, and Clinical Centers (MIRECCs). The NIH, the VA CT, and the Philadelphia VA MIRECCs had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 45 TC 9 Z9 9 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2014 VL 39 IS 2 SI SI BP 473 EP 479 DI 10.1016/j.addbeh.2013.10.021 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 286OU UT WOS:000329479400018 PM 24238782 ER PT J AU Sabbath, EL Hurtado, DA Okechukwu, CA Tamers, SL Nelson, C Kim, SS Wagner, G Sorenson, G AF Sabbath, Erika L. Hurtado, David A. Okechukwu, Cassandra A. Tamers, Sara L. Nelson, Candace Kim, Seung-Sup Wagner, Gregory Sorenson, Glorian TI Occupational Injury Among Hospital Patient-Care Workers: What Is the Association With Workplace Verbal Abuse? SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupational injury; workplace violence; workplace harassment; workplace abuse; non-physical violence ID SEXUAL-HARASSMENT; RISK-FACTORS; MUSCULOSKELETAL DISORDERS; RACIAL-DISCRIMINATION; PREVENTION PROGRAM; VIOLENCE; CONSEQUENCES; AGGRESSION; NURSES; PAIN AB ObjectiveTo test the association between workplace abuse exposure and injury risk among hospital workers. We hypothesized that exposed workers would have higher injury rates than unexposed workers. MethodsSurvey of direct-care workers (n=1,497) in two hospitals. Exposure to workplace abuse was assessed through self-report; occupational injury reports were extracted from employee records. We tested associations between non-physical workplace violence and injury using log-binomial regression and multilevel modeling. ResultsAdjusted prevalence ratio (PR) for injury associated with being yelled at was 1.52 (95% CI 1.19, 1.95); for experiencing hostile/offensive gestures 1.43 (1.11, 1.82); and for being sworn at 1.41 (1.09, 1.81). In analyses by injury subtypes, musculoskeletal injuries were more strongly associated with abuse than were acute traumatic injuries. Associations operated on group and individual levels and were most consistently associated with abuse perpetrated by patients. ConclusionExposure to workplace abuse may be a risk factor for injuries among hospital workers. Am. J. Ind. Med. 57:222-232, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Sabbath, Erika L.] Harvard Ctr Populat & Dev Studies, Cambridge, MA 02138 USA. [Hurtado, David A.; Okechukwu, Cassandra A.; Tamers, Sara L.; Sorenson, Glorian] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Tamers, Sara L.; Sorenson, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Nelson, Candace; Wagner, Gregory] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Kim, Seung-Sup] Korea Univ, Dept Healthcare Management, Seoul, South Korea. [Kim, Seung-Sup] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Washington, DC USA. [Wagner, Gregory] NIOSH, Washington, DC USA. RP Sabbath, EL (reprint author), Harvard Ctr Populat & Dev Studies, 9 Bow St, Cambridge, MA 02138 USA. EM esabbath@hsph.harvard.edu FU National Institute for Occupational Safety and Health [5U19OH008861-06] FX Contract grant sponsor: National Institute for Occupational Safety and Health; Contract grant number: 5U19OH008861-06. NR 45 TC 11 Z9 11 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 2014 VL 57 IS 2 BP 222 EP 232 DI 10.1002/ajim.22271 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286YP UT WOS:000329505500010 PM 24151093 ER PT J AU Sun, M Sammon, JD Becker, A Roghmann, F Tian, Z Kim, SP Larouche, A Abdollah, F Hu, JC Karakiewicz, PI Trinh, QD AF Sun, Maxine Sammon, Jesse D. Becker, Andreas Roghmann, Florian Tian, Zhe Kim, Simon P. Larouche, Alexandre Abdollah, Firas Hu, Jim C. Karakiewicz, Pierre I. Quoc-Dien Trinh TI Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluation SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; prostatectomy; radiotherapy; observation ID QUALITY-OF-LIFE; UNITED-STATES; MEDICARE DATA; POPULATION; OUTCOMES; THERAPY; RISK; SURVEILLANCE; MORTALITY; TRENDS AB Objective To compare efficacy between radical prostatectomy (RP), radiotherapy and observation with respect to overall survival (OS) in patients with clinically localized prostate cancer (PCa). Methods Using data (1988-2005) from the Surveillance, Epidemiology, and End Results-Medicare linked database, 67 087 men with localized PCa were identified. The prevalence of the initial treatment strategy was quantified according to patients' life expectancy ([LE] <10 vs 10 years) at initial diagnosis and according to tumour stage. To reduce the unmeasured bias associated with treatment, we performed an instrumental variable analysis. Stratified (by stage and LE) Cox regression and competing-risks regression analyses were generated for the prediction of OS and cancer-specific mortality, respectively. Results Among patients with <10 years of LE, most were treated with radiotherapy (49%) or observation (47%). Among patients with 10 years of LE, most received radiotherapy (49%), followed by RP (26%). In men with <10 years of LE, RP and radiotherapy were not different with respect to OS (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.45-1.48, P = 0.499). Conversely, in men with 10 years of LE, RP was associated with an improved OS compared with observation (HR: 0.59, 95% CI: 0.49-0.71, P < 0.001) and radiotherapy (HR: 0.66, 95% CI: 0.56-0.79, P < 0.001). Similar results were recorded in competing-risks regression analyses. Conclusion In patients with an estimated LE 10 years at initial diagnosis, RP was associated with improved survival compared with radiotherapy and observation, regardless of disease stage. C1 [Sun, Maxine; Becker, Andreas; Roghmann, Florian; Tian, Zhe; Larouche, Alexandre; Abdollah, Firas; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 1P, Canada. [Sammon, Jesse D.] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA. [Kim, Simon P.] Yale Univ, Dept Urol, New Haven, CT USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ H2X 1P, Canada. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Surg,Div Urol, Boston, MA 02115 USA. RP Sun, M (reprint author), Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, 264,Blvd Rene-Levesque East,Room 228, Montreal, PQ H2X 1P, Canada. EM mcw.sun@umontreal.ca NR 32 TC 19 Z9 21 U1 1 U2 9 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 FEB PY 2014 VL 113 IS 2 BP 200 EP 208 DI 10.1111/bju.12321 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 287LV UT WOS:000329544200008 PM 23937636 ER PT J AU Feng, HJ Jounaidi, Y Haburcak, M Yang, X Forman, SA AF Feng, H-J Jounaidi, Y. Haburcak, M. Yang, X. Forman, S. A. TI Etomidate produces similar allosteric modulation in alpha 1 beta 3 delta and alpha 1 beta 3 gamma 2L GABA(A) receptors SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE allosteric modulation; etomidate; general anaesthetics; GABA(A) receptors; subunits; concatenated subunit assemblies; electrophysiology ID 1ST TRANSMEMBRANE DOMAIN; A RECEPTORS; DELTA-SUBUNIT; NEUROACTIVE STEROIDS; ARRIVE GUIDELINES; BINDING-SITE; RECOMBINANT; STOICHIOMETRY; SUBTYPES; PHARMACOLOGY AB Background and PurposeNeuronal GABA(A) receptors are pentameric chloride ion channels, which include synaptic and extrasynaptic isoforms, mediating phasic and tonic inhibition respectively. Although the subunit arrangement of receptors is established as ----, that of receptors is uncertain and possibly variable. We compared receptors formed from free 1, 3 and or 2L subunits and concatenated 3-1- and 3-1 subunit assemblies (placing in the established position) by investigating the effects of R-(+)-etomidate (ETO), an allosteric modulator that selectively binds to transmembrane interfacial sites between 3 and 1. Experimental ApproachGABA-activated receptor-mediated currents in Xenopus oocytes were measured electrophysiologically, and ETO-induced allosteric shifts were quantified using an established model. Key ResultsETO (3.2M) similarly enhanced maximal GABA (1mM)-evoked currents in oocytes injected with 5ng total mRNA and varying subunit ratios, for 13(1:1), 13(1:1:1) and 13(1:1:3), but this potentiation by ETO was significantly greater for 3-1-/3-1(1:1) receptors. Reducing the amount of 13(1:1:3) mRNA mixture injected (0.5ng) increased the modulatory effect of ETO, matching that seen with 3-1-/3-1(1:1, 1ng). ETO similarly reduced EC(50)s and enhanced maxima of GABA concentration-response curves for both 13 and 3-1-/3-1 receptors. Allosteric shift parameters derived from these data depended on estimates of maximal GABA efficacy, and the calculated ranges overlap with allosteric shift values for 132L receptors. Conclusion and ImplicationsReducing total mRNA unexpectedly increased subunit incorporation into receptors on oocyte plasma membranes. Our results favour homologous locations for and 2L subunits in 132/ GABA(A) receptors. C1 [Feng, H-J] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Feng, H-J] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Feng, HJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM hfeng3@partners.org FU [P01GM058448]; [R01GM089745] FX We thank Mayo Hotta for preliminary studies using reduced mRNA injection and Dr Kunpeng Liu for helpful discussion. This work was supported by P01GM058448 and R01GM089745 to S. A. F. NR 49 TC 9 Z9 9 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD FEB PY 2014 VL 171 IS 3 SI SI BP 789 EP 798 DI 10.1111/bph.12507 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 287MA UT WOS:000329544700007 PM 24199598 ER PT J AU Murakami, Y Matsumoto, H Roh, M Giani, A Kataoka, K Morizane, Y Kayama, M Thanos, A Nakatake, S Notomi, S Hisatomi, T Ikeda, Y Ishibashi, T Connor, KM Miller, JW Vavvas, DG AF Murakami, Y. Matsumoto, H. Roh, M. Giani, A. Kataoka, K. Morizane, Y. Kayama, M. Thanos, A. Nakatake, S. Notomi, S. Hisatomi, T. Ikeda, Y. Ishibashi, T. Connor, K. M. Miller, J. W. Vavvas, D. G. TI Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE retina; neuroprotection; necrosis; macula; degeneration ID MOBILITY GROUP BOX-1; TOLL-LIKE RECEPTORS; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; PIGMENT-EPITHELIUM; TNF-ALPHA; 1 PROTEIN; DEATH; DETACHMENT; RELEASE AB There is no known treatment for the dry form of an age-related macular degeneration (AMD). Cell death and inflammation are important biological processes thought to have central role in AMD. Here we show that receptor-interacting protein (RIP) kinase mediates necrosis and enhances inflammation in a mouse model of retinal degeneration induced by dsRNA, a component of drusen in AMD. In contrast to photoreceptor-induced apoptosis, subretinal injection of the dsRNA analog poly(I : C) caused necrosis of the retinal pigment epithelium (RPE), as well as macrophage infiltration into the outer retinas. In Rip3(-/-) mice, both necrosis and inflammation were prevented, providing substantial protection against poly(I : C)-induced retinal degeneration. Moreover, after poly(I : C) injection, Rip3(-/-) mice displayed decreased levels of pro-inflammatory cytokines (such as TNF-alpha and IL-6) in the retina, and attenuated intravitreal release of high-mobility group box-1 (HMGB1), a major damage-associated molecular pattern (DAMP). In vitro, poly(I : C)-induced necrosis were inhibited in Rip3-deficient RPE cells, which in turn suppressed HMGB1 release and dampened TNF-alpha and IL-6 induction evoked by necrotic supernatants. On the other hand, Rip3 deficiency did not modulate directly TNF-alpha and IL-6 production after poly(I : C) stimulation in RPE cells or macrophages. Therefore, programmed necrosis is crucial in dsRNA-induced retinal degeneration and may promote inflammation by regulating the release of intracellular DAMPs, suggesting novel therapeutic targets for diseases such as AMD. C1 [Murakami, Y.; Matsumoto, H.; Roh, M.; Giani, A.; Kataoka, K.; Morizane, Y.; Kayama, M.; Thanos, A.; Connor, K. M.; Miller, J. W.; Vavvas, D. G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv,Angiogenesis Lab, Boston, MA 02114 USA. [Murakami, Y.; Nakatake, S.; Notomi, S.; Hisatomi, T.; Ikeda, Y.; Ishibashi, T.] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 812, Japan. RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv,Angiogenesis Lab, 243 Charles St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu RI Kataoka, Keiko/B-2806-2016; OI Kataoka, Keiko/0000-0002-8795-6536; Hisatomi, Toshio/0000-0003-2552-9595; Connor, Kip/0000-0002-2048-9080; Vavvas, Demetrios/0000-0002-8622-6478 FU Research to Prevent Blindness Physician Scientist Award; NIH [NEI R21EY023079-01A1, R01EY022084-01/S1]; Foundation Lions Eye Research Fund; Onassis Foundation; Yeatts Family Foundation; Rena Family Foundation; Bausch & Lomb Vitreoretinal Fellowship; NEI grant [EY014104]; Japanese Ministry of Education, Culture, Sports, Science, and Technology grant [25861637] FX We thank N Michaud (MEEI) and F Morikawa (Kyushu U) for technical assistance, and W Chao (MEEI) for her support in critical review. This work was supported by Research to Prevent Blindness Physician Scientist Award (DGV), NIH NEI R21EY023079-01A1 (DGV) Foundation Lions Eye Research Fund (DGV), Onassis Foundation (DGV), The Yeatts Family Foundation (JWM, DGV), Rena Family Foundation (JWM, DGV), Bausch & Lomb Vitreoretinal Fellowship (HM, Y Morizane and KM), NEI grant EY014104 (MEEI Core Grant), NIH R01EY022084-01/S1 (KMC) and the Japanese Ministry of Education, Culture, Sports, Science, and Technology grant 25861637 (Y. Murakami). NR 51 TC 47 Z9 50 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2014 VL 21 IS 2 BP 270 EP 277 DI 10.1038/cdd.2013.109 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 290VY UT WOS:000329787800012 PM 23954861 ER PT J AU Petersenn, S Newell-Price, J Findling, JW Gu, F Maldonado, M Sen, K Salgado, LR Colao, A Biller, BMK AF Petersenn, S. Newell-Price, J. Findling, J. W. Gu, F. Maldonado, M. Sen, K. Salgado, L. R. Colao, A. Biller, B. M. K. CA Pasireotide B2305 Study Grp TI High variability in baseline urinary free cortisol values in patients with Cushing's disease SO CLINICAL ENDOCRINOLOGY LA English DT Article ID OPPORTUNISTIC INFECTIONS; DIFFERENTIAL-DIAGNOSIS; MORTALITY; REPRODUCIBILITY; CABERGOLINE AB ObjectiveTwenty-four-hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's disease, we analysed baseline UFC in a large patient cohort with moderate-to-severe Cushing's disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data. DesignObservational study (enrolment phase of Phase III study). MethodsPatients (n=152) with persistent/recurrent or de novo Cushing's disease and mean UFC (mUFC) 15xULN (normal: 30-145nmol/24h) were included. Mean UFC level was calculated from four 24-h urine samples collected over 2weeks. ResultsOver 600 24-h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000nmol/24h (SD 1872) and 940nmol/24h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48-56). The intrapatient CV was 51% (95% CI: 44-58) for samples 1 and 2, 49% (95% CI: 43-56) for samples 3 and 4 and 54% (95% CI: 49-59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism. ConclusionsThere is intrapatient variability of approximately 50% in 24-h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24-h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity. C1 [Petersenn, S.] ENDOC Ctr Endocrine Tumors, D-20357 Hamburg, Germany. [Newell-Price, J.] Univ Sheffield, Sch Med, Sheffield, S Yorkshire, England. [Findling, J. W.] Med Coll Wisconsin, Div Endocrinol Metab & Clin Nutr, Milwaukee, WI 53226 USA. [Gu, F.] Beijing Union Med Coll Hosp, Minist Hlth, Key Lab Endocrinol, Dept Endocrinol, Beijing, Peoples R China. [Maldonado, M.] Novartis Pharma AG, Oncol Business Unit, Clin Dev, Basel, Switzerland. [Sen, K.] Novartis Pharmaceut, Oncol Biometr & Data Management, Florham Pk, NJ USA. [Salgado, L. R.] Univ Sao Paulo, Sch Med, Hosp Clin, Gen Internal Med Serv, Sao Paulo, Brazil. [Colao, A.] Univ Naples Federico II, Sez Endocrinol, Dipartimento Med Clin & Chirurg, Naples, Italy. [Biller, B. M. K.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. RP Petersenn, S (reprint author), ENDOC Ctr Endocrine Tumors, Altonaer Str 59, D-20357 Hamburg, Germany. EM stephan.petersenn@endoc-med.de OI Brue, Thierry/0000-0001-8482-6691; Carvalho, Davide/0000-0002-3156-3741 FU Novartis Pharma AG; Novartis Pharmaceuticals Corporation FX This study was funded by Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank Keri Wellington, PhD, for medical editorial assistance with this manuscript. NR 29 TC 30 Z9 30 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD FEB PY 2014 VL 80 IS 2 BP 261 EP 269 DI 10.1111/cen.12259 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 286HU UT WOS:000329459200014 PM 23746264 ER PT J AU Hahn, NM Yiannoutsos, CT Kirkpatrick, K Sharma, J Sweeney, CJ AF Hahn, Noah M. Yiannoutsos, Constantin T. Kirkpatrick, Kristina Sharma, Jaya Sweeney, Christopher J. TI Failure to Suppress Markers of Bone Turnover on First-Line Hormone Therapy for Metastatic Prostate Cancer Is Associated With Shorter Time to Skeletal-Related Event SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Androgen deprivation therapy; Bone turnover; Prostate cancer; Skeletal-related events ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; ORAL SODIUM CLODRONATE; ZOLEDRONIC ACID; MINERAL DENSITY; LONG-TERM; PREDNISONE; SURVIVAL; PLACEBO; MEN AB Biomarkers to identify patients with metastatic prostate cancer who are destined to have a shorter response to testosterone suppression are limited. In a cohort of 63 patients, failure to suppress markers of bone turnover while receiving therapy was associated with a shorter time to progression. This suggests that more durable anti-prostate cancer activity is associated with less cancer-associated bone turnover. Background: Elevated markers of bone turnover are prognostic for shorter survival in castration-resistant prostate cancer. We aimed to determine the prognostic value of bone turnover markers in metastatic hormone-sensitive prostate cancer. Patients and Methods: Markers of bone turnover (urine deoxypyridinoline [DPD] and N-telopeptide, serum bone alkaline phosphatase (AP), and osteocalcin [OC]) from baseline and after 6 months of study were assessed in men enrolled in a prospective metastatic prostate cancer trial with androgen deprivation therapy (ADT) with or without risedronate (ClinicalTrials.gov, NCT00216060). Results: Serum samples were collected from 63 patients with bone involvement and a median follow-up of 39.7 months. A multivariate model using Cox regression-which included prostate-specific antigen (PSA) nadir, bisphosphonate treatment, and extent of metastases-showed that suppression of bone turnover markers after 6 months of therapy compared with baseline was significantly associated with longer skeletal-related event (SRE)-free survival. ADT without bisphosphonate therapy was also associated with a decline in markers of bone turnover, presumably resulting from direct anticancer activity. Elevated baseline bone turnover markers were not prognostic. Conclusion: Failure to suppress bone turnover while receiving ADT, even when otherwise responding to therapy, may identify patients with hormone-sensitive metastatic prostate cancer who are destined for a shorter time to SREs and progression. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hahn, Noah M.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Yiannoutsos, Constantin T.] Indiana Univ, Sch Med, Dept Biostat, Indianapolis, IN USA. [Kirkpatrick, Kristina] Hoosier Oncol Grp, Indianapolis, IN USA. [Sharma, Jaya; Sweeney, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sweeney, CJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Suite D1230, Boston, MA 02215 USA. EM christopher_sweeney@dfci.harvard.edu FU Sanofi FX Sanofi provided financial support for the conduct of the clinical trial and provided scientific input. The manuscript was written solely by the authors, and Sanofi reviewed the final manuscript. NR 29 TC 2 Z9 2 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD FEB PY 2014 VL 12 IS 1 BP 33 EP + DI 10.1016/j.clgc.2013.07.002 PG 12 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 287YK UT WOS:000329578200013 PM 24126237 ER PT J AU Jones, D Zhao, FM Fisch, MJ Wagner, LI Patrick-Miller, LJ Cleeland, CS Mendoza, TR AF Jones, Desiree Zhao, Fengmin Fisch, Michael J. Wagner, Lynne I. Patrick-Miller, Linda J. Cleeland, Charles S. Mendoza, Tito R. TI The Validity and Utility of the MD Anderson Symptom Inventory in Patients With Prostate Cancer: Evidence From the Symptom Outcomes and Practice Patterns (SOAPP) Data From the Eastern Cooperative Oncology Group SO CLINICAL GENITOURINARY CANCER LA English DT Article DE ECOG; MDASI; Patient-reported outcome; Symptom assessment; Validation ID QUALITY-OF-LIFE; REPORTED OUTCOMES; INSTRUMENT; VALIDATION; MODULE; QUESTIONNAIRE; PREVALENCE; SEVERITY; THERAPY; TRIAL AB The MD Anderson Symptom Inventory (MDASI) assesses the severity and impact of multiple symptoms related to cancer and its treatment. Psychometric analysis of data from a national study of 320 patients with prostate cancer showed the MDASI to be a valid, reliable, and sensitive instrument that can be used in descriptive and clinical studies of symptom status in this patient population. Background: The MD Anderson Symptom Inventory (MDASI) is a psychometrically validated patient-reported outcome measure that assesses the severity and impact of multiple symptoms related to cancer and its treatment and has the potential to guide treatment specific to patients with prostate cancer. Although the original MDASI validation study encompassed various cancer types, the instrument's psychometric properties have not been examined in a large homogeneous sample of patients with prostate cancer. Patients and Methods: This study involved secondary analysis of data from the nationwide multicenter Eastern Cooperative Oncology Group (ECOG) SOAPP (Symptom Outcomes and Practice Patterns) study, which enrolled patients from 38 ECOG-affiliated institutions, including 6 academic centers and 32 community clinics. Data were used to establish the psychometric properties of the MDASI in a subsample of 320 patients with prostate cancer. The instrument was administered twice, approximately 1 month apart. Results: The MDASI demonstrated good internal consistency and test-retest reliability (with Cronbach alphas of >= .84 and intraclass correlations of >= 0.76 for all subscales), strong ability to discriminate between clinically different patient groups (by performance status, tumor response, and disease stage), and high sensitivity in detecting symptom change (with respect to patient-reported quality of life [QOL] between the baseline and 1-month follow-up visits). Conclusion: The MDASI is a valid, reliable, and sensitive symptom-assessment instrument that can be used with confidence in descriptive and clinical studies of symptom status in patients with prostate cancer. (C) 2014 Elsevier Inc. All rights reserved. C1 [Jones, Desiree; Cleeland, Charles S.; Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. [Wagner, Lynne I.] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA. [Wagner, Lynne I.] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Patrick-Miller, Linda J.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Patrick-Miller, Linda J.] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. RP Jones, D (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, 1515 Holcombe Blvd,Unit 410, Houston, TX 77030 USA. EM Djones1@mdanderson.org FU National Cancer Institute of the National Institutes of Health [NCI U10 CA37403, NCI U10 CA17145]; National Cancer Institute [R01 CA026582]; MD Anderson Cancer Center Support Grant [NCI P30 CA016672]; Hawn Foundation, Dallas, TX FX Research support was provided in part by grants to the Eastern Cooperative Oncology Group from the National Cancer Institute of the National Institutes of Health, including NCI U10 CA37403 and NCI U10 CA17145. Additional support came from National Cancer Institute R01 CA026582 to CSC and MD Anderson Cancer Center Support Grant NCI P30 CA016672 to R. A. DePinho, DJ was supported by a grant from the Hawn Foundation, Dallas, TX. NR 24 TC 4 Z9 5 U1 0 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD FEB PY 2014 VL 12 IS 1 BP 41 EP 49 DI 10.1016/j.clgc.2013.07.003 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 287YK UT WOS:000329578200014 PM 24126238 ER PT J AU Baltzell, LS Billings, CJ AF Baltzell, Lucas S. Billings, Curtis J. TI Sensitivity of offset and onset cortical auditory evoked potentials to signals in noise SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE CAEP; Offset; Onset; Auditory; N1; N2; ERP; Evoked; Potential ID EVENT-RELATED POTENTIALS; BROAD-BAND NOISE; STIMULUS-INTENSITY; COMBINED TONE; BRAIN-STEM; RESPONSES; CORTEX; NEURONS; CAT; SPEECH AB Objective: The purpose of this study was to determine the effects of SNR and signal level on the offset response of the cortical auditory evoked potential (CAEP). Successful listening often depends on how well the auditory system can extract target signals from competing background noise. Both signal onsets and offsets are encoded neurally and contribute to successful listening in noise. Neural onset responses to signals in noise demonstrate a strong sensitivity to signal-to-noise ratio (SNR) rather than signal level; however, the sensitivity of neural offset responses to these cues is not known. Methods: We analyzed the offset response from two previously published datasets for which only the onset response was reported. For both datasets, CAEPs were recorded from young normal-hearing adults in response to a 1000-Hz tone. For the first dataset, tones were presented at seven different signal levels without background noise, while the second dataset varied both signal level and SNR. Results: Offset responses demonstrated sensitivity to absolute signal level in quiet, SNR, and to absolute signal level in noise. Conclusions: Offset sensitivity to signal level when presented in noise contrasts with previously published onset results. Significance: This sensitivity suggests a potential clinical measure of cortical encoding of signal level in noise. Published by Elsevier Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 [Baltzell, Lucas S.; Billings, Curtis J.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Billings, Curtis J.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. RP Billings, CJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW S Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM Curtis.Billings2@va.gov FU Department of Veterans Affairs through the Rehabilitation Research and Development Service with Career Development and Center of Excellence Grants [C6971M]; National Institutes of Health [NIDCD:DC010914, T32-DC05361, R01-DC007705, P30-DC004661, F31-DC007296] FX We are grateful for helpful comments from Drs. Garnett McMillan, Erick Gallun, Melissa Papesh, and Tina Penman. This work is supported by the Department of Veterans Affairs through the Rehabilitation Research and Development Service with Career Development and Center of Excellence Grants (C6971M) and National Institutes of Health (NIDCD:DC010914). We are thankful to Kelly Tremblay and the Brain and Behavior Lab at the University of Washington where study design and collection of original data occurred with funding support from National Institutes of Health (T32-DC05361, R01-DC007705, P30-DC004661, and F31-DC007296). NR 37 TC 7 Z9 7 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD FEB PY 2014 VL 125 IS 2 BP 370 EP 380 DI 10.1016/j.clinph.2013.08.003 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 289HO UT WOS:000329672800023 PM 24007688 ER PT J AU Urdaneta, RA Leary, J Panetta, KM Chuang, SK AF Urdaneta, Rainier A. Leary, Joseph Panetta, Kimberly M. Chuang, Sung-Kiang TI The effect of opposing structures, natural teeth vs. implants on crestal bone levels surrounding single-tooth implants SO CLINICAL ORAL IMPLANTS RESEARCH LA English DT Article DE crestal bone; dental implants; opposing structures; risk factors; single-implant crowns ID LOCKING-TAPER IMPLANTS; ROOT-FORM IMPLANTS; DENTAL IMPLANTS; HISTOLOGIC EVALUATION; TACTILE SENSIBILITY; EDENTULOUS PATIENTS; TITANIUM IMPLANTS; CANCELLOUS BONE; ORAL IMPLANTS; BITE FORCE AB ObjectivesTo evaluate the effect of opposing structures in crestal bone levels around single-tooth implants. Materials and methodsA retrospective cohort study design was conducted. Descriptive statistics, univariate and multifactor mixed-effects regression models, adjusted for multiple implants in the same patient were utilized to evaluate the effect of opposing structures in crestal bone levels after insertion of single-tooth replacements. ResultsEighty-one subjects who received 320 Bicon implants were included in the present study. Two hundred and thirty-one implant restorations were opposing natural teeth, 75 implants were opposing implant-supported restorations, 10 implants had no opposing structure and four implants were opposed by a complete denture. The average change in crestal bone levels overtime (AvBL) on implants opposing natural teeth and implant-supported restorations was -0.20 and -0.62mm, respectively. Hydroxyapatite-coated (HA) mandibular implants opposing natural teeth demonstrated AvBL of +0.01 (indicating bone gain), whereas titanium-plasma sprayed (TPS)-coated mandibular implants opposing implants restored with composite abutment bases demonstrated AvBL of -1.95mm. When the structure opposing an HA-coated mandibular implant was a natural tooth, it was a predictor of peri-implant bone gain (P=0.007). While TPS-coated mandibular implants, which had been restored with composite abutment bases, were correlated with peri-implant bone loss when opposed by implant-supported restorations (P=0.003). ConclusionsThis study suggests that the type of opposing structure plays a significant role in mandibular crestal bone levels surrounding single-tooth implants following crown insertion but this effect differ around implants with dissimilar surface coatings and can be exacerbated by local irritating factors. C1 [Urdaneta, Rainier A.] Implant Dent Ctr, Boston, MA USA. [Panetta, Kimberly M.] Implant Dent Ctr, Norwood, MA USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Urdaneta, RA (reprint author), 25 Prairie Ave, Auburndale, MA USA. EM rainieru@yahoo.com NR 72 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-7161 EI 1600-0501 J9 CLIN ORAL IMPLAN RES JI Clin. Oral Implant. Res. PD FEB PY 2014 VL 25 IS 2 BP E179 EP E188 DI 10.1111/clr.12087 PG 10 WC Dentistry, Oral Surgery & Medicine; Engineering, Biomedical SC Dentistry, Oral Surgery & Medicine; Engineering GA 286IK UT WOS:000329461200032 PM 23278549 ER PT J AU Tare, A Lane, JM Cade, BE Grant, SFA Chen, TH Punjabi, NM Lauderdale, DS Zee, PC Gharib, SA Gottlieb, DJ Scheer, FAJL Redline, S Saxena, R AF Tare, Archana Lane, Jacqueline M. Cade, Brian E. Grant, Struan F. A. Chen, Ting-hsu Punjabi, Naresh M. Lauderdale, Diane S. Zee, Phyllis C. Gharib, Sina A. Gottlieb, Daniel J. Scheer, Frank A. J. L. Redline, Susan Saxena, Richa TI Sleep duration does not mediate or modify association of common genetic variants with type 2 diabetes SO DIABETOLOGIA LA English DT Article DE Circadian genes; Genetic association studies; Genetic risk score; Sleep duration; Type 2 diabetes ID IMPAIRED GLUCOSE-TOLERANCE; FASTING PLASMA-GLUCOSE; METABOLIC SYNDROME; INCREASED RISK; QUALITY; MTNR1B; METAANALYSIS; POPULATION; DESIGN; IMPACT AB Short and long sleep duration are associated with increased risk of type 2 diabetes. We aimed to investigate whether genetic variants for fasting glucose or type 2 diabetes associate with short or long sleep duration and whether sleep duration modifies the association of genetic variants with these traits. We examined the cross-sectional relationship between self-reported habitual sleep duration and prevalence of type 2 diabetes in individuals of European descent participating in five studies included in the Candidate Gene Association Resource (CARe), totalling 1,474 cases and 8,323 controls. We tested for association of 16 fasting glucose-associated variants, 27 type 2 diabetes-associated variants and aggregate genetic risk scores with continuous and dichotomised (a parts per thousand currency sign5 h or a parts per thousand yen9 h) sleep duration using regression models adjusted for age, sex and BMI. Finally, we tested whether a gene x behaviour interaction of variants with sleep duration had an impact on fasting glucose or type 2 diabetes risk. Short sleep duration was significantly associated with type 2 diabetes in CARe (OR 1.32; 95% CI 1.08, 1.61; p = 0.008). Variants previously associated with fasting glucose or type 2 diabetes and genetic risk scores were not associated with sleep duration. Furthermore, no study-wide significant interaction was observed between sleep duration and these variants on glycaemic traits. Nominal interactions were observed for sleep duration and PPARG rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05). Our findings suggest that differences in habitual sleep duration do not mediate or modify the relationship between common variants underlying glycaemic traits (including in circadian rhythm genes) and diabetes. C1 [Tare, Archana; Lane, Jacqueline M.; Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Tare, Archana; Lane, Jacqueline M.; Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Lane, Jacqueline M.; Saxena, Richa] Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Lane, Jacqueline M.; Cade, Brian E.; Gottlieb, Daniel J.; Scheer, Frank A. J. L.; Redline, Susan; Saxena, Richa] Harvard Univ, Sch Med, Boston, MA USA. [Cade, Brian E.; Gottlieb, Daniel J.; Scheer, Frank A. J. L.; Redline, Susan] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Grant, Struan F. A.] Childrens Hosp Philadelphia, Res Inst, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Grant, Struan F. A.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chen, Ting-hsu; Gottlieb, Daniel J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Baltimore, MD USA. [Lauderdale, Diane S.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Zee, Phyllis C.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Zee, Phyllis C.] Northwestern Univ, Sleep Disorders Ctr, Chicago, IL 60611 USA. [Gharib, Sina A.] Univ Washington, UW Med Sleep Ctr, Ctr Lung Biol, Computat Med Core, Seattle, WA 98195 USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Dept Med, Sleep Disorders Ctr, Boston, MA USA. RP Saxena, R (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-806, Boston, MA 02114 USA. EM rsaxena@chgr.mgh.harvard.edu FU NIDDK NIH [DK089378]; Harvard Catalyst of the Harvard Clinical and Translational Science Center (National Center for Research Resources); National Center for Advancing Translational Sciences, National Institutes of Health [8UL1TR000170-05]; Harvard University; National Heart, Lung, and Blood Institute [U01HL53941, U01HL53916, U01HL53934, U01HL 53937, U01HL63429, U01HL 63463]; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL105756]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [AG023629] FX This study was conducted with support to RS and FAJLS from NIDDK NIH R21 (DK089378) and from Harvard Catalyst of 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 centres). 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 centres or the National Institutes of Health. CARe and SHHS are supported by the National Heart, Lung, and Blood Institute cooperative agreement U01HL53941 (Boston University), U01HL53916 (University of California, Davis), U01HL53934 (University of Minnesota), U01HL 53937 and U01HL63429 (Johns Hopkins University) and U01HL 63463 (Case Western Reserve University). The CHS was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083 and N01HC85086 and by NHLBI grants HL080295, HL087652 and HL105756, with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS principal investigators and institutions can be found at www.chs-nhlbi.org/pi. NR 44 TC 5 Z9 5 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2014 VL 57 IS 2 BP 339 EP 346 DI 10.1007/s00125-013-3110-y PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 288MC UT WOS:000329615100010 PM 24280871 ER PT J AU Bucerius, J Mani, V Moncrieff, C Machac, J Fuster, V Farkouh, ME Tawakol, A Rudd, JHF Fayad, ZA AF Bucerius, Jan Mani, Venkatesh Moncrieff, Colin Machac, Josef Fuster, Valentin Farkouh, Michael E. Tawakol, Ahmed Rudd, James H. F. Fayad, Zahi A. TI Optimizing F-18-FDG PET/CT imaging of vessel wall inflammation: the impact of F-18-FDG circulation time, injected dose, uptake parameters, and fasting blood glucose levels SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE FDG PET; FDG dose; FDG circulation time; Prescan glucose; Vessel wall inflammation ID POSITRON-EMISSION-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE INFLAMMATION; VASCULAR INFLAMMATION; FDG UPTAKE; MALIGNANT-TUMORS; SERUM GLUCOSE; DAL-PLAQUE; INSULIN; CANCER; DISEASE AB F-18-FDG PET is increasingly used for imaging of vessel wall inflammation. However, limited data are available on the impact of methodological variables, i.e. prescan fasting glucose, FDG circulation time and injected FDG dose, and of different FDG uptake parameters, in vascular FDG PET imaging. Included in the study were 195 patients who underwent vascular FDG PET/CT of the aorta and the carotids. Arterial standardized uptake values (meanSUVmax), target-to-background ratios (meanTBRmax) and FDG blood-pool activity in the superior vena cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake values classified according to the tertiles of prescan fasting glucose levels, the FDG circulation time, and the injected FDG dose were compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood-pool FDG uptake. Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l, showing a favorable relationship between arterial and blood-pool FDG uptake. FDG circulation times showed negative associations with aortic meanSUVmax values as well as SVC and JV FDG blood-pool activity, but positive correlations with aortic and carotid meanTBRmax values. Prescan glucose levels were negatively associated with aortic and carotid meanTBRmax and carotid meanSUVmax values, but were positively correlated with SVC blood-pool uptake. The injected FDG dose failed to show any significant association with vascular FDG uptake. FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT. The injected FDG dose was less critical. Therefore, circulation times of about 2.5 h and prescan glucose levels less than 7.0 mmol/l should be preferred in this setting. C1 [Bucerius, Jan; Mani, Venkatesh; Moncrieff, Colin; Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Bucerius, Jan; Mani, Venkatesh; Moncrieff, Colin; Fayad, Zahi A.] Mt Sinai Sch Med, Dept Radiol, New York, NY USA. [Bucerius, Jan] Maastricht Univ, Med Ctr, Dept Nucl Med, Maastricht, Netherlands. [Bucerius, Jan] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands. [Bucerius, Jan] Rhein Westfal TH Aachen, Univ Hosp, Dept Nucl Med, D-52062 Aachen, Germany. [Mani, Venkatesh; Fuster, Valentin; Farkouh, Michael E.; Fayad, Zahi A.] Mt Sinai Sch Med, Zena & Michael A Weiner Cardiovasc Inst, Dept Cardiol, New York, NY USA. [Mani, Venkatesh; Fuster, Valentin; Farkouh, Michael E.; Fayad, Zahi A.] Mt Sinai Sch Med, Marie Josee & Henry R Kravis Cardiovasc Hlth Ctr, New York, NY USA. [Machac, Josef] Mt Sinai Sch Med, Dept Radiol, Div Nucl Med, New York, NY USA. [Fuster, Valentin] Ctr Nacl Invest Cardiovasc, Madrid, Spain. [Farkouh, Michael E.] Mt Sinai Sch Med, Cardiovasc Imaging Clin Trials Unit, New York, NY USA. [Tawakol, Ahmed] Harvard Univ, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02115 USA. [Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. RP Fayad, ZA (reprint author), Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, 1 Gustave L Levy Pl,POB 1234, New York, NY 10029 USA. EM zahi.fayad@gmail.com RI Mani, Venkatesh/B-8939-2011; Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Rudd, James/0000-0003-2243-3117; Mani, Venkatesh/0000-0002-0432-2918 FU NIHR Cambridge Biomedical Research Centre; NIH/NHLBI [R01 HL071021, R01 HL078667]; NIH/NCATS CTSA [UL1TR000067] FX The authors wish to thank Ash Rafique, RT, BS, CNMT, for his assistance with image acquisition. This work was partly supported by the NIHR Cambridge Biomedical Research Centre (J.H.F.R.). Partial support was provided by: NIH/NHLBI R01 HL071021 (Z.A.F.), NIH/NHLBI R01 HL078667 (Z.A.F and M. E.F.) and NIH/NCATS CTSA UL1TR000067 [Imaging Core] (Z.A.F.). NR 33 TC 24 Z9 25 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD FEB PY 2014 VL 41 IS 2 BP 369 EP 383 DI 10.1007/s00259-013-2569-6 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 288VF UT WOS:000329639300023 PM 24271038 ER PT J AU Preston, MA Blute, ML AF Preston, Mark A. Blute, Michael L. TI Positive Surgical Margins After Radical Prostatectomy: Does It Matter? SO EUROPEAN UROLOGY LA English DT Editorial Material ID BIOCHEMICAL RECURRENCE; CANCER; RISK C1 [Preston, Mark A.; Blute, Michael L.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Blute, ML (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM mblute@partners.org NR 12 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD FEB PY 2014 VL 65 IS 2 BP 314 EP 315 DI 10.1016/j.eururo.2013.08.037 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 289EL UT WOS:000329664100013 PM 23993160 ER PT J AU Lopez-Vicario, C Gonzalez-Periz, A Rius, B Moran-Salvador, E Garcia-Alonso, V Lozano, JJ Bataller, R Cofan, M Kang, JX Arroyo, V Claria, J Titos, E AF Lopez-Vicario, Cristina Gonzalez-Periz, Ana Rius, Bibiana Moran-Salvador, Eva Garcia-Alonso, Veronica Jose Lozano, Juan Bataller, Ramon Cofan, Montserrat Kang, Jing X. Arroyo, Vicente Claria, Joan Titos, Esther TI Molecular interplay between Delta 5/Delta 6 desaturases and long-chain fatty acids in the pathogenesis of non-alcoholic steatohepatitis SO GUT LA English DT Article DE NONALCOHOLIC STEATOHEPATITIS; LIPID MEDIATORS; INFLAMMATION; BASIC SCIENCES; GENE TARGETING ID INDUCED INSULIN-RESISTANCE; LIVER-DISEASE; HEPATIC STEATOSIS; TRANSGENIC MICE; PPAR-GAMMA; OBESITY; INFLAMMATION; FAT-1; N-3; OMEGA-3-FATTY-ACIDS AB Objective The mechanisms underlying non-alcoholic steatohepatitis (NASH) are not completely elucidated. In the current study we integrated gene expression profiling of liver biopsies from NASH patients with translational studies in mouse models of steatohepatitis and pharmacological interventions in isolated hepatocytes to identify new molecular targets in NASH. Design and results Using oligonucleotide microarray analysis we identified a significant enrichment of genes involved in the multi-step catalysis of long-chain polyunsaturated fatty acids, namely, -5 desaturase (5D) and 6D in NASH. Increased expression of 5D and 6D at both mRNA and protein level were confirmed in livers from mice with high-fat diet-induced obesity and NASH. Gas chromatography analysis revealed impaired desaturation fluxes toward the -6 and -3 pathways resulting in increased -6 to -3 ratio and reduced -3 index in human and mouse fatty livers. Restoration of hepatic -3 content in transgenic fat-1 mice expressing an -3 desaturase, which allows the endogenous conversion of -6 into -3 fatty acids, produced a significant reduction in hepatic insulin resistance, steatosis, macrophage infiltration, necroinflammation and lipid peroxidation, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were mostly reproduced by feeding obese mice with an exogenous -3-enriched diet. A combined 5D/6D inhibitor, CP-24879, significantly reduced intracellular lipid accumulation and inflammatory injury in hepatocytes. Interestingly, CP-24879 exhibited superior antisteatotic and anti-inflammatory actions in fat-1 and -3-treated hepatocytes. Conclusions These findings indicate that impaired hepatic fatty acid desaturation and unbalanced -6 to -3 ratio play a role in the pathogenesis of NASH. C1 [Lopez-Vicario, Cristina; Gonzalez-Periz, Ana; Rius, Bibiana; Moran-Salvador, Eva; Garcia-Alonso, Veronica; Cofan, Montserrat; Claria, Joan; Titos, Esther] Hosp Clin Barcelona, IDIBAPS Esther Koplowitz Ctr, Dept Biochem & Mol Genet, E-08036 Barcelona, Spain. [Gonzalez-Periz, Ana; Jose Lozano, Juan; Arroyo, Vicente; Claria, Joan; Titos, Esther] CIBERehd, Barcelona, Spain. [Bataller, Ramon] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Bataller, Ramon] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Cofan, Montserrat] CIBERobn, Barcelona, Spain. [Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Arroyo, Vicente] Hosp Clin Barcelona, Liver Unit, IDIBAPS Esther Koplowitz Ctr, E-08036 Barcelona, Spain. [Claria, Joan] Univ Barcelona, Dept Physiol Sci 1, Barcelona, Spain. RP Claria, J (reprint author), CIBERehd, Barcelona, Spain. EM jclaria@clinic.ub.es; esther.titos@ciberehd.org RI Arroyo, Vicente/F-9189-2015 OI Arroyo, Vicente/0000-0002-2728-1848 FU Ministerio de Ciencia e Innovacion (MICINN) [SAF09/08767, SAF12/32789, BES-2010-034193]; Instituto de Salud Carlos III; IDIBAPS FX This study was supported by grants from the Ministerio de Ciencia e Innovacion (MICINN) (SAF09/08767 and SAF12/32789). CIBERehd and CIBERobn are funded by the Instituto de Salud Carlos III. Our laboratory is a Consolidated Research Group recognised by the Generalitat de Catalunya (2009SGR1484). Cristina Lopez-Vicario is supported by IDIBAPS. Veronica Garcia-Alonso has a fellowship from MICINN (BES-2010-034193). NR 43 TC 31 Z9 31 U1 2 U2 16 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD FEB PY 2014 VL 63 IS 2 BP 344 EP 355 DI 10.1136/gutjnl-2012-303179 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 286SD UT WOS:000329488100006 PM 23492103 ER PT J AU Gill, CM Taneja, AK Bredella, MA Torriani, M DeSilva, JM AF Gill, Corey M. Taneja, Atul K. Bredella, Miriam A. Torriani, Martin DeSilva, Jeremy M. TI Osteogenic relationship between the lateral plantar process and the peroneal tubercle in the human calcaneus SO JOURNAL OF ANATOMY LA English DT Article DE Australopithecus afarensis; Australopithecus sediba; calcaneus; lateral plantar process; peroneal tubercle; retrotrochlear eminence ID AUSTRALOPITHECUS-SEDIBA; HUMAN FOOT; EVOLUTION; TENDON; LONGUS; AFARENSIS; TENOSYNOVITIS; BIPEDALITY; LOCOMOTOR AB The osteogenic relationship between the lateral plantar process and the peroneal tubercle has been an uncertainty for researchers over several decades. While some argue there to be no developmental relationship between these two calcaneal structures, others have suggested that there is an inverse relationship, the lateral plantar process forming from a part of the peroneal tubercle. However, no previous studies have offered quantitative measurements to test these hypotheses. In this study, we measured the size of the peroneal tubercle, retrotrochlear eminence, and the size and area of the lateral plantar process in 73 subjects using magnetic resonance imaging (MRI). Navicular height was measured using weight-bearing radiographs as a measurement of longitudinal arch in 35 of these subjects. Age, body mass, and body mass index (BMI) were also recorded for all subjects. We determined that there was a significant positive correlation between the lateral plantar process and size of the peroneal tubercle, body mass, and BMI. Thus, assertions that there is an inverse relationship between the size of the lateral plantar process and the peroneal tubercle are here unfounded. We also determined there to be a positive correlation between the peroneal tubercle and both the size of the retrotrochlear eminence and the height of the navicular. In conclusion, we relate these novel findings to hominin fossil calcanei and discuss the evolutionary and biomechanical implications. C1 [Gill, Corey M.; Taneja, Atul K.; Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Gill, Corey M.; Taneja, Atul K.; Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA USA. [Gill, Corey M.; DeSilva, Jeremy M.] Boston Univ, Dept Anthropol, Boston, MA 02215 USA. RP DeSilva, JM (reprint author), Boston Univ, Dept Anthropol, 232 Bay State Rd,104B, Boston, MA 02215 USA. EM jdesilva@bu.edu RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 NR 34 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8782 EI 1469-7580 J9 J ANAT JI J. Anat. PD FEB PY 2014 VL 224 IS 2 BP 173 EP 179 DI 10.1111/joa.12135 PG 7 WC Anatomy & Morphology SC Anatomy & Morphology GA 290IB UT WOS:000329747000008 PM 24188397 ER PT J AU Belstrom, D Fiehn, NE Nielsen, CH Kirkby, N Twetman, S Klepac-Ceraj, V Paster, BJ Holmstrup, P AF Belstrom, Daniel Fiehn, Nils-Erik Nielsen, Claus H. Kirkby, Nikolai Twetman, Svante Klepac-Ceraj, Vanja Paster, Bruce J. Holmstrup, Palle TI Differences in bacterial saliva profile between periodontitis patients and a control cohort SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE 16S rRNA; bacteria; biomarker; HOMIM; periodontitis; saliva ID MICROBE IDENTIFICATION MICROARRAY; HUMAN ORAL MICROBIOME; REFRACTORY PERIODONTITIS; DISEASE PROGRESSION; SUBGINGIVAL PLAQUE; HEALTH; PREVALENCE; BIOMARKERS AB AimPeriodontitis is a multifactorial disease in which subgingival bacteria play an important role in the pathogenesis of the disease. The objective of this study was to determine if periodontitis is associated with a characteristic salivary bacterial profile. This was accomplished by comparing the bacterial profile of saliva from subjects with chronic periodontitis with that of saliva from a control cohort. Materials and methodsStimulated saliva samples from 139 chronic periodontitis patients and 447 samples from a control cohort were analysed using the Human Oral Microbe Identification Microarray (HOMIM). Frequency and levels (mean HOMIM-value) of around 300 bacterial taxa/clusters in samples were used as parameters for investigation. Differences at taxon/cluster values between groups were analysed using Mann-Whitney U-test with Benjamini-Hochberg correction for multiple comparisons. Principal component analysis was used to visualize bacterial community profiles obtained by the HOMIM. ResultsEight bacterial taxa, including putative periodontal pathogens as Parvimonas micra and Filifactor alocis, and four bacterial clusters were identified statistically more frequently and at higher levels in samples from periodontitis patients than in samples from the control cohort. These differences were independent of the individuals' smoking status. ConclusionsPeriodontitis is associated with a characteristic bacterial profile of saliva different from that of a control cohort. C1 [Belstrom, Daniel; Holmstrup, Palle] Univ Copenhagen, Fac Hlth Sci, Sch Dent, Sect Periodontol, DK-2200 Copenhagen, Denmark. [Fiehn, Nils-Erik] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen, Denmark. [Nielsen, Claus H.] Rigshosp, Dept Infect Dis & Rheumatol, Inst Inflammat Res, Copenhagen Univ Hosp, DK-2100 Copenhagen, Denmark. [Kirkby, Nikolai] Copenhagen Univ Hosp, Dept Med Microbiol, Rigshosp, Copenhagen, Denmark. [Twetman, Svante] Univ Copenhagen, Fac Hlth Sci, Sch Dent, Sect Cariol, DK-2200 Copenhagen, Denmark. [Klepac-Ceraj, Vanja] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02181 USA. [Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Belstrom, D (reprint author), Univ Copenhagen, Fac Hlth Sci, Sch Dent, Sect Periodontol, Norre Alle 20, DK-2200 Copenhagen, Denmark. EM dbel@sund.ku.dk OI Klepac-Ceraj, Vanja/0000-0001-5387-5706 FU Danish Dental Association; Danish Foundation for Mutual Efforts in Dental Care; TrygFonden; Health Insurance Foundation; Simon Spies Foundation FX This study was supported by external financial support by: the Danish Dental Association, the Danish Foundation for Mutual Efforts in Dental Care, TrygFonden, the Health Insurance Foundation and the Simon Spies Foundation. NR 32 TC 30 Z9 35 U1 3 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 EI 1600-051X J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD FEB PY 2014 VL 41 IS 2 BP 104 EP 112 DI 10.1111/jcpe.12190 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 287YU UT WOS:000329579300002 PM 24303924 ER PT J AU Janket, SJ Baird, AE Jones, JA Jackson, EA Surakka, M Tao, W Meurman, JH Van Dyke, TE AF Janket, Sok-Ja Baird, Alison E. Jones, Judith A. Jackson, Elizabeth A. Surakka, Markku Tao, Wen Meurman, Jukka H. Van Dyke, Thomas E. TI Number of teeth, C-reactive protein, fibrinogen and cardiovascular mortality: a 15-year follow-up study in a Finnish cohort SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE C-reactive protein; CVD mortality; fibrinogen; mediation analyses; number of teeth ID CORONARY-HEART-DISEASE; DWELLING OLDER PERSONS; PERIODONTAL-DISEASE; TOOTH LOSS; SALIVARY LYSOZYME; ENDOTHELIAL DYSFUNCTION; HUMAN NEUTROPHILS; RISK-FACTORS; ORAL-HEALTH; WOMEN AB AimTo test whether the number of teeth, an inverse proxy for composite oral infection scores is associated with better survival. Materials and MethodsThe Kuopio Oral Health and Heart study initiated a case-control study in 1995-1996 consisting of 256 consecutive coronary artery disease patients and 250 age and gender-matched controls. We appended the mortality data and formulated a longitudinal study. By May 31st, 2011, 124 mortalities had occurred and 80 of which were of cardiovascular origin. Using Cox proportional hazards models, we assessed the association of the teeth group (Teethgrp) - consisting of 10 teeth - with cardiovascular and all-cause mortality after 15.8years of median follow-up. ResultsIn multivariate models, with the edentulous state as reference, one level increase in Teethgrp was associated with significantly increased survival from cardiovascular disease (CVD) mortality with a Hazard Ratio (HR) 0.73, p-value=0.02 but not with all-cause mortality (HR=0.87, p=0.13). The findings were not mediated by C-reactive protein (CRP) levels 3mg/L or by median fibrinogen levels, but were mediated by CRP levels >5mg/L. ConclusionEach increment of 10 teeth from the edentulous state was associated with a 27% improved CVD survival, independent of low-grade systemic inflammation. C1 [Janket, Sok-Ja; Jones, Judith A.] Boston Univ, Henry M Goldman Sch Dent Med, Boston, MA 02118 USA. [Baird, Alison E.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Jackson, Elizabeth A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Surakka, Markku] Univ Kuopio, FIN-70211 Kuopio, Finland. [Tao, Wen] Boston Univ, Dept Biostat, Boston, MA 02118 USA. [Meurman, Jukka H.] Univ Helsinki, Cent Hosp, Dept Oral & Maxillofacial Dis, Helsinki, Finland. [Meurman, Jukka H.] Univ Helsinki, Inst Dent, Helsinki, Finland. [Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA USA. RP Janket, SJ (reprint author), Boston Univ, Sch Dent Med, 100 East Newton St,Rm G-107C, Boston, MA 02118 USA. EM skjanket@bu.edu OI Meurman, Jukka/0000-0001-6702-6836 FU American Heart Association [0635351N]; NIH [R01 EB010087, R21 MH097639, R01 AG-045136, RO1 HL115295, U01 NR004061]; Neurology Research Education Program [U01 NINDS]; Medical Society of Finland; Helsinki University Central Hospital Research Funds; USPHS [DE15566] FX The funding sources listed below had no influence in our results. This study was supported by an award from the American Heart Association # 0635351N to Dr. Sok-Ja Janket. Dr. Baird is supported by NIH grants R01 EB010087 and R21 MH097639. Dr. Baird is also a co-investigator on R25 NINDS R Train, Neurology Research Education Program and U01 NINDS Neuro-NEXT Clinical Trials (U01) at SUNY Downstate Medical Center. Dr. Jackson is supported by NIH grants R01 AG-045136, RO1 HL115295 and U01 NR004061. Dr. Meurman is supported by the Medical Society of Finland and Helsinki University Central Hospital Research Funds. Dr. Van Dyke is supported in part by USPHS grant DE15566. NR 57 TC 8 Z9 9 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 EI 1600-051X J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD FEB PY 2014 VL 41 IS 2 BP 131 EP 140 DI 10.1111/jcpe.12192 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 287YU UT WOS:000329579300005 PM 24354534 ER PT J AU Griffin, WC Haun, HL Hazelbaker, CL Ramachandra, VS Becker, HC AF Griffin, William C., III Haun, Harold L. Hazelbaker, Callan L. Ramachandra, Vorani S. Becker, Howard C. TI Increased Extracellular Glutamate In the Nucleus Accumbens Promotes Excessive Ethanol Drinking in Ethanol Dependent Mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ethanol; dependence; glutamate; drinking; microdialysis; mouse ID AMINO-ACID TRANSPORTERS; CENTRAL-NERVOUS-SYSTEM; ALCOHOL DEPENDENCE; C57BL/6J MICE; AGONIST LY379268; WITHDRAWAL; RATS; EXPOSURE; RECEPTOR; HISTORY AB Using a well-established model of ethanol dependence and relapse, this study examined adaptations in glutamatergic transmission in the nucleus accumbens (NAc) and their role in regulating voluntary ethanol drinking. Mice were first trained to drink ethanol in a free-choice, limited access (2 h/day) paradigm. One group (EtOH mice) received repeated weekly cycles of chronic intermittent ethanol (CIE) exposure with intervening weeks of test drinking sessions, whereas the remaining mice (CTL mice) were similarly treated but did not receive CIE treatment. Over repeated cycles of CIE exposure, EtOH mice exhibited significant escalation in drinking (up to B3.5 g/kg), whereas drinking remained relatively stable at baseline levels (2-2.5 g/kg) in CTL mice. Using in vivo microdialysis procedures, extracellular glutamate (GLU(EX)) levels in the NAc were increased approximately twofold in EtOH mice compared with CTL mice, and this difference was observed 7 days after final CIE exposure, indicating that this hyperglutamatergic state persisted beyond acute withdrawal. This finding prompted additional studies examining the effects of pharmacologically manipulating GLU(EX) in the NAc on ethanol drinking in the CIE model. The non-selective glutamate reuptake antagonist, threo-beta-benzyloxyaspartate (TBOA), was bilaterally microinjected into the NAc and found to dose-dependently increase drinking in nondependent (CTL) mice to levels attained by dependent (EtOH) mice. TBOA also further increased drinking in EtOH mice. In contrast, reducing glutamatergic transmission in the NAc via bilateral injections of the metabotropic glutamate receptor-2/3 agonist LY379268 reduced drinking in dependent (EtOH) mice to nondependent (CTL) levels, whereas having a more modest effect in decreasing ethanol consumption in CTL mice. Taken together, these data support an important role of glutamatergic transmission in the NAc in regulating ethanol drinking. Additionally, these results indicate that ethanol dependence produces adaptations that favor elevated glutamate activity in the NAc which, in turn, promote excessive levels of ethanol consumption associated with dependence. C1 [Griffin, William C., III; Haun, Harold L.; Hazelbaker, Callan L.; Ramachandra, Vorani S.; Becker, Howard C.] Med Univ S Carolina, Charleston Alcohol Res Ctr, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Becker, Howard C.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Becker, Howard C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Griffin, WC (reprint author), Med Univ S Carolina, Charleston Alcohol Res Ctr, Dept Psychiat & Behav Sci, MSC 861, Charleston, SC 29425 USA. EM griffinw@musc.edu FU NIH [P50 AA10716, F32 AA021321]; Department of Veterans Affairs Medical Research FX This work was supported by NIH grant P50 AA10716 (WCG and HCB), F32 AA021321 (VSR). Dr Becker's research program is funded by NIH and the Department of Veterans Affairs Medical Research. Dr Becker also has conducted contractual work and served as a consultant for Eli Lilly and Company, but those activities have no relationship to the present report. The authors declare no conflict of interest. NR 67 TC 31 Z9 31 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2014 VL 39 IS 3 BP 707 EP 717 DI 10.1038/npp.2013.256 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 291PZ UT WOS:000329842600019 PM 24067300 ER PT J AU Park, ER Streck, JM Gareen, IF Ostroff, JS Hyland, KA Rigotti, NA Pajolek, H Nichter, M AF Park, Elyse R. Streck, Joanna M. Gareen, Ilana F. Ostroff, Jamie S. Hyland, Kelly A. Rigotti, Nancy A. Pajolek, Hannah Nichter, Mark TI A Qualitative Study of Lung Cancer Risk Perceptions and Smoking Beliefs Among National Lung Screening Trial Participants SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID COMPUTED-TOMOGRAPHY; UNREALISTIC OPTIMISM; SELF-REGULATION; FOLLOW-UP; CESSATION; SMOKERS; DISEASE; MAMMOGRAMS; INTERVIEWS; BEHAVIOR AB The National Comprehensive Cancer Network and the American Cancer Society recently released lung screening guidelines that include smoking cessation counseling for smokers undergoing screening. Previous work indicates that smoking behaviors and risk perceptions of the National Lung Screening Trial (NLST) participants were relatively unchanged. We explored American College of Radiology Imaging Network (ACRIN)/NLST former and current smokers risk perceptions specifically to (a) determine whether lung screening is a cue for behavior change, (b) elucidate risk perceptions for lung cancer and smoking-related diseases, and (c) explore postscreening behavioral intentions and changes. A random sample of 35 participants from 4 ACRIN sites were qualitatively interviewed 12 years postscreen. We used a structured interview guide based on Health Belief Model and Self-Regulation Model constructs. Content analyses were conducted with NVivo 8. Most participants endorsed high-risk perceptions for lung cancer and smoking-related diseases, but heightened concern about these risks did not appear to motivate participants to seek screening. Risk perceptions were mostly attributed to participants heavy smoking histories; former smokers expressed greatly reduced risk. Lung cancer and smoking-related diseases were perceived as very severe although participants endorsed low worry. Current smokers had low confidence in their ability to quit, and none reported quitting following their initial screen. Lung screening did not appear to be a behavior change cue to action, and high-risk perceptions did not translate into quitting behaviors. Cognitive and emotional dissonance and avoidance strategies may deter engagement in smoking behavior change. Smoking cessation and prevention interventions during lung screening should explore risk perceptions, emotions, and quit confidence. C1 [Park, Elyse R.; Streck, Joanna M.; Hyland, Kelly A.; Rigotti, Nancy A.; Pajolek, Hannah] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Park, Elyse R.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Gareen, Ilana F.] Brown Univ, Sch Med, Ctr Stat Sci, Providence, RI 02912 USA. [Gareen, Ilana F.] Brown Univ, Sch Med, Dept Epidemiol, Providence, RI 02912 USA. [Ostroff, Jamie S.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Nichter, Mark] Univ Arizona, Sch Anthropol, Tucson, AZ USA. RP Park, ER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org RI Gareen, Ilana/I-2816-2014; OI Gareen, Ilana/0000-0002-0457-5595; Ostroff, Jamie/0000-0003-2671-5680 FU American Cancer Society's Mentored Research Scholar Award [MRSG-005-05-CPPB]; American College of Radiology Imaging Network/National Lung Screening Trial [U01 CA079778, U01 CA080098] FX This work was supported by a grant from the American Cancer Society's Mentored Research Scholar Award (MRSG-005-05-CPPB), the American College of Radiology Imaging Network/National Lung Screening Trial (U01 CA079778, U01 CA080098). NR 52 TC 8 Z9 8 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2014 VL 16 IS 2 BP 166 EP 173 DI 10.1093/ntr/ntt133 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 284FZ UT WOS:000329302800006 PM 23999653 ER PT J AU Carpenter, MJ Saladin, ME LaRowe, SD McClure, EA Simonian, S Upadhyaya, HP Gray, KM AF Carpenter, Matthew J. Saladin, Michael E. LaRowe, Steven D. McClure, Erin A. Simonian, Susan Upadhyaya, Himanshu P. Gray, Kevin M. TI Craving, Cue Reactivity, and Stimulus Control Among Early-Stage Young Smokers: Effects of Smoking Intensity and Gender SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID ADOLESCENT CIGARETTE SMOKERS; NICOTINE DEPENDENCE; WITHDRAWAL SYMPTOMS; TOBACCO DEPENDENCE; COLLEGE-STUDENTS; LIGHT SMOKERS; RISK-FACTORS; CESSATION; QUESTIONNAIRE; TRAJECTORIES AB Smoking initiation usually begins in adolescence, but how and for whom nicotine dependence emerges during this period is unclear. The cue-reactivity paradigm is well suited to examine one marker of dependence: craving-related stimulus control, i.e., the ability of environmental cues to elicit craving to smoke. This study examined the effects of both level of smoking involvement (daily vs. occasional smoking) and gender on reactivity to both smoking and alcohol cues. Young (age range 1620; 42% female) daily (n 55) and occasional (n 52) smokers were exposed to each of three counterbalanced cues: (a) in vivo smoking (e.g., sight, smell, lighting of cigarette), (b) alcohol (e.g., opening, pouring, and smell of preferred beverage), and (c) neutral cue. Daily smokers exhibited higher levels of tonic (i.e., noncue-elicited) craving than did occasional smokers. Both groups showed significant increases in craving in response to cues (i.e., cue-elicited craving), with little evidence that cue-elicited craving differed between groups. Females were more cue reactive to both the alcohol and smoking cues than males, particularly for the positively reinforced aspects of smoking (i.e., hedonic craving). There were no gender group interaction effects in response to either the alcohol or the smoking cue. Findings show the presence of cue-elicited craving even among occasional smokers and are consistent with literature demonstrating heightened sensitivity to environmental cues among females. Cue-elicited craving may be one mechanism that contributes to the maintenance of smoking behavior and perhaps to the development of nicotine dependence within early stage smokers. C1 [Carpenter, Matthew J.; Saladin, Michael E.; LaRowe, Steven D.; McClure, Erin A.; Upadhyaya, Himanshu P.; Gray, Kevin M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Carpenter, Matthew J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Saladin, Michael E.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [LaRowe, Steven D.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Simonian, Susan] Coll Charleston, Dept Psychol, Charleston, SC 29401 USA. RP Carpenter, MJ (reprint author), Med Univ S Carolina, Dept Psychiat, Hollings Canc Ctr, Charleston, SC 29425 USA. EM carpente@musc.edu FU NIDA [K23 DA020482, K12 DA000357] FX This work was supported by Career Development Awards from NIDA (K23 DA020482 to M.J.C.; K12 DA000357 to K.M.G). NR 55 TC 13 Z9 13 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2014 VL 16 IS 2 BP 208 EP 215 DI 10.1093/ntr/ntt147 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 284FZ UT WOS:000329302800010 PM 24042699 ER PT J AU Sharma, J Gray, KP Evan, C Nakabayashi, M Fichorova, R Rider, J Mucci, L Kantoff, PW Sweeney, CJ AF Sharma, Jaya Gray, Kathryn P. Evan, Carolyn Nakabayashi, Mari Fichorova, Raina Rider, Jennifer Mucci, Lorelei Kantoff, Philip W. Sweeney, Christopher J. TI Elevated Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) in Men With Metastatic Prostate Cancer Starting Androgen Deprivation Therapy (ADT) Is Associated With Shorter Time to Castration Resistance and Overall Survival SO PROSTATE LA English DT Article DE insulin-like growth factor; adiponectin; leptin; prostate cancer ID METABOLIC SYNDROME; FACTOR-I; RANDOMIZED-TRIAL; RISK; INCREASES; MODELS; PROLIFERATION; PROGRESSION; SENSITIVITY; EXPRESSION AB BACKGROUNDInsulin-like growth factor (IGF) and adipokines have been implicated in prostate cancer carcinogenesis. METHODData from 122 men with serum samples drawn within 3 months of starting ADT for metastatic prostate cancer was accessed retrospectively. IGF-1, IGF binding protein (BP)-1, leptin, and adiponectin levels were measured by multiplex electrochemiluminescence assays. A multivariable Cox model assessed the association of time to castration resistant prostate cancer (CRPC) and overall survival by the protein levels, adjusted for clinical variables, age and prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, extent of metastases and were reported as hazard ratio (HR) with 95% confidence interval (CI). RESULTSMedian follow-up and overall survival were 44 and 42.2 months, respectively. ECOG performance status (1 vs. 0) was negatively associated with overall survival [HR=2.8 (1.1-7.0), P=0.03], and PSA nadir <0.2 was predictive of longer time to CRPC [HR=0.3 (0.2-0.5), P<0.0001]. The median time to CRPC by low, middle, and top IGFBP-1 tertile distribution was 20.7, 18.1, and 12.4 months, respectively, with HR for middle versus low tertile levels 3.1 (1.7-5), P=0.0003, and for top versus low tertile levels was 2.4 (1.3-4.2), P=0.003. The median overall survival by low, middle and top tertile IGFBP-1 level was 48.5, 46.4, and 32.8 months, respectively, with HR for top versus low tertile 2.5 (1.2-5.1), P=0.01. There was no association with IGF-1, adiponectin and leptin. CONCLUSIONElevated IGFBP-1 appears to be associated with shorter time to CRPC and lower overall survival in men with metastatic prostate cancer. Prostate 74:225-234, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Sharma, Jaya; Evan, Carolyn; Nakabayashi, Mari; Kantoff, Philip W.; Sweeney, Christopher J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Gray, Kathryn P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gray, Kathryn P.; Rider, Jennifer; Mucci, Lorelei] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fichorova, Raina; Rider, Jennifer] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fichorova, Raina; Kantoff, Philip W.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Sweeney, Christopher J.] Hoosier Oncol Grp, Indianapolis, IN USA. RP Sweeney, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,D1230, Boston, MA 02215 USA. EM christopher_sweeney@dfci.harvard.edu RI Fichorova, Raina/G-9969-2014; OI Rider, Jennifer/0000-0002-2637-6036 NR 44 TC 10 Z9 11 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD FEB PY 2014 VL 74 IS 3 BP 225 EP 234 DI 10.1002/pros.22744 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 287HE UT WOS:000329531900004 PM 24132762 ER PT J AU Jakubowski, JA Zhou, CM Jurcevic, S Winters, KJ Lachno, DR Frelinger, AL Gupta, N Howard, J Payne, CD Mant, TG AF Jakubowski, Joseph A. Zhou, Chunmei Jurcevic, Stipo Winters, Kenneth J. Lachno, D. Richard Frelinger, Andrew L., III Gupta, Neehar Howard, Jo Payne, Christopher D. Mant, Timothy G. TI A phase 1 study of prasugrel in patients with sickle cell disease: Effects on biomarkers of platelet activation and coagulation SO THROMBOSIS RESEARCH LA English DT Article DE ADP; Biomarkers; P2Y(12) receptor antagonist; Platelets; Prasugrel; Sickle cell disease ID ACTIVE METABOLITE; DOUBLE-BLIND; ANEMIA; HYPERCOAGULABILITY; ANTIPLATELET; INFLAMMATION; CLOPIDOGREL; INHIBITION; MONOCYTE AB Introduction: Prasugrel, a P2Y(12) adenosine diphosphate (ADP) receptor antagonist effectively inhibits ADP-mediated platelet activation and aggregation, and may be useful in reducing vaso-occlusive crises in sickle cell disease (SCD). In this study, we assess the effect of prasugrel on biomarkers of platelet activation and coagulation in patients with SCD. Materials and Methods: Twelve adult patients with SCD and 13 healthy subjects were examined before and after 12 +/- 2 days of 5.0 or 7.5 mg/day oral prasugrel. Assessed cellular biomarkers included monocyte-and neutrophil-platelet aggregates, activated glycoprotein IIb-IIIa (GPIIbIIIa), P-selectin, CD40 ligand (CD40L), tissue factor (TF) expression on circulating platelets and on monocyte-platelet aggregates, and platelet-erythrocyte aggregates. Soluble biomarkers included CD40L, prothrombin fragment 1.2 (F1.2), thromboxane B-2 (TXB2), P-selectin, and TF. Results: Patients with SCD had increased platelet baseline activation compared to healthy subjects, as measured by percentages ofmonocyte-platelet aggregates, neutrophil-platelet aggregates, and platelets expressing CD40L. Likewise, baseline levels of soluble F1.2 and TXB2 were elevated in patients with SCD compared to healthy subjects. After 12 days of prasugrel, patients with SCD had a significant reduction in platelet-monocyte aggregates that was not observed in healthy subjects. Following prasugrel administration, those with SCDmaintained higher levels of monocyte-platelet aggregates and soluble F1.2, but had lower levels of platelet-erythrocyte aggregates and soluble TF compared to healthy subjects. Conclusions: These results provide evidence for chronic platelet activation in the SCD steady state, activation that was in part attenuated by prasugrel, thereby suggesting that ADP may mediate platelet activation in SCD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Jakubowski, Joseph A.; Zhou, Chunmei; Winters, Kenneth J.; Gupta, Neehar] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Jurcevic, Stipo] Kings Coll London, London WC2R 2LS, England. [Lachno, D. Richard; Payne, Christopher D.] Eli Lilly & Co, Lilly Res Labs, Windlesham, Surrey, England. [Frelinger, Andrew L., III] Harvard Univ, Dana Farber Canc Inst, Boston Childrens Hosp, Ctr Platelet Res Studies,Div Hematol Oncol,Med Sc, Cambridge, MA 02138 USA. [Howard, Jo] Guys & St Thomas Hosp, London SE1 9RT, England. [Mant, Timothy G.] Guys Hosp, Quintiles Drug Res Unit, London SE1 9RT, England. RP Jakubowski, JA (reprint author), Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM joseph@lilly.com FU Daiichi Sankyo Company, Ltd.; Eli Lilly and Company; National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London FX This research was supported by Daiichi Sankyo Company, Ltd., and Eli Lilly and Company. Sponsors were involved in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. Appreciation is expressed to Tamara Ball, MD, (inVentiv Health Clinical) for writing and editorial contributions. Also acknowledged is Julie Sherman, AAS, of Eli Lilly for assistance with graphics. Dr. Mant is supported by the National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. NR 30 TC 11 Z9 11 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD FEB PY 2014 VL 133 IS 2 BP 190 EP 195 DI 10.1016/j.thromres.2013.12.008 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 287WI UT WOS:000329572600013 PM 24368019 ER PT J AU van der Wilden, GM Yeh, DD Hwabejire, JO Klein, EN Fagenholz, PJ King, DR de Moya, MA Chang, YC Velmahos, GC AF van der Wilden, Gwendolyn M. Yeh, D. Dante Hwabejire, John O. Klein, Eric N. Fagenholz, Peter J. King, David R. de Moya, Marc A. Chang, Yuchiao Velmahos, George C. TI Trauma Whipple: Do or Don't After Severe Pancreaticoduodenal Injuries? An Analysis of the National Trauma Data Bank (NTDB) SO WORLD JOURNAL OF SURGERY LA English DT Article ID COMBINED PANCREATODUODENAL INJURIES; SURGEON VOLUME; MANAGEMENT; OUTCOMES; PANCREAS; MORTALITY AB Pancreaticoduodenectomy for trauma (PDT) is a rare procedure, reserved for severe pancreaticoduodenal injuries. Using the National Trauma Data Bank (NTDB), our aim was to compare outcomes of PDT patients to similarly injured patients who did not undergo a PDT. Patients with pancreatic or duodenal injuries treated with PDT (ICD-9-CM 52.7) were identified in the NTDB 2008-2010 Research Data Sets. We excluded those who underwent delayed PDT (> 4 days). The PDT group (n = 39) was compared to patients with severe combined pancreaticoduodenal injuries (grade 4 or 5) who did not undergo PDT (non-PDT group, n = 38). Patients who died in the emergency department or did not undergo a laparotomy were excluded. Our primary outcome was death. Secondary outcomes were intensive care unit length of stay (LOS), hospital LOS, and total ventilator days. A multivariate model was used to determine predictors of in-hospital mortality within each group and in the overall cohort. The non-PDT group had a significantly lower systolic blood pressure and Glasgow Coma Scale values at baseline and more severe duodenal, pancreatic, and liver injuries. There were no significant differences in outcomes between the two groups. The Injury Severity Score was the only independent predictor of mortality among PDT patients [odds ratio (OR) 1.12, 95 % confidence interval (CI) 1.01-1.24] and in the entire cohort (OR 1.06, 95 % CI 1.01-1.12). The operative technique did not influence any of the outcomes. Compared to non-PDT, PDT did not result in improved outcomes despite a lower physiologic burden among PDT patients. More conservative procedures for high-grade injuries of the pancreaticoduodenal complex may be appropriate. C1 [van der Wilden, Gwendolyn M.; Yeh, D. Dante; Hwabejire, John O.; Klein, Eric N.; Fagenholz, Peter J.; King, David R.; de Moya, Marc A.; Chang, Yuchiao; Velmahos, George C.] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. [van der Wilden, Gwendolyn M.] Leiden Univ, Med Ctr, Dept Trauma Surg, Leiden, Netherlands. [van der Wilden, Gwendolyn M.] Leiden Univ, Leiden, Netherlands. RP van der Wilden, GM (reprint author), Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM G.M.van_der_Wilden@lumc.nl; dyeh2@partners.org OI King, David/0000-0003-1028-1478 NR 30 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD FEB PY 2014 VL 38 IS 2 BP 335 EP 340 DI 10.1007/s00268-013-2257-5 PG 6 WC Surgery SC Surgery GA 288UV UT WOS:000329638300009 PM 24121363 ER PT J AU Stanton, RC AF Stanton, Robert C. TI Frontiers in Diabetic Kidney Disease: Introduction SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID ALBUMINURIA; MORTALITY; RISK C1 Joslin Diabet Ctr, Kidney & Hypertens Div, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Kidney & Hypertens Div, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu NR 12 TC 4 Z9 4 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2014 VL 63 IS 2 SU 2 BP S1 EP S2 DI 10.1053/j.ajkd.2013.10.051 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CL1SM UT WOS:000356724700001 PM 24461726 ER PT J AU Stanton, RC AF Stanton, Robert C. TI Clinical Challenges in Diagnosis and Management of Diabetic Kidney Disease SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Diabetic kidney disease (DKD); diabetes mellitus; renal disease; prevalence; public health ID BLOOD-PRESSURE CONTROL; GLOMERULAR-FILTRATION-RATE; RENIN-ANGIOTENSIN SYSTEM; STAGE RENAL-DISEASE; DIETARY-PROTEIN RESTRICTION; URINARY ALBUMIN EXCRETION; CALCIUM-CHANNEL BLOCKERS; CARDIORENAL END-POINTS; DUAL RAAS BLOCKADE; ACE-INHIBITOR AB Diabetic kidney disease (DKD) is a major and increasing worldwide public health issue. There is a great need for implementing treatments that either prevent or significantly slow the progression of DKD. Although there have been significant improvements in management, the increasing numbers of patients with DKD illustrate that current management is not wholly adequate. The reasons for suboptimal management include the lack of early diagnosis, lack of aggressive interventions, and lack of understanding about which interventions are most successful. There are a number of challenges and controversies regarding the current management of patients with DKD. Understanding of these issues is needed in order to provide the best care to patients with DKD. This article describes some of the clinically important challenges associated with DKD: the current epidemiology and cost burden and the role of biopsy in the diagnosis of DKD. Treatment controversies regarding current pharmacologic and nonpharmacologic approaches are reviewed and recommendations based on the published literature are made. (C) 2014 by the National Kidney Foundation, Inc. C1 Joslin Diabet Ctr, Kidney & Hypertens Div, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Kidney & Hypertens Div, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu NR 134 TC 15 Z9 18 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2014 VL 63 IS 2 SU 2 BP S3 EP S21 DI 10.1053/j.ajkd.2013.10.050 PG 19 WC Urology & Nephrology SC Urology & Nephrology GA CL1SM UT WOS:000356724700002 PM 24461728 ER PT J AU Williams, ME Garg, R AF Williams, Mark E. Garg, Rajesh TI Glycemic Management in ESRD and Earlier Stages of CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease (CKD); hyperglycemia; diabetes mellitus; hemoglobin A(1c) (HbA(1c)); end-stage renal disease (ESRD) ID TYPE-2 DIABETES-MELLITUS; CHRONIC KIDNEY-DISEASE; CHRONIC-RENAL-FAILURE; CHRONIC-HEMODIALYSIS PATIENTS; HEMOGLOBIN A(1C) LEVELS; BLOOD-GLUCOSE CONTROL; INSULIN-RESISTANCE; PERITONEAL-DIALYSIS; GLYCATED ALBUMIN; ACUTE-PANCREATITIS AB The management of hyperglycemia in patients with kidney failure is complex, and the goals and methods regarding glycemic control in chronic kidney disease (CKD) are not clearly defined. Although aggressive glycemic control seems to be advantageous in early diabetic nephropathy, outcome data supporting tight glycemic control in patients with advanced CKD (including end-stage renal disease [ESRD]) are lacking. Challenges in the management of such patients include therapeutic inertia, monitoring difficulties, and the complexity of available treatments. In this article, we review the alterations in glucose homeostasis that occur in kidney failure, current views on the value of glycemic control and issues with its determination, and more recent approaches to monitor or measure glycemic control. Hypoglycemia and treatment options for patients with diabetes and ESRD or earlier stages of CKD also are addressed, discussing the insulin and noninsulin agents that currently are available, along with their indications and contraindications. The article provides information to help clinicians in decision making in order to provide individualized glycemic goals and appropriate therapy for patients with ESRD or earlier stages of CKD. (C) 2014 by the National Kidney Foundation, Inc. C1 [Williams, Mark E.] Joslin Diabet Ctr, Renal Div, Boston, MA 02215 USA. [Garg, Rajesh] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. RP Williams, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 133 TC 18 Z9 20 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2014 VL 63 IS 2 SU 2 BP S22 EP S38 DI 10.1053/j.ajkd.2013.10.049 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA CL1SM UT WOS:000356724700003 PM 24461727 ER PT J AU Hemingway, M Ferguson, J AF Hemingway, Maureen Ferguson, Joanne TI Boston Bombings: Response to Disaster SO AORN JOURNAL LA English DT Article DE perioperative disaster care; OR triage; terrorist bombings; Boston Marathon; shelter in care; city lockdown AB Disasters disrupt everyone's lives, and they can disrupt the flow and function of an OR as well as affect personnel on a professional and personal level even though perioperative departments and their personnel are used to caring for trauma patients and coping with surprises. The Boston Marathon bombing was a new experience for personnel at Massachusetts General Hospital, Boston. This article discusses the incidents surrounding the bombing and how personnel at this hospital met the challenge of caring for patients and the changes we made after the experience to be better prepared in the event a response to a similar incident is needed. (C) AORN, Inc, 2014. C1 [Hemingway, Maureen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ferguson, Joanne] Massachusetts Gen Hosp, Perioperat Serv, Operat Planning & Environm Care, Boston, MA 02114 USA. RP Hemingway, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0001-2092 J9 ASSOC OPER ROOM NURS JI AORN J. PD FEB PY 2014 VL 99 IS 2 BP 277 EP 288 DI 10.1016/j.aorn.2013.07.019 PG 12 WC Nursing SC Nursing GA V42YE UT WOS:000209648300015 PM 24472590 ER PT J AU Boylan, MR Khalili, H Huang, ES Michaud, DS Izard, J Joshipura, KJ Chan, AT AF Boylan, Matthew R. Khalili, Hamed Huang, Edward S. Michaud, Dominique S. Izard, Jacques Joshipura, Kaumudi J. Chan, Andrew T. TI A Prospective Study of Periodontal Disease and Risk of Gastric and Duodenal Ulcer in Male Health Professionals SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI; TOOTH LOSS; CARDIOVASCULAR-DISEASE; ADULT PERIODONTITIS; PANCREATIC-CANCER; DENTAL PLAQUE; ORAL HYGIENE; ASSOCIATION; ADENOCARCINOMA; POPULATION AB OBJECTIVES: Periodontal disease has been associated with higher circulating levels of inflammatory markers and conditions associated with chronic inflammation, including vascular disease, diabetes mellitus, and cancer. Limited data exist on the relationship between periodontal disease and gastric and duodenal ulcer. METHODS: We conducted a prospective cohort study of 49,120 men in the Health Professionals Follow-up Study, aged 40-75 years at enrollment in 1986. Biennially, we assessed periodontal disease, tooth loss, and other risk factors for gastric and duodenal ulcer. We validated diagnoses of gastric and duodenal ulcer through medical record review. We used Cox proportional hazards modeling, adjusting for potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 138 cases of gastric ulcer and 124 cases of duodenal ulcer with available information on Helicobacter pylori status over 24 years of follow-up. After adjustment for risk factors, including smoking and regular use of aspirin and nonsteroidal anti-inflammatory drugs, men with periodontal disease with bone loss had a multivariate HR of ulcer of 1.62 (95% CI, 1.24-2.12). Periodontal disease appeared to be associated with a similar risk of developing ulcers that were H. pylori negative (HR 1.75; 95% CI, 1.26-2.43) than H. pylori positive (HR 1.40; 95% CI, 0.87-2.24), as well as ulcers in the stomach (HR 1.75; 95% CI, 1.21-2.53) than ulcers in the duodenum (HR 1.47; 95% CI, 0.98-2.19). CONCLUSIONS: Periodontal disease is associated with an increased risk of incident gastric and duodenal ulcer. This relationship may be mediated by alterations in the oral and gastrointestinal microbiome and/or systemic inflammatory factors. C1 [Boylan, Matthew R.; Khalili, Hamed; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Boylan, Matthew R.; Khalili, Hamed; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Huang, Edward S.] Palo Alto Med Fdn, Dept Gastroenterol, Mountain View, CA USA. [Michaud, Dominique S.] Brown Univ, Div Biol & Med, Div Epidemiol, Providence, RI 02912 USA. [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Izard, Jacques] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Joshipura, Kaumudi J.] Univ Puerto Rico, Sch Dent Med, Ctr Clin Res & Hlth Promot, San Juan, PR 00936 USA. [Joshipura, Kaumudi J.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,GRJ-825CA, Boston, MA 02114 USA. EM achan@partners.org RI Michaud, Dominique/I-5231-2014; OI Joshipura, Kaumudi/0000-0003-1964-7579; Izard, Jacques/0000-0002-5904-5436 FU NCI/NIH [UM1 CA167552, R21 CA139193]; NIDDK/NIH [K24 DK098311]; Crohn's and Colitis Foundation of America (CCFA) FX Funded by UM1 CA167552 (Willett) and R21 CA139193 (J.I.) from NCI/NIH and K24 DK098311 (A. T. C.) from the NIDDK/NIH. A.T.C. is a Damon Runyon Cancer Research Foundation Clinical Investigator. H.K. is supported by a career development award from the Crohn's and Colitis Foundation of America (CCFA). NR 38 TC 6 Z9 6 U1 4 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD FEB PY 2014 VL 5 AR e49 DI 10.1038/ctg.2013.14 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ5LU UT WOS:000355529800002 PM 24522171 ER PT J AU Tirumani, SH Shinagare, AB Jagannathan, JP Krajewski, KM Ramaiya, NH AF Tirumani, S. H. Shinagare, A. B. Jagannathan, J. P. Krajewski, K. M. Ramaiya, N. H. TI Multidetector-row CT of tumour-bowel fistula: Experience at a tertiary cancer centre SO CLINICAL RADIOLOGY LA English DT Article ID OF-THE-LITERATURE; PNEUMATOSIS-INTESTINALIS; OVARIAN-CARCINOMA; TARGETED THERAPY; SIGMOID COLON; BEVACIZUMAB; PERFORATION; RADIOLOGISTS; MANAGEMENT; TOXICITY AB AIM: To study the clinical and multidetector computed tomography (MDCT) features of tumour-bowel fistula (TBF). MATERIALS AND METHODS: Fifty-one patients (27 women; mean age 57.4 years, range 30-77years) with TBF presenting to our institution between January 2005 and February 2012 were identified retrospectively from the radiology database. MDCT images before, at, and subsequent to diagnosis of TBF were reviewed by three radiologists in consensus; clinical presentation, management, and outcome were documented from electronic medical records. RESULTS: Of 51 patients, small bowel (n = 22) was the most common site with gastrointestinal stromal tumour (GIST) being the most common sarcoma subtype (n = 10). TBF was treatment-associated (TTBF) in 40 patients [78%; 22 of whom had received molecular targeted therapy (MTT)], and spontaneous (STBF) in 11 patients (22%). Thirty-one patients (61%) were symptomatic at the time of TBF detection. TTBF was more often asymptomatic (19/40 versus 1/11; Fisher's exact test p = 0.03). In the TTBF group, 16 had a partial response, seven had stable disease, and 17 had progressive disease. Treatment was discontinued or changed to an alternative regimen in 27/40 patients, and 13/40 patients continued with the same regimen. TBF persisted in 27/33 patients (82%) who underwent CT follow-up. Thirty-one of the 51 patients were deceased at the time of analysis. Time from diagnosis of TBF to death was shorter with STBF (1.8 months) than with TTBF (6.4 months). CONCLUSION: TBF is often associated with MTT and can be seen with treatment response or progression. TTBF is more frequently asymptomatic. TBF is usually managed conservatively by discontinuing treatment, but often persists on CT follow-up. (C) 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Tirumani, S. H.; Shinagare, A. B.; Jagannathan, J. P.; Krajewski, K. M.; Ramaiya, N. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, S. H.; Shinagare, A. B.; Jagannathan, J. P.; Krajewski, K. M.; Ramaiya, N. H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 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 14 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 EI 1365-229X J9 CLIN RADIOL JI Clin. Radiol. PD FEB PY 2014 VL 69 IS 2 BP E100 EP E107 DI 10.1016/j.crad.2013.09.020 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY4AM UT WOS:000347520600006 PM 24290835 ER PT J AU Gaggin, HK Szymonifka, J Bhardwaj, A Belcher, A De Berardinis, B Motiwala, S Wang, TJ Januzzi, JL AF Gaggin, Hanna K. Szymonifka, Jackie Bhardwaj, Anju Belcher, Arianna De Berardinis, Benedetta Motiwala, Shweta Wang, Thomas J. Januzzi, James L., Jr. TI Head-to-Head Comparison of Serial Soluble ST2, Growth Differentiation Factor-15, and Highly-Sensitive Troponin T Measurements in Patients With Chronic Heart Failure SO JACC-HEART FAILURE LA English DT Article DE biomarker; heart failure; prognosis ID NATRIURETIC PEPTIDE; BIOMARKERS; ASSAY; THERAPY; PLASMA AB Objectives This analysis aimed to perform a head-to-head comparison of 3 of the promising biomarkers of cardiovascular (CV) outcomes in heart failure (HF)-dsoluble ST2 (sST2), growth differentiation factor (GDF)-15, and highly-sensitive troponin T (hsTnT)-and to evaluate the role of serial measurement of these biomarkers in patients with chronic HF. Background sST2, GDF-15, and hsTnT are strongly associated with CV outcomes in HF. Methods This post-hoc analysis used data from a study in which 151 patients with chronic HF due to left ventricular systolic dysfunction were followed up over 10 months. At each visit, N-terminal pro-B-type natriuretic peptide (NT-proBNP), sST2, GDF-15, and hsTnT were measured and any major CV events were recorded. Results Baseline values of all 3 novel biomarkers independently predicted total CV events even after adjusting for clinical and biochemical characteristics, including NT-proBNP, with the best model including all 3 biomarkers (p < 0.001). Adding serial measurement to the base model appeared to improve the model's predictive ability (with sST2 showing the most promise), but it is not clear whether this addition is a unique contribution. However, when timedependent factors were included, only sST2 serial measurement independently added to the risk model (odds ratio: 3.64; 95% confidence interval: 1.37 to 9.67; p = 0.009) and predicted reverse myocardial remodeling (odds ratio: 1.22; 95% confidence interval: 1.04 to 1.43; p = 0.01). Conclusions In patients with chronic HF, baseline measurement of novel biomarkers added independent prognostic information to clinical variables and NT-proBNP. Only serial measurement of sST2 appeared to add prognostic information to baseline concentrations and predicted change in left ventricular function. (C) 2014 by the American College of Cardiology Foundation C1 [Gaggin, Hanna K.; Szymonifka, Jackie; Bhardwaj, Anju; Belcher, Arianna; De Berardinis, Benedetta; Motiwala, Shweta; Wang, Thomas J.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Ruth and James Clark Fund for Cardiac Research Innovation; Dennis and Marilyn Barry Cardiology Fellowship; DiaSorin; Brahms; Critical Diagnostics; Critical Diagnostics, LabCorp; Siemens Diagnostics; Roman W. DeSanctis Clinical Scholar Endowment; Roche Diagnostics; Siemens; Singulex; Thermo Fisher FX From the Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts. Dr. Gaggin is supported in part by the Ruth and James Clark Fund for Cardiac Research Innovation. Drs. Bhardwaj and Motiwala were supported by the Dennis and Marilyn Barry Cardiology Fellowship. Dr. Wang has received research or assay support from DiaSorin, Brahms, Critical Diagnostics, LabCorp, and Siemens Diagnostics; has received honoraria from Roche, DiaSorin, and Quest Diagnostics; has served on the medical advisory board of Singulex; and is named as coinventor on patent applications relating to the use of metabolomic or neurohormonal biomarkers in risk prediction. Dr. Januzzi is supported in part by the Roman W. DeSanctis Clinical Scholar Endowment and has received grants from Roche Diagnostics, Siemens, Critical Diagnostics, Singulex, and Thermo Fisher. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John R. Teerlink, MD, served as Guest Editor for this paper. NR 19 TC 48 Z9 52 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD FEB PY 2014 VL 2 IS 1 BP 65 EP 72 DI 10.1016/j.jchf.2013.10.005 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4CT UT WOS:000365646600009 PM 24622120 ER PT J AU Ughi, GJ Steigerwald, K Adriaenssens, T Desmet, W Guagliumi, G Joner, M D'hooge, J AF Ughi, Giovanni J. Steigerwald, Kristin Adriaenssens, Tom Desmet, Walter Guagliumi, Giulio Joner, Michael D'hooge, Jan TI Automatic characterization of neointimal tissue by intravascular optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical coherence tomography; tissue characterization; stent; intravascular; image analysis; texture analysis ID ELUTING STENT THROMBOSIS; STRUT COVERAGE; IMPLANTATION; TEXTURE AB Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method of choice for assessing vessel healing after stent implantation due to its unique axial resolution <20 mu m. The amount of neointimal coverage is an important parameter. In addition, the characterization of neointimal tissue maturity is also of importance for an accurate analysis, especially in the case of drug-eluting and bioresorbable stent devices. Previous studies indicated that well-organized mature neointimal tissue appears as a high-intensity, smooth, and homogeneous region in IVOCT images, while lower-intensity signal areas might correspond to immature tissue mainly composed of acellular material. A new method for automatic neointimal tissue characterization, based on statistical texture analysis and a supervised classification technique, is presented. Algorithm training and validation were obtained through the use of 53 IVOCT images supported by histology data from atherosclerotic New Zealand White rabbits. A pixel-wise classification accuracy of 87% and a two-dimensional region-based analysis accuracy of 92% (with sensitivity and specificity of 91% and 93%, respectively) were found, suggesting that a reliable automatic characterization of neointimal tissue was achieved. This may potentially expand the clinical value of IVOCT in assessing the completeness of stent healing and speed up the current analysis methodologies (which are, due to their time-and energy-consuming character, not suitable for application in large clinical trials and clinical practice), potentially allowing for a wider use of IVOCT technology. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Ughi, Giovanni J.; Adriaenssens, Tom; Desmet, Walter; D'hooge, Jan] Katholieke Univ Leuven Hosp, Dept Cardiovasc Dis, B-3000 Leuven, Belgium. [Ughi, Giovanni J.; Adriaenssens, Tom; Desmet, Walter; D'hooge, Jan] Katholieke Univ Leuven, Dept Cardiovasc Sci, B-3000 Louvain, Belgium. [Steigerwald, Kristin; Joner, Michael] Deutsch Herzzentrum Munich, D-80636 Munich, Germany. [Steigerwald, Kristin; Joner, Michael] Tech Univ Munich, Klinikum Rechts Isar, Med Klin, D-80636 Munich, Germany. [Guagliumi, Giulio] Osped Papa Giovanni XXIII, Cardiovasc Dept, I-24100 Bergamo, Italy. RP Ughi, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM gughi@mgh.harvard.edu OI Ughi, Giovanni J./0000-0003-3354-0698 FU Research Foundation Flanders (FWO) [G.0690.09N]; Industrial Research Foundation KU Leuven (IOF) [ZKC2992]; European Union [260309]; FWO; Boston Scientific; St. Jude Medical; Abbot Vascular FX This work was supported by the Research Foundation Flanders (FWO-Grant No. G.0690.09N), Industrial Research Foundation KU Leuven (IOF-Grant No. ZKC2992), and the European Union under the Seventh Framework Programme (FP7, PRESTIGE-Grant No. 260309). Tom Adriaenssens is also supported by a clinical doctoral grant of the FWO. Dr. G. Guagliumi received consulting fees from Boston Scientific and St. Jude Medical and grant support from Abbot Vascular, Boston Scientific, and St. Jude Medical. NR 31 TC 3 Z9 4 U1 0 U2 0 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD FEB PY 2014 VL 19 IS 2 AR 021104 DI 10.1117/1.JBO.19.2.021104 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AC9CE UT WOS:000332830900006 ER PT J AU Ackerman, K Sokoloff, NC Maffazioli, G Singhal, V Slattery, M Clarke, H Derrico, N Misra, M AF Ackerman, Kathryn Sokoloff, Natalia Cano Maffazioli, Giovana Singhal, Vibha Slattery, Meghan Clarke, Hannah Derrico, Nicholas Misra, Madhusmita TI Fracture History in Oligo-amenorrheic Athletes, Eumenorrheic Athletes, and Non-athletes: Correlations with Bone Density and Microarchitecture. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Ackerman, Kathryn] Boston Childrens Hosp, Dept Orthoped, Div Sports Med, Boston, MA USA. [Ackerman, Kathryn; Sokoloff, Natalia Cano; Singhal, Vibha; Slattery, Meghan; Clarke, Hannah] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ackerman, Kathryn; Sokoloff, Natalia Cano; Singhal, Vibha; Slattery, Meghan; Clarke, Hannah; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Maffazioli, Giovana] Massachusetts Gen Hosp & Med Sch, Neuroendocrine Unit, Cambridge, MA USA. [Singhal, Vibha] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Cambridge, MA USA. [Derrico, Nicholas] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SA0052 BP S139 EP S139 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701110 ER PT J AU Bahar, H Maeda, A Reyes, M Dean, T Schipani, E Pajevic, PD Neer, R Kostenuik, P Potts, J Gardella, T AF Bahar, Hila Maeda, Akira Reyes, Monica Dean, Thomas Schipani, Ernestina Pajevic, Paola Divieti Neer, Robert Kostenuik, Paul Potts, John Gardella, Thomas TI Chronic Inhibition of RANKL Induces an Osteoclast-Independent Mechanism of PTH-induced Calcium Mobilization. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Bahar, Hila; Maeda, Akira; Reyes, Monica; Dean, Thomas; Pajevic, Paola Divieti; Neer, Robert; Potts, John; Gardella, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bahar, Hila] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Schipani, Ernestina] Univ Michigan, Ann Arbor, MI 48109 USA. [Kostenuik, Paul] Amgen Inc, Thousand Oaks, CA 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0138 BP S251 EP S251 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701447 ER PT J AU Balani, D Ono, N Kronenberg, H AF Balani, Deepak Ono, Noriaki Kronenberg, Henry TI Parathyroid Hormone (1-34) Increases the Numbers and Differentiation of Osteoblast Progenitor Cells in Vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Balani, Deepak; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Balani, Deepak] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ono, Noriaki] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0239 BP S280 EP S280 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701545 ER PT J AU Bi, RY Zhao, WP Segawa, H Thorens, B Mannstadt, M AF Bi, Ruiye Zhao, Wenping Segawa, Hiroko Thorens, Bernard Mannstadt, Michael TI Phosphate and calcium phenotype of GLUT2-/- mice, an animal model for Fanconi-Bickel-Syndrome. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Bi, Ruiye; Zhao, Wenping] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Segawa, Hiroko] Univ Tokushima, Grad Sch, Tokushima, Japan. [Thorens, Bernard] Univ Lausanne, CH-1015 Lausanne, Switzerland. [Mannstadt, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 FEB PY 2014 VL 29 SU 1 MA SA0115 BP S146 EP S146 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701128 ER PT J AU Bischoff, D Zhu, JH Makhijani, N Yamaguchi, D AF Bischoff, David Zhu, Jian-hua Makhijani, Nalini Yamaguchi, Dean TI Induction of CXC Chemokines in Human Mesenchymal Stem Cells (hMSCs) by Stimulation with Secreted Frizzled-Related Proteins (sFRPs) through Non-Canonical Wnt Signaling SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Bischoff, David; Zhu, Jian-hua; Makhijani, Nalini; Yamaguchi, Dean] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0428 BP S483 EP S483 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702573 ER PT J AU Cauley, J Greendale, G Ruppert, K Lian, YJ Randolph, J Lo, J Neer, R Burnett-Bowie, SA Finkelstein, J AF Cauley, Jane Greendale, Gail Ruppert, Kristine Lian, Yinjuan Randolph, John Lo, Joan Neer, Robert Burnett-Bowie, Sherri-Ann Finkelstein, Joel TI Serum 25 Hydroxyvitamin D (25(OH)D), Bone Mineral Density (BMD) and Fracture Risk across the Menopausal Transition: Study of Women's Health Across the Nation (SWAN). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Cauley, Jane] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Greendale, Gail] Univ Calif Los Angeles, Los Angeles, CA USA. [Ruppert, Kristine; Lian, Yinjuan] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Randolph, John] Univ Michigan, Ann Arbor, MI 48109 USA. [Lo, Joan] Kaiser Permanente, Beaverton, OR USA. [Neer, Robert; Burnett-Bowie, Sherri-Ann; Finkelstein, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1076 BP S25 EP S26 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700077 ER PT J AU Clarke, BL Mannstadt, M Shoback, DM Vokes, TJ Warren, ML Levine, MA Lagast, H Bilezikian, JP AF Clarke, Bart L. Mannstadt, Michael Shoback, Dolores M. Vokes, Tamara J. Warren, Mark L. Levine, Michael A. Lagast, Hjalmar Bilezikian, John P. TI Long-Term Effect of Recombinant Human Parathyroid Hormone, rhPTH(1-84), on Skeletal Dynamics in Patients With Hypoparathyroidism: One-Year Data From the Open-Label RACE Study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Clarke, Bart L.] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Rochester, MN USA. [Mannstadt, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mannstadt, Michael] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Shoback, Dolores M.] Univ Calif San Francisco, SF Dept Vet Affairs Med Ctr, San Francisco, CA USA. [Vokes, Tamara J.] Univ Chicago Med, Chicago, IL USA. [Warren, Mark L.] Phys East, Endocrinol & Metab, Greenville, NC USA. [Levine, Michael A.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Lagast, Hjalmar] NPS Pharmaceut Inc, New York, NY USA. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA FR0013 BP S55 EP S55 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700159 ER PT J AU David, V Martin, A Zumbrennen-Bullough, K Sun, CC Lin, H Isakova, T Babitt, J Wolf, M AF David, Valentin Martin, Aline Zumbrennen-Bullough, Kimberly Sun, Chia Chi Lin, Herbert Isakova, Tamara Babitt, Jodie Wolf, Myles TI Inflammation and iron deficiency stimulate FGF23 production. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [David, Valentin] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Martin, Aline] Univ Miami, Coral Gables, FL 33124 USA. [Zumbrennen-Bullough, Kimberly; Sun, Chia Chi; Lin, Herbert; Babitt, Jodie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Isakova, Tamara; Wolf, Myles] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0003 BP S209 EP S209 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701318 ER PT J AU Fan, Y Lanske, B Kobayashi, T Sato, T Densmore, M AF Fan, Yi Lanske, Beate Kobayashi, Tatsuya Sato, Tadatoshi Densmore, Michael TI Deletion of PTH1R expression from limb mesenchyme affects systemic mineral ion homeostasis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Fan, Yi; Sato, Tadatoshi] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Lanske, Beate] Harvard Univ, Sch Dent Med, Sch Med, Cambridge, MA 02138 USA. [Kobayashi, Tatsuya] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1058 BP S20 EP S20 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700059 ER PT J AU Fulzele, K Saini, V Tuck, P Liu, XL Dedic, C Garr, J Zoubine, V Shah, P Rosen, E Pajevic, PD AF Fulzele, Keertik Saini, Vaibhav Tuck, Padrig Liu, Xiaolong Dedic, Christopher Garr, Jenna Zoubine, Vladimir Shah, Pankaj Rosen, Evan Pajevic, Paola Divieti TI Gs alpha-deficient osteoblasts and osteocytes induce beige adipogenesis and a lean phenotype via interactions with skeletal muscle. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Fulzele, Keertik; Pajevic, Paola Divieti] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fulzele, Keertik; Pajevic, Paola Divieti] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Saini, Vaibhav] Harvard Univ, Sch Med, MGH, Cambridge, MA 02138 USA. [Tuck, Padrig; Liu, Xiaolong; Dedic, Christopher; Garr, Jenna; Zoubine, Vladimir; Shah, Pankaj] Harvard Univ, Sch Med, MGH, Endocrine Unit, Cambridge, MA 02138 USA. [Rosen, Evan] Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. 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PD FEB PY 2014 VL 29 SU 1 MA FR0139 BP S75 EP S75 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700225 ER PT J AU Hsu, YH Estrada, K Leo, P Teumer, A Liu, CT Duncan, E Zheng, HF Minster, R Lyytikainen, LP Amin, N Pengelly, R Guerrero, RC Marc, J Nielson, C Yerges-Armstrong, L Claussnitzer, M Oei, L van Schoor, NM Medina-Gomez, C Zhou, YH Cheng, CH Liu, YM Volker, U Kahonen, M Cooper, C Uitterlinden, A Hannemann, A Karasik, D Mencej-Bedrac, S Moral, JAR Holloway, J Lehtimaki, T Jackson, R Cupples, LA Harris, T Wallaschofski, H Rivadeneira, F Richards, B Chasman, D Brown, M Kiel, D AF Hsu, Yi-Hsiang Estrada, Karol Leo, Paul Teumer, Alexander Liu, Ching-Ti Duncan, Emma Zheng, HouFeng Minster, Ryan Lyytikainen, Leo-Pekka Amin, Najaf Pengelly, Ruben Cruz Guerrero, Raquel Marc, Janja Nielson, Carrie Yerges-Armstrong, Laura Claussnitzer, Melina Oei, Ling van Schoor, N. M. Medina-Gomez, Carolina Zhou, Yanhua Cheng, Chao-Ho Liu, Yongmei Voelker, Uwe Kahonen, Mika Cooper, Cyrus Uitterlinden, Andre Hannemann, Anke Karasik, David Mencej-Bedrac, Simona Riancho Moral, Jose Antonio Holloway, John Lehtimaki, Terho Jackson, Rebecca Cupples, L. Adrienne Harris, Tamara Wallaschofski, Henri Rivadeneira, Fernando Richards, Brent Chasman, Daniel Brown, Matthew Kiel, Douglas TI Rare Protein-Coding Variants Are Associated with Osteoporotic Fracture: An Exome-Chip Analysis of 44,130 Adult Caucasians in CHARGE and GEFOS Consortia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Hsu, Yi-Hsiang; Claussnitzer, Melina; Cheng, Chao-Ho] Hebrew SeniorLife, Inst Aging Res, Roslindale, MA USA. [Hsu, Yi-Hsiang; Claussnitzer, Melina; Chasman, Daniel] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Leo, Paul] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia. [Teumer, Alexander; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Liu, Ching-Ti; Cupples, L. Adrienne] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Duncan, Emma] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. [Zheng, HouFeng] McGill Univ, Dept Med, Montreal, PQ H3A 2T5, Canada. [Zheng, HouFeng] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2T5, Canada. [Zheng, HouFeng] McGill Univ, Dept Epidemiol, Montreal, PQ H3A 2T5, Canada. [Zheng, HouFeng] McGill Univ, Dept Biostat, Montreal, PQ H3A 2T5, Canada. [Minster, Ryan] Univ Pittsburgh, Dept Human Genet & Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Helsinki, Finland. [Amin, Najaf] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Pengelly, Ruben; Holloway, John] Univ Southampton, Fac Med, Human Genet & Genom Med, Southampton SO9 5NH, Hants, England. [Cruz Guerrero, Raquel] Univ Santiago de Compostela, La Coruna, Spain. [Marc, Janja] Univ Ljubljana, Div Clin Biochem, Ljubljana 61000, Slovenia. [Nielson, Carrie] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Yerges-Armstrong, Laura] Univ Maryland, Sch Med, Baltimore, MD USA. [Oei, Ling; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [van Schoor, N. M.] EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Rotterdam, Netherlands. [Medina-Gomez, Carolina] Erasmus MC, Rotterdam, Netherlands. [Zhou, Yanhua] Boston Univ, Boston, MA 02215 USA. [Liu, Yongmei] Wake Forest Sch Med, Ctr Human Genet, Div Publ Hlth Sci, Winston Salem, NC USA. [Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Cooper, Cyrus] Univ Southampton, Southampton SO9 5NH, Hants, England. [Hannemann, Anke] Univ Med, Inst Clin Chem & Lab Med, Berlin, Germany. [Karasik, David; Kiel, Douglas] Hebrew SeniorLife, New York, NY USA. [Karasik, David] Bar Ilan Univ, New York, NY USA. [Mencej-Bedrac, Simona] Univ Ljubljana, Fac Pharm, Ljubljana 61000, Slovenia. [Riancho Moral, Jose Antonio] Univ Cantabria, Hosp UM Valdecilla IFIMAV, Santander, Spain. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem & Lab Med, Inst Community Med, Greifswald, Germany. [Richards, Brent] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Chasman, Daniel] Brigham & Womens Hosp, Boston, MA 02115 USA. [Brown, Matthew] Diamantina Inst Canc Immunol & Metab Med, Sydney, NSW, Australia. RI Oei, Ling/E-8163-2013 OI Oei, Ling/0000-0003-3523-458X 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1027 BP S10 EP S11 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700028 ER PT J AU Hussein, A Lybrand, K De Giacomo, A Tabattanon, K Hogue, B De Bakker, C Demay, M Morgan, E Gerstenfeld, L AF Hussein, Amira Lybrand, Kyle De Giacomo, Anthony Tabattanon, Kamolnat Hogue, Brenna De Bakker, Chantal Demay, Marie Morgan, Elise Gerstenfeld, Louis TI The Effect of Phosphate Deficiency on Callus Composition. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Hussein, Amira; Lybrand, Kyle; De Giacomo, Anthony; Hogue, Brenna; Gerstenfeld, Louis] Boston Univ, Sch Med, Boston, MA 02215 USA. [Tabattanon, Kamolnat; De Bakker, Chantal; Morgan, Elise] Boston Univ, Boston, MA 02215 USA. [Demay, Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Demay, Marie] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0067 BP S229 EP S229 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701380 ER PT J AU Jueppner, H Molinaro, A Tiosano, D Russell, W Chrysis, D Makitie, O Takatani, R Tonacchera, M AF Jueppner, Harald Molinaro, Angelo Tiosano, Dov Russell, William Chrysis, Dionisios Makitie, Outi Takatani, Rieko Tonacchera, Massimo TI TSH elevation as first laboratory evidence for pseudohypoparathyroidism type Ib (PHP-Ib). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Jueppner, Harald; Takatani, Rieko] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Molinaro, Angelo] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Tiosano, Dov] Rambam Hlth Care Campus, Meyer Childrens Hosp, Div Pediat Endocrinol, Haifa, Israel. [Russell, William] Vanderbilt Univ, Sch Med, Div Pediat Endocrinol & Diabet, Nashville, TN USA. [Chrysis, Dionisios] Univ Patras, Sch Med, Dept Pediat, Div Endocrinol, GR-26110 Patras, Greece. [Makitie, Outi] Univ Helsinki, Cent Hosp, Childrens Hosp, FIN-00014 Helsinki, Finland. [Takatani, Rieko] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Tonacchera, Massimo] Univ Pisa, Dept Internal Med, Endocrinol Unit, I-56100 Pisa, Italy. RI Tonacchera, Massimo/K-8523-2016 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SA0145 BP S150 EP S150 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701142 ER PT J AU Keenan, H Hastings, S King, G AF Keenan, Hillary Hastings, Stephanie King, George TI Protection from Fracture Risk in Long Term Type 1 Diabetes: 50-Year Medalist Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Keenan, Hillary] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Hastings, Stephanie; King, George] Joslin Diabet Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0110 BP S383 EP S383 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702263 ER PT J AU Leder, B Banks, K O'Dea, L Lyttle, CR Yates, J Hattersley, G AF Leder, Benjamin Banks, Kathleen O'Dea, Louis Lyttle, C. R. Yates, John Hattersley, Gary TI Responder Analysis of the Effects of Abaloparatide and Teriparatide on Bone Mineral Density in Postmenopausal Women With Osteoporosis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Leder, Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Banks, Kathleen; O'Dea, Louis; Lyttle, C. R.; Hattersley, Gary] Radius, Kutztown, PA USA. [Yates, John] Radius Hlth, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA FR0379 BP S111 EP S111 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701030 ER PT J AU Leder, B Tsai, J Uihlein, A Zhu, YL Foley, K Neer, R Burnett-Bowie, SA AF Leder, Benjamin Tsai, Joy Uihlein, Alexander Zhu, Yuli Foley, Katelyn Neer, Robert Burnett-Bowie, Sherri-Ann TI The Transition from Denosumab to Teriparatide or from Teriparatide to Denosumab in Postmenopausal Women with Osteoporosis: The DATA-Switch Study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Leder, Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Tsai, Joy; Zhu, Yuli; Foley, Katelyn; Neer, Robert; Burnett-Bowie, Sherri-Ann] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Uihlein, Alexander] Northwestern Mem Fac Fdn, Chicago, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1150 BP S52 EP S52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700151 ER PT J AU Li, YW Zhu, CL Guo, J Demay, M Jueppner, H Bergwitz, C AF Li, Yuwen Zhu, Chuanlong Guo, Jun Demay, Marie Jueppner, Harald Bergwitz, Clemens TI Role of renal phosphate excretion in the pathogenesis of renal stone disease and nephrocalcinosis: insights from the Npt2a knockout mouse model. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Li, Yuwen; Zhu, Chuanlong; Guo, Jun; Demay, Marie; Jueppner, Harald; Bergwitz, Clemens] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Demay, Marie; Bergwitz, Clemens] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0137 BP S251 EP S251 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701446 ER PT J AU Liu, E Raimann, A Brooks, D Bouxsein, M Demay, M AF Liu, Eva Raimann, Adalbert Brooks, Daniel Bouxsein, Mary Demay, Marie TI 1,25 dihydroxyvitamin D treatment improves bone microarchitecture in Hyp mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Liu, Eva] Brigham & Womens Hosp, Boston, MA 02115 USA. [Liu, Eva; Demay, Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raimann, Adalbert] Med Univ Vienna, Vienna, Austria. [Brooks, Daniel; Bouxsein, Mary] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Demay, Marie] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0124 BP S387 EP S388 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702277 ER PT J AU McLean, R Weiner, L Cypess, A Kiel, D AF McLean, Robert Weiner, Lauren Cypess, Aaron Kiel, Douglas TI Brown adipose tissue (BAT) activity is inversely associated with bone mineral density (BMD) in healthy young adults SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [McLean, Robert; Kiel, Douglas] Hebrew SeniorLife Inst Aging Res, Roslindale, MA USA. [McLean, Robert; Weiner, Lauren; Cypess, Aaron; Kiel, Douglas] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Weiner, Lauren; Cypess, Aaron] Joslin Diabet Ctr, 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0329 BP S450 EP S450 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702476 ER PT J AU Mcnabb, B Vittinghoff, E Schwartz, A Bauer, D Ensrud, K Barrett-Connor, E Eastell, R Black, D AF Mcnabb, Brian Vittinghoff, Eric Schwartz, Ann Bauer, Douglas Ensrud, Kristine Barrett-Connor, Elizabeth Eastell, Richard Black, Dennis TI Using Bone Turnover Markers to Predict Changes in BMD After Alendronate Therapy in Postmenopausal Women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Mcnabb, Brian] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Vittinghoff, Eric; Schwartz, Ann; Bauer, Douglas; Black, Dennis] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ensrud, Kristine] Univ Minnesota, Minneapolis, MN 55455 USA. [Ensrud, Kristine] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, San Diego, CA 92103 USA. [Eastell, Richard] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0283 BP S291 EP S291 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701589 ER PT J AU Mirzamohammadi, F Papaioannou, G Paltrinieri, E Kobayashi, T AF Mirzamohammadi, Fatemeh Papaioannou, Garyfallia Paltrinieri, Elena Kobayashi, Tatsuya TI MiR-17-92 Family MicroRNAs Play an Essential Role in Limb Development by Suppressing TGF-b Signaling. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Mirzamohammadi, Fatemeh; Papaioannou, Garyfallia; Paltrinieri, Elena; Kobayashi, Tatsuya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mirzamohammadi, Fatemeh] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1141 BP S49 EP S49 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700142 ER PT J AU Mitchell, D Lee, H Greendale, G Cauley, J Burnett-Bowie, SA Finkelstein, J AF Mitchell, Deborah Lee, Hang Greendale, Gail Cauley, Jane Burnett-Bowie, Sherri-Ann Finkelstein, Joel TI Increasing 25-hydroxyvitamin D levels over time: The Study of Women's Health Across the Nation (SWAN) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Mitchell, Deborah; Lee, Hang; Burnett-Bowie, Sherri-Ann; Finkelstein, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greendale, Gail] Univ Calif Los Angeles, Los Angeles, CA USA. [Cauley, Jane] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1075 BP S25 EP S25 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700076 ER PT J AU Nakamura, Y Kikugawa, S Inagaki, H Kobayashi, T Kurahashi, H Kato, H AF Nakamura, Yukio Kikugawa, Shingo Inagaki, Hidehito Kobayashi, Tatsuya Kurahashi, Hiroki Kato, Hiroyuki TI Identification of a novel PCSK5 frameshift mutation in a patient with the VACTERL association SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Nakamura, Yukio] Shinshu Univ, Dept Orthopaed Surg, Sch Med, Shinshu, Japan. [Kikugawa, Shingo] DNA Chip Res Inc, Tokyo, Japan. [Inagaki, Hidehito; Kurahashi, Hiroki] Fujita Hlth Univ, Fujita, Japan. [Kobayashi, Tatsuya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kato, Hiroyuki] Shinshu Univ, Sch Med, Shinshu, Japan. 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0127 BP S248 EP S248 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701437 ER PT J AU Neumeyer, A O'Rourke, J Massa, A Lee, H Lawson, E McDougle, C Misra, M AF Neumeyer, Ann O'Rourke, Julia Massa, Alexandra Lee, Hang Lawson, Elizabeth McDougle, Christopher Misra, Madhusmita TI Bone Fractures in Children and Adults with Autism Spectrum Disorder SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Neumeyer, Ann; O'Rourke, Julia; Massa, Alexandra; McDougle, Christopher] Massachusetts Gen Hosp, Lurie Ctr Autism, Boston, MA 02114 USA. [Neumeyer, Ann; O'Rourke, Julia; Massa, Alexandra; McDougle, Christopher; Misra, Madhusmita] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Lawson, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1098 BP S33 EP S33 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700099 ER PT J AU Nishimori, S Lai, F Wein, M Kozhemyakina, E Lassar, A Olson, E Kronenberg, H AF Nishimori, Shigeki Lai, Forest Wein, Marc Kozhemyakina, Elena Lassar, Andrew Olson, Eric Kronenberg, Henry TI PTHrP Uses HDAC4 and 5 to Suppress Mef2 Action and Inhibit Chondrocyte Hypertrophy SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Nishimori, Shigeki; Lai, Forest; Wein, Marc; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kozhemyakina, Elena; Lassar, Andrew] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Olson, Eric] UT Southwestern Med Ctr, Dallas, TX 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0094 BP S379 EP S379 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702247 ER PT J AU Nistala, H Roening, C Zenger, S Takeyama, K Gori, F Baron, R AF Nistala, Harikiran Roening, Coco Zenger, Serhan Takeyama, Ken-ichi Gori, Francesca Baron, Roland TI Zinc Finger Protein 521 regulates retinoblastoma protein-dependent cell-cycle progression: Potential implications for osteosarcoma. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Nistala, Harikiran] Harvard Univ, Cambridge, MA 02138 USA. [Roening, Coco] Massachusetts Coll Pharm & Hlth Sci, Cambridge, MA USA. [Zenger, Serhan; Takeyama, Ken-ichi] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Baron, Roland] Harvard Univ, Sch Med & Dent Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SA0086 BP S142 EP S142 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701117 ER PT J AU Ono, N Ono, W Kronenberg, H AF Ono, Noriaki Ono, Wanida Kronenberg, Henry TI PTHrP is a candidate marker of slowly replicating "resting'' chondrocytes in the postnatal growth plate cartilage. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Ono, Noriaki] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Ono, Wanida; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA FR0089 BP S66 EP S66 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700198 ER PT J AU Ono, W Ono, N Kronenberg, H AF Ono, Wanida Ono, Noriaki Kronenberg, Henry TI Parathyroid hormone receptor signaling in dental mesenchymal progenitors is essential for tooth root formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Ono, Wanida; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ono, Noriaki] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0467 BP S494 EP S494 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702611 ER PT J AU Panaroni, C Fulzele, K Saini, V Chubb, R Pajevic, PD Wu, J AF Panaroni, Cristina Fulzele, Keertik Saini, Vaibhav Chubb, Rhiannon Pajevic, Paola Divieti Wu, Joy TI PTH/PTHrP Receptor Signaling in Osteoprogenitors is Essential for B Lymphocyte Differentiation, Maturation, and Mobilization in Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Panaroni, Cristina; Wu, Joy] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Fulzele, Keertik; Pajevic, Paola Divieti] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fulzele, Keertik; Pajevic, Paola Divieti] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Saini, Vaibhav] Harvard Univ, Sch Med, MGH, Cambridge, MA 02138 USA. [Chubb, Rhiannon] Massachusetts Gen Hosp, Endocrine Unit, 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1056 BP S20 EP S20 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700057 ER PT J AU Papaioannou, G Mirzamohammadi, F Nishimori, S Wein, M Kronenberg, H Olson, EN Kobayashi, T AF Papaioannou, Garyfallia Mirzamohammadi, Fatemeh Nishimori, Shigeki Wein, Marc Kronenberg, Henry Olson, Eric 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 Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Papaioannou, Garyfallia; Mirzamohammadi, Fatemeh; Nishimori, Shigeki; Wein, Marc; Kronenberg, Henry; Kobayashi, Tatsuya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mirzamohammadi, Fatemeh] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Olson, Eric N.] Univ Texas Southwestern Med Ctr, Dallas, TX 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1114 BP S40 EP S40 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700115 ER PT J AU Park, D Spencer, JA Lin, CP Scadden, DT AF Park, Dongsu Spencer, Joel A. Lin, Charles P. Scadden, David T. TI A subset of mesenchymal stem/progenitor cells responds to stress and constitutes a major source of new osteoblasts during fracture repair in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Park, Dongsu] Baylor Coll Med, Houston, TX 77030 USA. [Spencer, Joel A.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Spencer, Joel A.; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Scadden, David T.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1024 BP S9 EP S10 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700025 ER PT J AU Parrish, R Rivoire, J Han, M Schafer, A Link, T Krug, R Kazakia, G AF Parrish, Robin Rivoire, Julien Han, Misung Schafer, Anne Link, Thomas Krug, Roland Kazakia, Galateia TI Multi-modality in vivo Imaging Identifies Marrow and Vasculature within Pathological Cortical Porosity SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Parrish, Robin] Univ Calif Berkeley, Berkeley, CA USA. [Rivoire, Julien; Han, Misung; Krug, Roland] UC San Francisco, San Francisco, CA USA. [Schafer, Anne; Link, Thomas; Kazakia, Galateia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schafer, Anne] San Francisco VA Med Ctr, San Francisco, CA 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA FR0291 BP S96 EP S97 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700298 ER PT J AU Qin, WP Li, XD Cao, J Collier, L Peng, YZ Feng, J Li, JL Qin, YW Brown, T Ke, HZ Bauman, WA Cardozo, C AF Qin, Weiping Li, Xiaodong Cao, Jay Collier, Lauren Peng, Yuanzhen Feng, Jerry Li, Jiliang Qin, Yiwen Brown, Tom Ke, Hua Zhu (David) Bauman, William A. Cardozo, Christopher TI Mice with Sclerostin Gene Deficiency are Resistant to Bone Loss after Acute Spinal Cord Injury SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Qin, Weiping; Collier, Lauren; Qin, Yiwen; Bauman, William A.; Cardozo, Christopher] James J Peters Va Med Ctr, Bronx, NY USA. [Li, Xiaodong; Brown, Tom; Ke, Hua Zhu (David)] Amgen Inc, Thousand Oaks, CA USA. [Cao, Jay] ARS, USDA, Lincoln, NE USA. [Peng, Yuanzhen] Mt Sinai Sch Med, New York, NY USA. [Feng, Jerry] Baylor Coll Dent, TX A&M, Dallas, TX 75246 USA. [Li, Jiliang] Indiana Univ Purdue Univ Indianapolis, Indianapolis, IN 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0118 BP S385 EP S386 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702271 ER PT J AU Robins, D Leder, B Krohn, K Alam, J Murphy, H Chiang, A Krege, J AF Robins, Deborah Leder, Benjamin Krohn, Kelly Alam, Jahangir Murphy, Heather Chiang, Alan Krege, John TI Very Early Responses of Biochemical Markers of Bone Turnover to Teriparatide. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Robins, Deborah; Chiang, Alan; Krege, John] Eli Lilly & Co, Indianapolis, IN USA. [Leder, Benjamin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Krohn, Kelly; Alam, Jahangir] Lilly USA LLC, Indianapolis, IN USA. [Murphy, Heather] InVentiv Hlth Clin LLC, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0283 BP S434 EP S434 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702430 ER PT J AU Saini, V Fulzele, K Liu, XL Dedic, CG Zoubine, V Spatz, J Saito, H Jahn, K Khaled, SF Held, KD Hesse, E Pajevic, PD AF Saini, Vaibhav Fulzele, Keertik Liu, Xiaolong Dedic, Christopher G. Zoubine, Vladimir Spatz, Jordan Saito, Hiroaki Jahn, Katharina Khaled, Saman F. Held, Kathryn D. Hesse, Eric Pajevic, Paola Divieti TI PTH/PTHrP Receptor (PPR) Signaling in Osteocytes Delays Osteocyte Senescence and Protects from Age-related Osteopenia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Saini, Vaibhav] Harvard Univ, Sch Med, MGH, Cambridge, MA 02138 USA. [Fulzele, Keertik] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Liu, Xiaolong; Dedic, Christopher G.; Zoubine, Vladimir; Khaled, Saman F.; Held, Kathryn D.] MGH, Boston, MA USA. [Spatz, Jordan] Harvard MIT Div Hlth Sci & Technol HST, Cambridge, MA USA. [Saito, Hiroaki; Jahn, Katharina; Hesse, Eric] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Pajevic, Paola Divieti] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pajevic, Paola Divieti] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0455 BP S347 EP S347 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702142 ER PT J AU Samant, M Olson, K Mukherjee, A Chen, H Gardella, T Annis, A AF Samant, Manoj Olson, Karen Mukherjee, Aditi Chen, Hubert Gardella, Thomas Annis, Allen TI Stapled Peptides as Long-Acting, Selective Parathyroid Hormone Antagonists. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Samant, Manoj; Olson, Karen; Mukherjee, Aditi; Annis, Allen] Aileron Therapeut Inc, Cambridge, MA USA. [Gardella, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SA0144 BP S150 EP S150 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701141 ER PT J AU Sato, K Idelevich, A Rowe, G Gori, F Baron, R AF Sato, Kazusa Idelevich, Anna Rowe, Glenn Gori, Francesca Baron, Roland TI Leptin is crucial for ventral hypothalamic FosB-mediated regulation of glucose and energy homeostasis but not for bone homeostasis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Sato, Kazusa; Baron, Roland] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Idelevich, Anna] Harvard Univ, Cambridge, MA 02138 USA. [Rowe, Glenn; Baron, Roland] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1120 BP S42 EP S42 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700121 ER PT J AU Schafer, A Schwartz, A Black, D Wheeler, A Stewart, L Rogers, S Carter, J Posselt, A Shoback, D Li, XJ AF Schafer, Anne Schwartz, Ann Black, Dennis Wheeler, Amber Stewart, Lygia Rogers, Stanley Carter, Jonathan Posselt, Andrew Shoback, Dolores Li, Xiaojuan TI Changes in Bone Marrow Fat During Gastric Bypass Surgery-Induced Weight Loss SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Schafer, Anne; Schwartz, Ann; Black, Dennis; Wheeler, Amber; Stewart, Lygia; Rogers, Stanley; Carter, Jonathan; Posselt, Andrew; Li, Xiaojuan] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schafer, Anne; Stewart, Lygia] San Francisco VA Med Ctr, San Francisco, CA USA. [Shoback, Dolores] VA Med Ctr, Nashville, TN 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0106 BP S242 EP S242 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701418 ER PT J AU Schafer, A Sellmeyer, D Weaver, C Wheeler, A Stewart, L Rogers, S Carter, J Posselt, A Black, D Shoback, D AF Schafer, Anne Sellmeyer, Deborah Weaver, Connie Wheeler, Amber Stewart, Lygia Rogers, Stanley Carter, Jonathan Posselt, Andrew Black, Dennis Shoback, Dolores TI Intestinal Calcium Absorption Decreases Dramatically After Gastric Bypass Surgery, Despite Optimization of Vitamin D Status SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Schafer, Anne; Wheeler, Amber; Stewart, Lygia; Rogers, Stanley; Carter, Jonathan; Posselt, Andrew; Black, Dennis] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schafer, Anne; Stewart, Lygia] San Francisco VA Med Ctr, San Francisco, CA USA. [Sellmeyer, Deborah] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Weaver, Connie] Purdue Univ, W Lafayette, IN 47907 USA. [Shoback, Dolores] VA Med Ctr, Ann Arbor, MI 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1077 BP S26 EP S26 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700078 ER PT J AU Solomon, D Ruppert, K Zhao, ZP Lian, YJ Greendale, G Finkelstein, J AF Solomon, Daniel Ruppert, Kristine Zhao, Zhenping Lian, YinJuan Greendale, Gail Finkelstein, Joel TI Bone Mineral Density Changes Among Women Initiating ACE Inhibitors, Beta Blockers, and Thiazide Diuretics: Results from the SWAN Bone Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Solomon, Daniel] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ruppert, Kristine; Zhao, Zhenping; Lian, YinJuan] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Greendale, Gail] Univ Calif Los Angeles, Los Angeles, CA USA. [Finkelstein, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0312 BP S444 EP S444 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702459 ER PT J AU Solomon, D Diem, S Ruppert, K Lian, YJ Liu, CC Wohlfarht, A Greendale, G Finkelstein, J AF Solomon, Daniel Diem, Susan Ruppert, Kristine Lian, YinJuan Liu, Chih-Chin Wohlfarht, Alyssa Greendale, Gail Finkelstein, Joel TI Bone Mineral Density Changes Among Women Initiating Proton Pump Inhibitors or H2 Receptor Antagonists: Results from the SWAN Bone Study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Solomon, Daniel] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Diem, Susan] Univ Minnesota, Minneapolis, MN 55455 USA. [Ruppert, Kristine; Lian, YinJuan] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Liu, Chih-Chin; Wohlfarht, Alyssa] Brigham & Womens Hosp, Boston, MA 02115 USA. [Greendale, Gail] Univ Calif Los Angeles, Los Angeles, CA USA. [Finkelstein, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA FR0373 BP S109 EP S110 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701027 ER PT J AU Takatani, R Minagawa, M Kinoshita, K Takatani, T Molinaro, A Jueppner, H AF Takatani, Rieko Minagawa, Masanori Kinoshita, Kaori Takatani, Tomozumi Molinaro, Angelo Jueppner, Harald TI Paternal Uniparental Isodisomy Involving Chromosome 20q (patUPD20q) as a Cause of Japanese Patients Affected by Sporadic Pseudohypoparathyroidism Type Ib. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Takatani, Rieko; Molinaro, Angelo; Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Takatani, Rieko; Molinaro, Angelo] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Minagawa, Masanori] Chiba Childrens Hosp, Chiba, Japan. [Kinoshita, Kaori; Takatani, Tomozumi] Chiba Univ, Chiba, Japan. 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0435 BP S340 EP S340 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702122 ER PT J AU Takeyama, K Nistala, H Addison, W Kota, S Kawahara, G Kunkel, L Mintseris, J Gygi, S Gori, F Baron, R AF Takeyama, Ken-ichi Nistala, Harikiran Addison, William Kota, Satya Kawahara, Genri Kunkel, Louis Mintseris, Julian Gygi, Steven Gori, Francesca Baron, Roland TI Formation of a Zinc finger protein 521-NuRD co-repressor complex is involved in osteoprogenitor commitment and Zebrafish skeletal development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Takeyama, Ken-ichi; Addison, William; Kota, Satya] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Nistala, Harikiran] Harvard Univ, Cambridge, MA 02138 USA. [Kawahara, Genri; Kunkel, Louis] Harvard Univ, Sch Med, Boston Childrens Hosp, Cambridge, MA 02138 USA. [Mintseris, Julian; Gygi, Steven] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Baron, Roland] Harvard Univ, Sch Med & Dent Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1116 BP S40 EP S41 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700117 ER PT J AU Tsai, J Lee, H Zhu, YL Foley, K Burnett-Bowie, SA Neer, R Leder, B AF Tsai, Joy Lee, Hang Zhu, Yuli Foley, Katelyn Burnett-Bowie, Sherri-Ann Neer, Robert Leder, Benjamin TI Acute Skeletal Effects of PTH in Combination with Denosumab or Alendronate. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Tsai, Joy; Burnett-Bowie, Sherri-Ann; Neer, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Zhu, Yuli; Foley, Katelyn] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Leder, Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA FR0377 BP S110 EP S111 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701029 ER PT J AU Tsai, J Uihlein, A Burnett-Bowie, SA Neer, R Zhu, YL Derrico, N Foley, K Lee, H Bouxsein, M Leder, B AF Tsai, Joy Uihlein, Alexander Burnett-Bowie, Sherri-Ann Neer, Robert Zhu, Yuli Derrico, Nicholas Foley, Katelyn Lee, Hang Bouxsein, Mary Leder, Benjamin TI Effects of Two Years of Teriparatide, Denosumab and Combination Therapy on Peripheral Bone Density and Microarchitecture: The DATA-HRpQCT Extension study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Tsai, Joy; Burnett-Bowie, Sherri-Ann; Neer, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Uihlein, Alexander] Northwestern Mem Fac Fdn, Chicago, IL USA. [Zhu, Yuli; Derrico, Nicholas; Foley, Katelyn] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Bouxsein, Mary] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Leder, Benjamin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1046 BP S16 EP S16 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700047 ER PT J AU Wang, LP Roth, TM Nguyen, TA Zhou, P Zhang, JS Nakamura, M Huang, EJ Farese, RV Nissenson, R AF Wang, Liping Roth, Theresa M. Nguyen, Thi A. Zhou, Ping Zhang, Jiasheng Nakamura, Mary Huang, Eric J. Farese, Robert V., Jr. Nissenson, Robert TI Loss of Progranulin Increases Bone Mass in Adult Mice in a Gender Dependent Manner. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Wang, Liping; Nissenson, Robert] VA Med Ctr, San Francisco, CA USA. [Roth, Theresa M.] VA Med Ctr, Endocrine Unit, San Francisco, CA USA. [Nguyen, Thi A.; Zhou, Ping; Farese, Robert V., Jr.] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA. [Zhang, Jiasheng; Huang, Eric J.] Univ Calif, Pathol, Berkeley, CA USA. [Nakamura, Mary; Nissenson, Robert] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nakamura, Mary] San Francisco VA Med Ctr, San Francisco, CA USA. [Huang, Eric J.] VA Med Ctr, Pathol Serv, Portland, OR USA. [Farese, Robert V., Jr.] Univ Calif, Med & Biochem & Biophys, Berkeley, CA 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA FR0462 BP S123 EP S124 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701065 ER PT J AU Watanabe, T Reyes, M Goltzman, D Potts, J Gardella, T AF Watanabe, Tomoyuki Reyes, Monica Goltzman, David Potts, John Gardella, Thomas TI Calcemic actions of a long-acting PTH analog in PTH knockout mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Watanabe, Tomoyuki; Reyes, Monica; Potts, John; Gardella, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goltzman, David] McGill Univ, Montreal, PQ H3A 2T5, Canada. 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA MO0136 BP S391 EP S391 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702289 ER PT J AU Watanabe, T Gidon, A Dean, T Potts, J Vilardaga, JP Gardella, T AF Watanabe, Tomoyuki Gidon, Alexandre Dean, Thomas Potts, John Vilardaga, Jean-Pierre Gardella, Thomas TI Mechanisms controlling duration of signaling at the PTH receptor 1. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Watanabe, Tomoyuki; Dean, Thomas; Potts, John; Gardella, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gidon, Alexandre; Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0140 BP S251 EP S252 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701449 ER PT J AU Wein, M Spatz, J Nishimori, S Doench, J Root, D Brooks, D Bouxsein, M Pajevic, PD Kronenberg, H AF Wein, Marc Spatz, Jordan Nishimori, Shigeki Doench, John Root, David Brooks, Daniel Bouxsein, Mary Pajevic, Paola Divieti Kronenberg, Henry TI HDAC5 Controls MEF2C-Driven Sclerostin Production by Osteocytes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Wein, Marc; Nishimori, Shigeki; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Spatz, Jordan] Harvard MIT Div Hlth Sci & Technol HST, Cambridge, MA USA. [Doench, John; Root, David] Broad Inst, Cambridge, MA USA. [Brooks, Daniel] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Bouxsein, Mary] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Pajevic, Paola Divieti] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pajevic, Paola Divieti] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1022 BP S9 EP S9 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700023 ER PT J AU Ye, L Morse, L Zhang, L Sasaki, H Mills, J Sibbel, G Zamarioli, A Battaglino, R AF Ye, Liang Morse, Leslie Zhang, Li Sasaki, Hajime Mills, Jason Sibbel, Greg Zamarioli, Ariane Battaglino, Ricardo TI Snx10-dependent osteoclastic activity and gastric acidification is required for bone and calcium homeostasis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Ye, Liang; Zhang, Li; Sasaki, Hajime; Battaglino, Ricardo] Forsyth Inst, Cambridge, MA USA. [Ye, Liang] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Morse, Leslie] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mills, Jason; Sibbel, Greg] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Zamarioli, Ariane] Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. RI Zamarioli, Ariane/K-7001-2012 OI Zamarioli, Ariane/0000-0002-7939-0528 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA FR0254 BP S88 EP S88 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700274 ER PT J AU Yu, E Putman, M Derrico, N Abrishamanian-Garcia, G Finkelstein, J Bouxsein, M AF Yu, Elaine Putman, Melissa Derrico, Nicolas Abrishamanian-Garcia, Gabriela Finkelstein, Joel Bouxsein, Mary TI Defects in cortical microarchitecture among postmenopausal African-American women with DM2. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Yu, Elaine; Finkelstein, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Putman, Melissa] Massachusetts Gen Hosp, Childrens Hosp, Boston, MA 02114 USA. [Derrico, Nicolas; Abrishamanian-Garcia, Gabriela] MGH, Boston, MA USA. [Bouxsein, Mary] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0408 BP S331 EP S331 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598702095 ER PT J AU Zalli, D Nagano, K Neff, L Takeyama, K Witke, W Gori, F Baron, R AF Zalli, Detina Nagano, Kenichi Neff, Lynn Takeyama, Ken-ichi Witke, Walter Gori, Francesca Baron, Roland TI The actin-binding protein Cofilin and its interaction with cortactin are required for podosome patterning in osteoclasts and bone resorption in vivo and in vitro. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Nagano, Kenichi; Neff, Lynn; Takeyama, Ken-ichi; Baron, Roland] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Witke, Walter] Univ Bonn, Prof Dr Walter Witke Inst Genet, D-53115 Bonn, Germany. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Baron, Roland] Harvard Univ, Sch Med, 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA 1130 BP S44 EP S44 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598700131 ER PT J AU Zheng, HF Forgetta, V Hsu, YH Estrada, K Leo, P Tobias, J Kooperberg, C Liu, CT Rosello-Diez, A Evans, D Nielson, C Pettersson-Kymmer, U Eriksson, J Kwan, T Walter, K Memari, Y McCarthy, S Min, J Huang, J Danecek, P Wilmot, B Li, R Chou, WC Mokry, L Moayyeri, A Claussnitzer, M Cheng, CH Cheung, W Medina-Gomez, C Ge, B Chen, SH Choi, K Oei, L Fraser, J Kraaij, R Hibbs, M Gregson, C Paquette, D Hofman, A Wibom, C Marshall, M Gardiner, B Auer, P Hsu, L Ring, S van der Velde, N Melin, B Kemp, J Sayers, A Zhou, YH Calderari, S Maurano, M van Rooij, J Carlson, C Peters, U Berlivet, S Dostie, J Ohlsson, C Uitterlinden, A Goltzman, D Pastinen, T Grundberg, E Gauguier, D Orwoll, E Karasik, D Dahia, C Davey-Smith, G Timpson, N Soranzo, N Durbin, R Wilson, S Brown, M Spector, T Cupples, LA Greenwood, C Loomis, C Ackert-Bicknell, C Joyner, A Jackson, R Duncan, E Evans, D Rivadeneira, F Kiel, D Richards, B AF Zheng, Hou-Feng Forgetta, Vince Hsu, Yi-Hsiang Estrada, Karol Leo, Paul Tobias, Jonathan Kooperberg, Charles Liu, Ching-Ti Rosello-Diez, Alberto Evans, Daniel Nielson, Carrie Pettersson-Kymmer, Ulrika Eriksson, Joel Kwan, Tony Walter, Klaudia Memari, Yasin McCarthy, Shane Min, Josine Huang, Jie Danecek, Petr Wilmot, Beth Li, Rui Chou, Wen-Chi Mokry, Lauren Moayyeri, Alireza Claussnitzer, Melina Cheng, Chia-Ho Cheung, Warren Medina-Gomez, Carolina Ge, Bing Chen, Shu-Huang Choi, Kwangbom Oei, Ling Fraser, James Kraaij, Robert Hibbs, Matthew Gregson, Celia Paquette, Denis Hofman, Albert Wibom, Carl Marshall, Mhairi Gardiner, Brooke Auer, Paul Hsu, Li Ring, Sue van der Velde, Nathalie Melin, Beatrice Kemp, John Sayers, Adrian Zhou, Yanhua Calderari, Sophie Maurano, Matthew van Rooij, Jeroen Carlson, Chris Peters, Ulrike Berlivet, Soizik Dostie, Josee Ohlsson, Claes Uitterlinden, Andre Goltzman, David Pastinen, Tomi Grundberg, Elin Gauguier, Dominique Orwoll, Eric Karasik, David Dahia, Chitra Davey-Smith, George Timpson, Nicholas Soranzo, Nicole Durbin, Richard Wilson, Scott Brown, Matthew Spector, Tim Cupples, L. Adrienne Greenwood, Celia Loomis, Cynthia Ackert-Bicknell, Cheryl Joyner, Alexandra Jackson, Rebecca Duncan, Emma Evans, David Rivadeneira, Fernando Kiel, Douglas Richards, Brent TI A large-scale whole genome sequence-based analysis discovered novel genetic variants influencing bone mineral density: Results from the GEFOS and UK10K Consortia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Zheng, Hou-Feng; Forgetta, Vince; Kwan, Tony; Li, Rui; Mokry, Lauren; Ge, Bing; Chen, Shu-Huang; Fraser, James; Paquette, Denis; Sayers, Adrian; Berlivet, Soizik; Dostie, Josee; Goltzman, David; Pastinen, Tomi; Grundberg, Elin; Greenwood, Celia; Richards, Brent] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Hsu, Yi-Hsiang; Claussnitzer, Melina] Hebrew SeniorLife, Inst Aging Res, Roslindale, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Leo, Paul; Marshall, Mhairi; Kemp, John; Evans, David] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Tobias, Jonathan; Min, Josine; Sayers, Adrian; Davey-Smith, George; Timpson, Nicholas] Univ Bristol, Bristol BS8 1TH, Avon, England. [Kooperberg, Charles; Hsu, Li; Carlson, Chris; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Liu, Ching-Ti; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Rosello-Diez, Alberto] Sloan Kettering Inst, New York, NY USA. [Evans, Daniel] Calif Pacific Med Ctr, San Francisco, CA USA. [Nielson, Carrie; Wilmot, Beth; Cheung, Warren; Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Eriksson, Joel] Ctr Bone & Arthrit Res, Stockholm, Sweden. [Kwan, Tony; Chen, Shu-Huang; Grundberg, Elin] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Walter, Klaudia; Memari, Yasin; McCarthy, Shane; Huang, Jie; Danecek, Petr; Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Chou, Wen-Chi; Cheng, Chia-Ho; Karasik, David; Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA. [Moayyeri, Alireza; Spector, Tim] Kings Coll London, London WC2R 2LS, England. [Claussnitzer, Melina] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Medina-Gomez, Carolina; Kraaij, Robert; Hofman, Albert; van der Velde, Nathalie; van Rooij, Jeroen] Erasmus MC, Utrecht, Netherlands. [Choi, Kwangbom; Hibbs, Matthew] Jackson Lab, New York, NY USA. [Oei, Ling] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Gregson, Celia] Univ Bristol, Bristol BS8 1TH, Avon, England. [Wibom, Carl; Melin, Beatrice] Umea Univ, S-90187 Umea, Sweden. [Gardiner, Brooke] Nivers Queensland, Diamantina Inst, Mundubbera, Qld, Australia. [Auer, Paul] Univ Wisconsin, Madison, WI 53706 USA. [Ring, Sue] Nivers Bristol, Bristol, Avon, England. [Zhou, Yanhua] Boston Univ, Boston, MA 02215 USA. [Calderari, Sophie; Gauguier, Dominique] Cordeliers Res Ctr, Lyon, France. [Maurano, Matthew] Univ Washington, Seattle, WA 98195 USA. [Ohlsson, Claes] Sahlgrens Acad, Ctr Bone & Arthrit Res, Stockholm, Sweden. [Uitterlinden, Andre] Erasmus MC, Montreal, PQ, Canada. [Karasik, David] Bar Ilan Univ, IL-52100 Ramat Gan, Israel. [Dahia, Chitra] Hosp Special Surg, Montreal, PQ, Canada. [Durbin, Richard] Wellcome Trust Res Labs, Sanger Inst, New York, NY USA. [Wilson, Scott] Univ Western Australia, Nedlands, WA 6009, Australia. [Brown, Matthew] Diamantina Inst Canc Immunol & Metab Med, Sydney, NSW, Australia. [Loomis, Cynthia] NYU, Sch Med, New York, NY 10003 USA. [Ackert-Bicknell, Cheryl] Univ Rochester, Rochester, NY 14627 USA. [Joyner, Alexandra] Sloan Kettering Inst, New York, NY USA. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. [Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. RI Gardiner, Brooke/C-7773-2011; Rivadeneira, Fernando/O-5385-2015; Oei, Ling/E-8163-2013; Rosello Diez, Alberto/K-7295-2016 OI Gardiner, Brooke/0000-0003-3740-3244; Rivadeneira, Fernando/0000-0001-9435-9441; Oei, Ling/0000-0003-3523-458X; Rosello Diez, Alberto/0000-0002-5550-9846 NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SA0308 BP S179 EP S179 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701229 ER PT J AU Zhu, Y Aydin, C Rubera, I Tauc, M Chen, M Weinstein, L Marshansky, V Bastepe, M AF Zhu, Yan Aydin, Cumhur Rubera, Isabelle Tauc, Michel Chen, Min Weinstein, Lee Marshansky, Vladimir Bastepe, Murat TI Segment specific role of Gs alpha in mediating parathyroid hormone actions in the renal proximal tubule. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Zhu, Yan; Bastepe, Murat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Aydin, Cumhur] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Aydin, Cumhur; Marshansky, Vladimir] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rubera, Isabelle; Tauc, Michel] Univ Nice Sophia Antipolis, CNRS LP2M 7370, Nice, France. [Chen, Min; Weinstein, Lee] NIDDK, Bethesda, MD USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SU0143 BP S252 EP S253 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701452 ER PT J AU Porteous, NB Bizra, E Cothron, A Yeh, CK AF Porteous, Nuala B. Bizra, Eamon Cothron, Annaliese Yeh, Chih-Ko TI A Survey of Infection Control Teaching in US Dental Schools SO JOURNAL OF DENTAL EDUCATION LA English DT Article DE infection control; dental schools; dental education; clinic management; clinical education; infection control teaching; infection control compliance in dental schools; bloodborne pathogen ID PERCUTANEOUS INJURIES; STUDENTS; PREVENTION; DENTISTRY; EDUCATION AB This study was conducted to determine the content of infection control (IC) curricula, the extent of IC monitoring and compliance, and the number of bloodborne pathogen (BBP) exposures/year in U.S. dental schools. A questionnaire was emailed to persons responsible for predoctoral IC programs. The response rate was 60 percent. Most schools did not have an independent course and used classroom lectures and clinic demonstrations to teach IC. Schools with an IC committee were more likely to use online learning (p<0.05), utilize multiple teaching methods (p<0.05), issue written warnings for IC violations (p<0.0001), and use multiple disciplinary actions (p<0.005) than schools without an IC committee. Schools with an IC coordinator were less likely to issue grade reductions for IC violations than schools with no IC coordinator (p<0.05). Thirty-eight percent reported >= 16 BBP exposures/year, and 18 percent reported <5. There was significant correlation between BBP exposure incidents and large class size (p<0.005). Respondents were satisfied with their IC curriculum and perceived that dental students had a high level of IC compliance and satisfaction, along with staff IC promotion and compliance. The findings suggest that schools without an IC committee should consider its benefits. Further investigation of schools with high numbers of BBP exposures is recommended. C1 [Porteous, Nuala B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, Sch Dent, San Antonio, TX 78229 USA. [Bizra, Eamon; Cothron, Annaliese; Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Sch Dent, San Antonio, TX 78229 USA. [Yeh, Chih-Ko] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr San Antonio, San Antonio, TX USA. RP Porteous, NB (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, Sch Dent, MC 7914,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM porteous@uthscsa.edu FU NIDCR NIH HHS [R01 DE021084, R21 DE015381] NR 32 TC 1 Z9 2 U1 1 U2 6 PU AMER DENTAL EDUCATION ASSOC-ADEA PI WASHINGTON PA 655 K STREET NW, SUITE 800, WASHINGTON, DC 20001 USA SN 0022-0337 EI 1930-7837 J9 J DENT EDUC JI J. Dent. Educ. PD FEB PY 2014 VL 78 IS 2 BP 187 EP 194 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AY0HW UT WOS:000347278900003 PM 24489026 ER PT J AU Thunemann, M Wen, L Feil, S Birk, B Russwurm, M Shuhaibar, L Jaffe, L de Wit, C Han, XX Fukumura, D Jain, R Feil, R AF Thunemann, Martin Wen Lai Feil, Susanne Birk, Barbara Russwurm, Michael Shuhaibar, Leia Jaffe, Laurinda de Wit, Cor Han Xiaoxing Fukumura, Dai Jain, Rakesh Feil, Robert TI cGMP indicator mice: Generation, characterization and first in vivo results SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie-e-V CY APR 01-03, 2014 CL Hannover, GERMANY SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V C1 [Thunemann, Martin; Wen Lai; Feil, Susanne; Birk, Barbara; Feil, Robert] Univ Tubingen, Interfak Inst Biochem, Tubingen, Germany. [Russwurm, Michael] Ruhr Univ Bochum, Inst Pharmakol & Toxikol, Bochum, Germany. [Shuhaibar, Leia; Jaffe, Laurinda] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT USA. [de Wit, Cor] Univ Lubeck, Inst Physiol, Lubeck, Germany. [Han Xiaoxing; Fukumura, Dai; Jain, Rakesh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Han Xiaoxing; Fukumura, Dai; Jain, Rakesh] Harvard Univ, Sch Med, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA USA. 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 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2014 VL 387 SU 1 MA 075 BP S20 EP S20 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CP0AP UT WOS:000359538500076 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Timing of endoscopy in gastrointestinal bleeding SO UNITED EUROPEAN GASTROENTEROLOGY JOURNAL LA English DT Editorial Material DE Decision analysis; gastrointestinal bleeding; gastrointestinal endoscopy; threshold analysis ID HIGH-RISK PATIENTS; VARICEAL HEMORRHAGE; PEPTIC-ULCER; MANAGEMENT; MORTALITY; OXYGEN AB Background: In gastrointestinal bleeding, a physician often has to make a decision between two possible choices. Endoscopic management of the bleeding could be initiated immediately, or it could be delayed until the patient has become haemodynamically stable or the conditions for a successful endoscopy have otherwise improved. Objective: The present article serves to present such situations and highlights their characteristic features. Methods: The choice between immediate and delayed endoscopy is analysed in terms of a decision tree, comparing the expected results of the two management alternatives. The decision tree is applied to three different clinical scenarios associated with gastrointestinal bleeding, where performing endoscopy later rather than sooner represents the preferred management option. Results: The work up of chronic iron-deficient anaemia in patients with serious cardiac problems should be deferred until resolution of their reduced cardiovascular status. It is also recommended that, even in acute bleeding, endoscopy is deferred until the patient has become haemodynamically stable. Lastly, for nonemergency treatment of oesophageal varices bleeding, a long rather than short interval between consecutive banding sessions appears more beneficial. Conclusions: The results illustrate how to use threshold analysis as a simple bedside tool to solve seemingly complex decisions associated with management of gastrointestinal bleeding. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 19 TC 1 Z9 1 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2050-6406 EI 2050-6414 J9 UNITED EUR GASTROENT JI United European Gastroenterol. J. PD FEB PY 2014 VL 2 IS 1 BP 5 EP 9 DI 10.1177/2050640613518773 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AY7ZG UT WOS:000347773700001 PM 24918002 ER PT J AU Miller, LL Scharf, JM Mathews, CA Ben-Shlomo, Y AF Miller, Laura L. Scharf, Jeremiah M. Mathews, Carol A. Ben-Shlomo, Yoav TI Tourette syndrome and chronic tic disorder are associated with lower socio-economic status: findings from the Avon Longitudinal Study of Parents and Children cohort SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID PREVALENCE; RISK AB AimOnly a few studies have examined the relationship between Tourette syndrome or chronic tic disorder and socio-economic status (SES). Existing studies are primarily cross-sectional, arise from specialty clinics, and use single measures of SES. In this study we examine this relationship in a longitudinal, population-based sample. MethodData are from 7152 children born during 1991 and 1992 in the county of Avon, UK, from the Avon Longitudinal Study of Parents and Children, who were followed up to age 13. After exclusions for intellectual disability* and autism, 6768 participants (3351 males [49.5%]) and 3417 females [50.5%]) remained. Parental SES was assessed using multiple measures during pregnancy and at 33months of age. Presence of Tourette syndrome or chronic tics was determined from repeated maternal questionnaires up to when the child was 13years of age. ResultsMultiple SES measures were associated with an approximately twofold increased risk of Tourette syndrome and chronic tics. A postnatal composite factor score (lowest vs highest tertile odds ratio 2.09, 95% confidence interval 1.38-3.47) provided the best fit to the data. InterpretationsAs is seen in several childhood conditions, such as cerebral palsy and autism, lower SES is a risk factor for Tourette syndrome/chronic tics. Potential explanations include differential exposure to environmental risk factors or parental psychopathology as a measure of an increased genetic risk leading to decreased parental SES. C1 [Miller, Laura L.; Ben-Shlomo, Yoav] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Miller, LL (reprint author), Univ Bristol, Sch Social & Community Med, Oakfield House, Bristol BS8 2BN, Avon, England. EM l.l.miller@bristol.ac.uk FU Tourette Syndrome Association, USA; NIH [MH085057]; University of Bristol; UK Medical Research Council [74882]; Wellcome Trust [076467] FX We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. LLM was funded by the Tourette Syndrome Association, USA. JMS was funded by the Tourette Syndrome Association, USA, and NIH MH085057. CAM was funded by the Tourette Syndrome Association, USA. YB-S was funded by a tenured position at the University of Bristol and the Tourette Syndrome Association, USA. No authors have any conflicts of interest. The UK Medical Research Council (grant ref. 74882) the Wellcome Trust (grant ref. 076467) and the University of Bristol provide core support for ALSPAC. This research was specifically funded by the Tourette Syndrome Association, USA. The funders had no role in the design, data collection, analysis, or manuscript preparation. NR 22 TC 10 Z9 11 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 EI 1469-8749 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD FEB PY 2014 VL 56 IS 2 BP 157 EP 163 DI 10.1111/dmcn.12318 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 287LU UT WOS:000329544100007 PM 24138188 ER PT J AU Lesnik, D Cunnane, ME Zurakowski, D Acar, GO Ecevit, C Mace, A Kamani, D Randolph, GW AF Lesnik, David Cunnane, Mary Elizabeth Zurakowski, David Acar, Gul Ozbilen Ecevit, Cenk Mace, Alasdair Kamani, Dipti Randolph, Gregory W. TI Papillary thyroid carcinoma nodal surgery directed by a preoperative radiographic map utilizing CT scan and ultrasound in all primary and reoperative patients SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE papillary thyroid cancer; neck dissection; macroscopic nodal metastasis; preoperative radiography; CT scan; ultrasonography ID CERVICAL LYMPH-NODES; POSTOPERATIVE THYROGLOBULIN LEVELS; 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; NECK DISSECTION; SURGICAL-MANAGEMENT; DIFFERENTIATED CARCINOMA; PROGNOSTIC-SIGNIFICANCE; ULTRASONOGRAPHIC DIFFERENTIATION; CLINICAL-SIGNIFICANCE; CONFIDENCE-INTERVALS AB BackgroundTo study the diagnostic accuracy of physical examination (PE), ultrasonography (US), contrastenhanced computed tomography (CT) and in preoperative detection of macroscopic nodal metastasis in primary/recurrent papillary thyroid carcinoma (PTC) patients to determine if the routine addition of CT would be beneficial in accurate preoperative lymph-node surgery planning. MethodsIn a tertiary center prospective study, 162 PTC patients underwent preoperative lymph-node evaluation by PE, US, and CT. Sensitivity, specificity, positive/negative predictive value (PPV/NPV) of each nodal detection technique were calculated in central/lateral cervical compartments. The gold standard for diagnostic-accuracy was surgical pathology. ResultsIn patients undergoing primary (Group I)/revision (Group II) surgical treatment for PTC, combined US/CT yielded significantly higher sensitivity for macroscopic lymph-node detection in both lateral and central neck, most marked in Group I-central compartment. ConclusionsCombined preoperative US/CT provides reliable, objective, preoperative macroscopic nodal metastasis map to design rational nodal surgery in primary/revision PTC patients. (c) 2013 Wiley Periodicals, Inc. Head Neck 36: 191-202, 2014 C1 [Lesnik, David; Kamani, Dipti; Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Thyroid & Parathyroid Surg,Dept Otol & Laryng, Boston, MA USA. [Cunnane, Mary Elizabeth] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Childrens Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Childrens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Acar, Gul Ozbilen; Ecevit, Cenk] Goztepe Res & Educ Hosp, Dept Otorhinolaryngol, Istanbul, Turkey. [Mace, Alasdair] Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, London SW7 2AZ, England. [Mace, Alasdair] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, London SW7 2AZ, England. [Randolph, Gregory W.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Endocrine Surg Serv, Boston, MA 02114 USA. RP Randolph, GW (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu FU John and Claire Bertucci Thyroid Research fund FX Contract grant sponsor: This work was funded by the John and Claire Bertucci Thyroid Research fund. NR 107 TC 17 Z9 17 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD FEB PY 2014 VL 36 IS 2 BP 191 EP 202 DI 10.1002/hed.23277 PG 12 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 286XO UT WOS:000329502800010 PM 23554058 ER PT J AU van den Bosch, GE El Marroun, H Schmidt, MN Tibboel, D Manoach, DS Calhoun, VD White, TJH AF van den Bosch, Gerbrich E. El Marroun, Hanan Schmidt, Marcus N. Tibboel, Dick Manoach, Dara S. Calhoun, Vince D. White, Tonya J. H. TI Brain Connectivity During Verbal Working Memory in Children and Adolescents SO HUMAN BRAIN MAPPING LA English DT Article DE adolescents; brain connectivity; children; development; fMRI; verbal working memory ID FUNCTIONAL MRI DATA; DEVELOPMENTAL-TRENDS; SCHIZOPHRENIA; FMRI; OPTIMIZATION; REGISTRATION; IMPAIRMENTS; RELIABILITY; PERFORMANCE; MATURATION AB Working memory (WkM) is a fundamental cognitive process that serves as a building block for higher order cognitive functions. While studies have shown that children and adolescents utilize similar brain regions during verbal WkM, there have been few studies that evaluate the developmental differences in brain connectivity. Our goal was to study the development of brain connectivity related to verbal WkM in typically developing children and adolescents. Thirty-five healthy children and adolescents, divided into three groups: 9-12 (children), 13-16 (young adolescents), and 17-19 (older adolescents) years, were included in this functional magnetic resonance imaging (fMRI) study. The verbal WkM task involved a modified Sternberg item recognition paradigm using three different loads. Brain connectivity analysis was performed using independent component analyses and regressing the components with the design matrix to determine task-related networks. Connectivity analyses resulted in four components associated solely with encoding, four solely with recognition and two with both. Two networks demonstrated age-related differences with respect to load, (1) the left motor area and right cerebellum, and 2) the left prefrontal cortex, left parietal lobe, and right cerebellum. Post hoc analyses revealed that the first network showed significant effects of age between children and the two older groups. There was increasing connectivity with increasing load for adolescents. The second network demonstrated age-related differences between children and older adolescents. Children have higher task-related connectivity at lower loads, but they tend to equalize with the adolescents with higher loads. Finally, a non-load related network involving the orbital frontal and anterior cingulate cortices showed less connectivity in children. Hum Brain Mapp 35:698-711, 2014. (c) 2012 Wiley Periodicals, Inc. C1 [van den Bosch, Gerbrich E.; Tibboel, Dick] Erasmus Univ, Med Ctr, Sophia Childrens Hosp, Rotterdam, Netherlands. [van den Bosch, Gerbrich E.; Tibboel, Dick] Erasmus Univ, Dept Pediat Surg, Med Ctr, Sophia Childrens Hosp, NL-3000 DR Rotterdam, Netherlands. [El Marroun, Hanan; Schmidt, Marcus N.; White, Tonya J. H.] Erasmus Univ, Sophia Childrens Hosp, Med Ctr, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands. [Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Neuroimaging Div, Charlestown, MA USA. [Calhoun, Vince D.] Univ New Mexico, Mind Res Network, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [White, Tonya J. H.] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. RP White, TJH (reprint author), Erasmus MC Sophia, POB 2060, NL-3000 CB Rotterdam, Netherlands. EM t.white@erasmusmc.nl FU Mental Illness and Neuroscience Discovery Research Network [NIMH K08 MH068540]; NIH [2R01EB000840]; ZonMw TOP [91211021]; Mind Research Network; National Alliance for Research in Schizophrenia and Depression (NARSAD); Essel and Blowitz-Ridgeway Foundations FX Contract grant sponsor: Mental Illness and Neuroscience Discovery Research Network; Contract grant number: NIMH K08 MH068540; Contract grant sponsor: NIH; Contract grant number: 2R01EB000840; Contract grant sponsor: ZonMw TOP; Contract grant number: 91211021; Contract grant sponsors: Mind Research Network, National Alliance for Research in Schizophrenia and Depression (NARSAD), Essel and Blowitz-Ridgeway Foundations. NR 51 TC 7 Z9 7 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD FEB PY 2014 VL 35 IS 2 BP 698 EP 711 DI 10.1002/hbm.22193 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 287HJ UT WOS:000329532400021 PM 23233279 ER PT J AU Pabayo, R Kawachi, I Gilman, SE AF Pabayo, Roman Kawachi, Ichiro Gilman, Stephen E. TI Income inequality among American states and the incidence of major depression SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article DE Depression; Inequalities; Cohort studies; Epidemiology; Mental Health ID SELF-RATED HEALTH; STRESSFUL LIFE EVENTS; UNITED-STATES; WOMENS STATUS; MULTILEVEL ANALYSIS; GENDER-DIFFERENCES; PHYSICAL HEALTH; SOCIAL-CONTEXT; MENTAL-HEALTH; HEART-DISEASE AB Background Although cross-sectional and ecological studies have shown that higher area-level income inequality is related to increased risk for depression, few longitudinal studies have been conducted. This investigation examines the relationship between state-level income inequality and major depression among adults participating in a population-based, representative longitudinal study. Methods We used data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=34653). Respondents completed structured diagnostic interviews at baseline (2001-2002) and follow-up (2004-2005). Weighted multilevel modelling was used to determine if US state-level income inequality (measured by the Gini coefficient) was a significant predictor of depression at baseline and at follow-up, while controlling for individual-level and state-level covariates. We also repeated the longitudinal analyses, excluding those who had a history of depression or at baseline, in order to test whether income inequality was related to incident depression. Results State-level inequality was associated with increased incidence of depression among women but not men. In comparison to women residing in states belonging to the lowest quintile of income inequality, women were at increased risk for depression in the second (OR=1.18, 95% CI 0.86 to 1.62), third (OR=1.22, 95% CI 0.91 to 1.62), fourth (OR=1.37, 95% CI 1.03 to 1.82) and fifth (OR=1.50, 95% CI 1.14 to 1.96) quintiles at follow-up (p<0.05 for the linear trend). Conclusions Living in a state with higher income inequality increases the risk for the development of depression among women. C1 [Pabayo, Roman; Kawachi, Ichiro; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pabayo, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave, Boston, MA 02115 USA. EM rpabayo@hsph.harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU NIH [MH087544]; Canadian Institutes of Health Research [234617] FX This work was supported by NIH-grant number MH087544. RP is a Canadian Institutes of Health Research postdoctoral fellowship recipient #234617. NR 51 TC 16 Z9 16 U1 2 U2 31 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD FEB PY 2014 VL 68 IS 2 BP 110 EP 115 DI 10.1136/jech-2013-203093 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286SB UT WOS:000329487900001 PM 24064745 ER PT J AU Larose, TL Chen, Y Camargo, CA Langhammer, A Romundstad, P Mai, XM AF Larose, Tricia L. Chen, Yue Camargo, Carlos A., Jr. Langhammer, Arnulf Romundstad, Pal Mai, Xiao-Mei TI Factors associated with vitamin D deficiency in a Norwegian population: the HUNT Study SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article DE Endocrinology; Epidemiology; Lifestyle ID SERUM 25-HYDROXYVITAMIN D; CARDIOVASCULAR-DISEASE; PROSPECTIVE COHORT; DIETARY-INTAKE; D LEVEL; HEALTH; PREVALENCE; NORWAY; ADULTS; SMOKING AB Vitamin D deficiency occurs worldwide. Winter season and high Body Mass Index (BMI) are associated with low levels of serum 25-hydroxyvitamin D (25(OH)D). We estimated the prevalence of vitamin D deficiency in a Norwegian adult population and examined factors associated with vitamin D deficiency. A cohort of 25616 adults (19-55years) who participated in both the second and third Nord-TrOndelag Health Study (HUNT 2 (1995-1997) and HUNT 3 (2006-2008)) was established in a previous study. A 10% random sample of the cohort population was recruited for serum 25(OH)D measurements (n=2584), which was used for the current cross-sectional study. Vitamin D deficiency was defined as serum 25(OH)D level <50nmol/L. The overall prevalence of vitamin D deficiency was 40%, but varied by season (winter: 64%; summer: 20%). Winter season (adjusted prevalence ratio (PR): 3.16, 95% CI 2.42 to 4.12) and obesity (BMI 30.0kg/m(2)) (PR: 1.74, 95% CI 1.45 to 2.10) were strongly associated with prevalent vitamin D deficiency. Current smoking also demonstrated an increased PR (1.41, 95% CI 1.21 to 1.65). Daily intake of cod liver oil (PR: 0.60, 95% CI 0.41 to 0.77), increased physical activity (PR: 0.80, 95% CI 0.68 to 0.95) and more frequent alcohol consumption (PR: 0.76, 95% CI 0.60 to 0.95) were associated with a reduced PR. The prevalence of vitamin D deficiency was high in Norwegian adults. Winter season, high BMI and current smoking were positively associated, and intake of cod liver oil, increased physical activity and more frequent alcohol consumption were inversely associated with vitamin D deficiency. C1 [Larose, Tricia L.; Langhammer, Arnulf; Romundstad, Pal; Mai, Xiao-Mei] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, N-7491 Trondheim, Norway. [Chen, Yue] Univ Ottawa, Dept Epidemiol & Community Hlth, Ottawa, ON, Canada. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Larose, TL (reprint author), Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, MTFS, Postboks 9805, N-7491 Trondheim, Norway. EM tricia.larose@ntnu.no OI Romundstad, Pal Richard/0000-0003-2061-4336 FU Research Council of Norway [201895/V50]; ExtraStiftelsen Helse og Rehabilitering and Landsforeningen [2011.2.0215]; Liason Committee Central Norway Regional Health Authority-NTNU FX This study was supported by the Research Council of Norway (project 201895/V50), ExtraStiftelsen Helse og Rehabilitering and Landsforeningen for hjerte-og lungesyke (project 2011.2.0215), and Liason Committee Central Norway Regional Health Authority-NTNU. NR 41 TC 28 Z9 28 U1 1 U2 20 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD FEB PY 2014 VL 68 IS 2 BP 165 EP 170 DI 10.1136/jech-2013-202587 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286SB UT WOS:000329487900002 PM 24197920 ER PT J AU Kim, GE Seidler, E Kimball, AB AF Kim, G. E. Seidler, E. Kimball, A. B. TI The relative impact of psoriasis and obesity on socioeconomic and medical outcomes in psoriasis patients SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Article ID BODY-MASS INDEX; LIFE QUALITY INDEX; METABOLIC SYNDROME; SUBSTANCE USE; OF-LIFE; DERMATOLOGY; PREVALENCE; OUTPATIENTS; DISORDERS AB BackgroundPsoriasis is a chronic, inflammatory skin disorder that is associated with obesity. Independently, both psoriasis and obesity likely impose impressive physical and psychosocial burdens on affected patients. ObjectiveThe purpose of this study was to evaluate the relative impact of body mass index (BMI) on the socioeconomic status, medical co-morbidities, and current and chronic quality of life of psoriasis patients. MethodsOverall, 114 subjects were examined and asked to complete a self-administered questionnaire regarding disabilities, relationships, education, as well as medical and economic outcomes. Participants also answered the ten questions used in the Dermatology Life Quality Index modified to ask over the last week', over the last year' and over your lifetime with psoriasis'. Survey responses were compared amongst the three patient groups based on BMI (normal, overweight, obese). ResultsPatients with elevated BMI were more likely to rate their general health lower (P<0.001), believe that psoriasis caused their weight gain (P=0.014), experience sleep problems over their lifetime (P=0.016), hide their psoriasis over their lifetime (P=0.010), have their self-confidence affected by their psoriasis over their lifetime (P=0.011) and avoid common activities over their lifetime (P=0.012). ConclusionThere are long-term negative effects of elevated BMI that impose additional burdens on psoriasis patients, including impairments in sleep quality and increased social anxiety. C1 [Kim, G. E.; Kimball, A. B.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Seidler, E.] Emory Univ, Sch Med, Atlanta, GA USA. [Kimball, A. B.] Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin CURTIS, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. EM harvardskinstudies@partners.org FU Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship FX This study was supported in part by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. The funder was not involved in any aspect of the study. NR 25 TC 5 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0926-9959 EI 1468-3083 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD FEB PY 2014 VL 28 IS 2 BP 216 EP 221 DI 10.1111/jdv.12089 PG 6 WC Dermatology SC Dermatology GA 287HI UT WOS:000329532300009 PM 23347229 ER PT J AU Citi, L Ba, D Brown, EN Barbieri, R AF Citi, Luca Ba, Demba Brown, Emery N. Barbieri, Riccardo TI Likelihood Methods for Point Processes with Refractoriness SO NEURAL COMPUTATION LA English DT Article ID NEURAL SPIKING ACTIVITY; TIME-RESCALING THEOREM; PRIMARY MOTOR CORTEX; FUNCTIONAL CONNECTIVITY; STATISTICAL-MODELS; ENCODING MODELS; ENSEMBLE; POPULATION; SYNCHRONY; DESIGN AB Likelihood-based encoding models founded on point processes have received significant attention in the literature because of their ability to reveal the information encoded by spiking neural populations. We propose an approximation to the likelihood of a point-process model of neurons that holds under assumptions about the continuous time process that are physiologically reasonable for neural spike trains: the presence of a refractory period, the predictability of the conditional intensity function, and its integrability. These are properties that apply to a large class of point processes arising in applications other than neuroscience. The proposed approach has several advantages over conventional ones. In particular, one can use standard fitting procedures for generalized linear models based on iteratively reweighted least squares while improving the accuracy of the approximation to the likelihood and reducing bias in the estimation of the parameters of the underlying continuous-time model. As a result, the proposed approach can use a larger bin size to achieve the same accuracy as conventional approaches would with a smaller bin size. This is particularly important when analyzing neural data with high mean and instantaneous firing rates. We demonstrate these claims on simulated and real neural spiking activity. By allowing a substantive increase in the required bin size, our algorithm has the potential to lower the barrier to the use of point-process methods in an increasing number of applications. C1 [Citi, Luca; Ba, Demba; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02129 USA. [Citi, Luca; Ba, Demba; Brown, Emery N.; Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02142 USA. RP Citi, L (reprint author), Univ Essex, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. EM lciti@neurostat.mit.edu; demba@neurostat.mit.edu; enb@neurostat.mit.edu; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833 FU NHLBI NIH HHS [R01-HL084502]; NIH HHS [DP1-OD003646] NR 48 TC 4 Z9 4 U1 0 U2 8 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0899-7667 EI 1530-888X J9 NEURAL COMPUT JI Neural Comput. PD FEB PY 2014 VL 26 IS 2 BP 237 EP 263 DI 10.1162/NECO_a_00548 PG 27 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 284BF UT WOS:000329290300001 PM 24206384 ER PT J AU Gordon, BR AF Gordon, Bruce R. TI Should Vitamin D Supplementation Be a Regular Part of Asthma Care ? SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Vitamin D; Vitamin D3; Calcitriol; Calcidiol; Allergy; Asthma; Hypersensitivity; Immunotherapy ID D DEFICIENCY; 1,25-DIHYDROXYVITAMIN D-3; CARDIOVASCULAR-DISEASE; ALLERGIC-ASTHMA; D HARMFUL; T-CELLS; 25-HYDROXYVITAMIN D; D-RECEPTOR; IMMUNOTHERAPY; EXPRESSION AB Vitamin D (vitD3) deficiency occurs frequently and has profound effects on health, especially asthma. This article examines how current knowledge of vitD3 actions and the worldwide distribution of vitD3 deficiency influences everyday clinical allergy practice. Within the limits of current knowledge, the article concisely explains the molecular nature of vitD3 actions, reviews key vitD3 research as it applies to clinical care, answers questions about the potential clinical impact of low vitD3 levels, and discusses use and safety of vitD3 supplements. C1 [Gordon, Bruce R.] Cape Cod ENT, Hyannis, MA 02601 USA. [Gordon, Bruce R.] Harvard Univ, Boston, MA 02115 USA. [Gordon, Bruce R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Gordon, BR (reprint author), Cape Cod ENT, 65 Cedar St, Hyannis, MA 02601 USA. EM docbruce@comcast.net NR 67 TC 3 Z9 3 U1 0 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD FEB PY 2014 VL 47 IS 1 BP 97 EP + DI 10.1016/j.otc.2013.08.013 PG 13 WC Otorhinolaryngology SC Otorhinolaryngology GA 283OF UT WOS:000329255700011 PM 24286683 ER PT J AU Mai, CL Yaster, M Chu, L Ahmed, Z Firth, PG AF Mai, Christine L. Yaster, Myron Chu, Larry Ahmed, Zulfiqar Firth, Paul G. TI The development of pediatric fluid resuscitation: an interview with Dr. Frederic A. 'Fritz' Berry SO PEDIATRIC ANESTHESIA LA English DT Article DE Frederic A; Berry; pediatric anesthesia; fluid management; balanced electrolyte solution; hyponatremia; seizures; American Society of Anesthesiologists refresher courses ID ANESTHESIA; MANAGEMENT; CHILDREN; NEONATE; THERAPY AB Dr. Frederic A. Fritz' Berry (1935), Professor Emeritus of Anesthesiology and Pediatrics at the University of Virginia, has played a pioneering role in the development of pediatric anesthesiology through training generations of anesthesiologists. He identifies his early advocacy of balanced electrolyte solution for perioperative fluid resuscitation as his defining contribution. Based on his clinical experiences, he pushed to extend the advances in adult fluid resuscitation into pediatric practice. He imparted these and other insights to his colleagues although textbooks, book chapters, original journal publications, and decades of Refresher Course Lectures at the American Society of Anesthesiologists' annual meetings. A model educator, clinician, and researcher, he shaped the careers of hundreds of physicians-in-training while advancing the field of pediatric anesthesiology. C1 [Mai, Christine L.; Firth, Paul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care Med & Pain Med, Boston, MA USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Univ, Dept Anesthesiol, Baltimore, MD USA. [Mai, Christine L.; Firth, Paul G.] Massachusetts Eye & Ear Infirm, Dept Anesthesia, Boston, MA 02114 USA. [Chu, Larry] Stanford Univ, Dept Anesthesia, Stanford Anesthesia Informat & Media Lab, Palo Alto, CA 94304 USA. [Ahmed, Zulfiqar] Wayne State Univ, Anesthesia Associates Ann Arbor, Detroit, MI USA. RP Mai, CL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care Med & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM cmai1@partners.org NR 20 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD FEB PY 2014 VL 24 IS 2 BP 217 EP 223 DI 10.1111/pan.12309 PG 7 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 284FF UT WOS:000329300800014 ER PT J AU Sivendran, S Agarwal, N Gartrell, B Ying, J Boucher, KM Choueiri, TK Sonpavde, G Oh, WK Galsky, MD AF Sivendran, Shanthi Agarwal, Neeraj Gartrell, Benjamin Ying, Jian Boucher, Kenneth M. Choueiri, Toni K. Sonpavde, Guru Oh, William K. Galsky, Matthew D. TI Metabolic complications with the use of mTOR inhibitors for cancer therapy SO CANCER TREATMENT REVIEWS LA English DT Review DE Cancer; mTOR inhibitor; Metabolic; Temsirolimus; Everolimus; Ridaforolimus; Adverse events ID RENAL-CELL CARCINOMA; PHASE-II TRIAL; RECURRENT GLIOBLASTOMA-MULTIFORME; MAMMALIAN TARGET; TEMSIROLIMUS CCI-779; BREAST-CANCER; RAPAMYCIN INHIBITOR; PANCREATIC-CANCER; LUNG-CANCER; DOSE LEVELS AB Background: mTOR inhibitors are now approved by regulatory agencies for the treatment of a variety of malignancies. The risk of metabolic complications with these agents is not well characterized. Methods: PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating temsirolimus, everolimus, and ridaforolimus in patients with all solid tumor malignancies. Sixteen eligible phase II clinical trials and 8 randomized controlled clinical trials were included in a systematic review and meta-analysis and the number of metabolic related AEs (hyperglycemia, hypercholesterolemia, and hypertriglyceridemia) was extracted. Incidence rates and incident rate ratios were calculated. Findings: Twenty-four trials, including 4261 patients, were included in the calculation of the incidence rate. The average incidence rate of all grade metabolic related events was 0.70 (95% CI, 0.47, 0.93). The average incidence rate of serious (grade 3 and 4) metabolic related adverse events was 0.11 (95% CI, 0.08, 0.15). The incidence rate ratio (IRR) of a metabolic adverse event with mTOR inhibitor therapy compared with control was 2.93 (95% CI, 2.33, 3.70) and of serious grade 3 and 4 metabolic adverse events was 4.58 (95% CI, 2.86, 7.34). The IRR of all grade hyperglycemia was 2.95 (95% CI, 2.14, 4.05) and of grade 3-4 hyperglycemia was 5.25 (95% CI, 3.07, 9.00). The IRR of all grade hypertriglyceridemia was 2.49 (95% CI, 1.76, 3.52) and of grade 3-4 hypertriglyceridemia was 2.01 (95% CI, 0.65, 6.27). The IRR of all grade hypercholesterolemia was 3.35 (95% CI, 2.17, 5.18) and of grade 3-4 hypercholesterolemia was 6.51 (95% CI, 1.48, 28.59). These findings suggest a statistically significant increase in the risk of hyperglycemia, hypercholesterolemia (all grades and grade 3 and 4), and all grade hypertriglyceridemia associated with mTOR therapy when compared with control. Interpretation: The risk of all grade and grade 3-4, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia, are increase in patients treated with mTOR inhibitors compared with control. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Sivendran, Shanthi] Lancaster Gen Hlth, Lancaster, PA USA. [Agarwal, Neeraj] Univ Utah, Sch Med, Div Hematol Oncol, Salt Lake City, UT 84112 USA. [Agarwal, Neeraj; Ying, Jian; Boucher, Kenneth M.] Huntsman Canc Inst, Salt Lake City, UT USA. [Gartrell, Benjamin] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Med Oncol, Bronx, NY 10467 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA USA. [Sonpavde, Guru] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA. [Oh, William K.; Galsky, Matthew D.] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol Oncol, New York, NY USA. RP Galsky, MD (reprint author), Mt Sinai Sch Med, Mt Sinai Med Ctr, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM matthew.galsky@mssm.edu OI Boucher, Kenneth/0000-0003-2833-0127 FU NCI NIH HHS [R21 CA176551] NR 31 TC 24 Z9 25 U1 1 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 EI 1532-1967 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD FEB PY 2014 VL 40 IS 1 BP 190 EP 196 DI 10.1016/j.ctrv.2013.04.005 PG 7 WC Oncology SC Oncology GA 278EF UT WOS:000328871200020 PM 23684373 ER PT J AU Klein, L Hsia, H AF Klein, Liviu Hsia, Henry TI Sudden Cardiac Death in Heart Failure SO CARDIOLOGY CLINICS LA English DT Article DE Heart failure; Implantable cardiac defibrillators; Ischemic heart disease; Nonischemic cardiomyopathy; Sudden death; Ventricular tachycardia ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; SIGNAL-AVERAGED ELECTROCARDIOGRAM; RANDOMIZED INTERVENTION TRIAL; ANTIARRHYTHMIC-DRUG THERAPY; T-WAVE ALTERNANS; EJECTION FRACTION; UNEXPECTED DEATH; RATE-VARIABILITY AB Sudden cardiac deaths account for 350,000 to 380,000 deaths in the United States annually. Implantable cardioverter-defibrillators have improved sudden death outcomes in patients with heart failure, but only a minority of patients with defibrillators receives appropriate therapy for ventricular arrhythmias. The risk prediction for sudden death and selection of patients for defibrillators is based largely on left ventricular ejection fraction and heart failure symptoms because there are no other risk stratification tools that can determine the individual patients who will derive the greatest benefit. There are several other pharmacologic strategies designed to prevent sudden death in patients with heart failure. C1 [Klein, Liviu] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [Hsia, Henry] Univ Calif San Francisco, Div Cardiol, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Hsia, H (reprint author), Univ Calif San Francisco, Div Cardiol, San Francisco Vet Affairs Med Ctr, Bldg 203,111C-6,Room 2A-52A,4150 Clement St, San Francisco, CA 94121 USA. EM henry.hsia@ucsf.edu FU St. Jude Medical; Medtronic, Inc FX Liviu Klein is a consultant for Boston Scientific, and Zoll Medical; and has received research grants from St. Jude Medical. Henri Hsia is a consultant for Vytron US, Inc; is on the Advisory Board for Biosense Webster, Medtronic, Inc; and has received research support from Medtronic, Inc. NR 71 TC 1 Z9 1 U1 3 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 EI 1558-2264 J9 CARDIOL CLIN JI Cardiol. Clin. PD FEB PY 2014 VL 32 IS 1 BP 135 EP + DI 10.1016/j.ccl.2013.09.008 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 281GD UT WOS:000329087100012 PM 24286584 ER PT J AU Corey, KE Kaplan, LM AF Corey, Kathleen E. Kaplan, Lee M. TI Obesity and Liver Disease The Epidemic of the Twenty-First Century SO CLINICS IN LIVER DISEASE LA English DT Article DE Obesity; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Cirrhosis; Weight loss; Fat mass; Energy balance ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; CHRONIC HEPATITIS-C; Y GASTRIC BYPASS; WEIGHT-LOSS; FATTY LIVER; NONALCOHOLIC STEATOHEPATITIS; HEPATOCELLULAR-CARCINOMA; BARIATRIC SURGERY AB Obesity is a rapidly growing health problem that is associated with more than 65 comorbidities and results in substantially increased all-cause mortality. The increase of obesity has played an important role in the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in the United States. Understanding the prevalence, comorbidities, and pathogenesis of obesity provides an essential foundation for clinicians who care for individuals with NAFLD. C1 [Corey, Kathleen E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Weight Ctr, Boston, MA 02114 USA. [Kaplan, Lee M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Weight Ctr Obes Metab & Nut, Charlestown, MA 02129 USA. RP Kaplan, LM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Weight Ctr Obes Metab & Nut, 149 13th St,Room 8219, Charlestown, MA 02129 USA. EM LMKaplan@partners.org RI Cirino, Ana/B-3797-2014 FU NIDDK NIH HHS [K23 DK099422, P30 DK040561] NR 85 TC 26 Z9 26 U1 1 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1089-3261 EI 1557-8224 J9 CLIN LIVER DIS JI Clin. Liver Dis. PD FEB PY 2014 VL 18 IS 1 BP 1 EP + DI 10.1016/j.cld.2013.09.019 PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 278VL UT WOS:000328917900002 PM 24274861 ER PT J AU Millard, SP Lutz, F Li, G Galasko, DR Farlowg, MR Quinn, JF Kaye, JA Leverenz, JB Tsuang, D Yu, CE Peskind, ER Bekris, LM AF Millard, Steven P. Lutz, Franziska Li, Ge Galasko, Douglas R. Farlowg, Martin R. Quinn, Joseph F. Kaye, Jeffrey A. Leverenz, James B. Tsuang, Debby Yu, Chang-En Peskind, Elaine R. Bekris, Lynn M. TI Association of cerebrospinal fluid A beta(42) with A2M gene in cognitively normal subjects SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Cerebrospinal fluid; A beta(42); alpha-2-Macroglobulin; A2M; APOE ID ARGYROPHILIC GRAIN DISEASE; BETA-SECRETASE ACTIVITY; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; AMYLOID FORMATION; GAMMA-SECRETASE; ALPHA-2-MACROGLOBULIN GENE; CLINICAL-DIAGNOSIS; PLASMA BIOMARKERS; CANDIDATE GENES AB Low cerebrospinal fluid (CSF) A beta(42) levels correlate with increased brain Ab deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Ab from the brain. In addition, APOE epsilon 4 carriers have lower CSF A beta(42) levels than non-carriers. The hypothesis of this investigation was that CSF A beta(42) levels would correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Ab from the brain. CSF A beta(42) levels were tested for associations with Ab degradation and clearance genes and APOE epsilon 4. Twenty-four SNPs located within the 5' and 3' regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF A beta(42) levels were associated with APOE epsilon 4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF A beta(42) levels in controls but not in AD patients, even after adjusting for APOE epsilon 4. These results suggest that genetic variation within the A2M gene influences CSF A beta(42) levels. (C) 2014 Elsevier Inc. All rights reserved. C1 [Millard, Steven P.; Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, Northwest Network VISN Mental Illness Res Educ &, Seattle, WA 98108 USA. [Lutz, Franziska; Tsuang, Debby; Yu, Chang-En; Bekris, Lynn M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Lutz, Franziska; Yu, Chang-En; Bekris, Lynn M.] Univ Washington, Dept Med, Seattle, WA USA. [Li, Ge; Leverenz, James B.; Tsuang, Debby; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Galasko, Douglas R.] VA Med Ctr San Diego, San Diego, CA USA. [Farlowg, Martin R.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Quinn, Joseph F.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Quinn, Joseph F.; Kaye, Jeffrey A.] Portland VA Med Ctr, Portland, OR USA. [Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Northwest Network VISN Parkinsons Dis Res Educ &, Seattle, WA 98108 USA. RP Millard, SP (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-116 MIRECC, Seattle, WA 98108 USA. EM SteveMillard@comcast.net RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Kaye, Jeffrey/0000-0002-9971-3478 FU US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program [1101BX000531]; National Institute of Health [NS48595, NS065070, NS062684, AG06781, AG10845, AG05136, AG05133, AG028383, AG008017, AG027224, AG10124, AG030653, K99 AG034214/5 R00 AG034214] FX This material is based on work supported in part by the US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program (Merit Review 1101BX000531). It is also supported by National Institute of Health grants NS48595, NS065070, NS062684, AG06781, AG10845, AG05136, AG05133, AG028383, AG008017, AG027224, AG10124, AG030653, and K99 AG034214/5 R00 AG034214. NR 66 TC 2 Z9 2 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2014 VL 35 IS 2 BP 357 EP 364 DI 10.1016/j.neurobiolaging.2013.07.027 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 275DD UT WOS:000328655600010 PM 24011543 ER PT J AU Stewart, T Sui, YT Gonzalez-Cuyar, LF Wong, DTW Akin, DM Tumas, V Aasly, J Ashmore, E Aro, P Ginghina, C Korff, A Zabetian, CP Leverenz, JB Shi, M Zhang, J AF Stewart, Tessandra Sui, Yu-Ting Gonzalez-Cuyar, Luis F. Wong, David T. W. Akin, David M. Tumas, Vitor Aasly, Jan Ashmore, Emily Aro, Patrick Ginghina, Carmen Korff, Ane Zabetian, Cyrus P. Leverenz, James B. Shi, Min Zhang, Jing TI Cheek cell-derived alpha-synuclein and DJ-1 do not differentiate Parkinson's disease from control SO NEUROBIOLOGY OF AGING LA English DT Article DE Parkinson's disease; Neurodegeneration; Movement disorder; alpha-Synuclein; DJ-1; Saliva; Biomarker AB Recently, alpha-synuclein (alpha-syn) and DJ-1, 2 proteins critically involved in Parkinson's disease (PD), have been shown to be present in saliva, suggesting their potential utility as biomarkers of PD. However, the origin and influence of demographic characteristics (e.g., age or sex) on these proteins are unknown. We identified cheek epithelium, which forms the majority of the cellular component of saliva and is readily accessible clinically, as 1 of several potential sources of salivary alpha-syn and DJ-1. However, no PD-related trend in the cellular component was present. In the supernatant collected from 198 healthy subjects, no correlation was seen between salivary DJ-1 or alpha-syn with age. When male and female subjects were analyzed separately, a weak age-dependent increase in DJ-1 level was present in male subjects, along with slightly increased alpha-syn in female subjects. These results, albeit largely negative, provide critical information for understanding the salivary gland pathology and saliva as a PD biomarker source, and must be considered in future investigations of salivary changes in PD. (C) 2014 Elsevier Inc. All rights reserved. C1 [Stewart, Tessandra; Sui, Yu-Ting; Gonzalez-Cuyar, Luis F.; Aro, Patrick; Ginghina, Carmen; Korff, Ane; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Wong, David T. W.; Akin, David M.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA. [Ashmore, Emily; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Shi, Min] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Shi, Min] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Tumas, Vitor] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurosci & Behav, Sao Paulo, Brazil. [Aasly, Jan] St Olavs Univ Hosp, Dept Neurol, Trondheim, Norway. RP Zhang, J (reprint author), Univ Washington, Sch Med, Harborview Med Ctr, Div Neuropathol, Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM zhangj@u.washington.edu RI Shi, Min/G-6165-2012; Tumas, Vitor/C-9949-2014 OI Shi, Min/0000-0002-6901-2558; FU Michael J. Fox Foundation; National Institutes of Health [AG033398, ES004696, 5897, ES007033, 6364, ES016873, ES019277, 02S1, NS057567, NS062684, 6221, NS065070, NS082137, T32ES015459]; National Institute of Neurological Disorders and Stroke [U24 NS072026]; National Institute on Aging [P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001] FX We thank all subjects for the generous donation of their time and the samples used in this study. We also appreciate the staff of the autopsy service affiliated with the University of Washington for their efforts in contributing cheek and submandibular gland samples. The research is supported by generous funds from the Michael J. Fox Foundation and from the National Institutes of Health (AG033398, ES004696 (subaward 5897), ES007033 (subaward 6364), ES016873, ES019277 (subaward 02S1), NS057567, NS062684 (subaward 6221), NS065070, NS082137, and T32ES015459). We are grateful to the Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona for providing human submandibular gland tissue. The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901, and 1001 to the Arizona Parkinson's Disease Consortium), The KS Ervik Donation, Norway, and the Michael J. Fox Foundation for Parkinson's Research. NR 5 TC 6 Z9 7 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2014 VL 35 IS 2 BP 418 EP 420 DI 10.1016/j.neurobiolaging.2013.08.008 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 275DD UT WOS:000328655600017 PM 24041968 ER PT J AU Tranah, GJ Yokoyama, JS Katzman, SM Nalls, MA Newman, AB Harris, TB Cesari, M Manini, TM Schork, NJ Cummings, SR Liu, Y Yaffe, K AF Tranah, Gregory J. Yokoyama, Jennifer S. Katzman, Shana M. Nalls, Michael A. Newman, Anne B. Harris, Tamara B. Cesari, Matteo Manini, Todd M. Schork, Nicholas J. Cummings, Steven R. Liu, Yongmei Yaffe, Kristine CA Hlth Aging and Body Composition TI Mitochondrial DNA sequence associations with dementia and amyloid-beta in elderly African Americans SO NEUROBIOLOGY OF AGING LA English DT Article DE Dementia; Mitochondria; mtDNA; Amyloid-beta; Oxidative stress ID ALPHA-KETOGLUTARATE DEHYDROGENASE; ACTIVITY ENERGY-EXPENDITURE; MILD COGNITIVE IMPAIRMENT; AMINO-ACID SUBSTITUTIONS; INDUCED OXIDATIVE STRESS; GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; CALORIE RESTRICTION; BODY-COMPOSITION; POINT MUTATIONS AB Mitochondrial dysfunction occurs early in the course of several neurodegenerative diseases, and is potentially related to increased oxidative damage and amyloid-beta (A beta) formation in Alzheimer's disease. The goals of this study were to assess mtDNA sequence associations with dementia risk, 10-year cognitive change, and markers of oxidative stress and A beta among 1089 African-Americans in the population-based Health, Aging, and Body Composition Study. Participants were free of dementia at baseline, and incidence was determined in 187 (18%) cases over 10 to 12 follow-up years. Haplogroup L1 participants were at increased risk for developing dementia (odds ratio = 1.88, 95% confidence interval = 1.23-2.88, p = 0.004), lower plasma A beta 42 levels (p = 0.03), and greater 10-year decline on the Digit Symbol Substitution Test (p = 0.04) when compared with common haplogroup L3. The p.V193I, ND2 substitution was associated with significantly higher A beta 42 levels (p = 0.0012), and this association was present in haplogroup L3 (p = 0.018) but not L1 (p = 0.90) participants. All associations were independent of potential confounders, including APOE epsilon 4 status and nuclear genetic ancestry. Identification of mtDNA sequence variation associated with dementia risk and cognitive decline may contribute to the development of new treatment targets and diagnostic tests that identify responders to interventions targeting mitochondria. (C) 2014 Published by Elsevier Inc. C1 [Tranah, Gregory J.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst San Francisco, San Francisco, CA USA. [Yokoyama, Jennifer S.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Katzman, Shana M.] Buck Inst Res Aging, Novato, CA USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Cesari, Matteo] Ctr Hospitalier Univ Toulouse, INSERM UMR 1027, Gerontopole, Toulouse, France. [Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Schork, Nicholas J.] Scripps Translat Sci Inst, La Jolla, CA USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Tranah, GJ (reprint author), UCSF, San Francisco Coordinating Ctr, Res Inst, Calif Pacific Med Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM gtranah@sfcc-cpmc.edu RI Cesari, Matteo/A-4649-2008; Newman, Anne/C-6408-2013 OI Cesari, Matteo/0000-0002-0348-3664; Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, R03-AG032498, 1R01AG032098-01A1]; NINR grant [R01-NR012459, Z01AG000951]; Intramural Research Program of the NIH, National Institute on Aging; National Institutes of Health [HHSN268200782096C] FX This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grants R01-AG028050 and R03-AG032498, NINR grant R01-NR012459; and Z01AG000951. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to Johns Hopkins University, contract number HHSN268200782096C. Data analyses for this study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 120 TC 6 Z9 6 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2014 VL 35 IS 2 AR 442.e1 DI 10.1016/j.neurobiolaging.2013.05.023 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 275DD UT WOS:000328655600020 PM 24140124 ER PT J AU Dietrich, J Klein, JP AF Dietrich, Joerg Klein, Joshua P. TI Imaging of Cancer Therapy-Induced Central Nervous System Toxicity SO NEUROLOGIC CLINICS LA English DT Article DE Neurotoxicity; Cancer; Chemotherapy; Radiation therapy; Central nervous system; Imaging ID CEREBRAL WHITE-MATTER; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; BRAIN; SURVIVORS; RADIONECROSIS; PATTERNS; GLIOMA; GRAY AB Cancer therapy, including radiation and chemotherapy, can be associated with harmful effects to the central nervous system. Recognition of classical neurotoxic syndromes is critical to appropriately guide and optimize patient management. As a result of cancer therapy-induced toxicity, patients may present with acute, subacute, and chronic neurologic symptoms that can be misinterpreted as tumor recurrence, infection, or paraneoplastic syndromes. In this review the advantages and limitations of various neuroimaging modalities such as computed tomography, magnetic resonance imaging, and positron emission tomography, frequently used in patients with cancer who present with diverse neurotoxic syndromes, are highlighted. C1 [Dietrich, Joerg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Canc Ctr,Dept Neurol,Div Neuroo, Boston, MA 02114 USA. [Klein, Joshua P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Dietrich, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Canc Ctr,Dept Neurol,Div Neuroo, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM Dietrich.Jorg@mgh.harvard.edu; jpklein@partners.org FU American Academy of Neurology Foundation; American Cancer Society; Stephen E. and Catherine Pappas Center Research Foundation FX The authors gratefully acknowledge the support of the American Academy of Neurology Foundation (J. Dietrich), the American Cancer Society (J. Dietrich), and the Stephen E. and Catherine Pappas Center Research Foundation (J. Dietrich). J. Dietrich is a Fellow of the Clinical Investigator Training Program (CITP) at Harvard Medical School. NR 29 TC 1 Z9 1 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 EI 1557-9875 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 2014 VL 32 IS 1 BP 147 EP + DI 10.1016/j.ncl.2013.07.004 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 278VI UT WOS:000328917600007 PM 24287388 ER PT J AU Meier, RH Heckman, JT AF Meier, Robert H., III Heckman, Jeffrey T. TI Principles of Contemporary Amputation Rehabilitation in the United States, 2013 SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Amputation; Rehabilitation; Veterans Health Administration; Follow-up care AB Providing rehabilitation services for the person with an amputation has become more difficult in today's health care environment. Amputation rehabilitation calls for specialized, multidisciplinary rehabilitation training. In examining the principles of amputation rehabilitation, one must understand the lessons learned from the Veterans Affairs Amputation System of Care and return to the founding principles of rehabilitation medicine. Persons with amputations must be reevaluated in a tight program of follow-up care. C1 [Meier, Robert H., III] Amputee Serv Amer, Denver, CO USA. [Heckman, Jeffrey T.] Univ Washington, Seattle Div, VA Puget Sound Hlth Care Syst,RAC, Dept Rehabil Med, Seattle, WA 98108 USA. RP Meier, RH (reprint author), Amputee Serv Amer, Denver, CO USA. EM skipdoc3@gmail.com NR 7 TC 1 Z9 1 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 EI 1558-1381 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD FEB PY 2014 VL 25 IS 1 BP 29 EP + DI 10.1016/j.pmr.2013.09.004 PG 7 WC Rehabilitation SC Rehabilitation GA 278UV UT WOS:000328916300005 PM 24287237 ER PT J AU Fagenholz, PJ de Moya, MA AF Fagenholz, Peter J. de Moya, Marc A. TI Acute Inflammatory Surgical Disease SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Appendicitis; Cholecystitis; Cholangitis; Pancreatitis; Diverticulitis; Clostridium difficile; Colitis ID CLOSTRIDIUM-DIFFICILE INFECTION; RANDOMIZED CONTROLLED-TRIAL; SEVERE ACUTE-PANCREATITIS; MILD ACUTE-PANCREATITIS; HIGH-RISK PATIENTS; BILE-DUCT STONES; NECROTIZING PANCREATITIS; UNITED-STATES; CLINICAL-TRIAL; DIVERTICULAR-DISEASE AB Infectious and inflammatory diseases comprise some of the most common gastrointestinal disorders resulting in hospitalization in the United States. Accordingly, they occupy a significant proportion of the workload of the acute care surgeon. This article discusses the diagnosis, management, and treatment of appendicitis, acute cholecystitis/cholangitis, acute pancreatitis, diverticulitis, and Clostridium difficile colitis. C1 [Fagenholz, Peter J.; de Moya, Marc A.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,CPZ 810, Boston, MA 02114 USA. EM pfagenholz@partners.org NR 97 TC 5 Z9 5 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2014 VL 94 IS 1 BP 1 EP + DI 10.1016/j.suc.2013.10.008 PG 31 WC Surgery SC Surgery GA 278VO UT WOS:000328918200003 PM 24267493 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Acute Care Surgery: From De Novo to De Facto Preface SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Editorial Material ID EMERGENCY; PERSPECTIVE; FUTURE; TRAUMA; IMPACT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 12 TC 0 Z9 0 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 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2014 VL 94 IS 1 BP XIII EP XV DI 10.1016/j.suc.2013.10.014 PG 3 WC Surgery SC Surgery GA 278VO UT WOS:000328918200002 PM 24267507 ER PT J AU Yeh, DD Alam, HB AF Yeh, D. Dante Alam, Hasan B. TI Hernia Emergencies SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Hernia; Emergencies; Acute care surgery ID ABDOMINAL-WALL DEFECTS; Y GASTRIC BYPASS; RANDOMIZED CLINICAL-TRIAL; ACELLULAR DERMAL MATRIX; SMALL-BOWEL OBSTRUCTION; MULTIDETECTOR COMPUTED-TOMOGRAPHY; COMPLICATED UMBILICAL HERNIAS; PROSTHETIC MESH REPAIR; LINEA ARCUATA HERNIA; LIFE-TABLE ANALYSIS AB Hernia emergencies are commonly encountered by the acute care surgeon. Although the location and contents may vary, the basic principles are constant: address the life-threatening problem first, then perform the safest and most durable hernia repair possible. Mesh reinforcement provides the most durable long-term results. Underlay positioning is associated with the best outcomes. Components separation is a useful technique to achieve tension-free primary fasciaL reapproximation. The choice of mesh is dictated by the degree of contamination. Internal herniation is rare, and preoperative diagnosis remains difficult. In all hernia emergencies, morbidity is high, and postoperative wound complications should be anticipated. C1 [Yeh, D. Dante] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Alam, Hasan B.] Univ Michigan Hlth Syst, Dept Surg, Ann Arbor, MI 48109 USA. RP Yeh, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM DYEH2@PARTNERS.ORG NR 166 TC 1 Z9 2 U1 2 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 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2014 VL 94 IS 1 BP 97 EP + DI 10.1016/j.suc.2013.10.009 PG 36 WC Surgery SC Surgery GA 278VO UT WOS:000328918200011 PM 24267501 ER PT J AU Kaafarani, HMA King, DR AF Kaafarani, Haytham M. A. King, David R. TI Necrotizing Skin and Soft Tissue Infections SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Necrotizing skin and soft tissue infection (NSSTI); Necrotizing fasciitis; Gas gangrene; Fournier's gangrene; Wide local debridement ID LABORATORY RISK INDICATOR; TOXIC-SHOCK-SYNDROME; HYPERBARIC-OXYGEN; LRINEC SCORE; FASCIITIS; IMMUNOGLOBULIN; MANAGEMENT; THERAPY; GUIDELINES; MORTALITY AB Necrotizing skin and soft tissue infections are severe bacterial infections resulting in rapid and life-threatening soft tissue destruction and necrosis along soft tissue planes. C1 [Kaafarani, Haytham M. A.; King, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hkaafarani@partners.org OI King, David/0000-0003-1028-1478 NR 17 TC 1 Z9 1 U1 2 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2014 VL 94 IS 1 BP 155 EP + DI 10.1016/j.suc.2013.10.011 PG 10 WC Surgery SC Surgery GA 278VO UT WOS:000328918200013 PM 24267503 ER PT J AU O'Malley, DP Zuckerberg, L Smith, LB Barry, TS Gunn, S Tam, W Orazi, A Kim, YS Weiss, LM AF O'Malley, Dennis P. Zuckerberg, Lawrence Smith, Lauren B. Barry, Todd S. Gunn, Shelly Tam, Wayne Orazi, Attilio Kim, Young S. Weiss, Lawrence M. TI The genetics of interdigitating dendritic cell sarcoma share some changes with Langerhans cell histiocytosis in select cases SO ANNALS OF DIAGNOSTIC PATHOLOGY LA English DT Article DE Interdigitating dendritic cell sarcoma; Genetics; Array comparative genomic hybridization; Langerhans cell histiocytosis ID LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA; DIFFERENTIATION; TRANSFORMATION; INVOLVEMENT; MALIGNANCY; MUTATIONS; PRECURSOR; DISEASE; TUMORS; NODE AB Histiocytic disorders have been noted to have evidence of transdifferentiation; examples of cases with combinations of different lineages have been shown. In our index case, we identified interdigitating dendritic cell (IDC) differentiation in a case of Langerhans cell histiocytosis (LCH). Little is currently known about the genetics of IDC sarcoma (IDCS) because they are exceedingly rare. Using array comparative genomic hybridization (aCGH), we evaluated 4 cases of IDCS and compared them with our index case, as well as genetic abnormalities previously found in LCH. Four cases of paraffin-embedded samples of IDCS and 1 case of LCH with IDC differentiation were evaluated using aCGH. Array CGH results showed no abnormalities in a case of LCH with interdigitating cell differentiation. In 3 of 4 cases of IDCS, genetic abnormalities were identified; 1 case had no identifiable abnormalities. Interdigitating dendritic cell sarcoma case 1 had gains of 3q and 13q; IDCS case 2 had trisomy 12; IDCS case 3 had deletions of 7p, 12p, 16p, 18q, 19q, and 22q; and IDCS case 4 had no detectable abnormalities. Our index case, LCH with IDC differentiation, showed no abnormalities by aCGH. A number of LCH cases do not have detectable genetic abnormalities. In contrast, 3 of 4 cases of IDCS evaluated had identifiable abnormalities by aCGH. Furthermore, 2 of these shared abnormalities, albeit of large genetic regions, with published abnormalities seen in LCH. No recurrent abnormalities were identified in the IDCS cases. However, the possibility of a relationship between IDCS and LCH cannot be entirely excluded by these results. (C) 2014 Elsevier Inc. All rights reserved. C1 [O'Malley, Dennis P.; Weiss, Lawrence M.] Clarient GE Healthcare, Aliso Viejo, CA 92656 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zuckerberg, Lawrence] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Lauren B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Barry, Todd S.] Spectrum Pathol, Mission Viejo, CA USA. [Gunn, Shelly] Oncopath Labs, San Antonio, TX USA. [Tam, Wayne; Orazi, Attilio] Weill Cornell Med Coll, New York, NY USA. [Kim, Young S.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP O'Malley, DP (reprint author), Clarient GE Healthcare, Aliso Viejo, CA 92656 USA. EM domalley@clarientinc.com; lzucker@partners.org; lbsmith@umich.edu; tsbarry@mac.com; shelly.gunn@stoh.com; wtam@med.cornell.edu; Ato9002@med.cornell.edu; yokim@coh.org; lweiss@clarientinc.com NR 30 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1092-9134 EI 1532-8198 J9 ANN DIAGN PATHOL JI Ann. Diagn. Pathol. PD FEB PY 2014 VL 18 IS 1 BP 18 EP 20 DI 10.1016/j.anndiagpath.2013.10.003 PG 3 WC Pathology SC Pathology GA 275DM UT WOS:000328656500005 PM 24321462 ER PT J AU Levitsky, LL AF Levitsky, Lynne L. TI Endocrinology, epigenetics, and environment SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Editorial Material C1 [Levitsky, Lynne L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Div Pediat Endocrinol, Boston, MA USA. RP Levitsky, LL (reprint author), Massachusetts Gen Hosp, 5th Floor,175 Cambridge St, Boston, MA 02114 USA. EM LLevitsky@partners.org NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2014 VL 21 IS 1 BP 28 EP 29 DI 10.1097/MED.0000000000000036 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 276IW UT WOS:000328745000006 PM 24300741 ER PT J AU Singhal, V Misra, M Klibanski, A AF Singhal, Vibha Misra, Madhusmita Klibanski, Anne TI Endocrinology of anorexia nervosa in young people: recent insights SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE bone microarchitecture; bone strength; brown adipose tissue; eating disorders; marrow fat ID BONE-MINERAL DENSITY; PHYSIOLOGICAL ESTROGEN REPLACEMENT; DOSE TRANSDERMAL TESTOSTERONE; PREADIPOCYTE FACTOR-I; NORMAL-WEIGHT WOMEN; ADOLESCENT GIRLS; GROWTH-HORMONE; SECRETORY DYNAMICS; MARROW FAT; HYPOTHALAMIC AMENORRHEA AB Purpose of reviewAnorexia nervosa is among the most prevalent chronic medical conditions in young adults. It has acute as well as long-term consequences, some of which, such as low bone mineral density (BMD), are not completely reversible even after weight restoration. This review discusses our current understanding of endocrine consequences of anorexia nervosa.Recent findingsAnorexia nervosa is characterized by changes in multiple neuroendocrine axes including acquired hypogonadotropic hypogonadism, growth hormone resistance with low insulin-like growth factor-1 (likely mediated by fibroblast growth factor-1), relative hypercortisolemia, alterations in adipokines such as leptin, adiponectin and resistin, and gut peptides including ghrelin, PYY and amylin. These changes in turn contribute to low BMD. Studies in anorexia nervosa have demonstrated abnormalities in bone microarchitecture and strength, and an association between increased marrow fat and decreased BMD. One study in adolescents reported an improvement in BMD following physiologic estrogen replacement, and another in adults demonstrated improved BMD following risedronate administration. Brown adipose tissue is reduced in anorexia nervosa, consistent with an adaptive response to the energy deficit state.SummaryAnorexia nervosa is associated with widespread physiologic adaptations to the underlying state of undernutrition. Hormonal changes in anorexia nervosa affect BMD adversely. Further investigation is underway to optimize therapeutic strategies for low BMD. C1 [Singhal, Vibha; Misra, Madhusmita] Harvard Univ, Sch Med, Pediat Endocrine Unit, Boston, MA USA. [Misra, Madhusmita; Klibanski, Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. EM mmisra@partners.org FU NIH [1 R01 HD060827, 1 K24 HD071843-01A1, 5 UL1 RR025758, 2 RO1 DK062249] FX This work was supported in part by NIH Grants 1 R01 HD060827, 1 K24 HD071843-01A1, 5 UL1 RR025758 and 2 RO1 DK062249. NR 86 TC 7 Z9 7 U1 1 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2014 VL 21 IS 1 BP 64 EP 70 DI 10.1097/MED.0000000000000026 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 276IW UT WOS:000328745000012 PM 24275621 ER PT J AU Swennes, AG Turk, ML Trowel, EM Cullin, C Shen, ZL Pang, J Petersson, KH Dewhirst, FE Fox, JG AF Swennes, Alton G. Turk, Michelle L. Trowel, Elise M. Cullin, Cassandra Shen, Zeli Pang, Jassia Petersson, Katherine H. Dewhirst, Floyd E. Fox, James G. TI Helicobacter canis Colonization in Sheep: A Zoonotic Link SO HELICOBACTER LA English DT Article DE Helicobacter infections; sheep diseases; zoonoses ID PYLORI INFECTION; BACTEREMIA; HEPATITIS; MICE; PATIENT; PREVALENCE; CELLULITIS; SHEPHERDS; BACTERIUM; ABORTION AB BackgroundHelicobacter canis has been associated with hepatobiliary and gastrointestinal disease in dogs, cats, and humans. Infection has not been documented in other species. Materials and MethodsSheep feces subjected to microaerobic culture. Isolates were characterized by genus-specific PCR, restriction fragment length polymorphism, biochemical profiling, and 16S rRNA sequence analysis. ResultsHelicobacter canis was isolated from sheep feces and confirmed by the above methods. These isolates are distinct from other sheep-origin enterohepatic Helicobacter species previously isolated. ConclusionsThis study identifies sheep as H. canis reservoirs potentially important in zoonotic or foodborne transmission. C1 [Swennes, Alton G.; Turk, Michelle L.; Trowel, Elise M.; Cullin, Cassandra; Shen, Zeli; Pang, Jassia; Fox, James G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Petersson, Katherine H.] Univ Rhode Isl, Dept Fisheries Anim & Vet Sci, Kingston, RI 02881 USA. [Dewhirst, Floyd E.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Swennes, AG (reprint author), Baylor Coll Med, Ctr Comparat Med, 1 Baylor Plaza, Houston, TX 77030 USA. EM swennes@bcm.edu FU NIH [T32 OD010978, R01 OD011141, P01 CA028842, P30 ES02109] FX This work was supported by NIH T32 OD010978, NIH R01 OD011141, NIH P01 CA028842, and NIH P30 ES02109. NR 26 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-4389 EI 1523-5378 J9 HELICOBACTER JI Helicobacter PD FEB PY 2014 VL 19 IS 1 BP 65 EP 68 DI 10.1111/hel.12097 PG 4 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 276GG UT WOS:000328736100008 PM 24188726 ER PT J AU Dorji, D Dendup, T Malaty, HM Wangchuk, K Yangzom, D Richter, JM AF Dorji, Dorji Dendup, Tashi Malaty, Hoda M. Wangchuk, Kinley Yangzom, Deki Richter, James M. TI Epidemiology of Helicobacter pylori in Bhutan: The Role of Environment and Geographic Location SO HELICOBACTER LA English DT Article DE Helicobacter pylori; epidemiology; Bhutan ID SOCIOECONOMIC-STATUS; GASTRIC-CANCER; RISK-FACTORS; INFECTION; POPULATION; ACQUISITION; PREVALENCE; AGE; IDENTIFICATION; TRANSMISSION AB BackgroundBhutan is small mountainous country bordering India and China and consists of four geographic regions, west, east, central, and south. The epidemiology of Helicobacter pylori infection and risk factors associated with in Bhutan are not previously studied. The World Health Organization reported the incidence of stomach cancer to be very high in Bhutan. AimWe conducted a cross-sectional study to determine the seroepidemiologic pattern of H.pylori among Bhutanese from the four regions with emphasis on water source and household sanitation. MethodsBetween June and November 2012, blood samples from patients with complaints of dyspepsia were collected after obtaining an informed consent. Demographic information, occupation, family size living in the same household, consumption of betel nut, and aspects of household environment including type of latrines, source of drinking water were collected. All serum samples were tested for H.pylori immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA) using MAGIWELL ELISA kit from United Biotech, USA. ResultsTwo hundred and forty-four patients between 17 and 75years of age participated in the study, of them, 102 were men, and the mean age was 38 (14.2) years. The overall prevalence of H.pylori among patients was 86% with no difference between men and women (90 vs 83%, respectively, p=.12). The prevalence was almost identical among all age groups: 81% at 17-20, 84% at 20-29, 93% at 30-39, 82% at 40-49, 87% at 50-59, and 82% at 60years (p=.51). H.pylori prevalence was lower in the southern region of Bhutan (78%) compared with the central region (97%) (OR=8.6; 95% CI=1.1-55; p=.02), eastern region (91%) (OR=2.7; 95% CI=1.1-7.2, p=.004) or the western region (83%) (OR=1.4, 95% CI=0.8-3.1, p=.07). The prevalence of H.pylori was significantly lower among household with less than 4 persons living in the same household. Source of drinking water, type of occupation, type of latrines, or consumption of betel nut showed no association with H.pylori prevalence. Logistic regression analysis revealed that residing region was the only significant variable. ConclusionsThe high prevalence of antibodies to H.pylori among patients and in all groups could contribute to the high incident rate of gastric cancer in Bhutan. Crowded living condition and the residing region contribute to the variation of the prevalence of the infection. The lowest prevalence in southern part of the country could be due to the difference in the ethnicity as most of its population is of Indian and Nepal origin. Further data regarding H.pylori in Bhutan are critical to developing surveillance and prevention strategies for gastric cancer. C1 [Dorji, Dorji; Wangchuk, Kinley; Yangzom, Deki] Jigme Dorji Wangchuck Natl Referral Hosp, Dept Lab Med, Microbiol Unit, Thimphu, Bhutan. [Dendup, Tashi] Jigme Dorji Wangchuck Natl Referral Hosp, Dept Surg, Thimphu, Bhutan. [Malaty, Hoda M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Richter, James M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Gastroenterol Associates, Boston, MA USA. RP Malaty, HM (reprint author), Vet Affairs Med Ctr 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Hmalaty@bcm.edu OI Yangzom, Deki/0000-0002-3791-7010 FU UICC International Cancer Technology Transfer Fellowship; National Cancer Institute, National Institutes of Health [NO2-CO-4110] FX This work has been supported by a UICC International Cancer Technology Transfer Fellowship and with Federal funds from the National Cancer Institute, National Institutes of Health under Contract NO2-CO-4110. The authors like to acknowledge: Dr. Lotay Tshering, Dr. Sonam Darjay, and Dr. Guru Dhakal in the Department of Surgery, JDWNRH for providing the gastric biopsy samples for the study; Dr. I. K. Mahanta, Dr. B.M. Dungyel, and Mr. Phulman Thing in the Department of Pathology, JDWNRH for providing the histopathologic results of the biopsy samples. NR 24 TC 3 Z9 6 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-4389 EI 1523-5378 J9 HELICOBACTER JI Helicobacter PD FEB PY 2014 VL 19 IS 1 BP 69 EP 73 DI 10.1111/hel.12088 PG 5 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 276GG UT WOS:000328736100009 PM 24102940 ER PT J AU Zhai, RH Yu, XJ Wei, YY Su, L Christiani, DC AF Zhai, Rihong Yu, Xiaojin Wei, Yongyue Su, Li Christiani, David C. TI Smoking and smoking cessation in relation to the development of co-existing non-small cell lung cancer with chronic obstructive pulmonary disease SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cigarette smoking; smoking cessation; non-small cell lung cancer; co-existing chronic obstructive pulmonary disease; risk ID CIGARETTE-SMOKING; HISTOLOGICAL TYPES; DOSE-RESPONSE; NEVER SMOKERS; WOMEN; RISK; COPD; MEN; GENDER; EPIDEMIOLOGY AB Previous studies have identified a mixed-phenotype of non-small cell lung cancer (NSCLC) with co-existing chronic obstructive pulmonary disease (COPD). Although NSCLC and COPD share a common risk factor in smoking, whether and how smoking may contribute to the coexistence of NSCLC with COPD (NSCLC-COPD) is unclear. Our study suggests that cigarette smoking is the major risk factor for the development of NSCLC-COPD, especially in females and among patients with squamous cell carcinoma subtype. C1 [Zhai, Rihong; Yu, Xiaojin; Wei, Yongyue; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,I-14017, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institute of Health [CA92824, CA74386, CA90578] FX Grant sponsor: National Institute of Health; Grant numbers: CA92824, CA74386, CA90578 NR 50 TC 5 Z9 6 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD FEB PY 2014 VL 134 IS 4 BP 961 EP 970 DI 10.1002/ijc.28414 PG 10 WC Oncology SC Oncology GA 264OX UT WOS:000327889700025 PM 23921845 ER PT J AU McKane, CK Marmarelis, M Mendu, ML Moromizato, T Gibbons, FK Christopher, KB AF McKane, Caitlin K. Marmarelis, Melina Mendu, Mallika L. Moromizato, Takuhiro Gibbons, Fiona K. Christopher, Kenneth B. TI Diabetes mellitus and community-acquired bloodstream infections in the critically ill SO JOURNAL OF CRITICAL CARE LA English DT Article DE Diabetes mellitus; Community-acquired bloodstream infections; HbA1c ID LOCALLY WEIGHTED REGRESSION; POPULATION-BASED ASSESSMENT; NEIGHBORHOOD POVERTY RATE; ACUTE ISCHEMIC-STROKE; STAPHYLOCOCCUS-AUREUS; GLYCEMIC CONTROL; NEUTROPHIL FUNCTION; UNITED-STATES; GENE-EXPRESSION; CARDIAC-SURGERY AB Introduction: Community-acquired bloodstream infections have not been studied related to diabetes mellitus in the critically ill. Hypothesis: We hypothesized that the diagnosis of diabetes mellitus and poor chronic glycemic control would increase the risk of community-acquired bloodstream infections (CA-BSIs) in the critically ill. Methods: We performed an observational cohort study between 1998 and 2007 in 2 teaching hospitals in Boston, Massachusetts. We studied 2551 patients 18 years or older, who received critical care within 48 hours of admission and had blood cultures obtained within 48 hours of admission. The exposure of interest was diabetes mellitus defined by International Classification of Diseases, Ninth Revision, Clinical Modification, code 250.xx in outpatient or inpatient records. The primary end point was CA-BSI (<48 hours of hospital admission). Patients with a single coagulase-negative Staphylococcus positive blood culture were not considered to have bloodstream infection. Associations between diabetes groups and bloodstream infection were estimated by bivariable and multivariable logistic regression models. Subanalyses included evaluation of the association between hemoglobin A1c (HbA1c) and bloodstream infection, diabetes and risk of sepsis, and the proportion of the association between diabetes and CA-BSI that was mediated by acute glycemic control. Results: Diabetes is a predictor of CA-BSI. After adjustment for age, sex, race, patient type (medical vs surgical), and acute organ failure, the risk of bloodstream infection was significantly higher in patients with diabetes (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.10-1.82; P=.006) relative to patients without diabetes. The adjusted risk of bloodstream infection was increased in patients with HbA1c of 6.5% or higher (OR, 1.31; 95% CI, 1.04-1.65; P=.02) relative to patients with HbA1c less than 6.5%. Furthermore, the adjusted risk of sepsis was significantly higher in patients with diabetes (OR, 1.26; 95% CI, 1.04-1.54; P=.02) relative to patients without diabetes. Maximum glucose did not significantly mediate the relationship between diabetes mellitus diagnosis and CA-BSI. Conclusions: A diagnosis of diabetes mellitus and HbA1c of 6.5% or higher is associated with the risk of CA-BSI in the critically ill. (C) 2014 Elsevier Inc. All rights reserved. C1 [McKane, Caitlin K.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Marmarelis, Melina] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Mendu, Mallika L.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Moromizato, Takuhiro; Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. EM kbchristopher@partners.org FU Department of Medicine at the Brigham and Women's Hospital; National Institutes of Health [K08AI060881] FX Dr Christopher was supported by the Department of Medicine at the Brigham and Women's Hospital and the National Institutes of Health (grant no. K08AI060881). NR 75 TC 5 Z9 7 U1 4 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD FEB PY 2014 VL 29 IS 1 BP 70 EP 76 DI 10.1016/j.jcrc.2013.08.019 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 275QT UT WOS:000328693000013 PM 24090695 ER PT J AU Hwang, DY Yagoda, D Perrey, HM Tehan, TM Guanci, M Ananian, L Currier, PF Cobb, JP Rosand, J AF Hwang, David Y. Yagoda, Daniel Perrey, Hilary M. Tehan, Tara M. Guanci, Mary Ananian, Lillian Currier, Paul F. Cobb, J. Perren Rosand, Jonathan TI Consistency of communication among intensive care unit staff as perceived by family members of patients surviving to discharge SO JOURNAL OF CRITICAL CARE LA English DT Article DE Intensive care; Family; Communication; Personal satisfaction; Decision making ID SATISFACTION; ICU; CONFLICTS; SUPPORT; ABILITY AB Purpose: We hypothesize that intensive care unit (ICU) families frequently perceive that they have received inconsistent information from staff about their relatives and that these inconsistencies influence abilities to make medical decisions, as well as satisfaction. Materials and Methods: We performed a prospective cohort study in the neurosciences and medical ICU at a university hospital. One hundred twenty-four family members of adult patients surviving to ICU discharge completed a questionnaire regarding perceptions of inconsistent information. Results: Of 193 eligible patients, 64.2% had family complete the survey. Thirty-one respondents (25.0%; 95% confidence interval, 7.7) reported at least 1 instance of inconsistent information during their family member's admission, with no difference between the neurosciences ICU (21.5%; 9.3) and the medical ICU (31.1%; 14.1; P = .28). Of those who did receive inconsistent information, 38.7% (95% confidence interval, 18.2) reported multiple episodes and 74.2% (16.3) indicated that episodes occurred within the first 48 hours of admission. These episodes had an adverse effect, with 19.4% (14.7) indicating that they affected satisfaction and 9.7% (11.0) indicating that they made decision making difficult. Conclusions: Episodes involving inconsistent information from staff as perceived by families may be quite prevalent and may influence decision-making abilities and satisfaction. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hwang, David Y.] Yale New Haven Med Ctr, Neurosci Intens Care Unit, New Haven, CT 06504 USA. [Hwang, David Y.] Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, New Haven, CT 06520 USA. [Yagoda, Daniel; Perrey, Hilary M.; Cobb, J. Perren] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tehan, Tara M.; Guanci, Mary; Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Ananian, Lillian; Currier, Paul F.] Massachusetts Gen Hosp, Med Intens Care Unit, Boston, MA 02114 USA. [Currier, Paul F.; Cobb, J. Perren; Rosand, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. RP Hwang, DY (reprint author), Yale Univ, Sch Med, Dept Neurol, POB 208018, New Haven, CT 06520 USA. EM david.hwang@yale.edu FU MGH Critical Care Center; MGH Neurosciences Intensive Care Research Fund FX This study was supported by the MGH Critical Care Center and the MGH Neurosciences Intensive Care Research Fund. The study sponsors were not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The authors have no conflicts of interest to declare. NR 19 TC 6 Z9 6 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD FEB PY 2014 VL 29 IS 1 BP 134 EP 138 DI 10.1016/j.jcrc.2013.09.009 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 275QT UT WOS:000328693000024 PM 24475496 ER PT J AU Liu, XH Kang, H Shahnazari, M Kim, H Wang, LP Larm, O Adolfsson, L Nissenson, R Halloran, B AF Liu, Xuhui Kang, Heejae Shahnazari, Mohammad Kim, Hubert Wang, Liping Larm, Olla Adolfsson, Lars Nissenson, Robert Halloran, Bernard TI A Novel Mouse Model of Trauma Induced Heterotopic Ossification SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE heterotopic ossification; trauma; bone morphogenetic protein; mouse model; MicroCT ID BONE-FORMATION; BRAIN-INJURY; RISK-FACTORS; PROGRESSIVA; PREVALENCE; CELLS AB Severe soft tissue trauma is associated with heterotopic ossification (HO), the abnormal deposition of bone at extra-skeletal sites. The pathophysiology of the development of trauma-induced HO remains largely unknown due in part to the lack of appropriate animal models. In this study, we sought to develop a new trauma-induced HO mouse model using muscle impact injury combined with low dose BMP-2. BMP-2 at doses ranging from 0 to 2 mu g was injected into quadriceps muscles of adult male C57/BL6 mice. Animals then received a one-time quadriceps impaction injury to mimic the trauma associated with severe injuries. HO was monitored using in vivo microCT scanning at 1, 2, 4, and 8 weeks after treatment. After trauma, the expression of BMP-2, -4, BMP receptor 1, SOX9 and RUNX2 were increased in muscle. Although little or no HO was observed in mice receiving 1 mu g BMP-2, combining this dose with muscle trauma produced an abundance of HO. At higher doses of BMP-2, trauma did not augment mineral deposition. These results suggest that BMP-2 signaling can sensitize muscle to trauma-induced HO. They also provide the basis for a new model to study the pathogenesis of trauma-induced HO. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:183-188, 2014. C1 [Liu, Xuhui; Kang, Heejae; Shahnazari, Mohammad; Kim, Hubert; Wang, Liping; Nissenson, Robert; Halloran, Bernard] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA 94404 USA. [Liu, Xuhui; Kim, Hubert] Univ Calif San Francisco, Dept Orthoped Surg, San Francisco, CA 94143 USA. [Shahnazari, Mohammad; Wang, Liping; Nissenson, Robert; Halloran, Bernard] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Larm, Olla; Adolfsson, Lars] Karolinska Inst, ExThera AB, SE-17177 Stockholm, Sweden. RP Halloran, B (reprint author), San Francisco VA Med Ctr, Dept Vet Affairs, 4150 Clement St, San Francisco, CA 94404 USA. EM bernard.halloran@ucsf.edu FU Department of Defense [W81XWH-11-2-0189]; Veterans Affairs Merit review program; Northern California Institute for Research and Education FX Grant sponsor: Department of Defense; Grant number: W81XWH-11-2-0189; Grant sponsor: Veterans Affairs Merit review program; Grant sponsor: Northern California Institute for Research and Education. NR 30 TC 9 Z9 9 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD FEB PY 2014 VL 32 IS 2 BP 183 EP 188 DI 10.1002/jor.22500 PG 6 WC Orthopedics SC Orthopedics GA 270JQ UT WOS:000328315100002 PM 24136593 ER PT J AU Onur, TS Wu, RB Chu, S Chang, WH Kim, HT Dang, ABC AF Onur, Tarik S. Wu, Ruobin Chu, Stacey Chang, Wenhan Kim, Hubert T. Dang, Alexis B. C. TI Joint Instability and Cartilage Compression in a Mouse Model of Posttraumatic Osteoarthritis SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE posttraumatic osteoarthritis; anterior cruciate ligament; compression; cartilage; mouse model ID ANTERIOR CRUCIATE LIGAMENT; SUBCHONDRAL BONE CHANGES; SINGLE-IMPACT LOAD; ARTICULAR-CARTILAGE; KNEE OSTEOARTHRITIS; ACL INJURY; DEGENERATION; ARTHRITIS; TIBIAE; MATRIX AB Joint instability and cartilage trauma have been previously studied and identified as key mediators in the development of posttraumatic osteoarthritis (PTOA). The purpose of this study was to use an in vivo model to compare the effect of joint instability, caused by the rupture of the anterior cruciate ligament (ACL), versus cartilage compression. In this study, mice were subjected to cyclical axial loads of twelve Newtons (N) for 240 cycles or until the ACL ruptured. One and eight weeks after this procedure, knees were sectioned coronally and evaluated for osteoarthritis by histology. Using a scoring scale established by [Pritzker K, Gay S, Jimenez S, et al. (2006): Osteoarthritis Cartilage 14:13-29], the articular cartilage across each surface was scored and combined to produce a total degeneration score. The ACL-ruptured group had a significantly greater total degeneration score than either control or compression treated joints at 1 and 8 weeks. Additionally, only sections from ACL-ruptured knees consistently showed synovitis after 1 week and osteophyte formation after 8 weeks. Thus, it appears using that ACL rupture consistently creates a severe osteoarthritis phenotype, while axial cartilage compression alone does not appear to be an appropriate method of inducing PTOA in vivo. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:318-323, 2014. C1 [Onur, Tarik S.; Wu, Ruobin; Chu, Stacey; Kim, Hubert T.; Dang, Alexis B. C.] San Francisco VA Med Ctr, Dept Orthopaed Surg, San Francisco, CA USA. [Chang, Wenhan] San Francisco VA Med Ctr, Dept Endocrinol, San Francisco, CA USA. [Chang, Wenhan] Univ Calif San Francisco, Dept Endocrinol, San Francisco, CA 94143 USA. [Kim, Hubert T.; Dang, Alexis B. C.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. RP Onur, TS (reprint author), San Francisco VA Med Ctr, Dept Orthopaed Surg, San Francisco, CA USA. EM t.s.onur17@gmail.com FU UCSF Department of Orthopaedic Surgery; Northern California Institute of Research and Education FX Grant sponsor: UCSF Department of Orthopaedic Surgery; Grant sponsor: Northern California Institute of Research and Education. NR 35 TC 16 Z9 16 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD FEB PY 2014 VL 32 IS 2 BP 318 EP 323 DI 10.1002/jor.22509 PG 6 WC Orthopedics SC Orthopedics GA 270JQ UT WOS:000328315100021 PM 24167068 ER PT J AU Senerchia, AA Ribeiro, KB Rodriguez-Galindo, C AF Senerchia, Andreza A. Ribeiro, Karina B. Rodriguez-Galindo, Carlos TI Trends in Incidence of Primary Cutaneous Malignancies in Children, Adolescents, and Young Adults: A Population-Based Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE adolescent; child; incidence; trends; skin neoplasms; young adult ID SQUAMOUS-CELL CARCINOMAS; NON-HODGKIN-LYMPHOMA; OF-THE-LITERATURE; UNITED-STATES; DERMATOFIBROSARCOMA PROTUBERANS; LYMPHOBLASTIC LYMPHOMA; INCIDENCE PATTERNS; BASAL-CELL; MELANOMA; EPIDEMIOLOGY AB BackgroundSkin cancer incidence among young adults is rising; however, the epidemiological characteristics of primary cutaneous lymphomas and cutaneous soft tissue sarcomas (CSTS) in individuals <30 years old has not been investigated. We analyzed the incidence and time-trends of primary cutaneous malignancies in children and adolescents/young adults (AYA). ProcedureSEER-17 and -13 data were used to assess the descriptive epidemiology and time-trends in incidence of primary cutaneous malignancies in children and AYA. SEERStat and Joinpoint softwares were utilized to estimate annual percent changes (APC) in incidence. ResultsIn total, 7,814 cases (ASR=25.66/1,000,000 habitants) of primary skin cancers in <30 years old were diagnosed in 2000-2008. Females had a higher incidence of melanoma (risk ratio (RR)=1.95; P<0.001) and a lower risk of developing CSTS (RR=0.64, P<0.001). Compared to whites, blacks have a lower incidence of melanoma (RR=0.03, P<0.001), and higher risk of CSTS (RR=2.28, P<0.001). Melanoma increased in females over a 15-year period (1992-2006) (APC=2.5, 95%CI=1.8; 3.2), and the incidence of cutaneous T-cell lymphomas increased over the period 1992-2008 (APC=9.5, 95% CI=6.7; 12.4). CSTS incidence decreased among males over the period 1992-1999 (APC=-21.4, 95% CI -27.2; -15.1), particularly due to a decrease in Kaposi sarcoma incidence (AAPC 1992-2008=-13.6, 95% CI=-22.4;-3.8), although with a notable racial disparity (whites, AAPC=-15.2, 95% CI=-23.2;-6.4; blacks, AAPC=-10.6, 95% CI=-13.2;-7.9). ConclusionsNon-melanoma skin cancer is very rare in children and AYA. We have shown variation in time-trends in incidence as well as in incidence patterns by race, sex, age, and histologic type, highlighting the importance of descriptive epidemiology to better understand the characteristics of these malignancies. Pediatr Blood Cancer 2014;61:211-216. (c) 2013 Wiley Periodicals, Inc. C1 [Senerchia, Andreza A.] Univ Fed Sao Paulo, EPM, GRAACC, IOP, Sao Paulo, Brazil. [Ribeiro, Karina B.] Santa Casa Sao Paulo, Dept Social Med, Fac Ciencias Med, Sao Paulo, Brazil. [Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. RP Rodriguez-Galindo, C (reprint author), Dana Farber Childrens Hosp Canc Ctr, 450 Brookline Ave SW350, Boston, MA 02215 USA. EM carlos_rodriguez-galindo@dfci.harvard.edu NR 27 TC 9 Z9 9 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2014 VL 61 IS 2 BP 211 EP 216 DI 10.1002/pbc.24639 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 275RF UT WOS:000328694300012 PM 24174376 ER PT J AU Huang, TT Chen, Y Dietz, AC Yasui, Y Donaldson, SS Stokes, DC Stovall, M Leisenring, WM Sklar, CA Diller, LR Mertens, AC Armstrong, GT Green, DM Robison, LL Ness, KK AF Huang, Tseng Tien Chen, Yan Dietz, Andrew C. Yasui, Yutaka Donaldson, Sarah S. Stokes, Dennis C. Stovall, Marilyn Leisenring, Wendy M. Sklar, Charles A. Diller, Lisa R. Mertens, Ann C. Armstrong, Gregory T. Green, Daniel M. Robison, Leslie L. Ness, Kirsten K. TI Pulmonary Outcomes in Survivors of Childhood Central Nervous System Malignancies: A Report From the Childhood Cancer Survivor Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE childhood survivors; CNS malignancy; craniospinal radiation; pulmonary late effect ID LUNG FIBROSIS; BRAIN-TUMORS; CRANIOSPINAL IRRADIATION; WILMS TUMOR; MEDULLOBLASTOMA; THERAPY; COMPLICATIONS; IMPAIRMENT; SEQUELAE; GROWTH AB BackgroundAdult survivors of childhood central nervous system (CNS) tumors may be at risk for pulmonary dysfunction. This study enumerates the incidence of pulmonary dysfunction and explores associations between craniospinal irradiation (CSI) and pulmonary dysfunction among survivors of childhood CNS tumors. MethodsParticipants included Childhood Cancer Survivor Study (CCSS) cohort members treated for CNS malignancies when 3.0 for asthma, chronic cough and need for extra oxygen. Rates of fibrosis (RR 2.0, 95% CI 1.0-3.9), chest wall abnormalities (RR 19.0, 95% CI 4.2-85.7), chronic cough (RR 1.6, 95% CI 1.2-2.1) and need for supplemental oxygen (RR 2.5, 95% CI 1.9-3.3) were higher among survivors than among siblings. Survivors treated with CSI were 10.4 (95% CI 7.6-14.4) times more likely than those not exposed to report chest wall deformity. ConclusionAdult survivors of CNS malignancy have high rates of pulmonary dysfunction 5+ years after diagnosis. Survivors treated with CSI should be monitored for pulmonary disease to permit early interventions. Pediatr Blood Cancer 2014;61:319-325. (c) 2013 Wiley Periodicals, Inc. C1 [Huang, Tseng Tien; Armstrong, Gregory T.; Green, Daniel M.; Robison, Leslie L.; Ness, Kirsten K.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Chen, Yan; Yasui, Yutaka] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada. [Dietz, Andrew C.] Univ Calif San Diego, Dept Pediat, Div Hematol Oncol BMT, San Diego, CA 92103 USA. [Dietz, Andrew C.] Rady Childrens Hosp, San Diego, CA USA. [Donaldson, Sarah S.] Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. [Stokes, Dennis C.] St Jude Childrens Res Hosp, Dept Pediat Pulm Med, Memphis, TN 38105 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Dept Clin Stat & Canc Prevent, Seattle, WA 98104 USA. [Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Diller, Lisa R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Diller, Lisa R.] Childrens Hosp, Boston, MA 02115 USA. [Mertens, Ann C.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Mertens, Ann C.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. RP Ness, KK (reprint author), St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 262 Danny Thomas Pl,Mail Stop 735, Memphis, TN 38105 USA. EM kiri.ness@stjude.org RI Yasui, Yutaka/E-2564-2015; OI Yasui, Yutaka/0000-0002-7717-8638; Stokes, Dennis/0000-0002-1162-9192 FU National Cancer Institute [U24-CA55727]; Cancer Center Support (CORE) [CA21765]; American Lebanese-Syrian Associated Charities (ALSAC) FX Grant sponsor: National Cancer Institute; Grant number: U24-CA55727; Grant sponsor: Cancer Center Support (CORE); Grant number: CA21765; Grant sponsor: American Lebanese-Syrian Associated Charities (ALSAC) NR 35 TC 3 Z9 3 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2014 VL 61 IS 2 BP 319 EP 325 DI 10.1002/pbc.24819 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 275RF UT WOS:000328694300031 PM 24127436 ER PT J AU Gandaglia, G Abdollah, F Schiffmann, J Trudeau, V Shariat, SF Kim, SP Perrotte, P Montorsi, F Briganti, A Trinh, QD Karakiewicz, PI Sun, M AF Gandaglia, Giorgio Abdollah, Firas Schiffmann, Jonas Trudeau, Vincent Shariat, Shahrokh F. Kim, Simon P. Perrotte, Paul Montorsi, Francesco Briganti, Alberto Quoc-Dien Trinh Karakiewicz, Pierre I. Sun, Maxine TI Distribution of Metastatic Sites in Patients With Prostate Cancer: A Population-Based Analysis SO PROSTATE LA English DT Article DE prostate cancer; metastatic disease; sites of metastases; bone metastases ID BONE; CARCINOMA; PATTERNS; SPREAD AB BACKGROUNDThere is few data on what constitutes the distribution of metastatic sites in prostate cancer (PCa). The aim of our study was to systematically describe the most common sites of metastases in a contemporary cohort of PCa patients. METHODSPatients with metastatic PCa were abstracted from the Nationwide Inpatient Sample (1998-2010). Most common metastatic sites within the entire population were described. Stratification was performed according to the presence of single or multiple (2 sites) metastases. Additionally, we evaluated the distribution of metastatic sites amongst patients with and without bone metastases. RESULTSOverall, 74,826 patients with metastatic PCa were identified. The most common metastatic sites were bone (84%), distant lymph nodes (10.6%), liver (10.2%), and thorax (9.1%). Overall, 18.4% of patients had multiple metastatic sites involved. When stratifying patients according to the site of metastases, only 19.4% of men with bone metastases had multiple sites involved. Conversely, among patients with lymph nodes, liver, thorax, brain, digestive system, retroperitoneum, and kidney and adrenal gland metastases the proportion of men with multiple sites involved was 43.4%, 76.0%, 76.7%, 73.0%, 52.2%, 60.9%, and 76.4%, respectively. When focusing exclusively on patients with bone metastases, the most common sites of secondary metastases were liver (39.1%), thorax (35.2%), distant lymph nodes (24.6%), and brain (12.4%). CONCLUSIONSAlthough the majority of patients with metastatic PCa experience bone location, the proportion of patients with atypical metastases is not negligible. These findings might be helpful when planning diagnostic imaging procedures in patients with advanced PCa. Prostate 74:210-216, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Gandaglia, Giorgio; Abdollah, Firas; Schiffmann, Jonas; Trudeau, Vincent; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 3J4, Canada. [Gandaglia, Giorgio; Abdollah, Firas; Montorsi, Francesco; Briganti, Alberto] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Urol Res Inst, Dept Urol, Milan, Italy. [Shariat, Shahrokh F.] Med Univ Vienna, Dept Urol, Vienna, Austria. [Kim, Simon P.] Yale Univ, Dept Urol, New Haven, CT USA. [Perrotte, Paul; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ H2X 3J4, Canada. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Div Urol,Med Sch, Boston, MA 02115 USA. RP Gandaglia, G (reprint author), Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, 1058 Rue St Denis, Montreal, PQ H2X 3J4, Canada. EM giorgio.gandaglia@gmail.com OI , Jonas/0000-0002-0654-5920 FU University of Montreal Health Centre Urology Specialists; Fonds de la Recherche en Santee du Quebec; Department of Surgery, University of Montreal; University of Montreal Health Centre (CHUM) Foundation FX Grant sponsor: University of Montreal Health Centre Urology Specialists; Grant sponsor: Fonds de la Recherche en Santee du Quebec; Grant sponsor: Department of Surgery, University of Montreal; Grant sponsor: University of Montreal Health Centre (CHUM) Foundation.. NR 25 TC 20 Z9 20 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD FEB PY 2014 VL 74 IS 2 BP 210 EP 216 DI 10.1002/pros.22742 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 275JC UT WOS:000328671100009 PM 24132735 ER PT J AU Miloslavsky, E Unizony, S AF Miloslavsky, Eli Unizony, Sebastian TI The Heart in Vasculitis SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Vasculitis; Takayasu arteritis; Churg-Strauss syndrome; Polyarteritis nodosa; Heart disease; Cardiomyopathy; Coronary arteritis ID CHURG-STRAUSS-SYNDROME; GIANT-CELL ARTERITIS; TERM-FOLLOW-UP; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; CARDIOVASCULAR MAGNETIC-RESONANCE; POSITRON-EMISSION-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; POOR-PROGNOSIS FACTORS; OF-THE-LITERATURE; POLYARTERITIS-NODOSA AB Any cardiac tissue can be affected in most primary vasculitides. However, certain entities such as eosinophilic granulomatosis with polyangiitis (or Churg-Strauss syndrome) and Takayasu arteritis involve the heart in up to 60% of patients. Vasculitic cardiac complications are important to recognize because they have been linked to increased mortality and impact the treatment decision-making process. This article reviews the spectrum of cardiac manifestations in adults with large-, medium-, and small-vessel primary systemic vasculitides as well as their diagnosis and treatment. C1 [Miloslavsky, Eli; Unizony, Sebastian] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Rheumatol Unit, Boston, MA 02114 USA. RP Unizony, S (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM sunizony@partners.org NR 101 TC 7 Z9 8 U1 2 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X EI 1558-3163 J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 2014 VL 40 IS 1 BP 11 EP + DI 10.1016/j.rdc.2013.10.006 PG 17 WC Rheumatology SC Rheumatology GA 278UY UT WOS:000328916600004 PM 24268007 ER PT J AU Cahana-Amitay, D Albert, ML Oveis, A AF Cahana-Amitay, Dalia Albert, Martin L. Oveis, Abigail TI Psycholinguistics of aphasia pharmacotherapy: Asking the right questions SO APHASIOLOGY LA English DT Review DE Aphasia; Pharmacotherapy; Psycholinguistics; Language ID PRIMARY PROGRESSIVE APHASIA; CHRONIC POSTSTROKE APHASIA; TRANSCORTICAL SENSORY APHASIA; OPEN-LABEL TRIAL; NONFLUENT APHASIA; DOUBLE-BLIND; BROMOCRIPTINE TREATMENT; CORTICAL STIMULATION; EXPERIMENTAL-DESIGN; LANGUAGE THERAPY AB Background: Among the obstacles to demonstrating efficacy of pharmacological intervention for aphasia is quantifying patients' responses to treatment in a statistically valid and reliable manner. In many of the review papers on this topic, detailed discussions of various methodological problems are highlighted, with some suggestions on how these shortcomings should be addressed. Given this deep understanding of caveats associated with the experimental design of aphasia pharmacotherapy studies, investigations continue to produce inconsistent results.Aim: In this review paper, we suggest that the inclusion of theory-driven linguistic measures in aphasia pharmacotherapy studies would add an important step toward elucidating precise patterns of improvement in language performance resulting from pharmacotherapeutic intervention.Main Contribution: We provide a brief review of the clinical approaches currently used in pharmacotherapy studies of aphasia, which often lack psycholinguistic grounding. We then present ways in which psycholinguistic models can complement this approach, offering a rationale for task selection, and as a result, lead to a better understanding of treatment effects. We then follow with an example of how such an integrative approach can be implemented in studies targeting stress reduction in people with aphasia, via beta-blocking agents, as a means to augment language performance, using the recently proposed psycholinguistic framework of linguistic anxiety as our guideline.Conclusion: We conclude that the incorporation of psycholinguistic models into aphasia pharmacotherapy studies can increase the resolution with which we can identify functional changes. C1 [Cahana-Amitay, Dalia; Albert, Martin L.; Oveis, Abigail] Boston Univ, Harold Goodglass Aphasia Res Ctr, Sch Med, Dept Neurol,VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Cahana-Amitay, D (reprint author), Boston Univ, Harold Goodglass Aphasia Res Ctr, Sch Med, Dept Neurol,VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM dcamitay@bu.edu FU National Institutes of Health, NIDCD [5P30DC005207]; NIA [2R01AG14345]; Boston University School of Medicine, Department of Neurology, Harold Goodglass Aphasia Research Center; VA Boston Healthcare System FX We thank Emmanuel Ojo for his contribution to the preparation of this manuscript. We also thank Ron Spiro and our anonymous reviewers for their insightful comments. Support for this research was provided by the National Institutes of Health, NIDCD grant 5P30DC005207 and NIA grant 2R01AG14345, Boston University School of Medicine, Department of Neurology, Harold Goodglass Aphasia Research Center and VA Boston Healthcare System, 150 South Huntington Avenue, Boston, MA 02130. NR 97 TC 3 Z9 3 U1 1 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0268-7038 EI 1464-5041 J9 APHASIOLOGY JI Aphasiology PD FEB 1 PY 2014 VL 28 IS 2 SI SI BP 133 EP 154 DI 10.1080/02687038.2013.818099 PG 22 WC Clinical Neurology SC Neurosciences & Neurology GA 268TA UT WOS:000328192200002 PM 24489425 ER PT J AU Kelly, JF Greene, MC AF Kelly, John F. Greene, M. Claire TI Beyond motivation: Initial validation of the commitment to sobriety scale SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Motivation; Addiction; Substance abuse treatment; Commitment; Sobriety; Young adults ID ALCOHOL AB From an addiction treatment and recovery standpoint maladaptive motivational hierarchies lie at the core of the challenge in mobilizing salutary behavior change. Motivation has been conceptualized as dynamic, interactive and modifiable, as well as multidimensional. Measures of recovery motivation have been developed and validated, but are generally only modest and variable predictors of future behavior. A related, but potentially more potent, construct, is that of commitment to sobriety as it denotes a clearer re-ranking of motivational hierarchies such that the recovery task is now given a top priority potentially less susceptible to the risks associated with undulating future circumstance. This study investigated the psychometric properties of a novel commitment to sobriety scale (CSS). Results revealed a coherent, psychometrically valid, and reliable tool that outperformed an existing commitment to abstinence scale (ATAQ; J. Morgenstern, R.M. Frey, B.S. McCrady, E. Labouvie, & C.J. Neighbors, 1996) and a gold standard measure of motivation (SOCRATES; W.R. Miller & J.S. Tonigan, 1996). This study highlights commitment to sobriety as an important addiction construct. Researchers and theoreticians may find the CSS useful in helping to explain how individuals achieve recovery, and practitioners may find clinical utility in the CSS in helping identify patients in need of more intensive or alternative intervention. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kelly, John F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jkelly11@partners.org FU NIAAA NIH HHS [R21 AA018185, 1R21AA01815-01A2] NR 29 TC 7 Z9 7 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD FEB PY 2014 VL 46 IS 2 BP 257 EP 263 DI 10.1016/j.jsat.2013.06.010 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 266GT UT WOS:000328012800024 PM 23953168 ER PT J AU Oshiro, N Rapley, J Avruch, J AF Oshiro, Noriko Rapley, Joseph Avruch, Joseph TI Amino Acids Activate Mammalian Target of Rapamycin (mTOR) Complex 1 without Changing Rag GTPase Guanyl Nucleotide Charging SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cell Signaling; GTPase; Insulin; Lysosomes; mTOR Complex (mTORC); Rag GTPase; Amino Acids; Raptor ID TSC1-TSC2 COMPLEX; CELL-GROWTH; CRYSTAL-STRUCTURE; TUMOR-SUPPRESSOR; G-PROTEINS; RHEB; BINDING; SUFFICIENCY; PATHWAY; RAPTOR AB Background: Signaling by mTOR complex 1 requires its amino acid-stimulated binding to Rag GTPase heterodimers. Results: mTOR complex 1-Rag binding in vitro is independent of Rag guanyl nucleotide charging, and withdrawal of amino acids from cells does not alter Rag GTP charging. Conclusion: Amino acids promote Rag binding to mTOR complex 1 without changing Rag GTP charging. Significance: Amino acids promote Rag-mTORC1 binding by undefined mechanisms. Activation of mammalian target of rapamycin complex 1 (mTORC1) by amino acids is mediated in part by the Rag GTPases, which bind the raptor subunit of mTORC1 in an amino acid-stimulated manner and promote mTORC1 interaction with Rheb-GTP, the immediate activator. Here we examine whether the ability of amino acids to regulate mTORC1 binding to Rag and mTORC1 activation is due to the regulation of Rag guanyl nucleotide charging. Rag heterodimers in vitro exhibit a very rapid, spontaneous exchange of guanyl nucleotides and an inability to hydrolyze GTP. Mutation of the Rag P-loop corresponding to Ras(Ser-17) abolishes guanyl nucleotide binding. Such a mutation in RagA or RagB inhibits, whereas in RagC or RagD it enhances, Rag heterodimer binding to mTORC1. The binding of wild-type and mutant Rag heterodimers to mTORC1 in vitro parallels that seen with transient expression, but binding to mTORC1 in vitro is entirely independent of Rag guanyl nucleotide charging. HeLa cells stably overexpressing wild-type or P-loop mutant RagC exhibit unaltered amino acid regulation of mTORC1. Despite amino acid-independent raptor binding to Rag, mTORC1 is inhibited by amino acid withdrawal as in parental cells. Rag heterodimers extracted from P-32-labeled whole cells, or just from the pool associated with the lysosomal membrane, exhibit constitutive [P-32]GTP charging that is unaltered by amino acid withdrawal. Thus, amino acids promote mTORC1 activation without altering Rag GTP charging. Raptor binding to Rag, although necessary, is not sufficient for mTORC1 activation. Additional amino acid-dependent steps couple Rag-mTORC1 to Rheb-GTP. C1 [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg 6408,185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU National Institutes of Health [R01CA73818, R37DK17776, P30DK057521] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01CA73818, R37DK17776, and P30DK057521. NR 40 TC 22 Z9 22 U1 2 U2 21 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 31 PY 2014 VL 289 IS 5 BP 2658 EP 2674 DI 10.1074/jbc.M113.528505 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AD6WW UT WOS:000333403000017 PM 24337580 ER PT J AU Kelleher, ZT Sha, YG Foster, MW Foster, WM Forrester, MT Marshall, HE AF Kelleher, Zachary T. Sha, Yonggang Foster, Matthew W. Foster, W. Michael Forrester, Michael T. Marshall, Harvey E. TI Thioredoxin-mediated Denitrosylation Regulates Cytokine-induced Nuclear Factor kappa B (NF-kappa B) Activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Lung Injury; NF-B; Nitric Oxide; S-nitrosylation; Thioredoxin ID DNA-BINDING ACTIVITY; S-NITROSYLATION; INTERACTING PROTEIN; NOS2 REGULATION; IDENTIFICATION; INFLAMMATION; REDUCTION; CYSTEINE; STRESS; CELLS AB Background: S-nitrosylation inhibits mediators of the immune response including the transcription factor NF-B (p50/p65). Results: Exogenous and endogenous inhibitors of thioredoxin prevent p65 denitrosylation and downstream activation of NF-B. Conclusion: Thioredoxin activates inflammatory signaling through targeted denitrosylation of NF-B. Significance: Mechanisms that augment protein S-nitrosylation can be utilized to suppress the immune response. S-nitrosylation of nuclear factor B (NF-B) on the p65 subunit of the p50/p65 heterodimer inhibits NF-B DNA binding activity. We have recently shown that p65 is constitutively S-nitrosylated in the lung and that LPS-induced injury elicits a decrease in SNO-p65 levels concomitant with NF-B activation in the respiratory epithelium and initiation of the inflammatory response. Here, we demonstrate that TNF-mediated activation of NF-B in the respiratory epithelium similarly induces p65 denitrosylation. This process is mediated by the denitrosylase thioredoxin (Trx), which becomes activated upon cytokine-induced degradation of thioredoxin-interacting protein (Txnip). Similarly, inhibition of Trx activity in the lung attenuates LPS-induced SNO-p65 denitrosylation, NF-B activation, and airway inflammation, supporting a pathophysiological role for this mechanism in lung injury. These data thus link stimulus-coupled activation of NF-B to a specific, protein-targeted denitrosylation mechanism and further highlight the importance of S-nitrosylation in the regulation of the immune response. C1 [Kelleher, Zachary T.; Sha, Yonggang; Foster, Matthew W.; Foster, W. Michael; Marshall, Harvey E.] Duke Univ Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Forrester, Michael T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Marshall, HE (reprint author), Duke Univ Med Ctr, Rm 201,MSRB,Box 2613, Durham, NC 27710 USA. EM harvey.marshall@dm.duke.edu FU National Institutes of Health [HL106121, HL 081672, HL092994] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL106121 (to M. W. F. and H. E. M.), HL 081672 (to W. M. F.), and HL092994 (H. E. M.). NR 26 TC 16 Z9 16 U1 3 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 31 PY 2014 VL 289 IS 5 BP 3066 EP 3072 DI 10.1074/jbc.M113.503938 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AD6WW UT WOS:000333403000052 PM 24338024 ER PT J AU Brooks, AN Choi, PS de Waal, L Sharifnia, T Imielinski, M Saksena, G Pedamallu, CS Sivachenko, A Rosenberg, M Chmielecki, J Lawrence, MS DeLuca, DS Getz, G Meyerson, M AF Brooks, Angela N. Choi, Peter S. de Waal, Luc Sharifnia, Tanaz Imielinski, Marcin Saksena, Gordon Pedamallu, Chandra Sekhar Sivachenko, Andrey Rosenberg, Mara Chmielecki, Juliann Lawrence, Michael S. DeLuca, David S. Getz, Gad Meyerson, Matthew TI A Pan-Cancer Analysis of Transcriptome Changes Associated with Somatic Mutations in U2AF1 Reveals Commonly Altered Splicing Events SO PLOS ONE LA English DT Article ID RNA-SEQ; SITE RECOGNITION; GENOME; GENES; QUANTIFICATION; IDENTIFICATION AB Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35) have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated. Here, we identified splicing alterations associated with U2AF1 mutations across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA). Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML), in which U2AF1 is somatically mutated in 3-4% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation. Of these, 30 splicing alterations were statistically significant in both lung adenocarcinoma and AML, including three genes in the Cancer Gene Census, CTNNB1, CHCHD7, and PICALM. Cell line experiments expressing U2AF1 S34F in HeLa cells and in 293T cells provide further support that these altered splicing events are caused by U2AF1 mutation. Consistent with the function of U2AF1 in 3' splice site recognition, we found that S34F/Y mutations cause preferences for CAG over UAG 3' splice site sequences. This report demonstrates consistent effects of U2AF1 mutation on splicing in distinct cancer cell types. C1 [Brooks, Angela N.; Choi, Peter S.; de Waal, Luc; Sharifnia, Tanaz; Imielinski, Marcin; Saksena, Gordon; Pedamallu, Chandra Sekhar; Sivachenko, Andrey; Rosenberg, Mara; Chmielecki, Juliann; Lawrence, Michael S.; DeLuca, David S.; Getz, Gad; Meyerson, Matthew] Broad Inst Harvard & Massachusetts Inst Technol, Canc Program, Cambridge, MA 02141 USA. [Brooks, Angela N.; Choi, Peter S.; de Waal, Luc; Sharifnia, Tanaz; Imielinski, Marcin; Pedamallu, Chandra Sekhar; Chmielecki, Juliann; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Broad Inst Harvard & Massachusetts Inst Technol, Canc Program, Cambridge, MA 02141 USA. EM matthew_meyerson@dfci.harvard.edu FU National Institutes of Health [5U24CA143867-03]; American Cancer Society AstraZeneca Postdoctoral Fellowship FX This work was supported by a National Institutes of Health Grant 5U24CA143867-03. ANB is a Merck Fellow of the Damon Runyon Cancer Research Foundation (DRG-2138-12). JC is supported by an American Cancer Society AstraZeneca Postdoctoral Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 43 Z9 44 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 31 PY 2014 VL 9 IS 1 AR e87361 DI 10.1371/journal.pone.0087361 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 302RF UT WOS:000330621900098 PM 24498085 ER PT J AU Cruz, NM Yuan, Y Leehy, BD Baid, R Kompella, U DeAngelis, MM Escher, P Haider, NB AF Cruz, Nelly M. Yuan, Yang Leehy, Barrett D. Baid, Rinku Kompella, Uday DeAngelis, Margaret M. Escher, Pascal Haider, Neena B. TI Modifier Genes as Therapeutics: The Nuclear Hormone Receptor Rev Erb Alpha (Nr1d1) Rescues Nr2e3 Associated Retinal Disease SO PLOS ONE LA English DT Article ID LEBER CONGENITAL AMAUROSIS; DOMINANT RETINITIS-PIGMENTOSA; S-CONE SYNDROME; PHOTORECEPTOR DEVELOPMENT; HUNTINGTONS-DISEASE; CIRCADIAN CLOCK; CYSTIC-FIBROSIS; IN-VIVO; MUTATION; DEGENERATION AB Nuclear hormone receptors play a major role in many important biological processes. Most nuclear hormone receptors are ubiquitously expressed and regulate processes such as metabolism, circadian function, and development. They function in these processes to maintain homeostasis through modulation of transcriptional gene networks. In this study we evaluate the effectiveness of a nuclear hormone receptor gene to modulate retinal degeneration and restore the integrity of the retina. Currently, there are no effective treatment options for retinal degenerative diseases leading to progressive and irreversible blindness. In this study we demonstrate that the nuclear hormone receptor gene Nr1d1 (Rev-Erba) rescues Nr2e3-associated retinal degeneration in the rd7 mouse, which lacks a functional Nr2e3 gene. Mutations in human NR2E3 are associated with several retinal degenerations including enhanced S cone syndrome and retinitis pigmentosa. The rd7 mouse, lacking Nr2e3, exhibits an increase in S cones and slow, progressive retinal degeneration. A traditional genetic mapping approach previously identified candidate modifier loci. Here, we demonstrate that in vivo delivery of the candidate modifier gene, Nr1d1 rescues Nr2e3 associated retinal degeneration. We observed clinical, histological, functional, and molecular restoration of the rd7 retina. Furthermore, we demonstrate that the mechanism of rescue at the molecular and functional level is through the re-regulation of key genes within the Nr2e3-directed transcriptional network. Together, these findings reveal the potency of nuclear receptors as modulators of disease and specifically of NR1D1 as a novel therapeutic for retinal degenerations. C1 [Cruz, Nelly M.; Leehy, Barrett D.; Haider, Neena B.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Cruz, Nelly M.; Haider, Neena B.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Yuan, Yang] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE USA. [Baid, Rinku; Kompella, Uday] Univ Colorado, Nanomed & Drug Delivery Lab, Dept Pharmaceut Sci, Aurora, CO USA. [Kompella, Uday] Univ Colorado, Dept Ophthalmol, Aurora, CO USA. [DeAngelis, Margaret M.] Univ Utah, Ctr Translat Med, John A Moran Eye Ctr, Salt Lake City, UT USA. [Escher, Pascal] Inst Res Ophthalmol, Grand Champsec Sion, Switzerland. RP Haider, NB (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. EM neena_haider@meei.harvard.edu RI DeAngelis, e/J-7863-2015 FU NIH-NCRR [P20-RRO18788-03]; NIH-NEI [RO1EY017653, RO1EY017653-01A2S1, T32EY007145-14]; Hope for Vision; Edward N. & Della L. Thome Memorial Foundation; Massachusetts Lions Eye Research Fund FX This work was supported by the following funding agencies: NIH-NCRR P20-RRO18788-03 (NBH), NIH-NEI RO1EY017653 (NBH), NIH-NEI RO1EY017653-01A2S1 (NBH), NIH-NEI T32EY007145-14 (NMC), Hope for Vision (NBH), Edward N. & Della L. Thome Memorial Foundation (NBH, MMD), Massachusetts Lions Eye Research Fund (NBH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 7 Z9 7 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 31 PY 2014 VL 9 IS 1 AR e87942 DI 10.1371/journal.pone.0087942 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 302RF UT WOS:000330621900197 PM 24498227 ER PT J AU Yang, C Brown, RE AF Yang, C. Brown, R. E. TI THE CHOLINERGIC AGONIST CARBACHOL INCREASES THE FREQUENCY OF SPONTANEOUS GABAERGIC SYNAPTIC CURRENTS IN DORSAL RAPHE SEROTONERGIC NEURONS IN THE MOUSE SO NEUROSCIENCE LA English DT Article DE patch-clamp; presynaptic modulation; sleep; GAD67-GFP knock-in mice; ventrolateral periaqueductal gray ID FREELY MOVING CATS; NICOTINIC ACETYLCHOLINE-RECEPTORS; LATERODORSAL TEGMENTAL NUCLEUS; PARADOXICAL REM SLEEP; EYE-MOVEMENT SLEEP; KNOCK-IN MICE; UNIT-ACTIVITY; RETICULAR-FORMATION; RAT; BRAIN AB Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 lM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods leads to excitation of 5-HT neurons via the activation of nicotinic receptors located postsynaptically and presynaptically on excitatory afferents. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 VA Boston Healthcare Syst, Dept Psychiat, Neurosci Lab, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Brockton, MA 02301 USA. RP Brown, RE (reprint author), VA Boston Healthcare Syst, Dept Psychiat, In Vitro Neurophysiol Lab, Res 151C,940,Belmont St, Brockton, MA 02301 USA. EM Ritchie_Brown@hms.harvard.edu FU Department of Veterans Affairs Medical Research Service Awards; NIMH [R01 MH039683, R21 MH094803] FX This work was supported by a Department of Veterans Affairs Medical Research Service Awards to R. W. McCarley, by NIMH R01 MH039683 (to R.W. McCarley) and by NIMH R21 MH094803 (to R.E. Brown). NR 55 TC 3 Z9 3 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD JAN 31 PY 2014 VL 258 BP 62 EP 73 DI 10.1016/j.neuroscience.2013.11.005 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 302IC UT WOS:000330596900005 PM 24231737 ER PT J AU Mulligan, G Lichter, DI Di Bacco, A Blakemore, SJ Berger, A Koenig, E Bernard, H Trepicchio, W Li, B Neuwirth, R Chattopadhyay, N Bolen, JB Dorner, AJ van de Velde, H Ricci, D Jagannath, S Berenson, JR Richardson, PG Stadtmauer, EA Orlowski, RZ Lonial, S Anderson, KC Sonneveld, P San Miguel, JF Esseltine, DL Schu, M AF Mulligan, George Lichter, David I. Di Bacco, Alessandra Blakemore, Stephen J. Berger, Allison Koenig, Erik Bernard, Hugues Trepicchio, William Li, Bin Neuwirth, Rachel Chattopadhyay, Nibedita Bolen, Joseph B. Dorner, Andrew J. van de Velde, Helgi Ricci, Deborah Jagannath, Sundar Berenson, James R. Richardson, Paul G. Stadtmauer, Edward A. Orlowski, Robert Z. Lonial, Sagar Anderson, Kenneth C. Sonneveld, Pieter San Miguel, Jesus F. Esseltine, Dixie-Lee Schu, Matthew TI Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy SO BLOOD LA English DT Article ID PLASMA-CELL LEUKEMIA; MULTIPLE-MYELOMA; K-RAS; N-RAS; ACTIVATING MUTATIONS; COLORECTAL-CANCER; REFRACTORY MYELOMA; GENE-MUTATIONS; H-RAS; REVEALS AB Various translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41 known oncogenes and tumor suppressor genes in tumor samples from 133 relapsed myeloma patients participating in phase 2 or 3 clinical trials of bortezomib. DNA mutations were identified in 14 genes. BRAF as well as RAS genes were mutated in a large proportion of cases (45.9%) and these mutations were mutually exclusive. New recurrent mutations were also identified, including in the PDGFRA and JAK3 genes. NRAS mutations were associated with a significantly lower response rate to single-agent bortezomib (7% vs 53% in patients with mutant vs wildtype NRAS, P = .00116, Bonferroni-corrected P = .016), as well as shorter time to progression in bortezomib-treated patients (P = .0058, Bonferroni-corrected P = .012). However, NRAS mutation did not impact outcome in patients treated with high-dose dexamethasone. KRAS mutation did not reduce sensitivity to bortezomib or dexamethasone. These findings identify a significant clinical impact of NRAS mutation in myeloma and demonstrate a clear example of functional differences between the KRAS and NRAS oncogenes. C1 [Mulligan, George; Lichter, David I.; Di Bacco, Alessandra; Blakemore, Stephen J.; Berger, Allison; Koenig, Erik; Bernard, Hugues; Trepicchio, William; Li, Bin; Neuwirth, Rachel; Chattopadhyay, Nibedita; Bolen, Joseph B.; Dorner, Andrew J.; Esseltine, Dixie-Lee; Schu, Matthew] Takeda Pharmaceut Int Co, Cambridge, MA 02139 USA. [van de Velde, Helgi] Janssen Res & Dev, Beerse, Belgium. [Ricci, Deborah] Janssen Res & Dev, Raritan, NJ USA. [Jagannath, Sundar] Mt Sinai Hosp, New York, NY 10029 USA. [Berenson, James R.] Inst Myeloma & Bone Canc Res, West Hollywood, CA USA. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Lonial, Sagar] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. [Sonneveld, Pieter] Univ Rotterdam Hosp, Erasmus Med Ctr, Dept Hematol, Rotterdam, Netherlands. [San Miguel, Jesus F.] Univ Navarra Clin, Ctr Invest Med Aplicada, Pamplona, Spain. RP Mulligan, G (reprint author), Takeda Pharmaceut Int Co, Translat Med, 35 Landsdowne St, Cambridge, MA 02139 USA. EM george.mulligan@takeda.com OI SAN MIGUEL, JESUS/0000-0002-9183-4857 FU Millennium: The Takeda Oncology Company; Takeda Pharmaceuticals International Co. FX The authors acknowledge all of the patients who participated in bortezomib trials, as well as the efforts of all of the investigators and research staff who have contributed to these trials and to sample collection and enrichment, particularly Drs D. H. Irwin, A. E. Traynor, B. Mavromatis, and S. Hegewisch-Becker. G. M. acknowledges the assistance and foresight of S. Kim, A. Bolt, J. Brown, and M. Kaufmann, as well as the contributions of B. Bryant and A. Boral. M. Quinlan provided valuable comments on the manuscript. The authors also acknowledge Steve Hill and Emma Landers, medical writers with FireKite, for writing support during the development of this manuscript, which was funded by Millennium: The Takeda Oncology Company.; This work was supported by Takeda Pharmaceuticals International Co. NR 46 TC 30 Z9 30 U1 2 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 30 PY 2014 VL 123 IS 5 BP 632 EP 639 DI 10.1182/blood-2013-05-504340 PG 8 WC Hematology SC Hematology GA AH0TE UT WOS:000335832500014 PM 24335104 ER PT J AU Tian, Z D'Arcy, P Wang, X Ray, A Tai, YT Hu, YG Carrasco, RD Richardson, P Linder, S Chauhan, D Anderson, KC AF Tian, Ze D'Arcy, Padraig Wang, Xin Ray, Arghya Tai, Yu-Tzu Hu, Yiguo Carrasco, Ruben D. Richardson, Paul Linder, Stig Chauhan, Dharminder Anderson, Kenneth C. TI A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance SO BLOOD LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; DEUBIQUITINATING ENZYME; CANCER-THERAPY; PROTEASOME; CELLS; TUMOR; DEGRADATION; ACTIVATION; MECHANISMS; EXPRESSION AB Proteasome inhibitors have demonstrated that targeting protein degradation is effective therapy in multiple myeloma (MM). Here we show that deubiquitylating enzymes (DUBs) USP14 and UCHL5 are more highly expressed in MM cells than in normal plasma cells. USP14 and UCHL5 short interfering RNA knockdown decreases MM cell viability. A novel 19S regulatory particle inhibitor b-AP15 selectively blocks deubiquitylating activity of USP14 and UCHL5 without inhibiting proteasome activity. b-AP15 decreases viability in MM cell lines and patient MM cells, inhibits proliferation of MM cells even in the presence of bone marrow stroma cells, and overcomes bortezomib resistance. Anti-MM activity of b-AP15 is associated with growth arrest via downregulation of CDC25C, CDC2, and cyclin B1 as well as induction of caspase-dependent apoptosis and activation of unfolded protein response. In vivo studies using distinct human MM xenograft models show that b-AP15 is well tolerated, inhibits tumor growth, and prolongs survival. Combining b-AP15 with suberoylanilide hydroxamic acid, lenalidomide, or dexamethasone induces synergistic anti-MM activity. Our preclinical data showing efficacy of b-AP15 in MM disease models validates targeting DUBs in the ubiquitin proteasomal cascade to overcome proteasome inhibitor resistance and provides the framework for clinical evaluation of USP14/UCHL5 inhibitors to improve patient outcome in MM. C1 [Tian, Ze; Ray, Arghya; Tai, Yu-Tzu; Hu, Yiguo; Carrasco, Ruben D.; Richardson, Paul; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. [Tian, Ze; Ray, Arghya; Tai, Yu-Tzu; Hu, Yiguo; Carrasco, Ruben D.; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [D'Arcy, Padraig; Wang, Xin; Linder, Stig] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden. RP Chauhan, D (reprint author), Dana Farber Canc Inst, M561,450 Brookline Ave, Boston, MA 02115 USA. EM dharminder_chauhan@dfci.harvard.edu OI D'Arcy, Padraig/0000-0001-6671-7600 FU National Institutes of Health Specialized Programs of Research Excellence (SPORE) [P50100707, PO1-CA078378, RO1 CA050947]; ACS [CRP-10-198-01-LIB]; Cancerfonden; Vetenskapsradet; Alex and Eva Wallstroms Foundation; Ake Olssons Foundation FX This work was supported by National Institutes of Health Specialized Programs of Research Excellence (SPORE) grants P50100707, PO1-CA078378, and RO1 CA050947. K.C.A. is an American Cancer Society Clinical Research Professor (ACS grant CRP-10-198-01-LIB). Funding was also provided by Cancerfonden (S.L.), Vetenskapsradet (S.L.), Alex and Eva Wallstroms Foundation (P. D.), and Ake Olssons Foundation (P.D.). NR 39 TC 61 Z9 62 U1 2 U2 16 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 30 PY 2014 VL 123 IS 5 BP 706 EP 716 DI 10.1182/blood-2013-05-500033 PG 11 WC Hematology SC Hematology GA AH0TE UT WOS:000335832500023 PM 24319254 ER PT J AU Liu, SY Yin, L Stroopinsky, D Rajabi, H Puissant, A Stegmaier, K Avigan, D Kharbanda, S Kufe, D Stone, R AF Liu, Suiyang Yin, Li Stroopinsky, Dina Rajabi, Hasan Puissant, Alexandre Stegmaier, Kimberly Avigan, David Kharbanda, Surender Kufe, Donald Stone, Richard TI MUC1-C oncoprotein promotes FLT3 receptor activation in acute myeloid leukemia cells SO BLOOD LA English DT Article ID INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; HEMATOPOIETIC-CELLS; OXIDATIVE STRESS; CLINICAL RESISTANCE; CARCINOMA ANTIGEN; REGULATORY LOOP; BETA-CATENIN; STEM-CELLS; MUTATION AB Blasts from approximately one-third of patients with acutemyeloid leukemia (AML) harbor activating mutations in the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase that confer a poor prognosis. The Mucin 1-C-terminal subunit (MUC1-C) oncoprotein is aberrantly expressed in AML blasts and stem cells; however, there is no known interaction between MUC1-C and FLT3. The present studies demonstrate that MUC1-C associates with wild-type and mutant FLT3 in AML cells. Targeting MUC1-C with the cell-penetrating peptide inhibitor GO-203 disrupts MUC1-C/FLT3 complexes and downregulates FLT3 activation. GO-203 treatment of AML cells was also associated with inhibition of the FLT3 downstream effectors AKT, extracellular signal-regulated kinase, and STAT5. The results further show that AML cells with FLT3-activating mutations and resistant to the FLT3 inhibitor midostaurin/PKC412 are sensitive to GO-203-induced growth arrest and death. Moreover, GO-203 increases sensitivity of mutant FLT3 AML cells to FLT3 inhibitor treatment. These results indicate that MUC1-C contributes to FLT3 activation in AML cells and that targeting MUC1-C inhibits the FLT3 signaling pathway. Our findings support the development of MUC1-C inhibitors alone and in combination with agents that target FLT3 for the treatment of wild-type and mutant FLT3 AML. C1 [Liu, Suiyang; Yin, Li; Rajabi, Hasan; Puissant, Alexandre; Stegmaier, Kimberly; Kharbanda, Surender; Kufe, Donald; Stone, Richard] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Stroopinsky, Dina; Avigan, David] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Stone, R (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D2053, Boston, MA 02215 USA. EM rstone@partners.org RI PUISSANT, ALEXANDRE/O-9575-2016 OI PUISSANT, ALEXANDRE/0000-0002-3997-9282 FU National Cancer Institute of the National Institutes of Health [CA42802, CA100707, CA66996]; Leukemia Lymphoma Society [6226-12] FX This work was supported by the National Cancer Institute of the National Institutes of Health (grants CA42802, CA100707, and CA66996) and by the Leukemia Lymphoma Society (grant 6226-12). NR 52 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 30 PY 2014 VL 123 IS 5 BP 734 EP 742 DI 10.1182/blood-2013-04-493858 PG 9 WC Hematology SC Hematology GA AH0TE UT WOS:000335832500026 PM 24282218 ER PT J AU Casillas, A Paroz, S Green, AR Wolff, H Weber, O Faucherre, F Ninane, F Bodenmann, P AF Casillas, Alejandra Paroz, Sophie Green, Alexander R. Wolff, Hans Weber, Orest Faucherre, Florence Ninane, Francoise Bodenmann, Patrick TI Cultural competency of health-care providers in a Swiss University Hospital: self-assessed cross-cultural skillfulnessin a cross-sectional study SO BMC MEDICAL EDUCATION LA English DT Article DE Cultural competency; Cross-cultural care; Medical education; Health disparities; Vulnerable populations; Immigrant populations ID PERCEIVED PREPAREDNESS; DISPARITIES; INTERVENTIONS; PROFESSIONALS; RESIDENTS; FRAMEWORK AB Background: As the diversity of the European population evolves, measuring providers' skillfulness in cross-cultural care and understanding what contextual factors may influence this is increasingly necessary. Given limited information about differences in cultural competency by provider role, we compared cross-cultural skillfulness between physicians and nurses working at a Swiss university hospital. Methods: A survey on cross-cultural care was mailed in November 2010 to front-line providers in Lausanne, Switzerland. This questionnaire included some questions from the previously validated Cross-Cultural Care Survey. We compared physicians' and nurses' mean composite scores and proportion of "3-good/4-very good" responses, for nine perceived skillfulness items (4-point Likert-scale) using the validated tool. We used linear regression to examine how provider role (physician vs. nurse) was associated with composite skillfulness scores, adjusting for demographics (gender, non-French dominant language), workplace (time at institution, work-unit "sensitized" to cultural-care), reported cultural-competence training, and cross-cultural care problem-awareness. Results: Of 885 questionnaires, 368 (41.2%) returned the survey: 124 (33.6%) physicians and 244 (66.4%) nurses, reflecting institutional distribution of providers. Physicians had better mean composite scores for perceived skillfulness than nurses (2.7 vs. 2.5, p < 0.005), and significantly higher proportion of "good/very good" responses for 4/9 items. After adjusting for explanatory variables, physicians remained more likely to have higher skillfulness (beta = 0.13, p = 0.05). Among all, higher skillfulness was associated with perception/ awareness of problems in the following areas: inadequate cross-cultural training (beta = 0.14, p = 0.01) and lack of practical experience caring for diverse populations (beta = 0.11, p = 0.04). In stratified analyses among physicians alone, having French as a dominant languag (beta = -0.34, p < 0.005) was negatively correlated with skillfulness. Conclusions: Overall, there is much room for cultural competency improvement among providers. These results support the need for cross-cultural skills training with an inter-professional focus on nurses, education that attunes provider awareness to the local issues in cross-cultural care, and increased diversity efforts in the work force, particularly among physicians. C1 [Casillas, Alejandra; Ninane, Francoise; Bodenmann, Patrick] Univ Lausanne Hosp, Dept Ambulatory Care & Community Med, Lausanne, Switzerland. [Paroz, Sophie] Univ Lausanne Hosp, Dept Community Med & Publ Hlth, Lausanne, Switzerland. [Green, Alexander R.] Harvard Univ, Massachusetts Gen Hosp, Dispar Solut Ctr, Sch Med, Cambridge, MA 02138 USA. [Wolff, Hans] Univ Hosp Geneva, Dept Primary Care Community Med & Emergencies, Geneva, Switzerland. [Weber, Orest; Faucherre, Florence] Univ Lausanne Hosp, Dept Psychiat, Lausanne, Switzerland. RP Casillas, A (reprint author), Univ Lausanne Hosp, Dept Ambulatory Care & Community Med, Lausanne, Switzerland. EM Doctorale05@gmail.com NR 28 TC 5 Z9 5 U1 3 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6920 J9 BMC MED EDUC JI BMC Med. Educ. PD JAN 30 PY 2014 VL 14 AR 19 DI 10.1186/1472-6920-14-19 PG 8 WC Education & Educational Research; Education, Scientific Disciplines SC Education & Educational Research GA AF0CL UT WOS:000334379100001 PM 24479405 ER PT J AU Tarbox, SI Addington, J Cadenhead, KS Cannon, TD Cornblatt, BA Perkins, DO Seidman, LJ Tsuang, MT Walker, EF Heinssen, R McGlashan, TH Woods, SW AF Tarbox, Sarah I. Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara A. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. Heinssen, Robert McGlashan, Thomas H. Woods, Scott W. TI Functional development in clinical high risk youth: Prediction of schizophrenia versus other psychotic disorders SO PSYCHIATRY RESEARCH LA English DT Article DE Adolescence; Diagnosis; Premorbid; Prodrome; Prospective; Psychosis; Social adjustment ID 1ST EPISODE PSYCHOSIS; ULTRA-HIGH-RISK; PREMORBID ADJUSTMENT; SCHIZOAFFECTIVE DISORDER; NEGATIVE SYMPTOMS; ADULT SCHIZOPHRENIA; PRODROMAL SYMPTOMS; BIPOLAR DISORDER; OBSTETRIC COMPLICATIONS; INTERRATER RELIABILITY AB This study evaluates premorbid social and academic functioning in clinical high-risk individuals as predictors of transition to schizophrenia versus another psychotic disorder. Participants were 54 individuals enrolled in phase one of the North American Prodrome Longitudinal Study who over two and a half years of follow-up met criteria for schizophrenia/schizophreniform disorder (n=28) or another psychotic disorder (n=26). Social and academic functioning in childhood, early adolescence, and late adolescence was assessed at baseline using the Cannon-Spoor Premorbid Adjustment Scale. Social maladjustment in late adolescence predicted significantly higher odds of transition to schizophrenia versus another psychotic disorder independent of childhood and early adolescent adjustment (OR = 4.02) and conveyed unique risk over academic maladjustment (O R= 5.64). Premorbid academic maladjustment was not associated with psychotic disorder diagnosis. Results support diagnostic specificity of premorbid social dysfunction to schizophrenia in clinical high-risk youth and underscore an important role for social maladjustment in the developmental pathology of schizophrenia and its prediction. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Tarbox, Sarah I.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cadenhead, Kristin S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Cornblatt, Barbara A.] North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Psychiat Res, Glen Oaks, NY 11004 USA. [Cornblatt, Barbara A.] Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10461 USA. [Cornblatt, Barbara A.] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat,Publ Psychiat Div,Massachusetts Men, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92037 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Tarbox, SI (reprint author), Yale Univ, Sch Med, Dept Psychiat, 34 Pk St,38D, New Haven, CT 06519 USA. EM sarah.tarbox@yale.edu FU National Institute of Mental Health [U01 MH066134, R01 MH060720, K24 MH76191, R01 MH065079, R01 MH061523, U01 MH066069, P50 MH064065, R01 MH065562, P50 MH080272, R21 MH075027, R01 MH062066, K05 MH01654, U01 MH066160]; Donaghue Foundation; Eli Lilly and Co FX This work was supported by National Institute of Mental Health (U01 MH066134 to J.A., R01 MH060720 and K24 MH76191 to K.S.C., R01 MH065079 to T.D.C., R01 MH061523 to B.A.C., U01 MH066069 and P50 MH064065 to D.O.P, R01 MH065562 and P50 MH080272 to L.J.S., R21 MH075027 to M.T.T, R01 MH062066 to E.F.W., K05 MH01654 to T.H.M., U01 MH066160 to S.W.W.); Donaghue Foundation (to S.W.W.); and Eli Lilly and Co (study HGGF to T.H.M., J.A., D.O.P.). NR 72 TC 4 Z9 4 U1 4 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JAN 30 PY 2014 VL 215 IS 1 BP 52 EP 60 DI 10.1016/j.psychres.2013.10.006 PG 9 WC Psychiatry SC Psychiatry GA AA9LF UT WOS:000331414300009 PM 24200216 ER PT J AU Nishi, M Sakai, Y Akutsu, H Nagashima, Y Quinn, G Masui, S Kimura, H Perrem, K Umezawa, A Yamamoto, N Lee, SW Ryo, A AF Nishi, M. Sakai, Y. Akutsu, H. Nagashima, Y. Quinn, G. Masui, S. Kimura, H. Perrem, K. Umezawa, A. Yamamoto, N. Lee, S. W. Ryo, A. TI Induction of cells with cancer stem cell properties from nontumorigenic human mammary epithelial cells by defined reprogramming factors SO ONCOGENE LA English DT Article DE cancer stem cell; reprogramming factors; oncogenesis; MCF-10A; p16INK4a ID GASTROINTESTINAL CANCER; BREAST-CANCER; EXPRESSION; PHOSPHORYLATION; IMMORTALIZATION; IDENTIFICATION; MARKER; TUMORS; LINE; PIN1 AB Cancer stem cells (CSCs), a small and elusive population of undifferentiated cancer cells within tumors that drive tumor growth and recurrence, are believed to resemble normal stem cells. Although surrogate markers have been identified and compelling CSC theoretical models abound, actual proof for the existence of CSCs can only be had retrospectively. Hence, great store has come to be placed in isolating CSCs from cancers for in-depth analysis. On the other hand, although induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, concern exists over the inadvertent co-transplantation of partially or undifferentiated stem cells with tumorigenic capacity. Here we demonstrate that the introduction of defined reprogramming factors (OCT4, SOX2, Klf4 and c-Myc) into MCF-10A nontumorigenic mammary epithelial cells, followed by partial differentiation, transforms the bulk of cells into tumorigenic CD44(+)/CD24(low) cells with CSC properties, termed here as induced CSC-like-10A or iCSCL-10A cells. These reprogrammed cells display a malignant phenotype in culture and form tumors of multiple lineages when injected into immunocompromised mice. Compared with other transformed cell lines, cultured iCSCL-10A cells exhibit increased resistance to the chemotherapeutic compounds, Taxol and Actinomycin D, but higher susceptibility to the CSC-selective agent Salinomycin and the Pin1 inhibitor Juglone. Restored expression of the cyclin-dependent kinase inhibitor p16INK4a abrogated the CSC properties of iCSCL-10A cells, by inducing cellular senescence. This study provides some insight into the potential oncogenicity that may arise via cellular reprogramming, and could represent a valuable in vitro model for studying the phenotypic traits of CSCs per se. C1 [Nishi, M.; Sakai, Y.; Quinn, G.; Ryo, A.] Yokohama City Univ, Sch Med, Dept Microbiol, Yokohama, Kanagawa 2360004, Japan. [Akutsu, H.; Umezawa, A.] Natl Res Inst Child Hlth & Dev, Dept Reprod Biol, Tokyo, Japan. [Nagashima, Y.] Yokohama City Univ, Sch Med, Dept Mol Pathol, Yokohama, Kanagawa 2360004, Japan. [Masui, S.] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Kyoto, Japan. [Kimura, H.] Natl Inst Infect Dis, Infect Dis Surveillance Ctr, Tokyo, Japan. [Perrem, K.] CSIRO, Dickson, ACT, Australia. [Yamamoto, N.] Natl Univ Singapore, Dept Microbiol, Singapore 117548, Singapore. [Lee, S. W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lee, S. W.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Ryo, A (reprint author), Yokohama City Univ, Sch Med, Dept Microbiol, Kanazawa Ku, 3-9 Fuku Ura, Yokohama, Kanagawa 2360004, Japan. EM aryo@yokohama-cu.ac.jp FU Japan Health Sciences Foundation; Uehara Memorial Foundation; Takeda Science Foundation FX We thank A Kondo, T Taniguchi, Y Kojima, Y Watanabe, M Tanaka and N Sakurai for technical assistance and discussion. This work was in part supported by Grant-in-Aid for Scientific Research on Innovative Areas and the Japan Health Sciences Foundation, and grants from the Uehara Memorial Foundation and Takeda Science Foundation to AR. NR 44 TC 31 Z9 32 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JAN 30 PY 2014 VL 33 IS 5 BP 643 EP 652 DI 10.1038/onc.2012.614 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AA5GW UT WOS:000331125100012 PM 23318426 ER PT J AU Atilla-Gokcumen, GE Muro, E Relat-Goberna, J Sasse, S Bedigian, A Coughlin, ML Garcia-Manyes, S Eggert, US AF Atilla-Gokcumen, G. Ekin Muro, Eleonora Relat-Goberna, Josep Sasse, Sofia Bedigian, Anne Coughlin, Margaret L. Garcia-Manyes, Sergi Eggert, Ulrike S. TI Dividing Cells Regulate Their Lipid Composition and Localization SO CELL LA English DT Article ID ATOMIC-FORCE MICROSCOPY; MASS-SPECTROMETRY; CLEAVAGE FURROW; MYOSIN-II; CYTOKINESIS; MEMBRANE; BILAYERS; NANOMECHANICS; SPECTROSCOPY; LEUKODYSTROPHY AB Although massive membrane rearrangements occur during cell division, little is known about specific roles that lipids might play in this process. We report that the lipidome changes with the cell cycle. LC- MSbased lipid profiling shows that 11 lipids with specific chemical structures accumulate in dividing cells. Using AFM, we demonstrate differences in the mechanical properties of live dividing cells and their isolated lipids relative to nondividing cells. In parallel, systematic RNAi knockdown of lipid biosynthetic enzymes identified enzymes required for division, which highly correlated with lipids accumulated in dividing cells. We show that cells specifically regulate the localization of lipids to midbodies, membrane- based structures where cleavage occurs. We conclude that cells actively regulate and modulate their lipid composition and localization during division, with both signaling and structural roles likely. This work has broader implications for the active and sustained participation of lipids in basic biology. C1 [Atilla-Gokcumen, G. Ekin; Sasse, Sofia; Bedigian, Anne; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Atilla-Gokcumen, G. Ekin; Sasse, Sofia; Bedigian, Anne; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Muro, Eleonora; Eggert, Ulrike S.] Kings Coll London, Dept Chem, London SE1 1UL, England. [Muro, Eleonora; Eggert, Ulrike S.] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England. [Relat-Goberna, Josep; Garcia-Manyes, Sergi] Kings Coll London, Dept Phys, London WC2R 2LS, England. [Relat-Goberna, Josep; Garcia-Manyes, Sergi] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England. [Sasse, Sofia] Univ Munster, Inst Neurobiol, D-48149 Munster, Germany. [Coughlin, Margaret L.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Eggert, US (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM ulrike.eggert@kcl.ac.uk FU Taplin Funds for Discovery Program at Harvard Medical School; NIH [R01 GM082834, R01 GM39565]; Human Frontier Science Program Young Investigator Award [304137]; ERC [306659]; Heinrich Hertz Foundation; "La Caixa'' PhD fellowship; Marie Curie CIG grant [293462]; BBSRC [J00992X/1]; EPSRC [K00641X/1] FX We thank Alan Saghatelian, Tim Mitchison, and Xin Zhang for helpful discussions. LC-MS data was acquired on an Agilent 6520 Q-TOF spectrometer supported by the Taplin Funds for Discovery Program at Harvard Medical School (PI, Suzanne Walker). We thank the Nikon Imaging Centres at King's College London and Harvard Medical School for help with light microscopy. We also thank the facilities of the EBN group of the Physics Department of King's College London. This work was funded by NIH grant R01 GM082834, Human Frontier Science Program Young Investigator Award, Marie Curie CIG grant 304137, ERC Starting Grant 306659 (to U.S.E.), the Heinrich Hertz Foundation (to S.S.), a "La Caixa'' PhD fellowship (to J. R.-G.), NIH grant R01 GM39565 (M.L.C., awarded to T.J. Mitchison), and Marie Curie CIG grant 293462, BBSRC grant J00992X/1, and EPSRC Fellowship K00641X/1 (to S.G.-M.). NR 63 TC 69 Z9 72 U1 9 U2 103 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 30 PY 2014 VL 156 IS 3 BP 428 EP 439 DI 10.1016/j.cell.2013.12.015 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 302DD UT WOS:000330580800011 PM 24462247 ER PT J AU Lee, JH Bhang, DH Beede, A Huang, TL Stripp, BR Bloch, KD Wagers, AJ Tseng, YH Ryeom, S Kim, CF AF Lee, Joo-Hyeon Bhang, Dong Ha Beede, Alexander Huang, Tian Lian Stripp, Barry R. Bloch, Kenneth D. Wagers, Amy J. Tseng, Yu-Hua Ryeom, Sandra Kim, Carla F. TI Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis SO CELL LA English DT Article ID THROMBIN-SENSITIVE PROTEIN; HUMAN-BLOOD PLATELETS; TUMOR-GROWTH; MOUSE; THROMBOSPONDIN-1; ALVEOLARIZATION; ANGIOGENESIS; EXPRESSION; PROLIFERATION; HETEROGENEITY AB Lung stem cells are instructed to produce lineage-specific progeny through unknown factors in their microenvironment. We used clonal 3D cocultures of endothelial cells and distal lung stem cells, bronchioalveolar stem cells (BASCs), to probe the instructive mechanisms. Single BASCs had bronchiolar and alveolar differentiation potential in lung endothelial cell cocultures. Gain-and loss-offunction experiments showed that BMP4-Bmpr1a signaling triggers calcineurin/ NFATc1-dependent expression of thrombospondin-1 (Tsp1) in lung endothelial cells to drive alveolar lineage-specific BASC differentiation. Tsp1 null mice exhibited defective alveolar injury repair, confirming a crucial role for the BMP4-NFATc1-TSP1 axis in lung epithelial differentiation and regeneration in vivo. Discovery of this pathway points to methods to direct the derivation of specific lung epithelial lineages from multipotent cells. These findings elucidate a pathway that may be a critical target in lung diseases and provide tools to understand the mechanisms of respiratory diseases at the single-cell level. C1 [Lee, Joo-Hyeon; Beede, Alexander; Kim, Carla F.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Lee, Joo-Hyeon; Beede, Alexander; Kim, Carla F.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Lee, Joo-Hyeon; Beede, Alexander; Kim, Carla F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Bhang, Dong Ha; Ryeom, Sandra] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA. [Huang, Tian Lian; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Huang, Tian Lian] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Stripp, Barry R.] Cedars Sinai Med Ctr, Dept Med, Womens Guild Lung Inst, Los Angeles, CA 90048 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wagers, Amy J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kim, CF (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM carla.kim@childrens.harvard.edu FU Hope Funds for Cancer Research [R01 CA118374, R01 DK077097, U01 HL100402, 1U01HL099997, NHLBI RFA-HL-09-004]; Harvard Stem Cell Institute; Foundation Leducq [RO1 HL090136]; American Cancer Society Research Scholar Grant [RSG-08-082-01-MGO]; Basil O'Conner March of Dimes Starter Award; Alfred A. and Gilda K. Slifka FX We thank the BCH FACS facility, members of the C. F. K. lab, L. Zon, D. Scadden, P. Oh, C. Han, C. Fillmore, K. Townsend, G. Evans, and J. Sage for technical assistance and/or helpful discussions, and R. Bronson for histopathology. This work was supported by the Hope Funds for Cancer Research (JHL), R01 CA118374 (to S. R.), R01 DK077097 (to Y.-H.T.), U01 HL100402 and 1U01HL099997 under NHLBI RFA-HL-09-004 (to C. F. K., B. R. S., and A. J. W.), the Harvard Stem Cell Institute (to Y.-H. T. and C. F. K.), the Foundation Leducq (to K. D. B.), and RO1 HL090136, American Cancer Society Research Scholar Grant RSG-08-082-01-MGO, and a Basil O'Conner March of Dimes Starter Award (to C. F. K.). This research was funded by Alfred A. and Gilda K. Slifka (to C.F.K.). NR 39 TC 63 Z9 68 U1 3 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 30 PY 2014 VL 156 IS 3 BP 440 EP 455 DI 10.1016/j.cell.2013.12.039 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 302DD UT WOS:000330580800012 PM 24485453 ER PT J AU Leder, K Pitter, K LaPlant, Q Hambardzumyan, D Ross, BD Chan, TA Holland, EC Michor, F AF Leder, Kevin Pitter, Ken LaPlant, Quincey Hambardzumyan, Dolores Ross, Brian D. Chan, Timothy A. Holland, Eric C. Michor, Franziska TI Mathematical Modeling of PDGF-Driven Glioblastoma Reveals Optimized Radiation Dosing Schedules SO CELL LA English DT Article ID CANCER STEM-CELLS; ENGINEERED MOUSE MODELS; TUMOR-INITIATING CELLS; HIGH-GRADE GLIOMA; IN-VIVO; THERAPEUTIC IMPLICATIONS; PERIVASCULAR NICHE; MALIGNANT GLIOMAS; SIMULATION-MODEL; RADIOTHERAPY AB Glioblastomas (GBMs) are the most common and malignant primary brain tumors and are aggressively treated with surgery, chemotherapy, and radiotherapy. Despite this treatment, recurrence is inevitable and survival has improved minimally over the last 50 years. Recent studies have suggested that GBMs exhibit both heterogeneity and instability of differentiation states and varying sensitivities of these states to radiation. Here, we employed an iterative combined theoretical and experimental strategy that takes into account tumor cellular heterogeneity and dynamically acquired radioresistance to predict the effectiveness of different radiation schedules. Using this model, we identified two delivery schedules predicted to significantly improve efficacy by taking advantage of the dynamic instability of radioresistance. These schedules led to superior survival inmice. Our interdisciplinary approach may also be applicable to other human cancer types treated with radiotherapy and, hence, may lay the foundation for significantly increasing the effectiveness of a mainstay of oncologic therapy. C1 [Leder, Kevin] Univ Minnesota, Dept Ind & Syst Engn, Minneapolis, MN 55455 USA. [Pitter, Ken; LaPlant, Quincey] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, Brain Tumor Ctr, New York, NY 10065 USA. [Hambardzumyan, Dolores] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44195 USA. [Hambardzumyan, Dolores] Dept Mol Med, Cleveland, OH 44195 USA. [Ross, Brian D.] Univ Michigan, Ctr Mol Imaging, Ann Arbor, MI 48109 USA. [Ross, Brian D.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Holland, Eric C.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Holland, Eric C.] Univ Washington, Alvord Brain Tumor Ctr, Seattle, WA 98109 USA. [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Holland, EC (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. EM eholland@fhcrc.org; michor@jimmy.harvard.edu FU National Science Foundation [RO1 CA100688, U54 CA163167, U54 CA143798, U01 CA141502-01, NSF DMS-1224362, MSTP GM07739, F31 NS076028, P01 CA085878] FX The authors would like to thank the Holland and Michor labs and Jasmine Foo for discussions and comments and National Institutes of Health and National Science Foundation grants RO1 CA100688, U54 CA163167, U54 CA143798, U01 CA141502-01 (to E. C. H.), U54 CA143798 (to F. M.), NSF DMS-1224362, U54 CA143798 (to K. L.), MSTP GM07739, F31 NS076028 (to K. P.), and P01 CA085878 (to B. D. R.). NR 60 TC 55 Z9 56 U1 2 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 30 PY 2014 VL 156 IS 3 BP 603 EP 616 DI 10.1016/j.cell.2013.12.029 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 302DD UT WOS:000330580800024 PM 24485463 ER PT J AU Zhang, YY Pan, CX Wu, X Dong, YL Culley, DJ Crosby, G Li, TZ Xie, ZC AF Zhang, Yiying Pan, Chuxiong Wu, Xu Dong, Yuanlin Culley, Deborah J. Crosby, Gregory Li, Tianzuo Xie, Zhongcong TI Different effects of anesthetic isoflurane on caspase-3 activation and cytosol cytochrorne mice levels between m neural progenitor cells and neurons SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE Alzheimer's disease; anesthesia; isoflurane; caspase-3; cytochrome c; neural progenitor cells; neurons ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; PROTEIN-LEVELS; MOUSE MODEL; SURGERY; SEVOFLURANE; DEMENTIA; NEUROTOXICITY; APPSWE/PS1DE9 AB Commonly used anesthetic isoflurane has been reported to promote Alzheimer's disease (AD) neuropathogenesis by inducing caspase-3 activation. However, the up-stream mechanisms of isoflurane's effects remain largely to be determined. Specifically, there is a lack of a good model/system to elucidate the underlying mechanism of the isoflurane-induced caspase-3 activation. We therefore set out to assess and compare the effects of isoflurane on caspase-3 activation in neural progenitor cells (NPCs) and in primary neurons from wild-type (WT) and AD transgenic (Tg) mice. The NPCs and neurons were obtained, cultured and then treated with either 2% isoflurane or under control condition for 6 h. The NPCs or neurons were harvested at the end of the treatment and were subjected to Western blot analysis. Here we showed for the first time that the isoflurane treatment induced caspase-3 activation in neurons, but not in NPCs, from either WT or AD Tg mice. Consistently, the isoflurane treatment increased cytosol levels of cytochrome c, a potential up stream mechanism of isoflurane-induced caspase-3 activation in the mice neurons, but not NPCs. Finally, the isoflurane treatment induced a greater casapse-3 activation in the neurons, but not the NPCs, from AD Tg mice as compared to the WT mice. These data demonstrated that investigation and comparison of isoflurane's effects between mice NPCs and neurons would serve as a model/system to determine the underlying mechanism by which isoflurane induces caspase-3 activation. These findings would promote more research to investigate the effects of anesthetics on AD neuropathogenes s and the underlying mechanisms. C1 [Zhang, Yiying; Pan, Chuxiong; Wu, Xu; Dong, Yuanlin; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Zhang, Yiying; Pan, Chuxiong; Wu, Xu; Dong, Yuanlin; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Pan, Chuxiong; Li, Tianzuo] Capital Med Univ, Beijing Tongren Hosp, Dept Anesthesia, Beijing, Peoples R China. [Wu, Xu] Capital Med Univ, Fac Forens Med, Dept Forens Pathol, Shenyang, Peoples R China. [Culley, Deborah J.; Crosby, Gregory] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Culley, Deborah J.; Crosby, Gregory] Harvard Univ, Sch Med, Boston, MA USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@mgh.harvard.edu FU National Institutes of Health, Bethesda, Maryland [R21AG038994, R01 GM088801, R01 AG041274]; Alzheimer's Association, Chicago, Illinois; Cure Alzheimer's Fund, Wellesley, Massachusetts FX This study was supported by R21AG038994, R01 GM088801, and R01 AG041274 from the National Institutes of Health, Bethesda, Maryland; Investigator initiated Research grant front Alzheimer's Association, Chicago, Illinois; and Cure Alzheimer's Fund, Wellesley, Massachusetts to Zhongcong Xie. The Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital and Harvard Medical School provided the cost of inhalation anesthetic isoflurane, NR 30 TC 3 Z9 3 U1 0 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD JAN 30 PY 2014 VL 8 AR 14 DI 10.3389/fncel.2014.00014 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AA4GN UT WOS:000331054100001 PM 24523673 ER PT J AU Hunt, DP Muse, VV Ly, A AF Hunt, Daniel P. Muse, Victorine V. Ly, Amy TI Case 4-2014: A 39-Year-Old Man with Night Sweats and Abdominal Pain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ERYTHEMA-NODOSUM; SARCOIDOSIS; MANIFESTATIONS; PSORIASIS; LYMPHOMA; COHORT AB A 39-year-old man with a history of psoriasis was admitted to the hospital because of night sweats and abdominal pain. Imaging studies showed numerous ill-defined, hypoattenuating lesions in the spleen and mediastinal and hilar lymphadenopathy. Presentation of CaseDr. Jordan B. Strom (Medicine): A 39-year-old man was admitted to this hospital because of night sweats and abdominal pain. The patient had been well until 1 week before admission, when night sweats developed, which he attributed to the summer heat. Three days before admission, episodes of sharp abdominal pain developed; the pain was greatest at the costal margin on the right side, and the patient rated it at up to 7 on a scale of 0 to 10 (with 10 indicating the most severe pain). The pain lasted up to 2.5 hours, increased with deep breaths, ... C1 [Hunt, Daniel P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ly, Amy] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hunt, Daniel P.] Harvard Med Sch, Dept Med, Boston, MA USA. [Muse, Victorine V.] Harvard Med Sch, Dept Radiol, Boston, MA USA. [Ly, Amy] Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Hunt, DP (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 30 PY 2014 VL 370 IS 5 BP 467 EP 473 DI 10.1056/NEJMcpc1305990 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 303AA UT WOS:000330645400012 PM 24476436 ER PT J AU Gortmaker, SL Taveras, EM AF Gortmaker, Steven L. Taveras, Elsie M. TI Who Becomes Obese during Childhood - Clues to Prevention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHILDREN AB The prevalence of childhood obesity in the United States has increased rapidly to historically high levels over recent decades and has begun to plateau in some communities and states. Given such a high prevalence, what are the risk factors that best predict incident obesity in later childhood? What are the contributory characteristics resulting in obesity? Can children at highest risk be targeted accurately for early intervention? In this issue of the Journal, Cunningham et al.(1) use a unique, nationally representative database to focus on the incidence of obesity and provide a useful perspective on early predictors of obesity from kindergarten ... C1 [Gortmaker, Steven L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Taveras, Elsie M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gortmaker, SL (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. NR 7 TC 7 Z9 7 U1 3 U2 12 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 30 PY 2014 VL 370 IS 5 BP 475 EP 476 DI 10.1056/NEJMe1315169 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 303AA UT WOS:000330645400013 PM 24476437 ER PT J AU Goldschmidt, MG Villarreal, MF de Achaval, D Drucaroff, LJ Costanzo, EY Castro, MN Pahissa, J Camprodon, J Nemeroff, C Guinjoan, SM AF Giuliana Goldschmidt, Micaela Fabiana Villarreal, Mirta de Achaval, Delfina Javier Drucaroff, Lucas Yolanda Costanzo, Elsa Nair Castro, Mariana Pahissa, Jaime Camprodon, Joan Nemeroff, Charles Martin Guinjoan, Salvador TI Cluster B personality symptoms in persons at genetic risk for schizophrenia are associated with social competence and activation of the right temporo-parietal junction during emotion processing SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE fMRI; Schizophrenia; Siblings; Personality; Cluster B; Temporo parietal junction ID CONSENSUS COGNITIVE BATTERY; MENTAL-ILLNESS; MIND; DISORDERS; PSYCHOSIS; MRI; ABNORMALITIES; PREDICTION; RELATIVES; RELIABILITY AB Personality disorders are common in nonpsychotic siblings of patients with schizophrenia and some personality traits in this group may be associated with an increased risk for full-blown psychosis. We sought to establish if faulty right-hemisphere activation induced by social cognitive tasks, as previously described in patients with schizophrenia, is associated with specific personality symptoms in their unaffected siblings. We observed that cluster B personality symptoms in this group were inversely related to activation in the right temporo parietal junction (rTPL, a structure critical in social cognitive processing) in response to a basic emotion processing task and also to social competence, whereas in contrast to our initial hypothesis, cluster A traits were not associated with right hemisphere activation during emotion processing or with social competence. These findings suggest the existence of clinical traits in at risk individuals which share a common neurobiological substrate with schizophrenia, in regards to social performance. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Giuliana Goldschmidt, Micaela; Fabiana Villarreal, Mirta; de Achaval, Delfina; Javier Drucaroff, Lucas; Yolanda Costanzo, Elsa; Nair Castro, Mariana; Pahissa, Jaime; Martin Guinjoan, Salvador] FLENI Cognit Neurol & Psychiat, Buenos Aires, DF, Argentina. [Giuliana Goldschmidt, Micaela; de Achaval, Delfina; Javier Drucaroff, Lucas; Yolanda Costanzo, Elsa; Nair Castro, Mariana; Martin Guinjoan, Salvador] Univ Buenos Aires, Dept Mental Hlth, Sch Med, FLENI Teaching Unit, Buenos Aires, DF, Argentina. [Fabiana Villarreal, Mirta; de Achaval, Delfina; Nair Castro, Mariana; Martin Guinjoan, Salvador] Argentine Natl Council Sci & Technol Res CONICET, Mendoza, Argentina. [Martin Guinjoan, Salvador] Univ Buenos Aires, Sch Psychol, Dept Neurophysiol, Buenos Aires, DF, Argentina. [Nemeroff, Charles] Univ Miami, Dept Psychiat & Behav Sci, Leonard M Miller Sch Med, Coral Gables, FL 33124 USA. [Camprodon, Joan] Massachusetts Gen Hosp, Lab Neuropsychiat & Neuromodulat, Boston, MA 02114 USA. RP Guinjoan, SM (reprint author), Univ Buenos Aires, Dept Mental Hlth FLENI, Sch Med, Montaneses 2325 8th Floor,C1428AQK, Buenos Aires, DF, Argentina. EM sguinjoan@fleni.org.ar OI Goldschmidt, Micaela/0000-0003-4531-8816 FU Agencia de Promocion, Ministerio de Ciencia y Tecnologia of the Argentine Government [PICT-2007-01643]; University of Buenos Aires [UBACyT 2011-2014]; FLENI Dept. of Teaching and Research FX Agencia de Promocion, Ministerio de Ciencia y Tecnologia of the Argentine Government (PICT-2007-01643), University of Buenos Aires (UBACyT 2011-2014, School of Psychology), and FLENI Dept. of Teaching and Research supported this work. SDG. DdA and MNC are doctoral research fellows from CONICET. CBN is a consultant to Xhale and Takeda, is a stockholder of CeNeRx BioPharma, NovaDel Pharma, Inc., PharmaNeuroBoost, Revaax Pharma, and Xhale, he is the owner of patents for method and devices for transdermal deliveiy of lithium (US 6,375,990B1) and method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2), he is in the board of directors of AFSP, NovaDel Pharma, Inc., and is in the scientific advisory board of American Foundation for Suicide Prevention (AFSP), CeNeRx BioPharma, National Alliance for Research on Schizophrenia and Depression (NARSAD), NovaDel Pharma, Inc., PharmaNeuroBoost, Anxiety Disorders Association of America (ADAA). All other authors report no conflict of interest. MCG, MFV, DdA, JC, CBN, and SMG designed the study. MCG, MFV, DdA, EYC, MNC, JP, and SMG run the experiments and analyzed the data, MCG, MFV, and SMG wrote the first version of the manuscript. All authors contributed to and approved the final version of the manuscript. We thank Ms. Sofia Abrevaya for her technical help with processing of MATRICS and TABS data. NR 47 TC 4 Z9 4 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JAN 30 PY 2014 VL 221 IS 1 BP 30 EP 36 DI 10.1016/j.pscychresns.2013.10.008 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 286HV UT WOS:000329459300005 PM 24262801 ER PT J AU Stallons, LJ Whitaker, RM Schnellmann, RG AF Stallons, L. Jay Whitaker, Ryan M. Schnellmann, Rick G. TI Suppressed mitochondrial biogenesis in folic acid-induced acute kidney injury and early fibrosis SO TOXICOLOGY LETTERS LA English DT Article DE Acute kidney injury; Mitochondrial biogenesis; Fibrosis; Folic acid ID ACUTE-RENAL-FAILURE; PERITUBULAR CAPILLARY LOSS; ENDOTHELIAL GROWTH-FACTOR; TUBULAR CELLS; PROGRESSION; DISEASE; PGC-1-ALPHA; EXPRESSION; RECOVERY; MICE AB Acute kidney injury (AKI) is a disease with mitochondrial dysfunction and a newly established risk factor for the development of chronic kidney disease (CKD) and fibrosis. We examined mitochondrial homeostasis in the folic acid (FA)-induced AKI model that develops early fibrosis over a rapid time course. Mice given a single dose of FA had elevated serum creatinine (3-fold) and urine glucose (2.2-fold) 1 and 2d after injection that resolved by 4d. In contrast, peroxisome proliferator gamma coactivator 1 alpha(PGC-1 alpha) and mitochondrial transcription factor A (TFAM), critical transcriptional regulators of mitochondrial biogenesis (MB), were down-regulated similar to 80% 1d after FA injection and remained depressed through 14d. Multiple electron transport chain and ATP synthesis genes were also down-regulated from 1 to 14d after FA, including NADH dehydrogenase (ubiquinone) 1 beta subcomplex 8 (NDUF beta 8), ATP synthase subunit beta (ATPS-beta), and cytochrome C oxidase subunit I (COXI). Mitochondrial DNA copy number was reduced similar to 50% from 2 to 14d after FA injection. Protein levels of early fibrosis markers alpha-smooth muscle actin and transforming growth factor beta 1 were elevated at 6 and 14d after FA. Picrosirius red staining and collagen 1A2 (COL1A2) IHC revealed staining for mature collagen deposition at 14d. We propose that mitochondrial dysfunction induced by AKI is a persistent cellular injury that promotes progression to fibrosis and CKD, and that this model can be used to test mitochondrial therapeutics that limit progression to fibrosis and CKD. Published by Elsevier Ireland Ltd. C1 [Stallons, L. Jay; Whitaker, Ryan M.; Schnellmann, Rick G.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Drug Discovery & Biomed Sci, 280 Calhoun St, Charleston, SC 29425 USA. EM stallons@musc.edu; whitakr@musc.edu; schnell@musc.edu FU National Institutes of Health [R01 GM084147, T32 HL007260, F32DK098053, F30DK096964, UL1 RR029882]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [BX000851]; SC COBRE in Oxidants, Redox Balance and Stress Signaling [P20 GM103542]; South Carolina Clinical and Translational Research (SCTR) Institute; Medical University of South Carolina CTSA FX This study was supported by the National Institutes of Health [R01 GM084147 to R.G.S., T32 HL007260 and F32DK098053 to L.J.S., and F30DK096964 to R.M.W.], and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [BX000851]. This publication was supported, in part, by the SC COBRE in Oxidants, Redox Balance and Stress Signaling [P20 GM103542], and the South Carolina Clinical and Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina CTSA, and funded by the National Institutes of Health [UL1 RR029882]. NR 40 TC 16 Z9 16 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD JAN 30 PY 2014 VL 224 IS 3 BP 326 EP 332 DI 10.1016/j.toxlet.2013.11.014 PG 7 WC Toxicology SC Toxicology GA 281OW UT WOS:000329111900003 PM 24275386 ER PT J AU Beauchamp, MK Schmidt, CT Pedersen, MM Bean, JF Jette, AM AF Beauchamp, Marla K. Schmidt, Catherine T. Pedersen, Mette M. Bean, Jonathan F. Jette, Alan M. TI Psychometric properties of the Late-Life Function and Disability Instrument: a systematic review SO BMC GERIATRICS LA English DT Article DE Function; Disability; Psychometric properties; Community-dwelling older adults ID RANDOMIZED CONTROLLED-TRIAL; SELF-RATED HEALTH; SYMPTOMATIC KNEE OSTEOARTHRITIS; GENERALIZED ANXIETY DISORDER; HOME-BASED DIET; OLDER-ADULTS; PHYSICAL FUNCTION; CANCER SURVIVORS; INTERNATIONAL CLASSIFICATION; MOBILITY LIMITATIONS AB Background: The choice of measure for use as a primary outcome in geriatric research is contingent upon the construct of interest and evidence for its psychometric properties. The Late-Life Function and Disability Instrument (LLFDI) has been widely used to assess functional limitations and disability in studies with older adults. The primary aim of this systematic review was to evaluate the current available evidence for the psychometric properties of the LLFDI. Methods: Published studies of any design reporting results based on administration of the original version of the LLFDI in community-dwelling older adults were identified after searches of 9 electronic databases. Data related to construct validity (convergent/divergent and known-groups validity), test-retest reliability and sensitivity to change were extracted. Effect sizes were calculated for within-group changes and summarized graphically. Results: Seventy-one studies including 17,301 older adults met inclusion criteria. Data supporting the convergent/divergent and known-groups validity for both the Function and Disability components were extracted from 30 and 18 studies, respectively. High test-retest reliability was found for the Function component, while results for the Disability component were more variable. Sensitivity to change of the LLFDI was confirmed based on findings from 25 studies. The basic lower extremity subscale and overall summary score of the Function component and limitation dimension of the Disability component were associated with the strongest relative effect sizes. Conclusions: There is extensive evidence to support the construct validity and sensitivity to change of the LLFDI among various clinical populations of community-dwelling older adults. Further work is needed on predictive validity and values for clinically important change. Findings from this review can be used to guide the selection of the most appropriate LLFDI subscale for use an outcome measure in geriatric research and practice. C1 [Beauchamp, Marla K.; Bean, Jonathan F.] Harvard Univ, Sch Med, Spaulding Outpatient Ctr Cambridge, Dept Phys Med & Rehabil, Cambridge, MA 02138 USA. [Schmidt, Catherine T.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Pedersen, Mette M.] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark. [Beauchamp, Marla K.; Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA USA. RP Beauchamp, MK (reprint author), Harvard Univ, Sch Med, Spaulding Outpatient Ctr Cambridge, Dept Phys Med & Rehabil, Cambridge, MA 02138 USA. EM mkbeauchamp@partners.org RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU Canadian Institutes of Health Research; Faculty of Health and Medical Sciences at the University of Copenhagen; National Institutes of Health K24 award [1K24HD070966-01]; National Institute on Disability and Rehabilitation Research [H133P120001]; Eunice Kennedy Shriver National institute of Child Health & Human Development [5R24HD065688] FX Marla Beauchamp is supported by a fellowship from the Canadian Institutes of Health Research, Mette Pedersen by the Faculty of Health and Medical Sciences at the University of Copenhagen, Jonathan Bean by a National Institutes of Health K24 award (1K24HD070966-01) and Alan Jette in part by the National Institute on Disability and Rehabilitation Research (H133P120001) and the Eunice Kennedy Shriver National institute of Child Health & Human Development (5R24HD065688). The sponsors had no role in aspect of the study design, methods, data collection, analysis or manuscript preparation. NR 80 TC 11 Z9 11 U1 8 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2318 J9 BMC GERIATR JI BMC Geriatr. PD JAN 29 PY 2014 VL 14 AR 12 DI 10.1186/1471-2318-14-12 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD2SH UT WOS:000333085000001 PM 24476510 ER PT J AU Zhang, MJ Wang, SP Mao, LL Leak, RK Shi, YJ Zhang, WT Hu, XM Sun, BL Cao, GD Gao, YQ Xu, Y Chen, J Zhang, F AF Zhang, Meijuan Wang, Suping Mao, Leilei Leak, Rehana K. Shi, Yejie Zhang, Wenting Hu, Xiaoming Sun, Baoliang Cao, Guodong Gao, Yanqin Xu, Yun Chen, Jun Zhang, Feng TI Omega-3 Fatty Acids Protect the Brain against Ischemic Injury by Activating Nrf2 and Upregulating Heme Oxygenase 1 SO JOURNAL OF NEUROSCIENCE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; CEREBRAL-ISCHEMIA; IN-VIVO; OXIDATIVE STRESS; EICOSAPENTAENOIC ACID; LIPID-PEROXIDATION; NEURONAL SURVIVAL; FISH CONSUMPTION; TRANSGENIC MICE AB Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies. C1 [Zhang, Meijuan; Mao, Leilei; Zhang, Wenting; Hu, Xiaoming; Gao, Yanqin; Chen, Jun; Zhang, Feng] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Zhang, Meijuan; Mao, Leilei; Zhang, Wenting; Hu, Xiaoming; Gao, Yanqin; Chen, Jun; Zhang, Feng] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Zhang, Meijuan; Wang, Suping; Mao, Leilei; Shi, Yejie; Hu, Xiaoming; Cao, Guodong; Chen, Jun; Zhang, Feng] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Zhang, Meijuan; Wang, Suping; Mao, Leilei; Shi, Yejie; Hu, Xiaoming; Cao, Guodong; Chen, Jun; Zhang, Feng] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Zhang, Meijuan; Xu, Yun] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Neurol, Nanjing 210008, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Sun, Baoliang; Zhang, Feng] Shandong Univ, Affiliated Hosp, Taishan Med Coll, Dept Neurol, Tai An 271000, Shandong, Peoples R China. [Sun, Baoliang; Zhang, Feng] Shandong Univ, Affiliated Hosp, Taishan Med Coll, Key Lab Cerebral Microcirculat, Tai An 271000, Shandong, Peoples R China. [Hu, Xiaoming; Cao, Guodong; Chen, Jun; Zhang, Feng] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res,Educ & Clin Ctr, Pittsburgh, PA 15240 USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507 Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu; zhanfx2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Zhang, Meijuan/0000-0002-5375-5349 FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS36736, NS43802, NS45048]; American Heart Association [10SDG2560122]; Natural Science Foundation of China [81228008, 81271276, 81271275, 81070947, 81020108021, 81171149, 81371306]; Doctoral Fund of Ministry of Education of China [20120071110042]; Natural Science Foundation of Shandong [Y2007C014] FX This work was supported by grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NS36736, NS43802, and NS45048 to J.C.), the American Heart Association (10SDG2560122 to F.Z.), the Natural Science Foundation of China (81228008 to J.C.; 81271276 to F.Z.; 81271275 and 81070947 to B. S.; 81020108021, 81171149, and 81371306 to Y.G.), the Doctoral Fund of Ministry of Education of China (20120071110042 to J.C.), and the Natural Science Foundation of Shandong (Y2007C014 to B.S.). We thank Dr. Richard M. LoPachin (Albert Einstein College of Medicine) for calculating the electrophilicity indexes of 4-HNE and 4-HHE. We also thank Carol Culver for editorial assistance and Pat Strickler for secretarial support. NR 76 TC 40 Z9 42 U1 3 U2 19 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 29 PY 2014 VL 34 IS 5 BP 1903 EP 1915 DI 10.1523/JNEUROSCI.4043-13.2014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AB0AU UT WOS:000331455000030 PM 24478369 ER PT J AU Xu, GG McMahan, CA Walter, CA AF Xu, Guogang McMahan, C. Alex Walter, Christi A. TI Early-Life Exposure to Benzo[a]pyrene Increases Mutant Frequency in Spermatogenic Cells in Adulthood SO PLOS ONE LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; LUNG-CANCER RISK; MALE GERM-CELLS; DNA-ADDUCTS; CHILDRENS HEALTH; SPONTANEOUS MUTATION; PHAGOCYTIC FUNCTION; SECONDHAND SMOKE; GENE-EXPRESSION; TRANSGENIC MICE AB Children are vulnerable to environmental mutagens, and the developing germline could also be affected. However, little is known about whether exposure to environmental mutagens in childhood will result in increased germline mutations in subsequent adult life. In the present study, male transgenic lacI mice at different ages (7, 25 and 60 days old) were treated with a known environmental mutagen (benzo[a]pyrene, B[a]P) at different doses (0, 50, 200 or 300 mg/kg body weight). Mutant frequency was then determined in a meiotic cell type (pachytene spermatocyte), a post-meiotic cell type (round spermatid) and epididymal spermatozoa after at least one cycle of spermatogenesis. Our results show that 1) mice treated with B[a]P at 7 or 25 days old, both being pre-adult ages, had significantly increased mutant frequencies in all spermatogenic cell types tested when they were 60 days old; 2) spermatogenic cells from mice treated before puberty were more susceptible to B[a]P-associated mutagenesis compared to adult mice; and 3) unexpectedly, epididymal spermatozoa had the highest mutant frequency among the spermatogenic cell types tested. These data show that pre-adult exposure to B[a]P increases the male germline mutant frequency in young adulthood. The data demonstrate that exposure to environmental genotoxins at different life phases (e.g., pre-adult and adult) can have differential effects on reproductive health. C1 [Xu, Guogang; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Sci, San Antonio, TX 78229 USA. [Walter, Christi A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM walter@uthscsa.edu FU [AG021163] FX Funding was provided by AG021163, http://www.nih.gov/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 4 Z9 4 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 29 PY 2014 VL 9 IS 1 AR e87439 DI 10.1371/journal.pone.0087439 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301ZC UT WOS:000330570000145 PM 24489914 ER PT J AU Liu, B Lou, Q Velez-Cortes, F Sayadi, O Dillmann, W Knollmann, B Armoundas, A Gyorke, S AF Liu, Bin Lou, Qing Velez-Cortes, Florencia Sayadi, Omid Dillmann, Wolfgang Knollmann, Bjoern Armoundas, Antonis Gyorke, Sandor TI Conditional Up-Regulation of SERCA2a Exacerbates Ventricular and Atrial Arrhythmias in the Setting of Catecholaminergic Polymorphic Ventricular Tachycardia SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 58th Annual Meeting of the Biophysical-Society CY FEB 15-19, 2014 CL San Francisco, CA SP Biophys Soc C1 [Liu, Bin; Lou, Qing; Gyorke, Sandor] Ohio State Univ, Columbus, OH 43210 USA. [Velez-Cortes, Florencia; Armoundas, Antonis] Massachusetts Gen Hosp, Charlestown, MA USA. [Dillmann, Wolfgang] Univ Calif San Diego, La Jolla, CA 92093 USA. [Knollmann, Bjoern] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 28 PY 2014 VL 106 IS 2 SU 1 BP 128A EP 128A PG 1 WC Biophysics SC Biophysics GA AI6QE UT WOS:000337000400641 ER PT J AU Morse, JC Siwik, DA Colucci, WS Hobai, IA AF Morse, Justin C. Siwik, Deborah A. Colucci, Wilson S. Hobai, Ion A. TI Cellular Mechanisms of Cardiac Depression and Recovery in Endotoxemic Mice SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 58th Annual Meeting of the Biophysical-Society CY FEB 15-19, 2014 CL San Francisco, CA SP Biophys Soc C1 [Morse, Justin C.; Siwik, Deborah A.] Boston Univ, Boston, MA 02215 USA. [Colucci, Wilson S.] Boston Univ, Med Ctr, Boston, MA USA. [Hobai, Ion A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hobai, Ion A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 28 PY 2014 VL 106 IS 2 SU 1 BP 128A EP 128A PG 1 WC Biophysics SC Biophysics GA AI6QE UT WOS:000337000400640 ER PT J AU Jiang, Y Fu, HX Yang, D Springer, TA Wong, WP AF Jiang, Yan Fu, Hongxia Yang, Darren Springer, Timothy A. Wong, Wesley P. TI Single-Molecule Imaging of Von Willebrand Factor Activation by Flow SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 58th Annual Meeting of the Biophysical-Society CY FEB 15-19, 2014 CL San Francisco, CA SP Biophys Soc C1 [Jiang, Yan; Fu, Hongxia; Yang, Darren; Springer, Timothy A.; Wong, Wesley P.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Jiang, Yan; Fu, Hongxia; Springer, Timothy A.; Wong, Wesley P.] Harvard Univ, Sch Med, Boston, MA USA. [Yang, Darren] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 28 PY 2014 VL 106 IS 2 SU 1 BP 194A EP 194A PG 1 WC Biophysics SC Biophysics GA AI6QE UT WOS:000337000401097 ER PT J AU Prentice-Mott, H Chang, CH Mahadevan, L Mitchison, T Irimia, D Shah, J AF Prentice-Mott, Harrison Chang, Chi-Han Mahadevan, L. Mitchison, Tim Irimia, Daniel Shah, Jagesh TI Barotaxis in a Confined Neutrophil SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 58th Annual Meeting of the Biophysical-Society CY FEB 15-19, 2014 CL San Francisco, CA SP Biophys Soc C1 [Prentice-Mott, Harrison] Harvard Univ, Sch Engn & Appl Sci, Needham, MA USA. [Chang, Chi-Han] Harvard Univ, Cambridge, MA 02138 USA. [Mahadevan, L.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Mitchison, Tim; Shah, Jagesh] Harvard Univ, Boston, MA 02115 USA. [Irimia, Daniel] Massachusetts Gen Hosp, Charlestown, MA USA. [Shah, Jagesh] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 28 PY 2014 VL 106 IS 2 SU 1 BP 360A EP 360A PG 1 WC Biophysics SC Biophysics GA AI6QE UT WOS:000337000402054 ER PT J AU Lou, Q Liu, B Belevych, AE Radwanski, P Kalyanasundaram, A Dillmann, WH Armoundas, AA Knollmann, BC Fedorov, VV Gyorke, S AF Lou, Qing Liu, Bin Belevych, Andriy E. Radwanski, Przemyslaw Kalyanasundaram, Anu Dillmann, Wolfgang H. Armoundas, Antonis A. Knollmann, Bjorn C. Fedorov, Vadim V. Gyoerke, Sandor TI Subcellular Origin and Tissue-Wide Synchronization of Abnormal Ca Release in the Genesis of Ca-Dependent Atrial Arrhythmia SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 58th Annual Meeting of the Biophysical-Society CY FEB 15-19, 2014 CL San Francisco, CA SP Biophys Soc C1 [Lou, Qing; Liu, Bin; Belevych, Andriy E.; Radwanski, Przemyslaw; Kalyanasundaram, Anu; Fedorov, Vadim V.; Gyoerke, Sandor] Ohio State Univ, Dept Physiol & Cell Biol, Powell, OH USA. [Dillmann, Wolfgang H.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Armoundas, Antonis A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Knollmann, Bjorn C.] Vanderbilt Univ, Nashville, TN 37235 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 28 PY 2014 VL 106 IS 2 SU 1 BP 431A EP 431A PG 1 WC Biophysics SC Biophysics GA AI6QE UT WOS:000337000402417 ER PT J AU Gaudet, S Lee, REC AF Gaudet, Suzanne Lee, Robin E. C. TI Leveraging Cell-To-Cell Variability to Understand Signal Transduction Networks SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 58th Annual Meeting of the Biophysical-Society CY FEB 15-19, 2014 CL San Francisco, CA SP Biophys Soc C1 [Gaudet, Suzanne; Lee, Robin E. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 28 PY 2014 VL 106 IS 2 SU 1 BP 445A EP 445A PG 1 WC Biophysics SC Biophysics GA AI6QE UT WOS:000337000402486 ER PT J AU Zhang, YH Jounaidi, Y Sarver, JL Zhou, XJ Cafiso, DS Miller, KW AF Zhang, Yinghui Jounaidi, Youssef Sarver, Jessica L. Zhou, Xiaojuan Cafiso, David S. Miller, Keith W. TI gamma-Aminobutyric Acid Induced Conformational Change in GABA(A)R Measured by Pulsed Electron Paramagnetic Resonance SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 58th Annual Meeting of the Biophysical-Society CY FEB 15-19, 2014 CL San Francisco, CA SP Biophys Soc C1 [Zhang, Yinghui; Jounaidi, Youssef; Zhou, Xiaojuan; Miller, Keith W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sarver, Jessica L.; Cafiso, David S.] Univ Virginia, Charlottesville, VA USA. [Miller, Keith W.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 28 PY 2014 VL 106 IS 2 SU 1 BP 547A EP 547A PG 1 WC Biophysics SC Biophysics GA AI6QE UT WOS:000337000403109 ER PT J AU Scripko, PD Amato, AA Puig, A AF Scripko, Patricia D. Amato, Anthony A. Puig, Alberto TI Mystery Case: A 63-year-old man with progressive proximal pain and weakness SO NEUROLOGY LA English DT Editorial Material ID NECROTIZING MYOPATHY AB A 63-year-old man with a history of type 2 diabetes presented with hip and shoulder pain in June 2010. He was on atorvastatin 80 mg daily and his creatine kinase (CK) was mildly elevated, so he was switched to simvastatin 20 mg daily. Three months later, he was referred to a rheumatologist. His CK was 142 U/L and his erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were mildly elevated (28 mm/hour and 14 mg/L, respectively). He was diagnosed with polymyalgia rheumatica. He was started on a methylprednisolone taper starting at 16 mg going to 8 mg daily with mild, although transient, improvement. He remained on 8 mg daily methylprednisolone for several months. Eight months later, he began to notice progressive proximal leg weakness and difficulty climbing stairs. His serum CK was 1,600 U/L. He stopped the simvastatin and was started on gemfibrozil. An EMG was normal. His CK rose to the 3,000s IU/L 3 months later. Nine months later, 8-day methylprednisolone tapers starting at 16 mg daily were symptomatically ineffective, as was a prednisone 60 mg daily tapered over 2 weeks. C1 [Scripko, Patricia D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Puig, Alberto] Massachusetts Gen Hosp, Clinician Educator Serv, Boston, MA 02114 USA. [Amato, Anthony A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Puig, Alberto] Harvard Univ, Sch Med, Boston, MA USA. RP Scripko, PD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 28 PY 2014 VL 82 IS 4 BP E26 EP E29 DI 10.1212/WNL.0000000000000052 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AH2YZ UT WOS:000335989500001 PM 24470605 ER PT J AU Weinberg, I Jaff, MR AF Weinberg, Ido Jaff, Michael R. TI Accelerated Thrombolysis for Pulmonary Embolism Will Clinical Benefit Be ULTIMAtely Realized? SO CIRCULATION LA English DT Editorial Material ID VENOUS THROMBOEMBOLISM; HYPERTENSION; HEPARIN; TRIAL C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, 55 Fruit St,Warren 905, Boston, MA 02114 USA. EM mjaff@partners.org NR 19 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 28 PY 2014 VL 129 IS 4 BP 420 EP 421 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AA8OK UT WOS:000331354600006 PM 24226804 ER PT J AU Heredia, A Davis, C Amin, MN Le, NM Wainberg, MA Oliveira, M Deeks, SG Wang, LX Redfield, RR AF Heredia, Alonso Davis, Charles Amin, Mohammed N. Le, Nhut M. Wainberg, Mark A. Oliveira, Maureen Deeks, Steven G. Wang, Lai-Xi Redfield, Robert R. TI Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1 SO AIDS LA English DT Article DE antiretroviral therapy; cytosine analogs; drug resistance; emtricitabine; HIV-1; M184V mutation; nucleoside analog reverse transcriptase inhibitors; resource-limited setting ID RESOURCE-LIMITED SETTINGS; REVERSE-TRANSCRIPTASE INHIBITORS; DRUG-RESISTANCE; RIBONUCLEOTIDE REDUCTASE; ANTIRETROVIRAL TREATMENT; SYNERGISTIC INHIBITION; VIROLOGICAL FAILURE; PROCESSIVITY DEFECT; LEUKEMIA-CELLS; DNA-SYNTHESIS AB Objective:The M184V mutation in the HIV-1 reverse transcriptase gene is frequent (>50%) in patients, both in resource-rich and resource-limited countries, conferring high-level resistance (>100-fold) to the cytosine analog reverse transcriptase inhibitors lamivudine and emtricitabine. The reverse transcriptase enzyme of M184V HIV-1 mutants has reduced processivity, resulting in reduced viral replication, particularly at low deoxynucleotide (dNTP) levels. We hypothesized that lowering intracellular dNTPs with resveratrol, a dietary supplement, could interfere with replication of M184V HIV-1 mutants.Design and methods:Evaluation of the activity of resveratrol on infection of primary peripheral blood lymphocytes by wild-type and M184V mutant HIV-1. We assayed both molecular clones and primary isolates of HIV-1, containing M184V alone and in combination with other reverse transcriptase mutations. Viral infection was quantified by p24 ELISA and by quantitative real-time PCR analysis. Cell viability was measured by colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays.Results:In virus-infectivity assays, resveratrol did not inhibit replication of wild-type NL4-3 (resveratrol EC50>10mol/l), but it inhibited NL4-3 184V mutant (resveratrol EC50=5.8mol/l). These results were confirmed by real-time PCR analysis of early and late products of reverse transcription. Resveratrol inhibited molecular clones and primary isolates carrying M184V, alone or in combination with other reverse transcriptase mutations (resveratrol EC50 values ranging from 2.5 to 7.7mol/l).Conclusions:Resveratrol inhibits HIV-1 strains carrying the M184V mutation in reverse transcriptase. We propose resveratrol as a potential adjuvant in HIV-1 therapy, particularly in resource-limited settings, to help control emtricitabine-resistant M184V HIV-1mutants. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Heredia, Alonso; Davis, Charles; Amin, Mohammed N.; Le, Nhut M.; Wang, Lai-Xi; Redfield, Robert R.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Wainberg, Mark A.; Oliveira, Maureen] McGill Univ, Jewish Gen Hosp, AIDS Ctr, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Deeks, Steven G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Heredia, A (reprint author), Inst Human Virol, 725 W Lombard St, Baltimore, MD 21201 USA. EM aheredia@ihv.umaryland.edu FU Institute of Human Virology; NIAID [K24AI069994]; UCSF/Gladstone Institute of Virology & Immunology CFAR [P30 AI027763]; UCSF Clinical and Translational Research Institute Clinical Research Center [UL1 RR024131]; Center for AIDS Prevention Studies [P30 MH62246]; CFAR Network of Integrated Systems [R24 AI067039] FX This work was supported in part by research funds from the Institute of Human Virology. HIV-1 primary isolates were from patients in the SCOPE cohort, which was supported by the NIAID (K24AI069994), the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131), the Center for AIDS Prevention Studies (P30 MH62246), and the CFAR Network of Integrated Systems (R24 AI067039). NR 44 TC 6 Z9 6 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 28 PY 2014 VL 28 IS 3 BP 317 EP 323 DI 10.1097/QAD.0000000000000168 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AB1OA UT WOS:000331560500004 PM 24326355 ER PT J AU Linas, BP Barter, DM Leff, JA DiLorenzo, M Schackman, BR Horsburgh, CR Assoumou, SA Salomon, JA Weinstein, MC Kim, AY Freedberg, KA AF Linas, Benjamin P. Barter, Devra M. Leff, Jared A. DiLorenzo, Madeline Schackman, Bruce R. Horsburgh, Charles R. Assoumou, Sabrina A. Salomon, Joshua A. Weinstein, Milton C. Kim, Arthur Y. Freedberg, Kenneth A. TI The cost-effectiveness of improved hepatitis C virus therapies in HIV/hepatitis C virus coinfected patients SO AIDS LA English DT Article DE cost-effectiveness; HIV/hepatitis C virus coinfection; interferon-free; telaprevir ID QUALITY-OF-LIFE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SUSTAINED VIROLOGICAL RESPONSE; TELAPREVIR COMBINATION TREATMENT; ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; INTERFERON PLUS RIBAVIRIN; HEALTH-STATE UTILITIES; HIV-INFECTED PATIENTS; UNITED-STATES AB Objectives:To evaluate the effectiveness and cost-effectiveness of strategies to treat hepatitis C virus (HCV) in HIV/HCV coinfected patients in the United States.Participants:Simulated cohort of HIV/HCV genotype 1 coinfected, noncirrhotic, HCV treatment-naive individuals enrolled in US HIV guideline-concordant care.Design/interventions:Monte Carlo simulation comparing five strategies: no treatment; dual therapy with pegylated-interferon (PEG) and ribavirin (RBV); PEG/RBV trial' in which all patients initiate dual therapy and switch to triple therapy upon failure; IL28B triage' in which patients initiate either dual therapy or triple therapy based on their IL28B allele type; and PEG/RBV and telaprevir (TPV) triple therapy. Sensitivity analyses varied efficacies and costs and included a scenario with interferon (IFN)-free therapy.Main measures:Sustained virologic response (SVR), life expectancy, discounted quality-adjusted life expectancy (QALE), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs) in $/quality-adjusted life years (QALY) gained.Results:PEG/RBV trial,' IL28B triage,' and triple therapy' each provided 72% SVR and extended QALE compared with dual therapy' by 1.12, 1.14, and 1.15 QALY, respectively. The ICER of PEG/RBV trial' compared with dual therapy' was $37500/QALY. IL28B triage' and triple therapy' provided little benefit compared with PEG/RBV trial,' and both had ICERs exceeding $300000/QALY. In sensitivity analyses, IFN-free treatment attaining 90% SVR had an ICER less than $100000/QALY compared with PEG/RBV trial' when its cost was $109000 or less (125% of the cost of PEG/RBV/TVR).Conclusion:HCV protease inhibitors are most efficiently used in HIV/HCV coinfection after a trial of PEG/RBV, sparing protease inhibitors for those who attain rapid virologic response and SVR. The cost-effectiveness of IFN-free regimens for HIV/HCV coinfection will depend on the cost of these therapies. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Linas, Benjamin P.; Barter, Devra M.; Horsburgh, Charles R.; Assoumou, Sabrina A.] Boston Med Ctr, Infect Dis Sect, Dept Med, Boston, MA 02118 USA. [Linas, Benjamin P.; Horsburgh, Charles R.; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Leff, Jared A.; Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [DiLorenzo, Madeline; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [DiLorenzo, Madeline; Kim, Arthur Y.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Salomon, Joshua A.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Weinstein, Milton C.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Linas, BP (reprint author), Boston Med Ctr, HIV Epidemiol & Outcomes Res Unit, 850 Harrison Ave,Dowling 3N Room 3205, Boston, MA 02118 USA. EM Benjamin.Linas@BMC.org RI Salomon, Joshua/D-3898-2009; OI Salomon, Joshua/0000-0003-3929-5515; Leff, Jared/0000-0001-6995-6009 FU National Institute on Drug Abuse [R01DA031059, R01DA027379]; National Institute of Allergy and Infectious Diseases [R37AI042006] FX The project described was supported by grants from the National Institute on Drug Abuse (R01DA031059, R01DA027379) and the National Institute of Allergy and Infectious Diseases (R37AI042006). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 99 TC 9 Z9 9 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 28 PY 2014 VL 28 IS 3 BP 365 EP 376 DI 10.1097/QAD.0000000000000093 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AB1OA UT WOS:000331560500009 PM 24670522 ER PT J AU Yukl, SA Sinclair, E Somsouk, M Hunt, PW Epling, L Killian, M Girling, V Li, PL Havlir, DV Deeks, SG Wong, JK Hatano, H AF Yukl, Steven A. Sinclair, Elizabeth Somsouk, Ma Hunt, Peter W. Epling, Lorrie Killian, Maudi Girling, Valerie Li, Peilin Havlir, Diane V. Deeks, Steven G. Wong, Joseph K. Hatano, Hiroyu TI A comparison of methods for measuring rectal HIV levels suggests that HIV DNA resides in cells other than CD4 R T cells, including myeloid cells SO AIDS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; LYMPHOID-TISSUE; GASTROINTESTINAL-TRACT; INTESTINAL-MUCOSA; VIRAL PERSISTENCE; POSITIVE PATIENTS; INFECTION; MACROPHAGES; GUT AB We compared different techniques for measuring gut HIV reservoirs and assessed for HIV in non-CD4(+) T cells. HIV DNA levels were similar when measured from rectal biopsies and isolated rectal cells, while HIV RNA tended to be higher in rectal cells. HIV DNA levels in total rectal cells were greater than those predicted from levels in sorted CD4(+) T cells, suggesting a reservoir in non-CD4(+) T cells, and HIV DNA was detected in sorted myeloid cells (7/7 subjects). C1 [Yukl, Steven A.; Li, Peilin; Wong, Joseph K.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Sinclair, Elizabeth; Somsouk, Ma; Hunt, Peter W.; Epling, Lorrie; Killian, Maudi; Girling, Valerie; Havlir, Diane V.; Deeks, Steven G.; Wong, Joseph K.; Hatano, Hiroyu] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Yukl, SA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,111W3, San Francisco, CA 94121 USA. EM steven.yukl@ucsf.edu FU U.S. Department of Veterans Affairs [1 IK2 CX000520-01, I01 BX000192]; Delaney AIDS Research Enterprise (DARE) [U19AI096109]; UCSF-Gladstone Center for AIDS Research (CFAR) [P30-AI027763]; National Cancer Institute [K23 CA157929]; National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R56AI091573, K24 AI069994] FX the U.S. Department of Veterans Affairs [1 IK2 CX000520-01 (to S.Y.), I01 BX000192 (to J.W.)]; the Delaney AIDS Research Enterprise (DARE) [U19AI096109]; the UCSF-Gladstone Center for AIDS Research (CFAR) [P30-AI027763]; the National Cancer Institute [K23 CA157929 (to M.S.)]; and the National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R56AI091573 [J.W., S.Y., A.S., D.H.] and K24 AI069994 (to S.D.)]. NR 24 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 28 PY 2014 VL 28 IS 3 BP 439 EP 442 DI 10.1097/QAD.0000000000000166 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AB1OA UT WOS:000331560500017 PM 24322272 ER PT J AU Xiang, M Birkbak, NJ Vafaizadeh, V Walker, SR Yeh, JE Liu, SH Kroll, Y Boldin, M Taganov, K Groner, B Richardson, AL Frank, DA AF Xiang, Michael Birkbak, Nicolai J. Vafaizadeh, Vida Walker, Sarah R. Yeh, Jennifer E. Liu, Suhu Kroll, Yasmin Boldin, Mark Taganov, Konstantin Groner, Bernd Richardson, Andrea L. Frank, David A. TI STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF-kappa B to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes SO SCIENCE SIGNALING LA English DT Article ID COLITIS-ASSOCIATED CANCER; MULTIPLE-MYELOMA CELLS; BREAST-CANCER; PROSTATE-CANCER; COLORECTAL-CANCER; EPITHELIAL-CELLS; DOWN-REGULATION; HUMAN TUMORS; EXPRESSION; SUPPRESSES AB Interleukin-6 (IL-6)-mediated activation of signal transducer and activator of transcription 3 (STAT3) is a mechanism by which chronic inflammation can contribute to cancer and is a common oncogenic event. We discovered a pathway, the loss of which is associated with persistent STAT3 activation in human cancer. We found that the gene encoding the tumor suppressor microRNA miR-146b is a direct STAT3 target gene, and its expression was increased in normal breast epithelial cells but decreased in tumor cells. Methylation of the miR-146b promoter, which inhibited STAT3-mediated induction of expression, was increased in primary breast cancers. Moreover, we found that miR-146b inhibited nuclear factor kappa B (NF-kappa B)-dependent production of IL-6, subsequent STAT3 activation, and IL-6/STAT3-driven migration and invasion in breast cancer cells, thereby establishing a negative feedback loop. In addition, higher expression ofmiR-146b was positively correlated with patient survival in breast cancer subtypes with increased IL6 expression and STAT3 phosphorylation. Our results identify an epigenetic mechanism of crosstalk between STAT3 and NF-kappa B relevant to constitutive STAT3 activation in malignancy and the role of inflammation in oncogenesis. C1 [Xiang, Michael; Walker, Sarah R.; Yeh, Jennifer E.; Liu, Suhu; Kroll, Yasmin; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Birkbak, Nicolai J.; Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Birkbak, Nicolai J.; Walker, Sarah R.; Richardson, Andrea L.; Frank, David A.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Vafaizadeh, Vida; Groner, Bernd] Inst Biomed Res, D-60956 Frankfurt, Germany. [Walker, Sarah R.; Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Boldin, Mark; Taganov, Konstantin] CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM david_frank@dfci.harvard.edu OI Boldin, Mark/0000-0003-4593-0669 FU National Cancer Institute [R01-CA160979]; Brent Leahey Fund; Breast Cancer Research Foundation-American Association for Cancer Research; National Institute of General Medical Sciences [T32GM007753, F30 CA165740-01] FX Funding: This work was supported by a grant from the National Cancer Institute (R01-CA160979), the Brent Leahey Fund, and a Breast Cancer Research Foundation-American Association for Cancer Research grant for Translational Breast Cancer Research. This work was also supported by award numbers T32GM007753 and F30 CA165740-01 from the National Institute of General Medical Sciences. NR 59 TC 42 Z9 44 U1 0 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JAN 28 PY 2014 VL 7 IS 310 AR ra11 DI 10.1126/scisignal.2004497 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AA4QW UT WOS:000331082000004 PM 24473196 ER PT J AU Dreze, M Calkins, AS Galicza, J Echelman, DJ Schnorenberg, MR Fell, GL Iwai, S Fisher, DE Szuts, D Iglehart, JD Lazaro, JB AF Dreze, Matija Calkins, Anne S. Galicza, Judit Echelman, Daniel J. Schnorenberg, Mathew R. Fell, Gillian L. Iwai, Shigenori Fisher, David E. Szuets, David Iglehart, J. Dirk Lazaro, Jean-Bernard TI Monitoring Repair of UV-Induced 6-4-Photoproducts with a Purified DDB2 Protein Complex SO PLOS ONE LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; DNA-BINDING PROTEIN; XERODERMA-PIGMENTOSUM; DAMAGED DNA; UBIQUITIN LIGASE; IN-VIVO; MOLECULAR-BASIS; RECOGNITION; PHOTOPRODUCTS; XPC AB Because cells are constantly subjected to DNA damaging insults, DNA repair pathways are critical for genome integrity [1]. DNA damage recognition protein complexes (DRCs) recognize DNA damage and initiate DNA repair. The DNA-Damage Binding protein 2 (DDB2) complex is a DRC that initiates nucleotide excision repair (NER) of DNA damage caused by ultraviolet light (UV) [2-4]. Using a purified DDB2 DRC, we created a probe ("DDB2 proteo-probe") that hybridizes to nuclei of cells irradiated with UV and not to cells exposed to other genotoxins. The DDB2 proteo-probe recognized UV-irradiated DNA in classical laboratory assays, including cyto-and histo-chemistry, flow cytometry, and slot-blotting. When immobilized, the proteo-probe also bound soluble UV-irradiated DNA in ELISA-like and DNA pull-down assays. In vitro, the DDB2 proteo-probe preferentially bound 6-4-photoproducts [(6-4) PPs] rather than cyclobutane pyrimidine dimers (CPDs). We followed UV-damage repair by cyto-chemistry in cells fixed at different time after UV irradiation, using either the DDB2 proteo-probe or antibodies against CPDs, or (6-4) PPs. The signals obtained with the DDB2 proteo-probe and with the antibody against (6-4) PPs decreased in a nearly identical manner. Since (6-4) PPs are repaired only by nucleotide excision repair (NER), our results strongly suggest the DDB2 proteo-probe hybridizes to DNA containing (6-4) PPs and allows monitoring of their removal during NER. We discuss the general use of purified DRCs as probes, in lieu of antibodies, to recognize and monitor DNA damage and repair. C1 [Dreze, Matija; Calkins, Anne S.; Echelman, Daniel J.; Schnorenberg, Mathew R.; Iglehart, J. Dirk; Lazaro, Jean-Bernard] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Dreze, Matija; Fell, Gillian L.; Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Galicza, Judit; Szuets, David] Hungarian Acad Sci, Inst Enzymol, Res Ctr Nat Sci, Budapest, Hungary. [Iwai, Shigenori] Osaka Univ, Div Chem, Grad Sch Engn Sci, Osaka, Japan. [Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Lazaro, JB (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jean-bernard_lazaro@dfci.harvard.edu OI , /0000-0001-7002-8488; Schnorenberg, Mathew/0000-0002-2876-573X; Szuts, David/0000-0001-7985-0136 FU Pallotta Investigator Fund; Susan F. Smith Center for Women's Cancers; Marjorie Powell Allen Memorial Fund; Barbara and Paul Ferry Fund for Cancer Research; Hungarian Academy of Sciences; Breast Cancer Research Foundation of New York FX This work was supported by the Pallotta Investigator Fund (J.-B.L.), the Susan F. Smith Center for Women's Cancers (J.-B.L. and J.D.I.), the Marjorie Powell Allen Memorial Fund (J.-B.L.), The Barbara and Paul Ferry Fund for Cancer Research (J.D.I.), and a Momentum Grant of the Hungarian Academy of Sciences (D. S.). J.D.I. is supported by The Breast Cancer Research Foundation of New York. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 1 Z9 1 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 28 PY 2014 VL 9 IS 1 AR e85896 DI 10.1371/journal.pone.0085896 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301CJ UT WOS:000330510000022 PM 24489677 ER PT J AU Faghih, RT Dahleh, MA Adler, GK Klerman, EB Brown, EN AF Faghih, Rose T. Dahleh, Munther A. Adler, Gail K. Klerman, Elizabeth B. Brown, Emery N. TI Deconvolution of Serum Cortisol Levels by Using Compressed Sensing SO PLOS ONE LA English DT Article ID MODEL; ALGORITHM; SIGNALS; FOCUSS AB The pulsatile release of cortisol from the adrenal glands is controlled by a hierarchical system that involves corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropin hormone (ACTH) from the pituitary, and cortisol from the adrenal glands. Determining the number, timing, and amplitude of the cortisol secretory events and recovering the infusion and clearance rates from serial measurements of serum cortisol levels is a challenging problem. Despite many years of work on this problem, a complete satisfactory solution has been elusive. We formulate this question as a non-convex optimization problem, and solve it using a coordinate descent algorithm that has a principled combination of (i) compressed sensing for recovering the amplitude and timing of the secretory events, and (ii) generalized cross validation for choosing the regularization parameter. Using only the observed serum cortisol levels, we model cortisol secretion from the adrenal glands using a second-order linear differential equation with pulsatile inputs that represent cortisol pulses released in response to pulses of ACTH. Using our algorithm and the assumption that the number of pulses is between 15 to 22 pulses over 24 hours, we successfully deconvolve both simulated datasets and actual 24-hr serum cortisol datasets sampled every 10 minutes from 10 healthy women. Assuming a one-minute resolution for the secretory events, we obtain physiologically plausible timings and amplitudes of each cortisol secretory event with R 2 above 0.92. Identification of the amplitude and timing of pulsatile hormone release allows (i) quantifying of normal and abnormal secretion patterns towards the goal of understanding pathological neuroendocrine states, and (ii) potentially designing optimal approaches for treating hormonal disorders. C1 [Faghih, Rose T.; Dahleh, Munther A.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Faghih, Rose T.; Dahleh, Munther A.] MIT, Lab Informat & Decis Syst, Cambridge, MA 02139 USA. [Faghih, Rose T.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Adler, Gail K.; Klerman, Elizabeth B.; Brown, Emery N.] Harvard Univ, Sch Med, Boston, MA USA. [Adler, Gail K.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Klerman, Elizabeth B.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Faghih, RT (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM rfaghih@mit.edu FU NSF Graduate Fellowship; NSF [0836720]; NIH [P01-AG09975, K24-HL105664, RC2-HL101340, R01-HL-11408, HFP01603, DP1 OD003646, K24 HL103845, R01AR43130, M01RR20635, K01AG00661, R01GM 53559]; National Space Biomedical Research Institute through NASA [HFP02802, NCC 9-58]; NASA [NCC9-58]; NSBRI; [EFRI-0735956] FX RTF's work was supported in part by the NSF Graduate Fellowship. For this work ENB is supported in part by NIH DP1 OD003646 and NSF 0836720. MAD is supported in part by EFRI-0735956 while EBK is supported in part by NIH P01-AG09975, K24-HL105664, RC2-HL101340, R01-HL-11408, and HFP01603 and HFP02802 from the National Space Biomedical Research Institute through NASA NCC 9-58. Finally, GKA is supported in part by NIH K24 HL103845. Clinical studies were performed on the Brigham and Women's Hospital General Clinical Research Center. Grants supporting the original data collection include NIH R01AR43130 (GKA), M01RR20635 (BWH GCRC), K01AG00661 (EBK), R01GM 53559 (ENB), and NASA NCC9-58 with the NSBRI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 5 Z9 5 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 28 PY 2014 VL 9 IS 1 AR e85204 DI 10.1371/journal.pone.0085204 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301CJ UT WOS:000330510000011 PM 24489656 ER PT J AU Poulin, C Shiner, B Thompson, P Vepstas, L Young-Xu, Y Goertzel, B Watts, B Flashman, L McAllister, T AF Poulin, Chris Shiner, Brian Thompson, Paul Vepstas, Linas Young-Xu, Yinong Goertzel, Benjamin Watts, Bradley Flashman, Laura McAllister, Thomas TI Predicting the Risk of Suicide by Analyzing the Text of Clinical Notes SO PLOS ONE LA English DT Article ID HEALTH SYSTEM; UNITED-STATES; PRIMARY-CARE; DEPRESSION; VETERANS; THOUGHTS; COMORBIDITY; IDEATION; ALTITUDE; OUTCOMES AB We developed linguistics-driven prediction models to estimate the risk of suicide. These models were generated from unstructured clinical notes taken from a national sample of U. S. Veterans Administration (VA) medical records. We created three matched cohorts: veterans who committed suicide, veterans who used mental health services and did not commit suicide, and veterans who did not use mental health services and did not commit suicide during the observation period (n = 70 in each group). From the clinical notes, we generated datasets of single keywords and multi-word phrases, and constructed prediction models using a machine-learning algorithm based on a genetic programming framework. The resulting inference accuracy was consistently 65% or more. Our data therefore suggests that computerized text analytics can be applied to unstructured medical records to estimate the risk of suicide. The resulting system could allow clinicians to potentially screen seemingly healthy patients at the primary care level, and to continuously evaluate the suicide risk among psychiatric patients. C1 [Poulin, Chris; Thompson, Paul; Flashman, Laura; McAllister, Thomas] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Poulin, Chris; Thompson, Paul; Flashman, Laura; McAllister, Thomas] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Poulin, Chris; Thompson, Paul; Vepstas, Linas] Durkheim Project, Portsmouth, NH USA. [Shiner, Brian; Young-Xu, Yinong; Watts, Bradley] US Dept Vet Affairs, White River Junct VA Med Ctr, White River Jct, VT USA. [Goertzel, Benjamin] Novamente LLC, Rockville, MD USA. RP Poulin, C (reprint author), Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. EM chris@durkheimproject.org FU Defense Advanced Research Projects Agency (DARPA); Space Warfare Systems Center Pacific [N66001-11-4006]; Intelligence Advanced Research Projects Activity (IARPA) via the Department of Interior National Business Center [N10PC20221] FX This material is based upon work supported by the Defense Advanced Research Projects Agency (DARPA), and Space Warfare Systems Center Pacific under Contract N66001-11-4006. Also supported by, the Intelligence Advanced Research Projects Activity (IARPA) via the Department of Interior National Business Center contract number N10PC20221. The opinions, findings and conclusions or recommendations expressed in this material are those of the authors(s) and do not necessarily reflect the views of the Defense Advanced Research Projects Agency (DARPA) and the Space Naval Warfare Systems Center Pacific, or IARPA, DOI/NBC, or the U. S. Government. The funders had no role in study design, data collection and analysis, or preparation of the manuscript. NR 36 TC 17 Z9 17 U1 4 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 28 PY 2014 VL 9 IS 1 AR e85733 DI 10.1371/journal.pone.0085733 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301CJ UT WOS:000330510000018 PM 24489669 ER PT J AU Wu, A Good, C Downs, JR Fine, MJ Pugh, MJV Anzueto, A Mortensen, EM AF Wu, Albert Good, Chester Downs, John R. Fine, Michael J. Pugh, Mary Jo V. Anzueto, Antonio Mortensen, Eric M. TI The Association of Cardioprotective Medications with Pneumonia-Related Outcomes SO PLOS ONE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; RESPIRATORY-DISTRESS-SYNDROME; ACUTE CORONARY SYNDROMES; HEART-DISEASE; INFECTION; COMPLICATION; POLYMORPHISM; MORTALITY; ACCURACY; RECEPTOR AB Introduction: Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes. Materials and Methods: We conducted a retrospective population-based study on male patients >= 65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events. Results: Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63-0.77), ACE inhibitors (OR 0.82, 95% CI 0.74-0.91), and ARBs (OR 0.58, 95% CI 0.44-0.77). However, none of the medications were significantly associated with decreased cardiovascular events. Discussion: While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects. C1 [Wu, Albert; Downs, John R.; Pugh, Mary Jo V.; Anzueto, Antonio] South Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX USA. [Wu, Albert; Downs, John R.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat, San Antonio, TX 78229 USA. [Good, Chester; Fine, Michael J.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Good, Chester; Fine, Michael J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Mortensen, Eric M.] VA North Texas Hlth Care Syst, Med Serv, Dallas, TX 75216 USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. RP Mortensen, EM (reprint author), VA North Texas Hlth Care Syst, Med Serv, Dallas, TX 75216 USA. EM Eric.Mortensen@UTSouthwestern.edu OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research [R01NR010828] FX This work was supported by grant number (R01NR010828) from the National Institute of Nursing Research. This material is the result of work supported with resources and the use of facilities at the South Texas Veterans Health Care System. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 5 Z9 5 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 28 PY 2014 VL 9 IS 1 AR e85797 DI 10.1371/journal.pone.0085797 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301CJ UT WOS:000330510000019 PM 24489672 ER PT J AU Huang, Y Chavez, L Chang, X Wang, X Pastor, WA Kang, J Zepeda-Martinez, JA Pape, UJ Jacobsen, SE Peters, B Rao, A AF Huang, Yun Chavez, Lukas Chang, Xing Wang, Xue Pastor, William A. Kang, Jinsuk Zepeda-Martinez, Jorge A. Pape, Utz J. Jacobsen, Steven E. Peters, Bjoern Rao, Anjana TI Distinct roles of the methylcytosine oxidases Tet1 and Tet2 in mouse embryonic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA methylation; DNA hydroxymethylation; epigenetics; DNA demethylation ID MYELOID CANCERS; POSTNATAL-DEVELOPMENT; DNA DEMETHYLATION; BASE-RESOLUTION; MAMMALIAN DNA; 5-HYDROXYMETHYLCYTOSINE; GENOME; 5-METHYLCYTOSINE; METHYLATION; CHROMATIN AB Dioxygenases of the Ten-Eleven Translocation (TET) family are 5-methylcytosine oxidases that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidation products in DNA. We show that Tet1 and Tet2 have distinct roles in regulating 5hmC in mouse embryonic stem cells (mESC). Tet1 depletion diminishes 5hmC levels at transcription start sites (TSS), whereas Tet2 depletion is predominantly associated with decreased 5hmC in gene bodies. Enrichment of 5hmC is observed at the boundaries of exons that are highly expressed, and Tet2 depletion results in substantial loss of 5hmC at these boundaries. In contrast, at promoter/TSS regions, Tet2 depletion results in increased 5hmC, potentially because of the redundant activity of Tet1. Together, the data point to a complex interplay between Tet1 and Tet2 in mESC, and to distinct roles for these two proteins in regulating promoter, exon, and polyadenylation site usage in cells. C1 [Huang, Yun; Chavez, Lukas; Chang, Xing; Wang, Xue; Pastor, William A.; Kang, Jinsuk; Zepeda-Martinez, Jorge A.; Rao, Anjana] La Jolla Inst Allergy & Immunol, Div Signalling & Gene Express, La Jolla, CA 92037 USA. [Peters, Bjoern] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA. [Huang, Yun; Chavez, Lukas; Chang, Xing; Rao, Anjana] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA. [Pastor, William A.; Jacobsen, Steven E.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. [Pastor, William A.; Jacobsen, Steven E.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. [Pastor, William A.; Jacobsen, Steven E.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA. [Pape, Utz J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Pape, Utz J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Rao, A (reprint author), La Jolla Inst Allergy & Immunol, Div Signalling & Gene Express, La Jolla, CA 92037 USA. EM arao@liai.org OI , chang xing/0000-0002-5072-9225; Huang, Yun/0000-0001-5950-9168; Chavez, Lukas/0000-0002-8718-8848 FU Leukemia and Lymphoma Society; Alexander von Humboldt Foundation; Jane Coffin Childs Memorial Fund for Medical Research; National Institutes of Health [R01 HL114093, U19 AI100275, R01 GM60398, R01 AI44432, HD065812, CA151535]; California Institute of Regenerative Medicine [RM1-01729]; Leukemia and Lymphoma Society Translational Research Program [6187-12] FX We thank Drs. Harri Lahdesmaki and Tarmo Aijo (Aalto University School of Science) for suggestions on data analysis and Dr. Bing Ren (University of California at San Diego) and Suhua Feng (University of California, Los Angeles) for assistance with next generation sequencing. Y.H. is supported by a postdoctoral Fellow Award from the Leukemia and Lymphoma Society, L.C. by a Feodor Lynen postdoctoral Research Fellowship from the Alexander von Humboldt Foundation, W.A.P. by an National Science Foundation predoctoral graduate research fellowship and a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research, and J.K. by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. S.E.J. is an Investigator of the Howard Hughes Medical Institute. This study was supported by National Institutes of Health Grants R01 HL114093, U19 AI100275 (to A.R. and B.P.), R01 GM60398 (to S.E.J.), R01 AI44432, HD065812, and CA151535, California Institute of Regenerative Medicine Grant RM1-01729, and Leukemia and Lymphoma Society Translational Research Program Grant 6187-12 (to A.R.). NR 48 TC 71 Z9 75 U1 2 U2 21 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 28 PY 2014 VL 111 IS 4 BP 1361 EP 1366 DI 10.1073/pnas.1322921111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297BV UT WOS:000330231100043 PM 24474761 ER PT J AU Zhao, L Borikova, AL Ben-Yair, R Guner-Ataman, B MacRae, CA Lee, RT Burns, CG Burns, CE AF Zhao, Long Borikova, Asya L. Ben-Yair, Raz Guner-Ataman, Burcu MacRae, Calum A. Lee, Richard T. Burns, C. Geoffrey Burns, Caroline E. TI Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE myocardial infarction; model organism ID MYOCARDIAL-INFARCTION; ACTIVATION; CELLS; CRYOINJURY; EXPRESSION; RENEWAL; PATHWAY; EPICARDIUM; CAPACITY; DISEASE AB The human heart's failure to replace ischemia-damaged myocardium with regenerated muscle contributes significantly to the worldwide morbidity and mortality associated with coronary artery disease. Remarkably, certain vertebrate species, including the zebrafish, achieve complete regeneration of amputated or injured myocardium through the proliferation of spared cardiomyocytes. Nonetheless, the genetic and cellular determinants of natural cardiac regeneration remain incompletely characterized. Here, we report that cardiac regeneration in zebrafish relies on Notch signaling. Following amputation of the zebrafish ventricular apex, Notch receptor expression becomes activated specifically in the endocardium and epicardium, but not the myocardium. Using a dominant negative approach, we discovered that suppression of Notch signaling profoundly impairs cardiac regeneration and induces scar formation at the amputation site. We ruled out defects in endocardial activation, epicardial activation, and dedifferentiation of compact myocardial cells as causative for the regenerative failure. Furthermore, coronary endothelial tubes, which we lineage traced from preexisting endothelium in wild-type hearts, formed in the wound despite themyocardial regenerative failure. Quantification of myocardial proliferation in Notch-suppressed hearts revealed a significant decrease in cycling cardiomyocytes, an observation consistent with a noncell autonomous requirement for Notch signaling in cardiomyocyte proliferation. Unexpectedly, hyperactivation of Notch signaling also suppressed cardiomyocyte proliferation and heart regeneration. Taken together, our data uncover the exquisite sensitivity of regenerative cardiomyocyte proliferation to perturbations in Notch signaling. C1 [Zhao, Long; Borikova, Asya L.; Ben-Yair, Raz; Guner-Ataman, Burcu; Burns, C. Geoffrey; Burns, Caroline E.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Zhao, Long; Borikova, Asya L.; Ben-Yair, Raz; Guner-Ataman, Burcu; Burns, C. Geoffrey; Burns, Caroline E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [MacRae, Calum A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [MacRae, Calum A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [MacRae, Calum A.; Lee, Richard T.; Burns, C. Geoffrey; Burns, Caroline E.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Lee, Richard T.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Cambridge, MA 02139 USA. [Lee, Richard T.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. RP Burns, CG (reprint author), Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM gburns@cvrc.mgh.harvard.edu; cburns6@partners.org RI Zhao, Long/A-6439-2014 FU Harvard Stem Cell Institute Young Investigator Program; Harvard Stem Cell Institute Cardiovascular Program FX We thank Myron Ignatius and David Langenau (Massachusetts General Hospital) for providing the murine DN-MAML-GFP cDNA construct; Neil Chi (University of California, San Diego) for providing the Tg(kdrl:mCherry-ras)s896 zebrafish strain; and Kazu Kikuchi and Kenneth Poss (Duke University) for providing the unpublished Tg (gata4:DsRed2) strain. This work was supported by awards from the Harvard Stem Cell Institute Young Investigator Program (to C.E.B.) and the Harvard Stem Cell Institute Cardiovascular Program (to C.A.M., R.T.L., C.G.B., and C.E.B.). NR 48 TC 50 Z9 51 U1 5 U2 26 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 28 PY 2014 VL 111 IS 4 BP 1403 EP 1408 DI 10.1073/pnas.1311705111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297BV UT WOS:000330231100050 PM 24474765 ER PT J AU Lia, WL Ai, NP Wang, SM Bhattacharya, N Vrbanac, V Collins, M Signoretti, S Hu, YH Boyce, FM Gravdal, K Halvorsen, OJ Nalwoga, H Akslen, LA Harlow, E Watnick, RS AF Lia, Wenliang Ai, Nanping Wang, Suming Bhattacharya, Nandita Vrbanac, Vladimir Collins, Michael Signoretti, Sabina Hu, Yanhui Boyce, Frederick M. Gravdal, Karsten Halvorsen, Ole J. Nalwoga, Hawa Akslen, Lars A. Harlow, Ed Watnick, Randolph S. TI GRK3 is essential for metastatic cells and promotes prostate tumor progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional screens; essential kinases; ADRBK2; TSP-1; PAI-2 ID RECEPTOR KINASE 2; CANCER-CELLS; CHROMOSOMAL LOCALIZATION; BREAST-CANCER; ANGIOGENESIS; REQUIREMENTS; EXPRESSION; ROLES; THROMBOSPONDIN-1; PROLIFERATION AB The biochemical mechanisms that regulate the process of cancer metastasis are still poorly understood. Because kinases, and the signaling pathways they comprise, play key roles in regulation of many cellular processes, we used an unbiased RNAi in vitro screen and a focused cDNA in vivo screen against human kinases to identify those with previously undocumented roles in metastasis. We discovered that G-protein-coupled receptor kinase 3 (GRK3; or beta-adrenergic receptor kinase 2) was not only necessary for survival and proliferation of metastatic cells, but also sufficient to promote primary prostate tumor growth and metastasis upon exogenous expression in poorly metastatic cells in mouse xenograft models. Mechanistically, we found that GRK3 stimulated angiogenesis, at least in part through down-regulation of thrombospondin-1 and plasminogen activator inhibitor type 2. Furthermore, GRK3 was found to be overexpressed in human prostate cancers, especially in metastatic tumors. Taken together, these data suggest that GRK3 plays an important role in prostate cancer progression and metastasis. C1 [Lia, Wenliang; Ai, Nanping] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA. [Lia, Wenliang] Univ Texas Hlth Sci Ctr Houston, Div Oncol, Dept Internal Med, Houston, TX 77030 USA. [Wang, Suming; Watnick, Randolph S.] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. [Wang, Suming; Watnick, Randolph S.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Bhattacharya, Nandita] Tufts Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02135 USA. [Vrbanac, Vladimir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Collins, Michael; Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hu, Yanhui; Harlow, Ed] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Boyce, Frederick M.] Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02139 USA. [Gravdal, Karsten; Halvorsen, Ole J.; Nalwoga, Hawa; Akslen, Lars A.] Univ Bergen, Dept Clin Med, Ctr Canc Biomarkers, N-5020 Bergen, Norway. [Gravdal, Karsten; Halvorsen, Ole J.; Nalwoga, Hawa; Akslen, Lars A.] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. RP Lia, WL (reprint author), Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA. EM wenliang.li@uth.tmc.edu; eharlow@hms.harvard.edu RI Akslen, Lars /C-1202-2017 OI Akslen, Lars /0000-0003-2710-9543 FU University of Texas System; National Institutes of Health [1R01DK089975, R01 CA135417, P01 CA045548]; Instituto Dermopatico dell'Immacolata (Italy); Elsa U. Pardee Foundation FX The authors thank all the members of the laboratories of W.L., E.H., and J. LaBaer for their support and help; the members of the RNAi Consortium, including D. Root, N. Hacohen, W. Hahn, E. Lander, D. Sabatini, S. Stewart, and B. Stockwell, for providing their library; Drs. I. Fidler and M. Herlyn for providing human cancer cell lines; and G. L. Hallseth and B. Nordanger for their assistance. This work was supported by a Rising STARS (Science and Technology Acquisition and Retention) Award from the University of Texas System (to W.L.); National Institutes of Health Grants 1R01DK089975 (to S.S.), R01 CA135417 (to R.W.), and P01 CA045548 (to R.W.); an award from Instituto Dermopatico dell'Immacolata (Italy) (to S.S.); and the Elsa U. Pardee Foundation (R.W.). NR 36 TC 3 Z9 3 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 28 PY 2014 VL 111 IS 4 BP 1521 EP 1526 DI 10.1073/pnas.1320638111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297BV UT WOS:000330231100070 ER PT J AU Seijffers, R Zhang, JW Matthews, JC Chen, A Tamrazian, E Babaniyi, O Selig, M Hynynen, M Woolf, CJ Brown, RH AF Seijffers, Rhona Zhang, Jiangwen Matthews, Jonathan C. Chen, Adam Tamrazian, Eric Babaniyi, Olusegun Selig, Martin Hynynen, Meri Woolf, Clifford J. Brown, Robert H., Jr. TI ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; C-JUN PHOSPHORYLATION; TRANSGENIC MICE; MOLECULAR-BIOLOGY; DISEASE; DEATH; DEGENERATION; MOTONEURONS; MECHANISMS; OUTGROWTH AB ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways. C1 [Seijffers, Rhona; Babaniyi, Olusegun; Woolf, Clifford J.] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Seijffers, Rhona; Babaniyi, Olusegun; Woolf, Clifford J.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Seijffers, Rhona; Babaniyi, Olusegun; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Zhang, Jiangwen] Harvard Univ, Fac Arts & Sci Res Comp, Cambridge, MA 02138 USA. [Matthews, Jonathan C.; Chen, Adam; Tamrazian, Eric; Hynynen, Meri; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Tamrazian, Eric] St Georges Univ, Sch Med, St Georges, ON, Canada. [Selig, Martin] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Seijffers, R (reprint author), Childrens Hosp, FM Kirby Neurobiol Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM rseijffers@gmail.com FU National Institutes of Health [P50NS40828, P30HD18655, NS038253]; ALS Therapy Alliance; Israel ALS Research Association (IsrALS); Medical Research Foundation; Angel Fund; Project ALS; P2ALS; ALS Research Fund; National Institute of Neurological Disorders and Stroke Awards [1RC2NS070342-01, 1RC1NS068391-01, R01NS050557-05, U01NS05225-03, R01NS065847-01A1] FX We thank Igor Bagayev at the Confocal Core Facility at Massachusetts General Hospital for assistance. We also thank the Molecular Genetics Core Facility at Children's Hospital of Boston for providing microarray support, which was supported by National Institutes of Health Grants P50NS40828 and P30HD18655. This study was supported by the ALS Therapy Alliance (R.S.), Israel ALS Research Association (IsrALS) (R.S.), National Institutes of Health Grant NS038253 (to C.J.W.), and the Miriam and Sheldon G. Adelson Medical Research Foundation (C.J.W.). R.H.B. was supported by the Angel Fund, the ALS Therapy Alliance, Project ALS, P2ALS, the Pierre L. De Bourgknecht ALS Research Fund, and National Institute of Neurological Disorders and Stroke Awards 1RC2NS070342-01, 1RC1NS068391-01, R01NS050557-05, U01NS05225-03, and R01NS065847-01A1. NR 46 TC 9 Z9 9 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 28 PY 2014 VL 111 IS 4 BP 1622 EP 1627 DI 10.1073/pnas.1314826111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297BV UT WOS:000330231100087 PM 24474789 ER PT J AU Zuk, O Schaffner, SF Samocha, K Do, R Hechter, E Kathiresan, S Daly, MJ Neale, BM Sunyaev, SR Lander, ES AF Zuk, Or Schaffner, Stephen F. Samocha, Kaitlin Do, Ron Hechter, Eliana Kathiresan, Sekar Daly, Mark J. Neale, Benjamin M. Sunyaev, Shamil R. Lander, Eric S. TI Searching for missing heritability: Designing rare variant association studies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mapping disease genes; power analysis; statistical genetics ID CORONARY-HEART-DISEASE; DE-NOVO MUTATIONS; COMMON SNPS; COMPLEX DISEASES; LOW-FREQUENCY; HUMAN EXOMES; HUMAN GENOME; HUMAN HEIGHT; GENES; POPULATION AB Genetic studies have revealed thousands of loci predisposing to hundreds of human diseases and traits, revealing important biological pathways and defining novel therapeutic hypotheses. However, the genes discovered to date typically explain less than half of the apparent heritability. Because efforts have largely focused on common genetic variants, one hypothesis is that much of the missing heritability is due to rare genetic variants. Studies of common variants are typically referred to as genomewide association studies, whereas studies of rare variants are often simply called sequencing studies. Because they are actually closely related, we use the terms common variant association study (CVAS) and rare variant association study (RVAS). In this paper, we outline the similarities and differences between RVAS and CVAS and describe a conceptual framework for the design of RVAS. We apply the framework to address key questions about the sample sizes needed to detect association, the relative merits of testing disruptive alleles vs. missense alleles, frequency thresholds for filtering alleles, the value of predictors of the functional impact of missense alleles, the potential utility of isolated populations, the value of gene-set analysis, and the utility of de novo mutations. The optimal design depends critically on the selection coefficient against deleterious alleles and thus varies across genes. The analysis shows that common variant and rare variant studies require similarly large sample collections. In particular, a well-powered RVAS should involve discovery sets with at least 25,000 cases, together with a substantial replication set. C1 [Zuk, Or; Schaffner, Stephen F.; Samocha, Kaitlin; Do, Ron; Hechter, Eliana; Kathiresan, Sekar; Daly, Mark J.; Neale, Benjamin M.; Sunyaev, Shamil R.; Lander, Eric S.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Zuk, Or] Toyota Technol Inst Chicago, Chicago, IL 60637 USA. [Samocha, Kaitlin; Daly, Mark J.; Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Samocha, Kaitlin; Daly, Mark J.; Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Samocha, Kaitlin] Harvard Univ, Sch Med, Program Genet & Genom, Boston, MA 02114 USA. [Do, Ron; Hechter, Eliana] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Sunyaev, Shamil R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Zuk, O (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM lander@broadinstitute.org RI Schaffner, Stephen/D-1189-2011 FU NHGRI NIH HHS [U54 HG003067] NR 60 TC 162 Z9 162 U1 7 U2 44 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 28 PY 2014 VL 111 IS 4 BP E455 EP E464 DI 10.1073/pnas.1322563111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297BV UT WOS:000330231100008 PM 24443550 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, Robert P. Braunwald, Eugene TI The Year in Acute Coronary Syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE biomarkers; coronary stent(s); myocardial infarction; plaque rupture; platelets; thrombosis; troponin ID ELEVATION MYOCARDIAL-INFARCTION; ST-SEGMENT-ELEVATION; CARDIOVASCULAR DATA REGISTRY; DUAL ANTIPLATELET THERAPY; BARE-METAL STENTS; OPTICAL COHERENCE TOMOGRAPHY; ASSOCIATION TASK-FORCE; TIMI RISK SCORE; EMERGENCY-DEPARTMENT; RANDOMIZED-TRIALS C1 [Giugliano, Robert P.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org FU Amgen; Daiichi-Sankyo; Merck; AstraZeneca; Johnson Johnson; Beckman Coulter; Roche Diagnostics; Sanofi-Aventis; GlaxoSmithKline; Bristol-Myers Squibb FX From the TIMI Study Group, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Dr. Giugliano has received grant support from Amgen, Daiichi-Sankyo, and Merck to the TIMI Study Group for clinical studies in which he is an investigator; and honoraria for continuing medical education lectures or consulting from Amgen, Beckman-Coulter, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen, Lexicon, Merck, Regeneron, and Sanofi. Dr. Braunwald has received grant support from AstraZeneca, Johnson & Johnson, Beckman Coulter, Daiichi-Sankyo, Merck, Roche Diagnostics, Sanofi-Aventis, GlaxoSmithKline, and Bristol-Myers Squibb to the TIMI Study Group for clinical studies in which he is (or was) study chairman; and honoraria for continuing medical education lectures or consulting from Amorcyte, The Medicines Company, Medscape, Bayer, Daiichi Sankyo, Menarini International, and Sanofi-Aventis. NR 98 TC 10 Z9 11 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 28 PY 2014 VL 63 IS 3 BP 201 EP 214 DI 10.1016/j.jacc.2013.10.041 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 295QI UT WOS:000330130200002 PM 24239661 ER PT J AU Kohli, P Udell, JA Murphy, SA Cannon, CP Antman, EM Braunwald, E Wiviott, SD AF Kohli, Payal Udell, Jacob A. Murphy, Sabina A. Cannon, Christopher P. Antman, Elliott M. Braunwald, Eugene Wiviott, Stephen D. TI Discharge Aspirin Dose and Clinical Outcomes in Patients With Acute Coronary Syndromes Treated With Prasugrel Versus Clopidogrel SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ASSOCIATION TASK-FORCE; MYOCARDIAL-INFARCTION; CYCLOOXYGENASE INHIBITION; PLATELET INHIBITION; PRACTICE GUIDELINES; UNSTABLE ANGINA; CARDIOLOGY; INTERVENTIONS; PHARMACOLOGY; TICAGRELOR AB Objectives The goal of this study was to determine whether there is a relationship between aspirin dose and the potent antiplatelet agent prasugrel in the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) study. Background Optimal aspirin dosing after acute coronary syndromes remains uncertain. Previous studies have raised questions regarding an interaction between high-dose aspirin and the potent antiplatelet agent ticagrelor. Methods In TRITON-TIMI 38, we classified 12,674 patients into low-dose (<150 mg) or high-dose (>= 150 mg) aspirin groups based on discharge dose. We identified independent correlates of dose selection and studied the impact of aspirin dose on the clinical effects of prasugrel. Results There was significant geographical variation in aspirin dosing, with North American patients receiving high-dose aspirin more frequently than other countries (66% vs. 28%; p < 0.001). Clinical factors correlating with high-dose aspirin included previous percutaneous coronary intervention and use of aspirin before randomization. Characteristics associated with the use of low-dose aspirin included age >= 75 years, white race, and use of bivalirudin or a glycoprotein Ilb/Illa inhibitor during coronary intervention. Regardless of low- or high-dose aspirin use, prasugrel had lower rates of the primary efficacy endpoint (cardiovascular death, myocardial infarction, or stroke [CVO/MI/stroke]) (hazard ratio [HR](cvo/mvstroke) = 0.78 [95% confidence interval (Cl) 0.64 to 0.95] and HRcvo/mvstroke = 0.87 [95% Cl 0.69 to 1.10], respectively; p value for interaction = 0.48) and higher rates of the primary safety endpoint (HR (TIMI major bleeding) = 1.40 [95% Cl 0.81 to 2.42] and TIMI (major bleeding) 1.30 [95% Cl 0.63 to 2.68], respectively; p value for interaction = 0.84) compared with clopidogrel. Conclusions In TRITON-TIMI 38, the safety and efficacy outcomes of prasugrel compared with those of clopidogrel were directionally consistent regardless of aspirin dose, although only the primary efficacy endpoint achieved statistical significance. There was no clinically meaningful interaction of aspirin with prasugrel, suggesting that previous observations with potent antiplatelet agents indicating differential results are not universal. (A Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591) (J Am Coll Cardiol 2014;63:225-32) (C) 2014 by the American College of Cardiology Foundation C1 [Kohli, Payal] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Udell, Jacob A.; Murphy, Sabina A.; Cannon, Christopher P.; Antman, Elliott M.; Braunwald, Eugene; Wiviott, Stephen D.] Dept Med, TIMI Study Grp, Div Cardiol, Boston, MA USA. [Udell, Jacob A.; Murphy, Sabina A.; Cannon, Christopher P.; Antman, Elliott M.; Braunwald, Eugene; Wiviott, Stephen D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Udell, Jacob A.; Murphy, Sabina A.; Cannon, Christopher P.; Antman, Elliott M.; Braunwald, Eugene; Wiviott, Stephen D.] Harvard Univ, Sch Med, Boston, MA USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM swiviott@partners.org NR 21 TC 14 Z9 15 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 28 PY 2014 VL 63 IS 3 BP 225 EP 232 DI 10.1016/j.jacc.2013.09.023 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 295QI UT WOS:000330130200004 PM 24140678 ER PT J AU Kaz, AM Grady, WM AF Kaz, Andrew M. Grady, William M. TI Epigenetic biomarkers in esophageal cancer SO CANCER LETTERS LA English DT Review DE DNA methylation; Biomarker; Barrett's esophagus; Esophageal adenocarcinoma; Esophageal squamous cell carcinoma ID SQUAMOUS-CELL CARCINOMA; CPG ISLAND HYPERMETHYLATION; TUMOR-SUPPRESSOR GENES; BARRETTS-ESOPHAGUS; PROMOTER HYPERMETHYLATION; NEOPLASTIC PROGRESSION; EARLY EVENT; PREDICTS PROGRESSION; POOR-PROGNOSIS; E-CADHERIN AB The aberrant DNA methylation of tumor suppressor genes is well documented in esophageal cancer, including adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) as well as in Barrett's esophagus (BE), a pre-malignant condition that is associated with chronic acid reflux. BE is a well-recognized risk factor for the development of EAC, and consequently the standard of care is for individuals with BE to be placed in endoscopic surveillance programs aimed at detecting early histologic changes that associate with an increased risk of developing EAC. Yet because the absolute risk of EAC in individuals with BE is minimal, a clinical need in the management of BE is the identification of additional risk markers that will indicate individuals who are at a significant absolute risk of EAC so that they may be subjected to more intensive surveillance. The best currently available risk marker is the degree of dysplasia in endoscopic biopsies from the esophagus; however, this marker is suboptimal for a variety of reasons. To date, there are no molecular biomarkers that have been translated to widespread clinical practice. The search for biomarkers, including hypermethylated genes, for either the diagnosis of BE, EAC, or ESCC or for risk stratification for the development of EAC in those with BE is currently an area of active research. In this review, we summarize the status of identified candidate epigenetic biomarkers for BE, EAC, and ESCC. Most of these aberrantly methylated genes have been described in the context of early detection or diagnostic markers; others might prove useful for estimating prognosis or predicting response to treatment. Finally, special attention will be paid to some of the challenges that must be overcome in order to develop clinically useful esophageal cancer biomarkers. Published by Elsevier Ireland Ltd. C1 [Kaz, Andrew M.; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. RP Kaz, AM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,D4-100, Seattle, WA 98109 USA. EM akaz@fhcrc.org; wgrady@fhcrc.org FU NIH [5KO8DK080630-05, 5U01CA152756-02, 1U54CA163060, 5U01CA 152756, 5U54CA143682]; Burroughs Wellcome Fund FX This work was supported by the NIH (5KO8DK080630-05, 5U01CA152756-02) to AMK; and NIH (1U54CA163060, 5U01CA 152756, 5U54CA143682) and Burroughs Wellcome Fund to WMG. We regret that we were not able to discuss all the outstanding research being done in this area, but space restraints prevented us from being able to cite all the relevant studies related to epigenetic alterations and esophageal cancer. NR 80 TC 23 Z9 24 U1 1 U2 20 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD JAN 28 PY 2014 VL 342 IS 2 SI SI BP 193 EP 199 DI 10.1016/j.canlet.2012.02.036 PG 7 WC Oncology SC Oncology GA 278ZJ UT WOS:000328928100005 PM 22406828 ER PT J AU Reese, PP Bloom, RD Shults, J Thomasson, A Mussell, A Rosas, SE Johansen, KL Abt, P Levine, M Caplan, A Feldman, HI Karlawish, J AF Reese, Peter P. Bloom, Roy D. Shults, Justine Thomasson, Arwin Mussell, Adam Rosas, Sylvia E. Johansen, Kirsten L. Abt, Peter Levine, Matthew Caplan, Arthur Feldman, Harold I. Karlawish, Jason TI Functional Status and Survival After Kidney Transplantation SO TRANSPLANTATION LA English DT Article DE Older age; Functional status; Kidney transplant; Survival ID DIALYSIS PATIENTS; RENAL-TRANSPLANTATION; HEMODIALYSIS-PATIENTS; PHYSICAL FUNCTION; OLDER-ADULTS; CANDIDATES; MORTALITY; ASSOCIATION; INFLAMMATION; POPULATION AB Background Older patients constitute a growing proportion of U.S. kidney transplant recipients and often have a high burden of comorbidities. A summary measure of health such as functional status might enable transplant professionals to better evaluate and counsel these patients about their prognosis after transplant. Methods We linked United Network for Organ Sharing registry data about posttransplantation survival with pretransplantation functional status data (physical function [PF] scale of the Medical Outcomes Study Short Form-36) among individuals undergoing kidney transplant from June 1, 2000 to May 31, 2006. We examined the relationship between survival and functional status with multivariable Cox regression, adjusted for age. Using logistic regression models for 3-year survival, we also estimated the reduction in deaths in the hypothetical scenario that recipients with poor functional status in this cohort experienced modest improvements in function. Results The cohort comprised 10,875 kidney transplant recipients with a mean age of 50 years; 14% were 65. Differences in 3-year mortality between highest and lowest PF groups ranged from 3% among recipients <35 years to 14% among recipients 65 years. In multivariable Cox regression, worse PF was associated with higher mortality (hazard ratio, 1.66 for lowest vs. highest PF quartiles; P<0.001). Interactions between PF and age were nonsignificant. We estimated that 11% fewer deaths would occur if kidney transplant recipients with the lowest functional status experienced modest improvements in function. Conclusions Across a wide age range, functional status was an independent predictor of posttransplantation survival. Functional status assessment may be a useful tool with which to counsel patients about posttransplantation outcomes. C1 [Reese, Peter P.; Bloom, Roy D.; Mussell, Adam; Rosas, Sylvia E.; Feldman, Harold I.] Univ Penn, Perelman Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Reese, Peter P.; Feldman, Harold I.; Karlawish, Jason] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Reese, Peter P.; Feldman, Harold I.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Reese, Peter P.; Karlawish, Jason] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Shults, Justine; Thomasson, Arwin] Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA. [Rosas, Sylvia E.] Philadelphia Veteran Affairs Med Ctr, Philadelphia, PA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Abt, Peter; Levine, Matthew] Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Caplan, Arthur] NYU, Div Med Eth, New York, NY USA. [Karlawish, Jason] Univ Penn, Perelman Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. RP Reese, PP (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 917 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.reese@uphs.upenn.edu RI Levine, Matthew/O-4809-2015 OI Levine, Matthew/0000-0003-4525-5827 FU Society of Specialty Professors; American Society of Nephrology; John A. Hartford Foundation; Atlantic Philanthropies; [R01-DK090388-01A1] FX P.P.R. was supported by R01-DK090388-01A1 and by a grant from the Society of Specialty Professors, the American Society of Nephrology, the John A. Hartford Foundation, and the Atlantic Philanthropies. NR 39 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 2014 VL 97 IS 2 BP 189 EP 195 DI 10.1097/TP.0b013e3182a89338 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AH0VE UT WOS:000335837900017 PM 24113514 ER PT J AU Wubben, TJ Guerrero, CM Salum, M Wolfe, GS Giovannelli, GP Ramsey, DJ AF Wubben, Thomas J. Guerrero, Christopher M. Salum, Marlo Wolfe, Gregory S. Giovannelli, Gerald P. Ramsey, David J. TI Presbyopia: a pilot investigation of the barriers and benefits of near visual acuity correction among a rural Filipino population SO BMC OPHTHALMOLOGY LA English DT Article DE Presbyopia; Quality of life; Survey; Near vision; Stereoacuity; Reading glasses ID QUALITY-OF-LIFE; UNCORRECTED PRESBYOPIA; FUNCTIONAL PRESBYOPIA; VISION IMPAIRMENT; REFRACTIVE ERRORS; ADULTS; EYE; ACCOMMODATION; IMPACT AB Background: Presbyopia is the age-related decline in accommodation that diminishes the ability of the eye to focus on near objects. Presbyopia is common and easy to correct; however, many communities lack access to basic eye care. The purpose of this project was to assess the burden of uncorrected presbyopia in a rural Filipino population and to pilot an intervention aimed at increasing access to reading glasses in the community. Methods: Individuals above the age of 40 who presented to a health outreach in the Philippines were invited to undergo a near vision exam to detect the presence of functional presbyopia and be fitted with ready-made, single-vision glasses. The change in stereoacuity was used as a surrogate measure of functional improvement after near vision correction. A questionnaire was administered to assess this population's perceived barriers and benefits to correcting near vision. Results: The average age of the participants was 57 +/- 11 years, with 87.6% of participants having an uncorrected near visual acuity of <20/50. Reading glasses improved near vision to 20/40 or better in 77.7% of participants having near-vision impairment ( uncorrected near visual acuity of <20/40). Over 75% of participants also showed improvement in stereoacuity. Cost, rather than availability, was perceived to be the greater barrier to the procurement of glasses, and 84% of participants reported that the glasses dispensed would greatly improve their ability to earn a living. Conclusions: Dispensing ready-made, single-vision glasses is a simple and cost-effective intervention to improve near vision and enhance depth perception. A greater understanding of the barriers and benefits to correcting near vision will inform the design and execution of a sustainable program to correct presbyopia in developing countries. C1 [Wubben, Thomas J.; Guerrero, Christopher M.] Univ Illinois, Chicago, IL USA. [Salum, Marlo] St Marys Univ, Bayombang, Nueva Vizcaya, Philippines. [Wolfe, Gregory S.] Southern Calif Coll Optometry, Fullerton, CA USA. [Giovannelli, Gerald P.] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Ramsey, David J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ramsey, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ramsey@post.harvard.edu NR 25 TC 2 Z9 2 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2415 J9 BMC OPHTHALMOL JI BMC Ophthalmol. PD JAN 27 PY 2014 VL 14 AR 9 DI 10.1186/1471-2415-14-9 PG 7 WC Ophthalmology SC Ophthalmology GA AF1CX UT WOS:000334453100001 PM 24467667 ER PT J AU Park, L Andrade, D Mastey, A Sun, J Hicks, L AF Park, Lee Andrade, Danielle Mastey, Andrew Sun, James Hicks, LeRoi TI Institution specific risk factors for 30 day readmission at a community hospital: a retrospective observational study SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Readmission; Hospital quality; Risk factors ID GENERAL MEDICINE PATIENTS; MEDICARE BENEFICIARIES; CARE; REHOSPITALIZATION; PROGRAM; MODEL AB Background: As of October 1, 2012, hospitals in the United States with excess readmissions based on the Centers for Medicare and Medicaid Services (CMS) risk-adjusted ratio began being penalized. Given the impact of high readmission rates to hospitals nationally, it is important for individual hospitals to identify which patients may be at highest risk of readmission. The objective of this study was to assess the association of institution specific factors with 30-day readmission. Methods: The study is a retrospective observational study using administrative data from January 1, 2009 through December 31, 2010 conducted at a 257 bed community hospital in Massachusetts. The patients included inpatient medical discharges from the hospitalist service with the primary diagnoses of congestive heart failure, pneumonia or chronic obstructive pulmonary disease. The outcome was 30-day readmission rates. After adjusting for known factors that impact readmission, provider associated factors (i. e. hours worked and census on the day of discharge) and hospital associated factors (i. e. floor of discharge, season) were compared. Results: Over the study time period, there were 3774 discharges by hospitalists, with 637 30-day readmissions (17% readmission rate). By condition, readmission rates were 19.6% (448/2284) for congestive heart failure, 13.0% (141/1083) for pneumonia, and 14.7% (200/1358) for chronic obstructive lung disease. After adjusting for known risk factors (gender, age, length of stay, Elixhauser sum score, admission in the previous year, insurance, disposition, primary diagnosis), we found that patients discharged in the winter remained significantly more likely to be readmitted compared to the summer (OR 1.54, p = 0.0008). Patients discharged from the cardiac floor had a trend toward decreased readmission compared a medical/oncology floor (OR 0.85, p = 0.08). Hospitalist work flow factors (census and hours on the day of discharge) were not associated with readmission. Conclusions: We found that 30 day hospital readmissions may be associated with institution specific risk factors, even after adjustment for patient factors. These institution specific risk factors may be targets for interventions to prevent readmissions. C1 [Park, Lee] Massachusetts Gen Hosp, Div Gen Internal Med, Hosp Med Unit, Boston, MA 02114 USA. [Andrade, Danielle] Newton Wellesley Hosp, Decis Support Grp, Newton, MA 02462 USA. [Mastey, Andrew] Univ Hlth Syst Consortium, Comparat Data & Informat Grp, Chicago, IL 60606 USA. [Sun, James] Harvard Univ, Harvard Coll, Cambridge, MA 02138 USA. [Hicks, LeRoi] Univ Massachusetts, Med Ctr, Div Hosp Med, Worcester, MA 01605 USA. RP Park, L (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Hosp Med Unit, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM Lpark2@partners.org FU CIMIT Young Clinician Award; CIMIT FX Lee Park MD, MPH partially funded for the study through the CIMIT Young Clinician Award for 2012. The CIMIT grant did not have any role in the design, collection, analysis or interpretation of the data. Nor did the CIMIT grant have any role in writing of the manuscript or the decision to submit the manuscript for publication. NR 19 TC 9 Z9 9 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JAN 27 PY 2014 VL 14 AR 40 DI 10.1186/1472-6963-14-40 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AA6AB UT WOS:000331180000001 PM 24467793 ER PT J AU Johnson, CS Frei, CR Metersky, ML Anzueto, AR Mortensen, EM AF Johnson, Christopher S. Frei, Christopher R. Metersky, Mark L. Anzueto, Antonio R. Mortensen, Eric M. TI Non-invasive mechanical ventilation and mortality in elderly immunocompromised patients hospitalized with pneumonia: a retrospective cohort study SO BMC PULMONARY MEDICINE LA English DT Article DE Mechanical ventilation; Mortality; Immunocompromised; Pneumonia ID ACUTE RESPIRATORY-FAILURE; COMMUNITY-ACQUIRED PNEUMONIA; IMMUNOSUPPRESSED PATIENTS; OUTCOMES; TRIAL AB Background: Mortality after pneumonia in immunocompromised patients is higher than for immunocompetent patients. The use of non-invasive mechanical ventilation for patients with severe pneumonia may provide beneficial outcomes while circumventing potential complications associated with invasive mechanical ventilation. The aim of our study was to determine if the use of non-invasive mechanical ventilation in elderly immunocompromised patients with pneumonia is associated with higher all-cause mortality. Methods: In this retrospective cohort study, data were obtained from the Department of Veterans Affairs administrative databases. We included veterans age >= 65 years who were immunocompromised and hospitalized due to pneumonia. Multilevel logistic regression analysis was used to determine the relationship between the use of invasive versus non-invasive mechanical ventilation and 30-day and 90-day mortality. Results: Of 1,946 patients in our cohort, 717 received non-invasive mechanical ventilation and 1,229 received invasive mechanical ventilation. There was no significant association between all-cause 30-day mortality and non-invasive versus invasive mechanical ventilation in our adjusted model (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.66-1.10). However, those patients who received non-invasive mechanical ventilation had decreased 90-day mortality (OR 0.66, 95% CI 0.52-0.84). Additionally, receipt of guideline-concordant antibiotics in our immunocompromised cohort was significantly associated with decreased odds of 30-day mortality (OR 0.31, 95% CI 0.24-0.39) and 90-day mortality (OR 0.41, 95% CI 0.31-0.53). Conclusions: Our findings suggest that physicians should consider the use of non-invasive mechanical ventilation, when appropriate, for elderly immunocompromised patients hospitalized with pneumonia. C1 [Johnson, Christopher S.; Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Johnson, Christopher S.; Mortensen, Eric M.] Dallas VA Med Ctr, VA North Texas Hlth Care Syst, Dallas, TX 75216 USA. [Frei, Christopher R.; Anzueto, Antonio R.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Frei, Christopher R.; Anzueto, Antonio R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Frei, Christopher R.] Univ Texas Austin, Austin, TX 78712 USA. [Metersky, Mark L.] Univ Connecticut, Sch Med, Farmington, CT 06030 USA. RP Mortensen, EM (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM eric.mortensen@utsouthwestern.edu OI Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research [R01NR010828] FX The project described was supported by Grant Number R01NR010828 from the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. This material is the result of work supported with resources and the use of facilities at the VA North Texas Health Care System. Funding agencies had no role in conducting the study, or role in the preparation, review, or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 23 TC 2 Z9 3 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2466 J9 BMC PULM MED JI BMC Pulm. Med. PD JAN 27 PY 2014 VL 14 AR 7 DI 10.1186/1471-2466-14-7 PG 10 WC Respiratory System SC Respiratory System GA AB1QT UT WOS:000331569100003 PM 24468062 ER PT J AU Montesi, SB Mathai, SK Brenner, LN Gorshkova, IA Berdyshev, EV Tager, AM Shea, BS AF Montesi, Sydney B. Mathai, Susan K. Brenner, Laura N. Gorshkova, Irina A. Berdyshev, Evgeny V. Tager, Andrew M. Shea, Barry S. TI Docosatetraenoyl LPA is elevated in exhaled breath condensate in idiopathic pulmonary fibrosis SO BMC PULMONARY MEDICINE LA English DT Article DE Idiopathic pulmonary fibrosis; Exhaled breath condensate; Lysophosphatidic acid ID LYSOPHOSPHATIDIC ACID; LUNG INJURY; OXIDATIVE STRESS; RECEPTOR; AUTOTAXIN; RECOMMENDATIONS; PATHOGENESIS; EICOSANOIDS; ACTIVATION; PLATELETS AB Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective medical therapies. Recent research has focused on identifying the biological processes essential to the development and progression of fibrosis, and on the mediators driving these processes. Lysophosphatidic acid (LPA), a biologically active lysophospholipid, is one such mediator. LPA has been found to be elevated in bronchoalveolar lavage (BAL) fluid of IPF patients, and through interaction with its cell surface receptors, it has been shown to drive multiple biological processes implicated in the development of IPF. Accordingly, the first clinical trial of an LPA receptor antagonist in IPF has recently been initiated. In addition to being a therapeutic target, LPA also has potential to be a biomarker for IPF. There is increasing interest in exhaled breath condensate (EBC) analysis as a non-invasive method for biomarker detection in lung diseases, but to what extent LPA is present in EBC is not known. Methods: In this study, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess for the presence of LPA in the EBC and plasma from 11 IPF subjects and 11 controls. Results: A total of 9 different LPA species were detectable in EBC. Of these, docosatetraenoyl (22: 4) LPA was significantly elevated in the EBC of IPF subjects when compared to controls (9.18 pM vs. 0.34 pM; p = 0.001). A total of 13 different LPA species were detectable in the plasma, but in contrast to the EBC, there were no statistically significant differences in plasma LPA species between IPF subjects and controls. Conclusions: These results demonstrate that multiple LPA species are detectable in EBC, and that 22: 4 LPA levels are elevated in the EBC of IPF patients. Further research is needed to determine the significance of this elevation of 22: 4 LPA in IPF EBC, as well as its potential to serve as a biomarker for disease severity and/or progression. C1 [Montesi, Sydney B.; Brenner, Laura N.; Tager, Andrew M.; Shea, Barry S.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Montesi, Sydney B.; Brenner, Laura N.; Tager, Andrew M.; Shea, Barry S.] Harvard Univ, Sch Med, Boston, MA USA. [Montesi, Sydney B.; Tager, Andrew M.; Shea, Barry S.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Mathai, Susan K.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Gorshkova, Irina A.; Berdyshev, Evgeny V.] Univ Illinois, Dept Med, Chicago, IL USA. RP Shea, BS (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. EM bsshea@mgh.harvard.edu FU U.S. National Institutes of Health [K08-HL105656, R01-HL108975] FX Acknowledgements The authors gratefully acknowledge that these studies were supported by U.S. National Institutes of Health grants K08-HL105656 (to B. S. S) and R01-HL108975 (to A. M. T.). The authors thank S. Engelstad, J. Oakley, and the rest of the staff in the Massachusetts General Hospital Clinical Research Program for their assistance with this study. NR 38 TC 8 Z9 10 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2466 J9 BMC PULM MED JI BMC Pulm. Med. PD JAN 27 PY 2014 VL 14 AR 5 DI 10.1186/1471-2466-14-5 PG 7 WC Respiratory System SC Respiratory System GA AB1QT UT WOS:000331569100001 PM 24468008 ER PT J AU Forster, N Saladi, SV van Bragt, M Sfondouris, ME Jones, FE Li, Z Ellisen, LW AF Forster, Nicole Saladi, Srinivas Vinod van Bragt, Maaike Sfondouris, Mary E. Jones, Frank E. Li, Zhe Ellisen, Leif W. TI Basal Cell Signaling by p63 Controls Luminal Progenitor Function and Lactation via NRG1 SO DEVELOPMENTAL CELL LA English DT Article ID MAMMARY-GLAND DEVELOPMENT; STEM-CELLS; GROWTH-FACTOR; GENE-EXPRESSION; P53 HOMOLOG; DIFFERENTIATION; MORPHOGENESIS; PROLIFERATION; EPITHELIUM; RECEPTOR AB The mammary epithelium is organized as a bilayer of luminal and basal/myoepithelial cells. During pregnancy, the luminal compartment expands for milk production, while basal cells are thought to provide structural and contractile support. Here, we reveal a pregnancy-specific role of basal epithelia as a central coordinator of lactogenesis. We demonstrate that genetic deletion of the transcription factor p63 (Trp63) gene exclusively within basal cells of the adult gland during pregnancy leads to dramatic defects in luminal cell proliferation and differentiation, resulting in lactation failure. This phenotype is explained by direct transcriptional activation of the epidermal growth factor family ligand gene Nrg1 by p63 selectively in basal cells, which is required for luminal ERBB4/STAT5A activation and consequent luminal progenitor cell maturation. Thus, paracrine basal-to-luminal cell signaling, controlled by p63 via NRG1, orchestrates the entire lactation program. Collectively, these findings redefine the paradigm for cellular interactions specifying the functional maturation of the mammary gland. C1 [Forster, Nicole; Saladi, Srinivas Vinod; Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Forster, Nicole; Saladi, Srinivas Vinod; Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [van Bragt, Maaike; Li, Zhe] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [van Bragt, Maaike; Li, Zhe] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sfondouris, Mary E.; Jones, Frank E.] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU NIDCR [RO1 DE015945]; Tracey Davis Breast Cancer Research Fund; German Research Foundation (DFG) Fellowship [FO 785/1-2]; Seed Grant from the Harvard Stem Cell Institute FX We wish to thank Alea A. Mills for the p63 conditional knockout mice, Dennis C. Sgroi for comments on the pathology, Andrea McClatchey, and members of the Ellisen laboratory for comments on the manuscript. We also thank the MGH and DF/HCC Core Facilities for assistance in processing and staining of murine mammary tissue, as well as the HSCI-CRM Flow Cytometry Core Facility for help with mammary sample sorting. This work was supported by NIDCR RO1 DE015945 (to L.W.E. and S.V.S.), by the Tracey Davis Breast Cancer Research Fund (to L.W.E.), by German Research Foundation (DFG) Fellowship FO 785/1-2 (to N.F.), and by a Seed Grant from the Harvard Stem Cell Institute (to Z.L.). NR 51 TC 31 Z9 31 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD JAN 27 PY 2014 VL 28 IS 2 BP 147 EP 160 DI 10.1016/j.devcel.2013.11.019 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 302EM UT WOS:000330584600006 PM 24412575 ER PT J AU Golberg, A Linshiz, G Kravets, I Stawski, N Hillson, NJ Yarmush, ML Marks, RS Konry, T AF Golberg, Alexander Linshiz, Gregory Kravets, Ilia Stawski, Nina Hillson, Nathan J. Yarmush, Martin L. Marks, Robert S. Konry, Tania TI Cloud-Enabled Microscopy and Droplet Microfluidic Platform for Specific Detection of Escherichia coli in Water SO PLOS ONE LA English DT Article ID 16S RIBOSOMAL-RNA; DRINKING-WATER; INFECTIOUS-DISEASES; SYSTEMS; BURDEN; QUALITY; AMPLIFICATION; ENUMERATION; SANITATION; BACTERIA AB We report an all-in-one platform - ScanDrop - for the rapid and specific capture, detection, and identification of bacteria in drinking water. The ScanDrop platform integrates droplet microfluidics, a portable imaging system, and cloud-based control software and data storage. The cloud-based control software and data storage enables robotic image acquisition, remote image processing, and rapid data sharing. These features form a "cloud'' network for water quality monitoring. We have demonstrated the capability of ScanDrop to perform water quality monitoring via the detection of an indicator coliform bacterium, Escherichia coli, in drinking water contaminated with feces. Magnetic beads conjugated with antibodies to E. coli antigen were used to selectively capture and isolate specific bacteria from water samples. The bead-captured bacteria were co-encapsulated in pico-liter droplets with fluorescently-labeled anti-E. coli antibodies, and imaged with an automated custom designed fluorescence microscope. The entire water quality diagnostic process required 8 hours from sample collection to online-accessible results compared with 2-4 days for other currently available standard detection methods. C1 [Golberg, Alexander; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Burns Inst, Boston, MA USA. [Linshiz, Gregory; Stawski, Nina; Hillson, Nathan J.] Joint BioEnergy Inst, Fuels Synth Div, Emeryville, CA USA. [Linshiz, Gregory; Stawski, Nina; Hillson, Nathan J.] Lawrence Berkeley Natl Labs, Phys BioSci Div, Berkeley, CA USA. [Linshiz, Gregory; Hillson, Nathan J.] DOE Joint Genome Inst, Walnut Creek, CA USA. [Kravets, Ilia] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08855 USA. [Marks, Robert S.] Ben Gurion Univ Negev, Natl Inst Biotechnol Negev, Dept Biotechnol Engn, IL-84105 Beer Sheva, Israel. [Marks, Robert S.] Nanyang Technol Univ, Sch Mat Sci & Engn, Singapore 639798, Singapore. [Marks, Robert S.] NRF CREATE Program Nanomat Energy & Water Managem, Singapore, Singapore. [Konry, Tania] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm Bouve, Coll Hlth Sci, Boston, MA 02115 USA. RP Konry, T (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm Bouve, Coll Hlth Sci, Boston, MA 02115 USA. EM t.konry@neu.edu FU Shriners Foundation [85120-BOS]; Office of Science, Office of Biological and Environmental Research, of the U.S. Department of Energy [DE-AC02-05CH11231]; Singapore National Research Foundation; Campus for Research Excellence And Technological Enterprise (CREATE) program for the project 'Nanomaterials for Energy and Water Management' FX AG and MY acknowledge Shriners Foundation Grant #85120-BOS for the support of this work. The portion of this work conducted by the Joint BioEnergy Institute, and the U.S. Department of Energy Joint Genome Institute, was supported by the Office of Science, Office of Biological and Environmental Research, of the U.S. Department of Energy (Contract No. DE-AC02-05CH11231). This research is funded in part by the Singapore National Research Foundation and the publication is supported under the Campus for Research Excellence And Technological Enterprise (CREATE) program for the project 'Nanomaterials for Energy and Water Management'. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 11 Z9 11 U1 4 U2 52 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 27 PY 2014 VL 9 IS 1 AR e86341 DI 10.1371/journal.pone.0086341 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301BI UT WOS:000330507300055 PM 24475107 ER PT J AU Mott, KR Allen, SJ Zandian, M Akbari, O Hamrah, P Maazi, H Wechsler, SL Sharpe, AH Freeman, GJ Ghiasi, H AF Mott, Kevin R. Allen, Sariah J. Zandian, Mandana Akbari, Omid Hamrah, Pedram Maazi, Hadi Wechsler, Steven L. Sharpe, Arlene H. Freeman, Gordon J. Ghiasi, Homayon TI Inclusion of CD80 in HSV Targets the Recombinant Virus to PD-L1 on DCs and Allows Productive Infection and Robust Immune Responses SO PLOS ONE LA English DT Article ID HERPES-SIMPLEX-VIRUS; HUMAN DENDRITIC CELLS; CD8(+) T-CELLS; IN-VIVO; TYPE-1 LATENCY; COSTIMULATORY MOLECULE; STROMAL KERATITIS; MICE; EXPRESSION; REPLICATION AB CD80 plays a critical role in stimulation of T cells and subsequent control of infection. To investigate the effect of CD80 on HSV-1 infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC. C1 [Mott, Kevin R.; Allen, Sariah J.; Zandian, Mandana; Ghiasi, Homayon] Cedars Sinai Med Ctr, Cedars Sinai Burns & Allen Res Inst, Ctr Neurobiol & Vaccine Dev, Dept Surg, Los Angeles, CA 90048 USA. [Akbari, Omid; Maazi, Hadi] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA. [Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Wechsler, Steven L.] Univ Calif Irvine, Sch Med, Dept Ophthalmol, Dept Microbiol & Mol Genet,Gavin Herbert Eye Inst, Irvine, CA 92717 USA. [Wechsler, Steven L.] Univ Calif Irvine, Sch Med, Ctr Virus Res, Irvine, CA 92717 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sharpe, Arlene H.] Womens Hosp Med Ctr, Boston, MA USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Med Oncol, Boston, MA 02115 USA. RP Ghiasi, H (reprint author), Cedars Sinai Med Ctr, Cedars Sinai Burns & Allen Res Inst, Ctr Neurobiol & Vaccine Dev, Dept Surg, Los Angeles, CA 90048 USA. EM ghiasih@CSHS.org FU Public Health Service [AI093941, EY13615, EY013191, P01 AI056299, 5P01AI078897] FX This work was supported by Public Health Service grants AI093941, EY13615, EY013191, P01 AI056299 and 5P01AI078897 (GJF and AHS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 6 Z9 6 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 27 PY 2014 VL 9 IS 1 AR e87617 DI 10.1371/journal.pone.0087617 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301BI UT WOS:000330507300208 PM 24475315 ER PT J AU Tamers, SL Okechukwu, C Bohl, AA Gueguen, A Goldberg, M Zins, M AF Tamers, Sara L. Okechukwu, Cassandra Bohl, Alex A. Gueguen, Alice Goldberg, Marcel Zins, Marie TI The Impact of Stressful Life Events on Excessive Alcohol Consumption in the French Population: Findings from the GAZEL Cohort Study SO PLOS ONE LA English DT Article ID LONGITUDINAL ANALYSIS; GENERAL-POPULATION; GENDER-DIFFERENCES; DRINKING BEHAVIOR; USE TRAJECTORIES; UNITED-STATES; OLDER-ADULTS; BASE-LINE; WOMEN; PATTERNS AB Background: Major life changes may play a causative role in health through lifestyle factors, such as alcohol. The objective was to examine the impact of stressful life events on heavy alcohol consumption among French adults. Methods: Trajectories of excessive alcohol consumption in 20,625 employees of the French national gas and electricity company for up to 5 years before and 5 years after an event, with annual measurements from 1992. We used repeated measures analysis of time series data indexed to events, employing generalized estimating equations. Results: For women, excessive alcohol use increased before important purchase (p = 0.021), children leaving home (p<0.001), and death of loved ones (p = 0.03), and decreased before widowhood (p = 0.015); in the year straddling the event, increased consumption was observed for important purchase (p = 0.018) and retirement (p = 0.002); at the time of the event, consumption decreased for marriage (p = 0.002), divorce, widowhood, and death of loved one (all p<0.001), and increased for retirement (p = 0.035). For men, heavy alcohol consumption increased in the years up to and surrounding the death of loved ones, retirement, and important purchase (all p<0.001), and decreased after (all p<0.001, except death of loved one: p = 0.006); at the time of the event, consumption decreased for all events except for children leaving home and retirement, where we observed an increase (all p<0.001). For women and men, heavy alcohol consumption decreased prior to marriage and divorce and increased after (all p<0.001, except for women and marriage: p = 0.01). Conclusion: Stressful life events promote healthy and unhealthy alcohol consumption. Certain events impact alcohol intake temporarily while others have longer-term implications. Research should disentangle women's and men's distinct perceptions of events over time. C1 [Tamers, Sara L.; Okechukwu, Cassandra] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Tamers, Sara L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Bohl, Alex A.] Mathemat Policy Res, Cambridge, MA USA. [Gueguen, Alice; Goldberg, Marcel; Zins, Marie] Ctr Res Epidemiol & Populat Hlth, INSERM, UMRS 1018, Villejuif, France. [Gueguen, Alice; Goldberg, Marcel; Zins, Marie] Univ Versailles St Quentin, Versailles, France. RP Tamers, SL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM stamers@post.harvard.edu FU EDF-GDF, l'INSERM, l'Association de la Recherche sur le Cancer, la Fondation de France, le Ministere de la Sante; NIH/NCI Harvard Education Program in Cancer Prevention [R25 CA057713]; NIH/NCI Reducing Social Disparities in Cancer Risk [K05 CA108663-05] FX This research was supported by the EDF-GDF, l'INSERM, l'Association de la Recherche sur le Cancer, la Fondation de France, le Ministere de la Sante, the NIH/NCI Harvard Education Program in Cancer Prevention (R25 CA057713; PI: Glorian Sorensen, PhD), and the NIH/NCI Reducing Social Disparities in Cancer Risk (K05 CA108663-05 to GS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 7 Z9 7 U1 9 U2 25 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 27 PY 2014 VL 9 IS 1 AR e87653 DI 10.1371/journal.pone.0087653 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301BI UT WOS:000330507300210 PM 24475318 ER PT J AU Wong, JYY De Vivo, I Lin, XH Fang, SC Christiani, DC AF Wong, Jason Y. Y. De Vivo, Immaculata Lin, Xihong Fang, Shona C. Christiani, David C. TI The Relationship between Inflammatory Biomarkers and Telomere Length in an Occupational Prospective Cohort Study SO PLOS ONE LA English DT Article ID C-REACTIVE PROTEIN; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; HEMATOPOIETIC STEM; AIR-POLLUTION; DNA-DAMAGE; CELLS; EXPOSURE; PM2.5; APOPTOSIS AB Background: Chronic inflammation from recurring trauma is an underlying pathophysiological basis of numerous diseases. Furthermore, it may result in cell death, scarring, fibrosis, and loss of tissue function. In states of inflammation, subsequent increases in oxidative stress and cellular division may lead to the accelerated erosion of telomeres, crucial genomic structures which protect chromosomes from decay. However, the association between plasma inflammatory marker concentrations and telomere length has been inconsistent in previous studies. Objective: The purpose of this study was to determine the longitudinal association between telomere length and plasma inflammatory biomarker concentrations including: CRP, SAA, sICAM-1, sVCAM-1, VEGF, TNF-alpha, IL-1 beta, IL-2, IL-6, IL-8, and IL-10. Methods: The longitudinal study population consisted of 87 subjects. The follow-up period was approximately 2 years. Plasma inflammatory biomarker concentrations were assessed using highly sensitive electrochemiluminescent assays. Leukocyte relative telomere length was assessed using Real-Time qPCR. Linear mixed effects regression models were used to analyze the association between repeated-measurements of relative telomere length as the outcome and each inflammatory biomarker concentration as continuous exposures separately. The analyses controlled for major potential confounders and white blood cell differentials. Results: At any follow-up time, each incremental ng/mL increase in plasma CRP concentration was associated with a decrease in telomere length of -2.6X10(-2) (95%CI: -4.3X10(-2), -8.2x10(-3), p = 0.004) units. Similarly, the estimate for the negative linear association between SAA and telomere length was -2.6x10(-2) (95%CI:-4.5x10(-2), -6.1x10(-3), p = 0.011). No statistically significant associations were observed between telomere length and plasma concentrations of pro-inflammatory interleukins, TNF-alpha, and VEGF. Conclusions: Findings from this study suggest that increased systemic inflammation, consistent with vascular injury, is associated with decreased leukocyte telomere length. C1 [Wong, Jason Y. Y.; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wong, Jason Y. Y.; Fang, Shona C.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wong, Jason Y. Y.; De Vivo, Immaculata] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [De Vivo, Immaculata; Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Fang, Shona C.] New England Res Inst, Watertown, MA 02172 USA. RP Wong, JYY (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM jyw285@mail.harvard.edu OI Wong, Jason/0000-0002-8167-540X FU National Institute of Environmental Health Sciences (NIEHS) [R01ES009860, P50ES00002]; Shona Fang's American Heart Association (AHA) training grant FX This project was made possible by funding from the National Institute of Environmental Health Sciences (NIEHS), grants R01ES009860 and P50ES00002, in addition to Shona Fang's American Heart Association (AHA) training grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 22 Z9 23 U1 1 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 27 PY 2014 VL 9 IS 1 AR e87348 DI 10.1371/journal.pone.0087348 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301BI UT WOS:000330507300174 PM 24475279 ER PT J AU Negahdar, M Aukrust, I Molnes, J Solheim, MH Johansson, BB Sagen, JV Dahl-Jorgensen, K Kulkarni, RN Sovik, O Flatmark, T Njolstad, PR Bjorkhaug, L AF Negahdar, Maria Aukrust, Ingvild Molnes, Janne Solheim, Marie H. Johansson, Bente B. Sagen, Jorn V. Dahl-Jorgensen, Knut Kulkarni, Rohit N. Sovik, Oddmund Flatmark, Torgeir Njolstad, Pal R. Bjorkhaug, Lise TI GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding, self-association and cellular degradation SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE Aggregation; Catalytic activity; Cellular protein degradation; GCK-MODY diabetes; Protein misfolding; Self-association ID PANCREATIC BETA-CELL; GLUCOKINASE DEFICIENCY; ALLOSTERIC ACTIVATION; GLUCOSE-HOMEOSTASIS; REGULATORY PROTEIN; HYPERGLYCEMIA; METABOLISM; MELLITUS; YOUNG; IDENTIFICATION AB GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C > T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (kat) and normal affinity for ct-D-glucose, and resistance to limited proteolysis by trypsin comparable with wildtype. When stably expressed in HEK293 cells and MIN6 13-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Negahdar, Maria; Aukrust, Ingvild; Molnes, Janne; Solheim, Marie H.; Johansson, Bente B.; Sagen, Jorn V.; Sovik, Oddmund; Njolstad, Pal R.; Bjorkhaug, Lise] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway. [Negahdar, Maria; Aukrust, Ingvild; Solheim, Marie H.; Johansson, Bente B.; Bjorkhaug, Lise] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Aukrust, Ingvild; Molnes, Janne; Solheim, Marie H.; Flatmark, Torgeir; Bjorkhaug, Lise] Univ Bergen, Dept Biomed, Bergen, Norway. [Aukrust, Ingvild; Kulkarni, Rohit N.] Harvard Univ, Brigham & Womens Hosp, Sect Islet Cell Biol & Regenerat Med, Joslin Diabet Ctr,Med Sch, Boston, MA 02115 USA. [Molnes, Janne; Johansson, Bente B.; Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Sagen, Jorn V.] Univ Bergen, Inst Med, Bergen, Norway. [Sagen, Jorn V.] Haukeland Hosp, Hormone Lab, N-5021 Bergen, Norway. [Dahl-Jorgensen, Knut] Oslo Univ Hosp, Pediat Dept Ullevaal, Oslo, Norway. [Dahl-Jorgensen, Knut] Univ Oslo, Fac Med, Oslo, Norway. RP Njolstad, PR (reprint author), Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway. EM pal.njolstad@uib.no OI Johansson, Bente Berg/0000-0001-8893-1915; Gundersen, Lise Bjorkhaug/0000-0002-9695-4559 FU Heise Vest, Innovest; Norwegian Research Council; Novo Nordisk Foundation; European Research Council; K.G. Jebsen Foundation; Nils Norman Foundation; Norwegian Diabetes Association; University of Bergen; Meltzer Foundation; National Program for Research in Functional Genomics (FUGE); NIH [RO1 DK67536] FX This investigation was supported by the Heise Vest, Innovest, the Norwegian Research Council, the Novo Nordisk Foundation, the European Research Council, the K.G. Jebsen Foundation, the Nils Norman Foundation, the Norwegian Diabetes Association, the University of Bergen, and the Meltzer Foundation. The mass spectrometry analyses were conducted by the Proteomics Unit at the University of Bergen (PROBE), supported by the National Program for Research in Functional Genomics (FUGE) funded by the Norwegian Research Council. RNK is supported by a NIH Grant RO1 DK67536. The 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 regarding manuscript submission. NR 42 TC 3 Z9 3 U1 0 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 25 PY 2014 VL 382 IS 1 BP 55 EP 65 DI 10.1016/j.mce.2013.08.020 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 299UQ UT WOS:000330421600007 PM 24001579 ER PT J AU Walker, SR Xiang, M Frank, DA AF Walker, Sarah R. Xiang, Michael Frank, David A. TI Distinct roles of STAT3 and STAT5 in the pathogenesis and targeted therapy of breast cancer SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE Signal transduction; Transcription factors; Gene expression; Oncology ID EPITHELIAL-MESENCHYMAL TRANSITION; MAMMARY-GLAND INVOLUTION; GENE-EXPRESSION SIGNATURE; POLYCYTHEMIA-VERA; SIGNALING PATHWAY; JAK2 INHIBITOR; CELL-DEATH; PROLACTIN; TRANSDUCER; ACTIVATION AB The transcription factors STAT3 and STAT5 play important roles in the regulation of mammary gland function during pregnancy, lactation, and involution. Given that STAT3 and STAT5 regulate genes involved in proliferation and survival, it is not surprising that inappropriate activation of STAT3 and STAT5 occurs commonly in breast cancer. Although these proteins are structurally similar, they have divergent and opposing effects on gene expression and cellular phenotype. Notably, when STAT5 and STAT3 are activated simultaneously, STAT5 has a dominant effect, and leads to decreased proliferation and increased sensitivity to cell death. Similarly, in breast cancer, activation of both STAT5 and STAT3 is associated with longer patient survival than activation of STAT3 alone. Pharmacological inhibitors of STAT3 and STAT5 are being developed for cancer therapy, though understanding the activation state and functional interaction of STAT3 and STAT5 in a patient's tumor may be critical for the optimal use of this strategy. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM david_frank@dfci.harvard.edu FU National Cancer Institute [R01-CA160979]; Brent Leahey Fund; Friends of the Dana-Farber Cancer Institute; BCRF-AACR grant for Translational Breast Cancer Research; Susan G. Komen for the Cure FX We would like to thank Anthony Letai and Jeremy S. Ryan for help with performing BH3 profiling. This work was supported by grants from the National Cancer Institute (R01-CA160979), Susan G. Komen for the Cure, the Brent Leahey Fund, Friends of the Dana-Farber Cancer Institute, and a BCRF-AACR grant for Translational Breast Cancer Research. NR 70 TC 19 Z9 25 U1 0 U2 20 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 25 PY 2014 VL 382 IS 1 BP 616 EP 621 DI 10.1016/j.mce.2013.03.010 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 299UQ UT WOS:000330421600066 PM 23531638 ER PT J AU Qin, R Zhou, JX Chen, C Xu, T Yan, Y Ma, YS Zheng, ZL Shen, YP Lu, YC Fu, D Chen, JX AF Qin, Rong Zhou, Jingxu Chen, Chao Xu, Tao Yan, Yong Ma, Yushui Zheng, Zongli Shen, Yiping Lu, Yicheng Fu, Da Chen, Juxiang TI LIN28 Is Involved in Glioma Carcinogenesis and Predicts Outcomes of Glioblastoma Multiforme Patients SO PLOS ONE LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; GROWTH-FACTOR RECEPTOR; BINDING PROTEIN LIN28; GERM-CELL TUMORS; PROMOTES TRANSFORMATION; MALIGNANT GLIOMAS; OVARIAN-CANCER; MICRORNA; EXPRESSION; LET-7 AB LIN28, an evolutionarily conversed RNA binding protein which can bind to the terminal loops of let-7 familymicroRNA precursors and block their processing to maturation, is highly expressed in several subsets of tumors that carry poor prognoses, such as ovarian carcinoma, hepatocellular carcinoma, colon carcinoma and germ cell carcinoma. However, there has been no study on the expression of LIN28 in glioma tissues or their importance as a prognostic predictor of glioma patients. This study aimed to examine the expression of LIN28 in glioma and correlate the results to patient outcome. We found that LIN28 expression was significantly higher in the group of patients with a poor prognosis compared to patients with a good prognosis by gene microarray. Log-rank analysis showed patients with higher LIN28 expression level in tumor had a shorter progression-free survival and overall survival times compared to those with lower LIN28 expression level. Similar results were also obtained from the tissue microarray analysis. Univariate andmultivariate analyses showed high LIN28 expression was an independent prognostic factor for a shorter progression-free survival and overall survival in GBM patients. Furthermore in vitro experiments showed that down-regulation of LIN28 in U251 and U373 cells caused cell cycle arrest in the G1 phase, delayed cell proliferation, increased apoptosis, and resulted in fewer colonies compared to controls. Summarily, our data provides a potential target for cancer therapy as an approach to overcome the poor options currently available for GBM patients. C1 [Qin, Rong; Chen, Chao; Xu, Tao; Yan, Yong; Lu, Yicheng; Chen, Juxiang] Second Mil Med Univ, Changzheng Hosp, Shanghai Inst Neurosurg, Dept Neurosurg, Shanghai, Peoples R China. [Zhou, Jingxu] PLA, Hosp 101, Dept Neurosurg, Wuxi, Jiangsu, Peoples R China. [Ma, Yushui; Fu, Da] Shanghai Jiao Tong Univ, Key Lab Stem Cell Biol, Inst Hlth Sci, Sch Med, Shanghai 200030, Peoples R China. [Ma, Yushui; Fu, Da] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. [Zheng, Zongli; Chen, Juxiang] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shen, Yiping] Harvard Univ, Sch Med, Dept Lab Med, Childrens Hosp Boston, Boston, MA USA. RP Fu, D (reprint author), Shanghai Jiao Tong Univ, Key Lab Stem Cell Biol, Inst Hlth Sci, Sch Med, Shanghai 200030, Peoples R China. EM fu800da900@126.com; juxiangchen.cz@gmail.com RI zheng, zongli/B-2917-2011 OI zheng, zongli/0000-0003-4849-4903 FU National Nature Science Foundation of China [81272781, 81201535]; Program for academic leaders in health sciences [XBR2011030]; "Shu Guang" project in Shanghai [11SG37]; Nature Science Foundation of Shanghai [12ZR1436000]; Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [2012KIP203] FX This work was supported by National Nature Science Foundation of China (NO. 81272781, 81201535), Program for academic leaders in health sciences (No. XBR2011030) and "Shu Guang" project (No. 11SG37) in Shanghai, Nature Science Foundation of Shanghai (12ZR1436000) and the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (2012KIP203). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 10 Z9 12 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 24 PY 2014 VL 9 IS 1 AR e86446 DI 10.1371/journal.pone.0086446 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 298QQ UT WOS:000330339800044 PM 24475120 ER PT J AU Gaiha, GD Brass, AL AF Gaiha, Gaurav D. Brass, Abraham L. TI The Fiery Side of HIV-Induced T Cell Death SO SCIENCE LA English DT Editorial Material ID PYROPTOSIS; INFECTION; APOPTOSIS; INFLAMMASOME; DEPLETION; SENSOR; IFI16 C1 [Gaiha, Gaurav D.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard U, Cambridge, MA 02139 USA. [Brass, Abraham L.] Univ Massachusetts, Sch Med, Microbiol & Physiol Syst Dept, Worcester, MA 01655 USA. RP Gaiha, GD (reprint author), Ragon Inst Massachusetts Gen Hosp MIT & Harvard U, Cambridge, MA 02139 USA. EM abraham.brass@umassmed.edu NR 14 TC 5 Z9 5 U1 1 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 24 PY 2014 VL 343 IS 6169 BP 383 EP 384 DI 10.1126/science.1250175 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294IR UT WOS:000330039300038 PM 24458634 ER PT J AU Mathalon, DH Ahn, KH Perry, EB Cho, HS Roach, BJ Blais, RK Bhakta, S Ranganathan, M Ford, JM D'Souza, DC AF Mathalon, Daniel H. Ahn, Kyung-Heup Perry, Edward B. Cho, Hyun-Sang Roach, Brian J. Blais, Rebecca K. Bhakta, Savita Ranganathan, Mohini Ford, Judith M. D'Souza, Deepak Cyril TI Effects of nicotine on the neurophysiological and behavioral effects of ketamine in humans SO FRONTIERS IN PSYCHIATRY LA English DT Article DE schizophrenia; nicotine; ketamine; N-methyl-D-aspartatereceptor; nicotinic acetylcholine receptor; event-related potential; mismatch negativity; P300 AB Background: N-methyl-d-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia and its associated neurocognitive impairments. The high rate of cigarette smoking in schizophrenia raises questions about how nicotine modulates putative NMDA receptor hypofunction in the illness. Accordingly, we examined the modulatory effects of brain nicotinic acetylcholine receptor (nAChR) stimulation on NMDA receptor hypofunction by examining the interactive effects of nicotine, a nAChR agonist, and ketamine, a non-competitive NMDA receptor antagonist, on behavioral and neurophysiological measures in healthy human volunteers. Methods: From an initial sample of 17 subjects (age range 1855 years), 8 subjects successfully completed 4 test sessions, each separated by at least 3 days, during which they received ketamine or placebo and two injections of nicotine or placebo in a double-blind, counterbalanced manner. Schizophrenia-like effects Positive and Negative Syndrome Scale, perceptual alterations Clinician Administered Dissociative Symptoms Scale, subjective effects Visual Analog Scale and auditory event-related brain potentials (mismatch negativity, MMN; P300) were assessed during each test session. Results: Consistent with existing studies, ketamine induced transient schizophrenia-like behavioral effects. P300 was reduced and delayed by ketamine regardless of whether it was elicited by a target (P3b) or novel (P3a) stimulus, while nicotine only reduced the amplitude of P3a. Nicotine did not rescue P300 from the effects of ketamine; the interactions of ketamine and nicotine were not significant. While nicotine significantly reduced MMN amplitude, ketamine did not. Conclusion: Nicotine failed to modulate ketamine-induced neurophysiological and behavioral effects in this preliminary study. Interestingly, ketamine reduced P3b amplitude and nicotine reduced P3a amplitude, suggesting independent roles of NMDA receptor and nAChR in the generation of P3b and P3a, respectively. C1 [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel H.; Roach, Brian J.; Ford, Judith M.] San Francisco VA Med Ctr, Mental Hlth Serv 116D, 4150 Clement St, San Francisco, CA USA. [Ahn, Kyung-Heup; Perry, Edward B.; Cho, Hyun-Sang; Blais, Rebecca K.; Bhakta, Savita; Ranganathan, Mohini; D'Souza, Deepak Cyril] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Ahn, Kyung-Heup; Perry, Edward B.; D'Souza, Deepak Cyril] VA Connecticut Healthcare Syst, Schizophrenia Biol Res Ctr 116A, West Haven, CT USA. [Ahn, Kyung-Heup; Perry, Edward B.; D'Souza, Deepak Cyril] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. [Cho, Hyun-Sang] Yonsei Univ, Coll Med, Dept Psychiat, Seoul, South Korea. RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv 116D, 4150 Clement St, San Francisco, CA USA. EM daniel.mathalon@ucsf.edu FU Department of Veterans Affairs Schizophrenia Biological Research Center; NARSAD FX The authors also thank Angelina Genovese, R.N.C., M.B.A.; Elizabeth O'Donnell, R.N.; Brenda Breault, R.N., B.S.N.; Sonah Yoo, R.Ph.; Robert Sturwold, R.Ph.; and Willie Ford of the Neurobiological Studies Unit at the VA Connecticut Healthcare System, West Haven Campus for their central contributions to the success of this project. The authors also acknowledge the contributions of John Krystal, MD for his role in providing the impetus in conducting the study. The Department of Veterans Affairs Schizophrenia Biological Research Center and a NARSAD Young Investigator Award to Hyun-Sang Cho supported this study. NR 141 TC 10 Z9 10 U1 0 U2 2 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-0640 J9 FRONT PSYCHIATRY JI Front. Psychiatry PD JAN 24 PY 2014 VL 4 AR 3 DI 10.3389/fpsyt.2014.00003 PG 16 WC Psychiatry SC Psychiatry GA V46QJ UT WOS:000209898400002 PM 24478731 ER PT J AU Tarhini, AA Lin, Y Yeku, O LaFramboise, WA Ashraf, M Sander, C Lee, S Kirkwood, JM AF Tarhini, Ahmad A. Lin, Yan Yeku, Oladapo LaFramboise, William A. Ashraf, Madeeha Sander, Cindy Lee, Sandra Kirkwood, John M. TI A four-marker signature of TNF-RII, TGF-alpha, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Melanoma; Adjuvant; TNF-RII; TGF-alpha; TIMP-1; CRP; E1694 ID C-REACTIVE PROTEIN; GROWTH-FACTOR-ALPHA; METASTATIC MELANOMA; TISSUE INHIBITOR; CANCER-PATIENTS; PHASE-II; RHEUMATOID-ARTHRITIS; SUPPRESSOR-CELLS; BREAST-CANCER; SERUM TIMP-1 AB Background: E1694 tested GM2-KLH-QS21 vaccine versus high-dose interferon-alpha 2b (HDI) as adjuvant therapy for operable stage IIB-III melanoma. We tested banked serum specimens from patients in the vaccine arm of E1694 for prognostic biomarkers. Methods: Aushon Multiplex Platform was used to quantitate baseline serum levels of 115 analytes from 40 patients. Least absolute shrinkage and selection operator proportional hazard regression (Lasso PH) was used to select markers that are most informative for relapse-free survival (RFS) and overall survival (OS). Regular Cox PH models were then fit with the markers selected by the Lasso PH. Survival receiver operating characteristic (ROC) analysis was used to evaluate the ability of the models to predict 1-year RFS and 5-year OS. Results: Four markers that include Tumor Necrosis Factor alpha Receptor II (TNF-RII), Transforming Growth Factor alpha (TGF-alpha), Tissue Inhibitor of Metalloproteinases 1 (TIMP-1), and C-reactive protein (CRP) were found to be most informative for the prediction of OS (high levels correlate with worse prognosis). The dichotomized risk score based on the four markers could significantly separate the OS curves (p = 0.0005). When using the four-marker PH model to predict 5-year OS, we achieved an area under the curve (AUC) of 89% (cross validated AUC = 72%). High baseline TNF-RII was also significantly associated with worse RFS. The RFS with high (above median) TNF-RII was significantly lower than low TNF-RII (p = 0.01). Conclusions: The biomarker signature consisting of TNFR-II, TGF-a, TIMP-1 and CRP is significantly prognostic of survival in patients with high-risk melanoma and warrants further investigation. C1 [Tarhini, Ahmad A.] Univ Pittsburgh, Inst Canc, UPMC Canc Pavil, Pittsburgh, PA 15232 USA. [Lin, Yan] Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA 15213 USA. [Yeku, Oladapo] Univ Pittsburgh, UPMC, Montefiore Hosp,Dept Med, UPMC Montefiore Presbyterian Internal Med Reside, Pittsburgh, PA 15213 USA. [LaFramboise, William A.] Univ Pittsburgh, Inst Canc, UPMC, Shadyside Hosp, Pittsburgh, PA 15213 USA. [Sander, Cindy; Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Lee, Sandra] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Tarhini, AA (reprint author), Univ Pittsburgh, Inst Canc, UPMC Canc Pavil, 5150 Ctr Ave,5th Floor,Suite 555, Pittsburgh, PA 15232 USA. EM tarhiniaa@upmc.edu FU NIH [P50CA121973, P30CA047904]; Public Health Service Grants [CA23318, CA66636, CA21115, CA16116, CA39229]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was supported by NIH award P50CA121973. UPCI shared resources that are supported in part by NIH award P30CA047904 were used for this project. This study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA16116, CA39229 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 50 TC 13 Z9 13 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JAN 23 PY 2014 VL 12 AR 19 DI 10.1186/1479-5876-12-19 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG6KO UT WOS:000335527700001 PM 24457057 ER PT J AU Marechal, A Li, JM Ji, XY Wu, CS Yazinski, SA Nguyen, HD Liu, SZ Jimenez, AE Jin, JP Zou, L AF Marechal, Alexandre Li, Ju-Mei Ji, Xiao Ye Wu, Ching-Shyi Yazinski, Stephanie A. Hai Dang Nguyen Liu, Shizhou Jimenez, Amanda E. Jin, Jianping Zou, Lee TI PRP19 Transforms into a Sensor of RPA-ssDNA after DNA Damage and Drives ATR Activation via a Ubiquitin-Mediated Circuitry SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRAND BREAKS; PRE-MESSENGER-RNA; PRP19-ASSOCIATED COMPLEX; SPLICEOSOME ACTIVATION; CHECKPOINT ACTIVATION; TRANSLESION SYNTHESIS; GENOME INTEGRITY; REPAIR PROTEINS; POLYMERASE-II; END RESECTION AB PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. C1 [Marechal, Alexandre; Ji, Xiao Ye; Wu, Ching-Shyi; Yazinski, Stephanie A.; Hai Dang Nguyen; Liu, Shizhou; Jimenez, Amanda E.; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Li, Ju-Mei; Jin, Jianping] Univ Texas Hlth Sci Ctr Houston, Dept Biochem & Mol Biol, Houston, TX 77030 USA. RP Zou, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. EM zou.lee@mgh.harvard.edu OI Wu, Ching-Shyi/0000-0001-9800-9844 FU FRSQ, Quebec; Department of Defense [BC120504]; Welch Foundation [AU-1711]; NIH [GM102529, GM076388]; Federal Share of MGH Proton Program FX We thank Drs. S. Elledge, J. Chen, M. Wold, X. Wu, and W. Wang for reagents and members of the Zou lab for helpful discussions. A.M. is supported by a postdoctoral fellowship from the FRSQ, Quebec. S.A.Y. is a recipient of a postdoctoral fellowship from the Department of Defense (BC120504). J.J. is a Pew Scholar, and L.Z. is a Jim and Ann Orr Massachusetts General Hospital Research Scholar. This work was supported by grants from the Welch Foundation (AU-1711) and NIH (GM102529) to J.J. and grants from NIH (GM076388) and the Federal Share of MGH Proton Program to L.Z. NR 68 TC 51 Z9 55 U1 0 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD JAN 23 PY 2014 VL 53 IS 2 BP 235 EP 246 DI 10.1016/j.molcel.2013.11.002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 300XD UT WOS:000330496400007 PM 24332808 ER PT J AU Fowler, T Ghatak, P Price, DH Conaway, R Conaway, J Chiang, CM Bradner, JE Shilatifard, A Roy, AL AF Fowler, Trent Ghatak, Payel Price, David H. Conaway, Ronald Conaway, Joan Chiang, Cheng-Ming Bradner, James E. Shilatifard, Ali Roy, Ananda L. TI Regulation of MYC Expression and Differential JQ1 Sensitivity in Cancer Cells SO PLOS ONE LA English DT Article ID RNA-POLYMERASE-II; BET BROMODOMAIN INHIBITION; PRIMARY RESPONSE GENES; C-MYC; TRANSCRIPTION ELONGATION; SELECTIVE-INHIBITION; LYMPHOMAS; OVEREXPRESSION; CHROMATIN; COMPLEX AB High level MYC expression is associated with almost all human cancers. JQ1, a chemical compound that inhibits MYC expression is therapeutically effective in preclinical animal models in midline carcinoma, and Burkitt's lymphoma (BL). Here we show that JQ1 does not inhibit MYC expression to a similar extent in all tumor cells. The BL cells showed a similar to 90% decrease in MYC transcription upon treatment with JQ1, however, no corresponding reduction was seen in several non-BL cells. Molecularly, these differences appear due to requirements of Brd4, the most active version of the Positive Transcription Elongation Factor B (P-TEFb) within the Super Elongation Complex (SEC), and transcription factors such as Gdown1, and MED26 and also other unknown cell specific factors. Our study demonstrates that the regulation of high levels of MYC expression in different cancer cells is driven by unique regulatory mechanisms and that such exclusive regulatory signatures in each cancer cells could be employed for targeted therapeutics. C1 [Fowler, Trent; Ghatak, Payel; Roy, Ananda L.] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. [Price, David H.] Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. [Conaway, Ronald; Conaway, Joan; Shilatifard, Ali] Stowers Inst Med Res, Kansas City, MO USA. [Chiang, Cheng-Ming] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Bradner, James E.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Roy, Ananda L.] Tufts Univ, Sch Med, Sackler Sch Biomed Sci, Genet Program, Boston, MA 02111 USA. [Roy, Ananda L.] Tufts Univ, Sch Med, Sackler Sch Biomed Sci, Program Immunol, Boston, MA 02111 USA. RP Roy, AL (reprint author), Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. EM ananda.roy@tufts.edu OI Conaway, Joan/0000-0002-2786-0663 FU NIH [CA103867]; CPRIT [RP110471]; Welch Foundation [I-1805]; American Heart Association [12GRNT12180023] FX This work was supported in part by funds to C-M. C (NIH CA103867, CPRIT RP110471, and Welch Foundation I-1805), and A. L. R (American Heart Association, 12GRNT12180023). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 22 Z9 22 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 23 PY 2014 VL 9 IS 1 AR e87003 DI 10.1371/journal.pone.0087003 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297XI UT WOS:000330288000182 PM 24466310 ER PT J AU Shin, M Hu, YY Tye, CE Guan, XM Deagle, CC Antone, JV Smith, CE Simmer, JP Bartlett, JD AF Shin, Masashi Hu, Yuanyuan Tye, Coralee E. Guan, Xiaomu Deagle, Craig C. Antone, Jerry V. Smith, Charles E. Simmer, James P. Bartlett, John D. TI Matrix Metalloproteinase-20 Over-Expression Is Detrimental to Enamel Development: A Mus musculus Model SO PLOS ONE LA English DT Article ID HYPOMATURATION AMELOGENESIS IMPERFECTA; DEVELOPING BOVINE ENAMEL; DENTAL ENAMEL; MMP-20; MICE; AMELOBLASTIN; TOOTH; GENE; CRYSTALS; CLEAVAGE AB Background: Matrix metalloproteinase-20 (Mmp20) ablated mice have enamel that is thin and soft with an abnormal rod pattern that abrades from the underlying dentin. We asked if introduction of transgenes expressing Mmp20 would revert this Mmp20 null phenotype back to normal. Unexpectedly, for transgenes expressing medium or high levels of Mmp20, we found opposite enamel phenotypes depending on the genetic background (Mmp20(-/-) or Mmp20(+/+)) in which the transgenes were expressed. Methodology/Principal Findings: Amelx-promoter-Mmp20 transgenic founder mouse lines were assessed for transgene expression and those expressing low, medium or high levels of Mmp20 were selected for breeding into the Mmp20 null background. Regardless of expression level, each transgene brought the null enamel back to full thickness. However, the high and medium expressing Mmp20 transgenes in the Mmp20 null background had significantly harder more mineralized enamel than did the low transgene expresser. Strikingly, when the high and medium expressing Mmp20 transgenes were present in the wild-type background, the enamel was significantly less well mineralized than normal. Protein gel analysis of enamel matrix proteins from the high and medium expressing transgenes present in the wild-type background demonstrated that greater than normal amounts of cleavage products and smaller quantities of higher molecular weight proteins were present within their enamel matrices. Conclusions/Significance: Mmp20 expression levels must be within a specific range for normal enamel development to occur. Creation of a normally thick enamel layer may occur over a wider range of Mmp20 expression levels, but acquisition of normal enamel hardness has a narrower range. Since over-expression of Mmp20 results in decreased enamel hardness, this suggests that a balance exists between cleaved and full-length enamel matrix proteins that are essential for formation of a properly hardened enamel layer. It also suggests that few feedback controls are present in the enamel matrix to prevent excessive MMP20 activity. C1 [Shin, Masashi; Tye, Coralee E.; Guan, Xiaomu; Antone, Jerry V.; Bartlett, John D.] Dept Mineralized Tissue Biol, Cambridge, MA USA. [Shin, Masashi; Tye, Coralee E.; Guan, Xiaomu; Antone, Jerry V.; Bartlett, John D.] Harvard Univ, Sch Dent Med, Forsyth Inst, Cambridge, MA 02138 USA. [Hu, Yuanyuan; Smith, Charles E.; Simmer, James P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Deagle, Craig C.] Harvard Univ, Sch Dent Med, Program Endodont, Boston, MA 02115 USA. [Smith, Charles E.] McGill Univ, Facil Electron Microscopy Res, Dept Anat & Cell Biol, Montreal, PQ, Canada. [Smith, Charles E.] McGill Univ, Fac Dent, Montreal, PQ, Canada. RP Bartlett, JD (reprint author), Dept Mineralized Tissue Biol, Cambridge, MA USA. EM jbartlett@forsyth.org FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [R01DE019775, R01DE016276]; National Institute of Health [1S10RR027553-01] FX Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award numbers R01DE019775 (JPS) and R01DE016276 (JDB). The Forsyth Institute micro-CT Core is partly supported by National Institute of Health grant 1S10RR027553-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 6 Z9 6 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 23 PY 2014 VL 9 IS 1 AR e86774 DI 10.1371/journal.pone.0086774 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297XI UT WOS:000330288000142 PM 24466234 ER PT J AU Lawrence, MS Stojanov, P Mermel, CH Robinson, JT Garraway, LA Golub, TR Meyerson, M Gabriel, SB Lander, ES Getz, G AF Lawrence, Michael S. Stojanov, Petar Mermel, Craig H. Robinson, James T. Garraway, Levi A. Golub, Todd R. Meyerson, Matthew Gabriel, Stacey B. Lander, Eric S. Getz, Gad TI Discovery and saturation analysis of cancer genes across 21 tumour types SO NATURE LA English DT Article ID MUTATIONS; HALLMARKS; GENOME AB Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 6005,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics. C1 [Lawrence, Michael S.; Stojanov, Petar; Mermel, Craig H.; Robinson, James T.; Garraway, Levi A.; Golub, Todd R.; Meyerson, Matthew; Gabriel, Stacey B.; Lander, Eric S.; Getz, Gad] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Stojanov, Petar; Garraway, Levi A.; Golub, Todd R.; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02215 USA. [Mermel, Craig H.; Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mermel, Craig H.; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Garraway, Levi A.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Lander, Eric S.] MIT, Cambridge, MA 02139 USA. RP Lander, ES (reprint author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM lander@broadinstitute.org; gadgetz@broadinstitute.org FU Howard Hughes Medical Institute; NCI NIH HHS [R01 CA157304]; NHGRI NIH HHS [U54 HG003067]; NIGMS NIH HHS [T32 GM007753] NR 13 TC 689 Z9 702 U1 19 U2 177 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 23 PY 2014 VL 505 IS 7484 BP 495 EP + DI 10.1038/nature12912 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293SW UT WOS:000329995000029 PM 24390350 ER PT J AU Bazari, H Mahindra, AK Farkash, EA AF Bazari, Hasan Mahindra, Anuj K. Farkash, Evan A. TI Case 3-2014-A 61-Year-Old Woman with Gastrointestinal Symptoms, Anemia, and Acute Kidney Injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEPATITIS-C VIRUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; MIXED CRYOGLOBULINEMIA; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; FIBRILLARY GLOMERULONEPHRITIS; IMMUNOLOGICAL FEATURES; MORPHOLOGIC SPECTRUM; VASCULITIS; LYMPHOMA; INFECTION AB A 61-year-old woman was admitted to the hospital because of vomiting, diarrhea, anemia, and acute kidney injury. Physical examination was normal. Laboratory testing and a diagnostic procedure were performed. Presentation of CaseDr. Meghan E. Shea (Medicine): A 61-year-old woman was admitted to this hospital because of epigastric pain, vomiting, diarrhea, anemia, and acute kidney injury. The patient had been well until approximately 3 weeks before admission, when vomiting, diarrhea, fevers, arthralgias, and episodes of epigastric pain of increasing frequency and severity developed, which she attributed to a viral gastroenteritis. Two weeks before admission, epigastric and midabdominal pain worsened, with diarrhea and one episode of vomiting. The next day, she came to the emergency department at this hospital. She rated the pain at 4 on a scale of 0 ... C1 [Bazari, Hasan; Mahindra, Anuj K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Farkash, Evan A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bazari, Hasan; Mahindra, Anuj K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Farkash, Evan A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bazari, H (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 42 TC 3 Z9 3 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 23 PY 2014 VL 370 IS 4 BP 362 EP 373 DI 10.1056/NEJMcpc1214220 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 294HP UT WOS:000330036200012 PM 24450895 ER PT J AU Goswami, ND Tsalik, EL Naggie, S Miller, WC Horton, JR Pfeiffer, CD Hicks, CB AF Goswami, Neela D. Tsalik, Ephraim L. Naggie, Susanna Miller, William C. Horton, John R. Pfeiffer, Christopher D. Hicks, Charles B. TI A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design SO TRIALS LA English DT Article DE Industry; Pharmaceutical; Bias; Randomization; Methodology; Trial ID CONFLICTS-OF-INTEREST; PHARMACEUTICAL-INDUSTRY; BIOMEDICAL-RESEARCH; CLINICALTRIALS.GOV; IMPACT; ONCOLOGY; QUALITY AB Background: The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials. gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials. gov registry into a searchable dataset to facilitate research on clinical trials themselves. Methods: We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials. gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. Results: The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. Conclusions: No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology. C1 [Goswami, Neela D.] Emory Univ, Sch Med, Rollins Sch Publ Hlth, Dept Endocrinol,Dept Med, Atlanta, GA 30322 USA. [Tsalik, Ephraim L.; Naggie, Susanna; Hicks, Charles B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Naggie, Susanna] Duke Clin Res Inst, Durham, NC USA. [Miller, William C.] Univ N Carolina, Gillings Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Horton, John R.] GlaxoSmithKline Hlth Care, Parsippany, NJ USA. [Pfeiffer, Christopher D.] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR USA. [Pfeiffer, Christopher D.] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA. [Tsalik, Ephraim L.] Durham VAMC, Res Serv, Durham, NC 27710 USA. RP Goswami, ND (reprint author), Emory Univ, Sch Med, Rollins Sch Publ Hlth, Dept Endocrinol,Dept Med, Atlanta, GA 30322 USA. EM neela.goswami@emory.edu RI Miller, William/H-4800-2014 OI Miller, William/0000-0002-1934-7827 FU FDA; Clinical Science Research and Development Service of the Veterans Health Administration Office of Research and Development [1IK2CX000530] FX This work was supported by a grant from the FDA awarded to Duke University. The study sponsor had no role in the design or performance of this study, or in the writing of the manuscript. We would like to thank Karen Chiswell, Sara Calvert, and Asba Tasneem for facilitating our use of data in the ClinicalTrials.gov registry.; Ephraim Tsalik was supported by Award Number 1IK2CX000530 from the Clinical Science Research and Development Service of the Veterans Health Administration Office of Research and Development. NR 29 TC 3 Z9 3 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD JAN 22 PY 2014 VL 15 AR 31 DI 10.1186/1745-6215-15-31 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AD7SH UT WOS:000333465600001 PM 24450313 ER PT J AU Bassett, IV Govindasamy, D Erlwanger, AS Hyle, EP Kranzer, K van Schaik, N Noubary, F Paltiel, AD Wood, R Walensky, RP Losina, E Bekker, LG Freedberg, KA AF Bassett, Ingrid V. Govindasamy, Darshini Erlwanger, Alison S. Hyle, Emily P. Kranzer, Katharina van Schaik, Nienke Noubary, Farzad Paltiel, A. David Wood, Robin Walensky, Rochelle P. Losina, Elena Bekker, Linda-Gail Freedberg, Kenneth A. TI Mobile HIV Screening in Cape Town, South Africa: Clinical Impact, Cost and Cost-Effectiveness SO PLOS ONE LA English DT Article ID ANTIRETROVIRAL THERAPY PROGRAMS; RESOURCE-LIMITED SETTINGS; POOR SETTINGS; COTE-DIVOIRE; METAANALYSIS; CARE; TRANSMISSION; PROPHYLAXIS; PREVENTION; MORTALITY AB Background: Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa. Methods and Findings: We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/mL, females 516/mL), CD4 count-dependent linkage to care rates (males 31%-58%, females 49%-58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs, $29.30 per negative result and $31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be "very cost-effective" when the ICER was less than South Africa's annual per capita Gross Domestic Product (GDP) ($8,200 in 2012). We projected that, with medical facility-based testing, the discounted (undiscounted) HIV-infected population life expectancy was 132.2 (197.7) months; this increased to 140.7 (211.7) months with the addition of the mobile unit. The ICER for the mobile unit was $2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities. Conclusion: The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority. C1 [Bassett, Ingrid V.; Hyle, Emily P.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bassett, Ingrid V.; Erlwanger, Alison S.; Hyle, Emily P.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Bassett, Ingrid V.; Erlwanger, Alison S.; Hyle, Emily P.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Bassett, Ingrid V.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res CFAR, Boston, MA 02115 USA. [Govindasamy, Darshini; van Schaik, Nienke; Wood, Robin; Bekker, Linda-Gail] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Kranzer, Katharina] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London WC1, England. [Noubary, Farzad] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Noubary, Farzad] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Paltiel, A. David] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT USA. [Wood, Robin] Univ Cape Town, Dept Med, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Bassett, IV (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM ibassett@partners.org RI Kranzer, Katharina/O-8845-2014; OI Kranzer, Katharina/0000-0001-5691-7270; Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Disease [R01 AI058736, T32 AI007433]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute of Mental Health [R01 MH090326, R01 MH073445]; President's Emergency Plan for AIDS Relief (PEPFAR); Claflin Distinguished Scholar Award; PEPFAR through the Anova Health Institute; United States Agency for International Development program; Agence Francaise de Developpement FX This work was supported in part by: the National Institute of Allergy and Infectious Disease: R01 AI058736, T32 AI007433; the Harvard University Center for AIDS Research P30 AI060354; the National Institute of Mental Health: R01 MH090326, R01 MH073445; the President's Emergency Plan for AIDS Relief (PEPFAR); and the Claflin Distinguished Scholar Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The mobile testing unit was partially funded by PEPFAR through the Anova Health Institute and the United States Agency for International Development program and received further funding through the Agence Francaise de Developpement. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 16 Z9 16 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 22 PY 2014 VL 9 IS 1 AR e85197 DI 10.1371/journal.pone.0085197 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297VL UT WOS:000330283100025 PM 24465503 ER PT J AU Wang, SQ Tasoglu, S Chen, PZ Chen, M Akbas, R Wach, S Ozdemir, CI Gurkan, UA Giguel, FF Kuritzkes, DR Demirci, U AF Wang, Shuqi Tasoglu, Savas Chen, Paul Z. Chen, Michael Akbas, Ragip Wach, Sonya Ozdemir, Cenk Ibrahim Gurkan, Umut Atakan Giguel, Francoise F. Kuritzkes, Daniel R. Demirci, Utkan TI Micro-a-fluidics ELISA for Rapid CD4 Cell Count at the Point-of-Care SO SCIENTIFIC REPORTS LA English DT Article ID RESOURCE-POOR SETTINGS; HIV-INFECTED PATIENTS; MICROFLUIDICS; ENUMERATION AB HIV has become one of the most devastating pathogens in human history. Despite fast progress in HIV-related basic research, antiretroviral therapy (ART) remains the most effective method to save AIDS patients' lives. Unfortunately, ART cannot be universally accessed, especially in developing countries, due to the lack of effective treatment monitoring diagnostics. Here, we present an inexpensive, rapid and portable micro-a-fluidic platform, which can streamline the process of an enzyme-linked immunosorbent assay (ELISA) in a fully automated manner for CD4 cell count. The micro-a-fluidic CD4 cell count is achieved by eliminating operational fluid flow via "moving the substrate", as opposed to "flowing liquid" in traditional ELISA or microfluidic methods. This is the first demonstration of capturing and detecting cells from unprocessed whole blood using the enzyme-linked immunosorbent assay (ELISA) in a microfluidic channel. Combined with cell phone imaging, the presented micro-a-fluidic ELISA platform holds great promise for offering rapid CD4 cell count to scale up much needed ART in resource-constrained settings. The developed system can be extended to multiple areas for ELISA-related assays. C1 [Wang, Shuqi; Tasoglu, Savas; Chen, Paul Z.; Chen, Michael; Wach, Sonya; Ozdemir, Cenk Ibrahim; Gurkan, Umut Atakan; Demirci, Utkan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Biomed Engn,Bioacoust MEMS Med BAMM, Boston, MA 02139 USA. [Akbas, Ragip] Ozyegin Univ, Dept Civil Engn, Istanbul, Turkey. [Giguel, Francoise F.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Kuritzkes, Daniel R.; Demirci, Utkan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Demirci, Utkan] Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Demirci, U (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Biomed Engn,Bioacoust MEMS Med BAMM, Boston, MA 02139 USA. EM udemirci@rics.bwh.harvard.edu OI Gurkan, Umut/0000-0002-0331-9960 FU W.H. Coulter Foundation [RO1A1081534, RO1AI093282, U54EB15408, R21AI087107]; Center for Integration of Medicine and Innovative Technology (CIMIT) under U.S. Army Medical Research Acquisition Activity Cooperative Agreements [DAMD17-02-2-0006, W81XWH-07-2-0011, W81XWH-09-2-0001]; U.S. Army Medical Research & Materiel Command (USAMRMC); Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD FX We would like to acknowledge the W.H. Coulter Foundation Young Investigator Award, RO1A1081534, RO1AI093282, U54EB15408 and R21AI087107. This work was supported by (i) the Center for Integration of Medicine and Innovative Technology (CIMIT) under U.S. Army Medical Research Acquisition Activity Cooperative Agreements DAMD17-02-2-0006, W81XWH-07-2-0011, and W81XWH-09-2-0001. We would also thank the Brigham and Women's Hospital (BWH) Biomedical Research Institute Translatable Technologies & Care Innovation Award and the Brigham Research Institute for the Bright Futures Award. Further the work was made possible by a research grant that was awarded and administered by the U.S. Army Medical Research & Materiel Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD. NR 22 TC 29 Z9 29 U1 2 U2 57 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 22 PY 2014 VL 4 AR 3796 DI 10.1038/srep03796 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294KK UT WOS:000330044300001 PM 24448112 ER PT J AU Roussos, P Haroutunian, V AF Roussos, Panos Haroutunian, Vahram TI Schizophrenia: susceptibility genes and oligodendroglial and myelin related abnormalities SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE systems biology; polygenic; node of Ranvier; disconnectivity; GWAS ID FAMILY-BASED ASSOCIATION; CHINESE HAN POPULATION; ANTERIOR CINGULATE CORTEX; MESSENGER-RNA; STRUCTURAL CONNECTIVITY; JAPANESE POPULATION; CONVERGENT EVIDENCE; EXPRESSION ANALYSIS; PREFRONTAL CORTEX; BIPOLAR DISORDER AB Given that the genetic risk for schizophrenia is highly polygenic and the effect sizes, even for rare or de novo events, are modest at best, it has been suggested that multiple biological pathways are likely to be involved in the etiopathogenesis of the disease. Most efforts in understanding the cellular basis of schizophrenia have followed a "neuroncentric" approach, focusing on alterations in neurotransmitter systems and synapse cytoarchitecture. However, multiple lines of evidence coming from genetics and systems biology approaches suggest that apart from neurons, oligodendrocytes and potentially other glia are affected from schizophrenia risk loci. Neurobiological abnormalities linked with genetic association signal could identify abnormalities that are more likely to be primary, versus environmentally induced changes or downstream events. Here, we summarize genetic data that support the involvement of oligodendrocytes in schizophrenia, providing additional evidence for a causal role with the disease. Given the undeniable evidence of both neuronal and glial abnormalities in schizophrenia, we propose a neuro-glial model that invokes abnormalities at the node of Ranvier as a functional unit in the etiopathogenesis of the disease. C1 [Roussos, Panos; Haroutunian, Vahram] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN 3, Bronx, NY USA. [Roussos, Panos; Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Roussos, Panos] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Roussos, Panos; Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Inst Multiscale Biol, New York, NY 10029 USA. [Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. RP Roussos, P (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM panagiotis.roussos@mssm.edu RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU NIH [MH066392, MH064673]; Veterans Administration MIRECC FX We thank Dr, Georgios Voloudakis for figures. We apologize for not citing some of papers due to space limitation. Work in the authors' laboratory has been supported by NIH grants MH066392 and MH064673 and Veterans Administration MIRECC. NR 79 TC 29 Z9 29 U1 1 U2 16 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD JAN 21 PY 2014 VL 8 AR 5 DI 10.3389/fncel.2014.00005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AA4FN UT WOS:000331051100001 PM 24478629 ER PT J AU Gow, DW Nied, AC AF Gow, David W., Jr. Nied, A. Conrad TI Rules from Words: A Dynamic Neural Basis for a Lawful Linguistic Process SO PLOS ONE LA English DT Article ID INFERIOR FRONTAL-CORTEX; EVENT-RELATED FMRI; SPEECH-PERCEPTION; PREFRONTAL CORTEX; LANGUAGE COMPREHENSION; CORTICAL ORGANIZATION; NONWORD REPETITION; BRAIN; COARTICULATION; COMPENSATION AB Listeners show a reliable bias towards interpreting speech sounds in a way that conforms to linguistic restrictions (phonotactic constraints) on the permissible patterning of speech sounds in a language. This perceptual bias may enforce and strengthen the systematicity that is the hallmark of phonological representation. Using Granger causality analysis of magnetic resonance imaging (MRI)-constrained magnetoencephalography (MEG) and electroencephalography (EEG) data, we tested the differential predictions of rule-based, frequency-based, and top-down lexical influence-driven explanations of processes that produce phonotactic biases in phoneme categorization. Consistent with the top-down lexical influence account, brain regions associated with the representation of words had a stronger influence on acoustic-phonetic regions in trials that led to the identification of phonotactically legal (versus illegal) word-initial consonant clusters. Regions associated with the application of linguistic rules had no such effect. Similarly, high frequency phoneme clusters failed to produce stronger feedforward influences by acoustic-phonetic regions on areas associated with higher linguistic representation. These results suggest that top-down lexical influences contribute to the systematicity of phonological representation. C1 [Gow, David W., Jr.; Nied, A. Conrad] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. [Gow, David W., Jr.] Salem State Univ, Dept Psychol, Salem, MA USA. [Gow, David W., Jr.; Nied, A. Conrad] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gow, David W., Jr.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Gow, DW (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. EM gow@helix.mgh.harvard.edu FU National Institute of Deafness and Communicative Disorders [R01 DC003108]; MIND Institute; NCRR Regional Resource Grant [41RR14075] FX This work was supported by the National Institute of Deafness and Communicative Disorders (R01 DC003108) to D. W. G. and benefited from support from the MIND Institute and the NCRR Regional Resource Grant (41RR14075) for the development of technology and analysis tools at the Athinoula A.Martinos Center for Biomedical Imaging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 100 TC 5 Z9 5 U1 3 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 21 PY 2014 VL 9 IS 1 AR e86212 DI 10.1371/journal.pone.0086212 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297GT UT WOS:000330244500207 PM 24465965 ER PT J AU Hagmann, H Bossung, V Belaidi, AA Fridman, A Karumanchi, SA Thadhani, R Schermer, B Mallmann, P Schwarz, G Benzing, T Brinkkoetter, PT AF Hagmann, Henning Bossung, Verena Belaidi, Abdel Ali Fridman, Alexander Karumanchi, S. Ananth Thadhani, Ravi Schermer, Bernhard Mallmann, Peter Schwarz, Guenter Benzing, Thomas Brinkkoetter, Paul T. TI Low-Molecular Weight Heparin Increases Circulating sFlt-1 Levels and Enhances Urinary Elimination SO PLOS ONE LA English DT Article ID GLOMERULAR CAPILLARY WALL; PLACENTAL GROWTH-FACTOR; TYROSINE KINASE 1; ANGIOGENIC FACTORS; PREGNANCY COMPLICATIONS; SOLUBLE ENDOGLIN; PREECLAMPSIA; WOMEN; RISK; PERMSELECTIVITY AB Rationale: Preeclampsia is a devastating medical complication of pregnancy which leads to maternal and fetal morbidity and mortality. While the etiology of preeclampsia is unclear, human and animal studies suggest that excessive circulating levels of soluble fms-like tyrosine-kinase-1 (sFlt-1), an alternatively spliced variant of VEGF-receptor1, contribute to the signs and symptoms of preeclampsia. Since sFlt-1 binds to heparin and heparan sulfate proteoglycans, we hypothesized that the anticoagulant heparin, which is often used in pregnancy, may interfere with the levels, distribution and elimination of sFlt-1 in vivo. Objective: We systematically determined serum and urine levels of angiogenic factors in preeclamptic women before and after administration of low molecular weight heparin and further characterized the interaction with heparin in biochemical studies. Methods and Results: Serum and urine samples were used to measure sFlt-1 levels before and after heparin administration. Serum levels of sFlt-1 increased by 25% after heparin administration in pregnant women. The magnitude of the increase in circulating sFlt-1 correlated with initial sFlt-1 serum levels. Urinary sFlt-1 levels were also elevated following heparin administration and levels of elimination were dependent on the underlying integrity of the glomerular filtration barrier. Biochemical binding studies employing cation exchange chromatography revealed that heparin bound sFlt-1 had decreased affinity to negatively charged surfaces when compared to sFlt-1 alone. Conclusion: Low molecular weight heparin administration increased circulating sFlt1 levels and enhanced renal elimination. We provide evidence that both effects may be due to heparin binding to sFlt1 and masking the positive charges on sFlt1 protein. C1 [Hagmann, Henning; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T.] Univ Cologne, Div Nephrol, Dept Internal Med, D-50931 Cologne, Germany. [Hagmann, Henning; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T.] Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany. [Bossung, Verena; Fridman, Alexander; Mallmann, Peter] Univ Cologne, Dept Obstet & Gynecol, D-50931 Cologne, Germany. [Belaidi, Abdel Ali; Schwarz, Guenter] Univ Cologne, Dept Biochem, D-50931 Cologne, Germany. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. [Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA USA. RP Hagmann, H (reprint author), Univ Cologne, Div Nephrol, Dept Internal Med, D-50931 Cologne, Germany. EM henning.hagmann@uk-koeln.de RI Schermer, Bernhard/E-9972-2014; OI Schermer, Bernhard/0000-0002-5194-9000; Belaidi, Abdel Ali/0000-0003-0792-8728 FU Forschungspool "Klinische Studien", Faculty of Medicine, University of Cologne; DFG [SFB 635, BR2955] FX This work was supported by Forschungspool "Klinische Studien", Faculty of Medicine, University of Cologne and by the DFG (SFB 635 to T. B. and BR2955 to P. T. B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 8 Z9 8 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 21 PY 2014 VL 9 IS 1 AR e85258 DI 10.1371/journal.pone.0085258 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297GT UT WOS:000330244500046 PM 24465515 ER PT J AU Pong, T Scherrer-Crosbie, M Atochin, DN Bloch, KD Huang, PL AF Pong, Terrence Scherrer-Crosbie, Marielle Atochin, Dmitriy N. Bloch, Kenneth D. Huang, Paul L. TI Phosphomimetic Modulation of eNOS Improves Myocardial Reperfusion and Mimics Cardiac Postconditioning in Mice SO PLOS ONE LA English DT Article ID NITRIC-OXIDE SYNTHASE; PERCUTANEOUS CORONARY INTERVENTION; BLOOD-FLOW; CONTRAST ECHOCARDIOGRAPHY; PARADIGM SHIFT; IN-VIVO; INJURY; INFARCTION; ISCHEMIA; HEART AB Objective: Myocardial infarction resulting from ischemia-reperfusion injury can be reduced by cardiac postconditioning, in which blood flow is restored intermittently prior to full reperfusion. Although key molecular mechanisms and prosurvival pathways involved in postconditioning have been identified, a direct role for eNOS-derived NO in improving regional myocardial perfusion has not been shown. The objective of this study is to measure, with high temporal and spatial resolution, regional myocardial perfusion during ischemia-reperfusion and postconditioning, in order to determine the contribution of regional blood flow effects of NO to infarct size and protection. Methods and Results: We used myocardial contrast echocardiography to measure regional myocardial blood flow in mice over time. Reperfusion after myocardial ischemia-reperfusion injury is improved by postconditioning, as well as by phosphomimetic eNOS modulation. Knock-in mice expressing a phosphomimetic S1176D form of eNOS showed improved myocardial reperfusion and significantly reduced infarct size. eNOS knock-out mice failed to show cardioprotection from postconditioning. The size of the no-reflow zone following ischemia-reperfusion is substantially reduced by postconditioning and by the phosphomimetic eNOS mutation. Conclusions and Significance: Using myocardial contrast echocardiography, we show that temporal dynamics of regional myocardial perfusion restoration contribute to reduced infarct size after postconditioning. eNOS has direct effects on myocardial blood flow following ischemia-reperfusion, with reduction in the size of the no-reflow zone. These results have important implications for ongoing clinical trials on cardioprotection, because the degree of protective benefit may be significantly influenced by the regional hemodynamic effects of eNOS-derived NO. C1 [Pong, Terrence; Scherrer-Crosbie, Marielle; Atochin, Dmitriy N.; Bloch, Kenneth D.; Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Pong, Terrence; Huang, Paul L.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Pong, Terrence; Huang, Paul L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM phuang1@partners.org RI Atochin, Dmitriy/Q-3150-2016 FU American Heart Association; NIH [R01 NS33335, HL57818] FX This work was funded by an American Heart Association predoctoral fellowship to T. Pong and by NIH R01 NS33335 and HL57818 to P. Huang. THe funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 0 Z9 0 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 21 PY 2014 VL 9 IS 1 AR e85946 DI 10.1371/journal.pone.0085946 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297GT UT WOS:000330244500152 PM 24465805 ER PT J AU Volgin, DV Lu, JW Stettner, GM Mann, GL Ross, RJ Morrison, AR Kubin, L AF Volgin, Denys V. Lu, Jackie W. Stettner, Georg M. Mann, Graziella L. Ross, Richard J. Morrison, Adrian R. Kubin, Leszek TI Time- and Behavioral State-Dependent Changes in Posterior Hypothalamic GABA(A) Receptors Contribute to the Regulation of Sleep SO PLOS ONE LA English DT Article ID SUBUNIT MESSENGER-RNAS; EYE-MOVEMENT SLEEP; ADULT-RAT BRAIN; OREXIN NEURONS; SUPRACHIASMATIC NUCLEUS; LATERAL HYPOTHALAMUS; PROTEIN-KINASE; BETA-SUBUNITS; PREOPTIC AREA; REM-SLEEP AB Sleep-wake behavior is regulated by a circadian rhythm, homeostatically and by additional mechanisms that determine the timing of slow-wave sleep and rapid eye movement sleep (REMS) episodes. The posterior hypothalamus coordinates the neural and humoral signals with the rest-activity cycle. It contains wake-active neurons, and is a site where stimulation of inhibitory GABA(A) receptors promotes sleep, whereas their antagonism enhances wakefulness. We explored whether GABAergic mechanisms present in the posterior hypothalamus contribute to the homeostatic and other aspects of sleepwake regulation. Using micropunches of tissue extracted from either the perifornical (PF) or dorsomedial (DM) regions of the posterior hypothalamus of rats, we determined that mRNA levels for selected subunits of GABA(A) receptors (beta(1), beta(3) and epsilon) were higher at the end of the active period or following sleep deprivation, when the need for sleep is high, than after several hours of sleep, when sleep need is partially fulfilled. Such a pattern was present in the PF region only, and was consistent with changes in beta(1) subunit and GABA synthesizing enzyme (GAD) protein levels. In contrast, in the DM region, the levels of GABA(A) receptor subunit mRNAs and proteins (alpha(1), alpha(2), beta 1) and GAD varied with circadian time, but were not responsive to sleep deprivation. Separate experiments with sleep-wake monitoring and local perfusion of the PF region with the GABA(A) receptor antagonist bicuculline revealed that the antagonist had a weaker sleep-reducing effect when sleep need was enhanced by sleep deprivation and that the increased amount of REMS characteristic of the late sleep period was dependent on endogenous GABAergic inhibition. These results support the concept that a varying magnitude of GABAergic inhibition exerted within the PF region contributes to the homeostatic regulation of sleep and shapes its temporal pattern, whereas GABAergic mechanisms in the DM region contribute to circadian regulation. C1 [Volgin, Denys V.; Lu, Jackie W.; Stettner, Georg M.; Mann, Graziella L.; Ross, Richard J.; Morrison, Adrian R.; Kubin, Leszek] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. [Ross, Richard J.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Ross, Richard J.] Philadelphia Vet Affairs Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. RP Kubin, L (reprint author), Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. EM lkubin@vet.upenn.edu FU United States National Institutes of Health [HL-071097]; Deutsche Forschungsgemeinschaft [Ste1899/1-1] FX Support was provided by United States National Institutes of Health grant HL-071097 and Deutsche Forschungsgemeinschaft fellowship DFG Ste1899/1-1 to GMS. Neither the funders nor the Department of Veterans Affairs had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 108 TC 5 Z9 5 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 21 PY 2014 VL 9 IS 1 AR e86545 DI 10.1371/journal.pone.0086545 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297GT UT WOS:000330244500258 PM 24466145 ER PT J AU Wallentin, L Lindholm, D Siegbahn, A Wernroth, L Becker, RC Cannon, CP Cornel, JH Himmelmann, A Giannitsis, E Harrington, RA Held, C Husted, S Katus, HA Mahaffey, KW Steg, PG Storey, RF James, SK AF Wallentin, Lars Lindholm, Daniel Siegbahn, Agneta Wernroth, Lisa Becker, Richard C. Cannon, Christopher P. Cornel, Jan H. Himmelmann, Anders Giannitsis, Evangelos Harrington, Robert A. Held, Claes Husted, Steen Katus, Hugo A. Mahaffey, Kenneth W. Steg, Ph. Gabriel Storey, Robert F. James, Stefan K. CA PLATO Study Grp TI Biomarkers in Relation to the Effects of Ticagrelor in Comparison With Clopidogrel in Non-ST-Elevation Acute Coronary Syndrome Patients Managed With or Without In-Hospital Revascularization A Substudy From the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) Trial SO CIRCULATION LA English DT Article DE acute coronary syndrome; biological markers; blood platelets; myocardial infarction; troponin ID GROWTH-DIFFERENTIATION FACTOR-15; INVASIVE TREATMENT STRATEGY; BRAIN NATRIURETIC PEPTIDE; CARDIAC TROPONIN-T; MYOCARDIAL-INFARCTION; SEGMENT ELEVATION; RISK STRATIFICATION; ARTERY-DISEASE; FRISC-II; UNIVERSAL DEFINITION AB Background Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We investigated the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor versus clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the Platelet Inhibition and Patient Outcomes (PLATO) trial. Methods and Results Of 18 624 patients in the PLATO trial, 9946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5357 were revascularized, and 4589 were managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cutoff levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of cardiovascular death, myocardial infarction, and stroke in medically managed patients (P<0.001), but not in those managed invasively. NT-proBNP and GDF-15 levels were associated with the same events independent of management strategy. Ticagrelor versus clopidogrel reduced the rate of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS and hs-TnT 14.0 ng/L in both invasively and noninvasively managed patients; in patients with hs-TnT <14.0 ng/L, there was no difference between ticagrelor and clopidogrel in the noninvasive group Conclusions Hs-TnT, NT-proBNP, and GDF-15 are predictors of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS managed noninvasively, and NT-proBNP and GDF-15 also in those managed invasively. Elevated hs-TnT predicts substantial benefit of ticagrelor over clopidogrel both in invasively and noninvasively managed patients, but no apparent benefit was seen at normal hs-TnT. Clinical Trial Registration URL:http://www.clinicaltrials.gov. Unique identifier: NCT00391872. C1 [Wallentin, Lars; Lindholm, Daniel; Siegbahn, Agneta; Wernroth, Lisa; Held, Claes; James, Stefan K.] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Wallentin, Lars; Lindholm, Daniel; Siegbahn, Agneta; Wernroth, Lisa; Held, Claes; James, Stefan K.] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Becker, Richard C.] Acad Hlth Ctr, Div Cardiovasc Hlth & Dis, Heart Lung & Vasc Inst, Cincinnati, OH USA. [Harrington, Robert A.; Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Cornel, Jan H.] Med Ctr Alkmaar, Dept Cardiol, Alkmaar, Netherlands. [Himmelmann, Anders] AstraZeneca Res & Dev, Molndal, Sweden. [Giannitsis, Evangelos; Katus, Hugo A.] Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany. [Husted, Steen] Hosp Unit West, Med Dept, Heming Holstbro, Denmark. [Steg, Ph. Gabriel] INSERM, U698, Paris, France. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France. [Steg, Ph. Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Steg, Ph. Gabriel] Royal Brompton Hosp, NHLI Imperial Coll, ICMS, London SW3 6LY, England. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. RP Wallentin, L (reprint author), Univ Uppsala Hosp, Uppsala Clin Res Ctr, Dag Hammarskjolds Vag 14B,Box 6363, S-75185 Uppsala, Sweden. EM Lars.Wallentin@ucr.uu.se RI Katus, Hugo/P-1712-2016 FU AstraZeneca FX The PLATO study was funded by AstraZeneca. Support for the analysis and interpretation of results and preparation of the manuscript was provided through funds to the Uppsala Clinical Research Center and Duke Clinical Research Institute as part of the Clinical Study Agreement. NR 34 TC 31 Z9 34 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 21 PY 2014 VL 129 IS 3 BP 293 EP 303 DI 10.1161/CIRCULATIONAHA.113.004420 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 292CV UT WOS:000329880700006 PM 24170388 ER PT J AU Dunn, GP Cheung, HW Agarwalla, PK Thomas, S Zektser, Y Karst, AM Boehm, JS Weir, BA Berlin, AM Zou, LH Getz, G Liu, JF Hirsch, M Vazquez, F Root, DE Beroukhim, R Drapkin, R Hahn, WC AF Dunn, Gavin P. Cheung, Hiu Wing Agarwalla, Pankaj K. Thomas, Sapana Zektser, Yulia Karst, Alison M. Boehm, Jesse S. Weir, Barbara A. Berlin, Aaron M. Zou, Lihua Getz, Gad Liu, Joyce F. Hirsch, Michelle Vazquez, Francisca Root, David E. Beroukhim, Rameen Drapkin, Ronny Hahn, William C. TI In vivo multiplexed interrogation of amplified genes identifies GAB2 as an ovarian cancer oncogene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional genomics; open reading frame; ORF ID BREAST-CANCER; LIVER-CANCER; AMPLIFICATION; CARCINOMA; TRANSFORMATION; SENSITIVITY; METASTASIS; COMPLEXITY; EXPRESSION; SUBTYPES AB High-grade serous ovarian cancers are characterized by widespread recurrent copy number alterations. Although some regions of copy number change harbor known oncogenes and tumor suppressor genes, the genes targeted by the majority of amplified or deleted regions in ovarian cancer remain undefined. Here we systematically tested amplified genes for their ability to promote tumor formation using an in vivo multiplexed transformation assay. We identified the GRB2-associated binding protein 2 (GAB2) as a recurrently amplified gene that potently transforms immortalized ovarian and fallopian tube secretory epithelial cells. Cancer cell lines overexpressing GAB2 require GAB2 for survival and show evidence of phosphatidylinositol 3-kinase (PI3K) pathway activation, which was required for GAB2-induced transformation. Cell lines overexpressing GAB2 were as sensitive to PI3K inhibition as cell lines harboring mutant PIK3CA. Together, these observations nominate GAB2 as an ovarian cancer oncogene, identify an alternative mechanism to activate PI3K signaling, and underscore the importance of PI3K signaling in this cancer C1 [Dunn, Gavin P.; Agarwalla, Pankaj K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Dunn, Gavin P.; Cheung, Hiu Wing; Agarwalla, Pankaj K.; Karst, Alison M.; Liu, Joyce F.; Beroukhim, Rameen; Drapkin, Ronny; Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Beroukhim, Rameen; Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Dunn, Gavin P.; Agarwalla, Pankaj K.; Beroukhim, Rameen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Karst, Alison M.; Drapkin, Ronny] Harvard Univ, Sch Med, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Dunn, Gavin P.; Cheung, Hiu Wing; Thomas, Sapana; Zektser, Yulia; Boehm, Jesse S.; Weir, Barbara A.; Berlin, Aaron M.; Zou, Lihua; Getz, Gad; Vazquez, Francisca; Root, David E.; Beroukhim, Rameen; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Agarwalla, Pankaj K.; Liu, Joyce F.; Beroukhim, Rameen; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hirsch, Michelle; Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hirsch, Michelle; Drapkin, Ronny] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM william_hahn@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; Boehm, Jesse/0000-0002-6795-6336 FU NIH [R25]; American Brain Tumor Association; Canadian Institutes of Health Research Fellowship; Kaleidoscope of Hope Foundation Young Investigator Research Award [U01 CA152990]; The Mary Kay Foundation; Sandy Rollman Ovarian Cancer Research Foundation; Robert and Debra First Fund; Executive Council of the Susan Smith Center forWomen's Cancers at Dana-Farber Cancer Institute; V Foundation for Cancer Research; American Cancer Society Institutional Research [IRG-97-219-14]; Marsha Rivkin Center for Ovarian Cancer Research; [RC2 CA148268]; [U01 CA176058]; [U54 CA143798]; [U54 CA112962] FX We thank John Doench, Glenn Cowley, and Carsten Russ from the Broad Institute for helpful discussions. The following grant support is acknowledged: RC2 CA148268 (to W.C.H.), U01 CA176058 (to W. C. H.), U54 CA143798 (to R.B.) U54 CA112962 (to W.C.H.), NIH R25 (to G.P.D.), the American Brain Tumor Association (G.P.D.), a Canadian Institutes of Health Research Fellowship (to A.M.K.), a Kaleidoscope of Hope Foundation Young Investigator Research Award (to A.M.K.), U01 CA152990 (to R.D.), The Mary Kay Foundation (R.D.), The Sandy Rollman Ovarian Cancer Research Foundation (R.D.), The Robert and Debra First Fund (R.D.), The Executive Council of the Susan Smith Center forWomen's Cancers at Dana-Farber Cancer Institute (R.D.), The V Foundation for Cancer Research (H.W.C.), American Cancer Society Institutional Research Grant IRG-97-219-14 (to H.W.C.), and The Marsha Rivkin Center for Ovarian Cancer Research (H.W.C.). NR 37 TC 15 Z9 19 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 21 PY 2014 VL 111 IS 3 BP 1102 EP 1107 DI 10.1073/pnas.1311909111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 292UQ UT WOS:000329928400057 PM 24385586 ER PT J AU Lui, VWY Peyser, ND Ng, PKS Hritz, J Zeng, Y Lu, YL Li, H Wang, L Gilbert, BR General, IJ Bahar, I Ju, ZL Wang, ZH Pendleton, KP Xiao, X Du, Y Vries, JK Hammerman, PS Garraway, LA Mills, GB Johnson, DE Grandis, JR AF Lui, Vivian Wai Yan Peyser, Noah D. Ng, Patrick Kwok-Shing Hritz, Jozef Zeng, Yan Lu, Yiling Li, Hua Wang, Lin Gilbert, Breean R. General, Ignacio J. Bahar, Ivet Ju, Zhenlin Wang, Zhenghe Pendleton, Kelsey P. Xiao, Xiao Du, Yu Vries, John K. Hammerman, Peter S. Garraway, Levi A. Mills, Gordon B. Johnson, Daniel E. Grandis, Jennifer R. TI Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE STAT3 activation; driver mutations; phosphatase mutations ID TUMOR-SUPPRESSOR; CELL-ADHESION; GLIOBLASTOMA; ACTIVATION; CARCINOMA; PTPRD; GENE AB The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a "driver" phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine-substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents. C1 [Lui, Vivian Wai Yan; Peyser, Noah D.; Zeng, Yan; Li, Hua; Wang, Lin; Gilbert, Breean R.; Pendleton, Kelsey P.; Xiao, Xiao; Du, Yu; Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Peyser, Noah D.; Johnson, Daniel E.; Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. [Hritz, Jozef] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15213 USA. [General, Ignacio J.; Bahar, Ivet; Vries, John K.] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15213 USA. [Hritz, Jozef] Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic. [Ng, Patrick Kwok-Shing; Lu, Yiling; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77054 USA. [Ju, Zhenlin] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77054 USA. [Wang, Zhenghe] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Wang, Zhenghe] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Hammerman, Peter S.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Johnson, Daniel E.] Univ Pittsburgh, Inst Canc, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA. [Johnson, Daniel E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. RP Grandis, JR (reprint author), Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15213 USA. EM jgrandis@pitt.edu RI LI, HUA/I-9569-2014; Hritz, Jozef/J-6887-2015; Lui, Vivian/I-5458-2016 OI Hritz, Jozef/0000-0002-4512-9241; FU National Institutes of Health [P50CA097190, R01CA77308, R01 CA137260, R01 CA127590, F31 DE024007]; American Cancer Society; Patricia L. Knebel Fund of the Pittsburgh Foundation; Department of Pharmacology and Chemical Biology; University of Pittsburgh School of Medicine; John S. Lazo Cancer Pharmacology Fellowship; International Outgoing Fellowship of the European Community program [PIOF-GA-2009-235902, P41 GM103712] FX This work was supported by National Institutes of Health Grants P50CA097190 and R01CA77308 and the American Cancer Society (to J.R.G.), the Patricia L. Knebel Fund of the Pittsburgh Foundation (V.W.Y.L.), National Institutes of Health Grants R01 CA137260 (to D.E.J.), R01 CA127590 (to Z.W.), and F31 DE024007, and a Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, John S. Lazo Cancer Pharmacology Fellowship (to N.D.P.). Support for training and career development of researchers (Marie Curie) came from an International Outgoing Fellowship of the European Community program, Contracts PIOF-GA-2009-235902 (to J.H.) and P41 GM103712 (to I.B.). NR 24 TC 25 Z9 25 U1 0 U2 22 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 21 PY 2014 VL 111 IS 3 BP 1114 EP 1119 DI 10.1073/pnas.1319551111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 292UQ UT WOS:000329928400059 PM 24395800 ER PT J AU Winnay, JN Dirice, E Liew, CW Kulkarni, RN Kahn, CR AF Winnay, Jonathon N. Dirice, Ercument Liew, Chong Wee Kulkarni, Rohit N. Kahn, C. Ronald TI p85 alpha deficiency protects beta-cells from endoplasmic reticulum stress-induced apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THIOREDOXIN-INTERACTING PROTEIN; ER STRESS; CHOP; KINASE; DEATH; INFLAMMASOME; TRANSLATION; MECHANISMS; INITIATION; 3-KINASE AB In insulin resistant states such as type 2 diabetes, there is a high demand on the beta-cell to synthesize and secrete insulin, which challenges the ability of the endoplasmic reticulum (ER) to synthesize and fold nascent proteins. This creates a state of ER stress that triggers a coordinated program referred to as the unfolded protein response (UPR) that attempts to restore ER homeostasis. We identified a role for the p85 alpha regulatory subunit of PI3K to modulate the UPR by promoting the nuclear localization of X-box binding protein 1, a transcription factor central to the UPR. In the present study we demonstrate that reducing p85a expression in beta-cells can markedly delay the onset and severity of the diabetic phenotype observed in Akita(+/-) mice, which express a mutant insulin molecule. This is due to a decrease in activation of ER stress-dependent apoptotic pathways and a preservation of beta-cell mass and function. These data demonstrate that modulation of p85 alpha can protect pancreatic beta-cells from ER stress, pointing to a potentially therapeutic target in diabetic states. C1 [Winnay, Jonathon N.; Kahn, C. Ronald] Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Dirice, Ercument; Kulkarni, Rohit N.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Dirice, Ercument; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Liew, Chong Wee] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60612 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Dirice, Ercument/B-2825-2017 FU National Institutes of Health (NIH) Pathway to Independence [R00 DK090210]; NIH National Institute of Diabetes and Digestive and Kidney [DK67536, DK055545] FX We thank Gordon C. Weir for helpful discussions, and Christopher Cahill and the Advanced Microscopy Core at the Joslin Diabetes Center for help in performing electron microscopy studies. The Specialized Assay Core at the Joslin Diabetes Center performed determination of hormone levels. C.W.L. is supported by National Institutes of Health (NIH) Pathway to Independence Award R00 DK090210. This research was supported by NIH National Institute of Diabetes and Digestive and Kidney Grants DK67536 (to R.N.K.) and DK055545 (to C.R.K.). NR 23 TC 9 Z9 10 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 21 PY 2014 VL 111 IS 3 BP 1192 EP 1197 DI 10.1073/pnas.1322564111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 292UQ UT WOS:000329928400072 PM 24395790 ER PT J AU Pinello, L Xu, J Orkin, SH Yuan, GC AF Pinello, Luca Xu, Jian Orkin, Stuart H. Yuan, Guo-Cheng TI Analysis of chromatin-state plasticity identifies cell-type-specific regulators of H3K27me3 patterns SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE polycomb; hematopoiesis; histone modifications; motifs ID POLYCOMB TARGET GENES; TRANSCRIPTIONAL REGULATORS; EPIGENOMIC ANNOTATION; HISTONE MODIFICATIONS; HUMAN GENOME; DNA; DIFFERENTIATION; PLURIPOTENT; EXPRESSION; ENHANCERS AB Chromatin states are highly cell-type-specific, but the underlying mechanisms for the establishment and maintenance of their genome- wide patterns remain poorly understood. Here we present a computational approach for investigation of chromatin-state plasticity. We applied this approach to investigate an ENCODE ChIP-seq dataset profiling the genome-wide distributions of the H3K27me3 mark in 19 human cell lines. We found that the high plasticity regions (HPRs) can be divided into two functionally and mechanistically distinct subsets, which correspond to CpG island (CGI) proximal or distal regions, respectively. Although the CGI proximal HPRs are typically associated with continuous variation across different cell-types, the distal HPRs are associated with binary-like variations. We developed a computational approach to predict putative cell-type-specific modulators of H3K27me3 patterns and validated the predictions by comparing with public ChIP-seq data. Furthermore, we applied this approach to investigate mechanisms for poised enhancer establishment in primary human erythroid precursors. Importantly, we predicted and experimentally validated that the principal hematopoietic regulator T-cell acute lymphocytic leukemia-1 (TAL1) is involved in regulating H3K27me3 variations in collaboration with the transcription factor growth factor independent 1B (GFI1B), providing fresh insights into the context-specific role of TAL1 in erythropoiesis. Our approach is generally applicable to investigate the regulatory mechanisms of epigenetic pathways in establishing cellular identity. C1 [Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Pinello, Luca; Yuan, Guo-Cheng] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Xu, Jian; Orkin, Stuart H.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Xu, Jian; Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu; gcyuan@jimmy.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award [K01DK093543]; National Institutes of Health [R01HL32259, P01HL03262, R01HG005085] FX We thank Drs. Zhen Shao and Kimberly Glass for helpful discussion. This work was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award K01DK093543 (to J.X.); and National Institutes of Health Grants R01HL32259 and P01HL03262 (to S.H.O.) and R01HG005085 (to G.-C.Y.). S.H.O. is a Howard Hughes Medical Institute investigator. NR 65 TC 19 Z9 19 U1 0 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 21 PY 2014 VL 111 IS 3 BP E344 EP E353 DI 10.1073/pnas.1322570111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 292UQ UT WOS:000329928400009 PM 24395799 ER PT J AU Januzzi, JL van Kimmenade, RRJ AF Januzzi, James L., Jr. van Kimmenade, Roland R. J. TI Importance of Rigorous Evaluation in Comparative Biomarker Studies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE biomarkers; heart failure; myocardial fibrosis; remodeling; survival ID HEART-FAILURE; GALECTIN-3 AB Following the introduction of B-type natriuretic peptide (BNP) and its amino-terminal equivalent (NT-proBNP), the use of biomarkers for the evaluation and management of heart failure (HF) has grown. Indeed, natriuretic peptide testing for diagnosis and prognosis recently earned a Class I Level of Evidence: A in the 2013 American Heart Association/American College of Cardiology clinical practice guidelines for HF (2). Although it took years to develop such support, this is indeed the proper recognition of the clinical role played by these important biomarkers. C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,32 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Kimmenade, R.R.J./L-4432-2015 NR 7 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 21 PY 2014 VL 63 IS 2 BP 167 EP 169 DI 10.1016/j.jacc.2013.09.005 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 291OW UT WOS:000329839200011 PM 24076530 ER PT J AU Goyal, L Deshpande, V Chung, DC Groeschl, RT Gamblin, TC Zhu, AX AF Goyal, Lipika Deshpande, Vikram Chung, Daniel C. Groeschl, Ryan Thomas Gamblin, T. Clark Zhu, Andrew X. TI Mismatch repair protein loss and microsatellite instability in cholangiocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 SU S MA 237 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100240 ER PT J AU Karpathakis, A Dibra, H Morris, T Oukrife, D Pipinikas, CP Pearce, K Francis, J Pericleous, M Mandair, D Feber, A Toumpanakis, C Luong, TV Meyerson, M Caplin, ME Beck, S Thirlwell, C AF Karpathakis, Anna Dibra, Harpreet Morris, Tiffany Oukrife, Dahmane Pipinikas, Christodoulos P. Pearce, Kerra Francis, Joshua Pericleous, Marinos Mandair, Dalvinder Feber, Andrew Toumpanakis, Christos Tu Vinh Luong Meyerson, Matthew Caplin, Martyn E. Beck, Stephan Thirlwell, Christina TI Genome-wide DNA methylation profiling of gastrointestinal neuroendocrine tumors to identify hypermethylation of mTOR, Wnt, and Notch pathways in GI NET pathogenesis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 UCL, Inst Canc, London, England. Royal Free Hosp, Neuroendocrine Tumour Unit, London NW3 2QG, England. UCL, London, England. Broad Inst, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JAN 20 PY 2014 VL 32 IS 3 SU S MA 212 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100215 ER PT J AU Korant, AK Dhar, VK Johnston, G Saha, SK Shaik, M Wiese, D Saha, S AF Korant, Alpesh K. Dhar, Vikrom K. Johnston, Gregory Saha, Supriya Kumar Shaik, Mohammed Wiese, David Saha, Sukamal TI Correlation of lymphovascular invasion and staging in patients undergoing lymphatic mapping for colon cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Michigan State Univ, McLaren Reg Med Ctr, Flint, MI USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. McLaren Macomb Med Ctr, Mt Clemens, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Michigan State Univ, Lansing, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 SU S MA 498 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100490 ER PT J AU Niedzwiecki, D Frankel, W Venook, AP Ye, X Friedman, PN Goldberg, RM Mayer, RJ Colacchio, TA Kennedy, RD Davison, T O'Brien, EJ Mulligan, J Johnston, PG Harkin, DP Schilsky, RL Bertagnolli, MM Innocenti, F AF Niedzwiecki, Donna Frankel, Wendy Venook, Alan Paul Ye, Xing Friedman, Paula N. Goldberg, Richard M. Mayer, Robert J. Colacchio, Thomas Anthony Kennedy, Richard D. Davison, Timothy O'Brien, Eamonn J. Mulligan, Jude Johnston, Patrick G. Harkin, D. Paul Schilsky, Richard L. Bertagnolli, Monica M. Innocenti, Federico TI Association between ColDx assay result and recurrence-free interval in stage II colon cancer patients on CALGB (Alliance) 9581 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Duke Univ, Durham, NC USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Chicago, Chicago, IL 60637 USA. Ohio State Univ, Ctr Comprehens Canc, Arthur G James Canc Hosp, Columbus, OH 43210 USA. Richard J Solove Res Inst, Columbus, OH USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Hanover, NH USA. Almac Diagnost Ltd, Craigavon, North Ireland. Queens Univ Belfast, Belfast, Antrim, North Ireland. Amer Soc Clin Oncol, Alexandria, VA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. RI Kennedy, Richard/J-3489-2012 OI Kennedy, Richard/0000-0003-4737-6163 NR 0 TC 1 Z9 1 U1 0 U2 1 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 JAN 20 PY 2014 VL 32 IS 3 SU S MA 455 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100448 ER PT J AU Noel, MS Allen, JN Abrams, TA Yurgelun, M Faris, JE Goyal, L Clark, JW Blaszkowsky, LS Murphy, JE Zheng, H Khorana, AA Connolly, GC Hyrien, O Ng, K Borger, DR Iafrate, AJ Hezel, AF Zhu, AX AF Noel, Marcus Smith Allen, Jill N. Abrams, Thomas Adam Yurgelun, Matthew Faris, Jason Edward Goyal, Lipika Clark, Jeffrey W. Blaszkowsky, Lawrence Scott Murphy, Janet E. Zheng, Hui Khorana, Alok A. Connolly, Gregory Clayton Hyrien, Ollivier Ng, Kimmie Borger, Darrell R. Iafrate, Anthony John Hezel, Aram F. Zhu, Andrew X. TI A single-arm phase II trial of gemcitabine, oxaliplatin, and panitumumab in KRAS wild-type advanced biliary tract cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Univ Rochester, Rochester, NY USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 SU S MA 255 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100258 ER PT J AU Pawlik, TM Borger, DR Kim, Y Cosgrove, D Alexandrescu, S Groeschl, RT Deshpande, V Lindberg, JM Ferrone, C Sempoux, C Popescu, I Bauer, TW Gamblin, TC Gigot, JF Anders, R Zhu, AX AF Pawlik, Timothy M. Borger, Darrell R. Kim, Yuhree Cosgrove, David Alexandrescu, Sorin Groeschl, Ryan Thomas Deshpande, Vikram Lindberg, James M. Ferrone, Cristina Sempoux, Christine Popescu, Irinel Bauer, Todd W. Gamblin, T. Clark Gigot, Jean Francois Anders, Robert Zhu, Andrew X. TI Genomic profiling of intrahepatic cholangiocarcinoma: Refining prognostic determinants and identifying therapeutic targets SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Fundeni Clin Inst Digest, Bucharest, Romania. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Virginia, Dept Surg, Charlottesville, VA USA. St Luc Univ Hosp, Brussels, Belgium. Fundeni Clin Inst Digest Dis & Liver Transplantat, Ctr Gen Surg & Liver Transplantat, Bucharest, Romania. Clin Univ St Luc, B-1200 Brussels, Belgium. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 7 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 SU S MA 210 PG 2 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100213 ER PT J AU Sabbatino, F Milham, L Deshpande, V Konstantinidis, IT Zhu, AX Santos, DD Bardeesy, N Hong, TS Tanabe, K Ferrone, S Lillemoe, K Ferrone, C AF Sabbatino, Francesco Milham, Lucia Deshpande, Vikram Konstantinidis, Ioannis T. Zhu, Andrew X. Santos, Daniela Dias Bardeesy, Nabeel Hong, Theodore S. Tanabe, Kenneth Ferrone, Soldano Lillemoe, Keith Ferrone, Cristina TI Variability in immune infiltrates and HLA expression in cholangiocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arizona, Tucson, AZ USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 SU S MA 230 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100233 ER PT J AU Saha, S Koduru, U Burke, J Korant, AK Saha, SK Dhar, VK Johnston, G Wiese, D Arora, ML Singh, T AF Saha, Sukamal Koduru, Ujwala Burke, Jacob Korant, Alpesh K. Saha, Supriya Kumar Dhar, Vikrom K. Johnston, Gregory Wiese, David Arora, Madan L. Singh, Trevor TI Comparison of sizes of sentinel and non-sentinel lymph nodes in colorectal cancers (CRCa). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Michigan State Univ, McLaren Reg Med Ctr, Flint, MI USA. McLaren Flint Med Ctr, Grand Blanc, MI USA. McLaren Flint Med Ctr, Flint, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. McLaren Macomb Med Ctr, Mt Clemens, MI USA. Michigan State Univ, Flint, MI USA. McLaren Reg Med Ctr, Flint, MI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JAN 20 PY 2014 VL 32 IS 3 SU S MA 557 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100547 ER PT J AU Schultes, BC Chu, CL Long, A Sun, E Kurtagic, E Beccati, D Pradines, J Miller, P Ryan, DP Flaherty, K Roach, J Kaundinya, GV AF Schultes, Birgit Corinna Chu, Chia Lin Long, Alison Sun, Elaine Kurtagic, Elma Beccati, Daniela Pradines, Joel Miller, Paul Ryan, David P. Flaherty, Keith Roach, James Kaundinya, Ganesh Venkataraman TI The effect and mechanism of M402 on gemcitabine uptake into pancreatic tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Momenta Pharmaceut, Cambridge, MA USA. Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JAN 20 PY 2014 VL 32 IS 3 SU S MA 215 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100218 ER PT J AU Shaik, M Saha, S Saha, SK Johnston, G Korant, AK Wiese, D Dhar, VK Eilander, D Arora, ML Singh, T AF Shaik, Mohammed Saha, Sukamal Saha, Supriya Kumar Johnston, Gregory Korant, Alpesh K. Wiese, David Dhar, Vikrom K. Eilander, David Arora, Madan L. Singh, Trivor TI Tumor size as a prognostic indicator in colon cancer (CCa) patients undergoing sentinel lymph node mapping (SLNM) versus conventional surgery (CS) in National Cancer Data Base (NCDB) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Michigan State Univ, Lansing, MI USA. Michigan State Univ, McLaren Reg Med Ctr, Flint, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. McLaren Macomb Med Ctr, Mt Clemens, MI USA. Michigan State Univ Coll Human Med, E Lansing, MI USA. McLaren Reg Med Ctr, Flint, MI USA. Michigan State Univ, Flint, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 SU S MA 411 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100407 ER PT J AU Shiovitz, S Hsu, L Qu, CH Harrison, TA Berndt, S Brenner, H Casey, G Chan, AT Chang-Claude, J Le Marchand, L Newcomb, PA Potter, JD Schoen, RE Slattery, ML White, E Peters, U Grady, WM Consortium, G AF Shiovitz, Stacey Hsu, Li Qu, Conghui Harrison, Tabitha A. Berndt, Sonja Brenner, Hermann Casey, Graham Chan, Andrew T. Chang-Claude, Jenny Le Marchand, Loic Newcomb, Polly A. Potter, John D. Schoen, Robert E. Slattery, Martha L. White, Emily Peters, Ulrike Grady, William M. Consortium, G. E. C. C. O. TI DCC and RET pathway analysis to identify factors associated with advanced colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, NIH, Bethesda, MD 20892 USA. German Canc Res Ctr, Heidelberg, Germany. Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JAN 20 PY 2014 VL 32 IS 3 SU S MA 457 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100450 ER PT J AU Spreafico, A Coate, LE Shen, XW Zhai, RH Xu, W Chen, ZF Chen, Z Patel, D Brown, C Kuang, Q Boyd, K Kulke, M Su, L Mackay, H Knox, JJ Wong, R Darling, G Christiani, DC Liu, G AF Spreafico, Anna Coate, Linda E. Shen, Xiaowei Zhai, Rihong Xu, Wei Chen, Zhen-Fei Chen, Zhuo Patel, Devalben Brown, Catherine Kuang, Qin Boyd, Kevin Kulke, Matthew Su, Li Mackay, Helen Knox, Jennifer J. Wong, Rebecca Darling, Gail Christiani, David C. Liu, Geoffrey TI Early adulthood body mass index, cumulative smoking, and esophageal adenocarcinoma survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Toronto, Ontario Canc Inst, Princess Margaret Canc Ctr, Toronto, ON M5S 1A1, Canada. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Ontario Canc Inst, Priincess Margaret Canc Ctr, Toronto, ON M4X 1K9, Canada. Ontario Canc Inst, Princess Margaret Canc Ctr, Toronto, ON M4X 1K9, Canada. Ontario Canc Inst, Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M4X 1K9, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Ontario Canc Inst, Princess Margaret Canc Ctr, Radiat Med Program, Toronto, ON M4X 1K9, Canada. Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Dept Surg,Div Thorac Surg, Toronto, ON M5G 1L7, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 SU S MA 10 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100019 ER PT J AU Zhu, AX Kudo, M Assenat, E Cattan, S Kang, YK Lim, HY Poon, RTP Blanc, JF Vogel, A Chen, CL Dorval, E Peck-Radosavljevic, M Santoro, A Daniele, B Furuse, J Jappe, A Perraud, K Anak, O Sellami, DB Chen, LT AF Zhu, Andrew X. Kudo, Masatoshi Assenat, Eric Cattan, Stephane Kang, Yoon-Koo Lim, Ho Yeong Poon, Ronnie Tung Ping Blanc, Jean-Frederic Vogel, Arndt Chen, Chao-Long Dorval, Etienne Peck-Radosavljevic, Markus Santoro, Armando Daniele, Bruno Furuse, Junji Jappe, Annette Perraud, Kevin Anak, Ozlem Sellami, Dalila B. Chen, Li-Tzong TI EVOLVE-1: Phase 3 study of everolimus for advanced HCC that progressed during or after sorafenib. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 16-18, 2014 CL San Francisco, CA C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Kinki Univ, Sch Med, Dept Gastroenterol & Hepatol, Osaka 589, Japan. Inst Canc Montpellier Val dAurelle, Montpellier, France. Univ Nord France, Lille, France. Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Kinki Univ, Sch Med, Dept Gastroenterol & Hepatol, Osaka 589, Japan. Inst Canc Montpellier Val dAurelle, Montpellier, France. Univ Nord France, Lille, France. Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea. Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. Hop St Andre, Bordeaux, France. Hannover Med Sch, Hannover, Germany. Kaohsiung Chang Gung Mem Hosp, Kaohsiung, Taiwan. CHRU Tours, Tours, France. Med Univ Vienna, Vienna, Austria. Ist Clin Humanitas, Humanitas Canc Ctr, Rozzano, Italy. G Rummo Hosp, Benevento, Italy. Kyorin Univ, Sch Med, Dept Internal Med, Tokyo, Japan. Novartis Pharma AG, Basel, Switzerland. Novartis Pharmaceut, E Hanover, NJ USA. Natl Hlth Res Inst, Natl Inst Canc Res, Tainan, Taiwan. RI Chen, Li-Tzong/D-2071-2010 NR 0 TC 10 Z9 10 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 JAN 20 PY 2014 VL 32 IS 3 SU S MA 172 PG 1 WC Oncology SC Oncology GA AE0UQ UT WOS:000333682100177 ER PT J AU Sholukh, AM Byrareddy, SN Shanmuganathan, V Hemashettar, G Lakhashe, SK Rasmussen, RA Watkins, JD Vyas, HK Thorat, S Brandstoetter, T Mukhtar, MM Yoon, JK Novembre, FJ Villinger, F Landucci, G Forthal, DN Ratcliffe, S Tuero, I Robert-Guroff, M Polonis, VR Bilska, M Montefiori, DC Johnson, WE Ertl, HC Ruprecht, RM AF Sholukh, Anton M. Byrareddy, Siddappa N. Shanmuganathan, Vivekanandan Hemashettar, Girish Lakhashe, Samir K. Rasmussen, Robert A. Watkins, Jennifer D. Vyas, Hemant K. Thorat, Swati Brandstoetter, Tania Mukhtar, Muhammad M. Yoon, John K. Novembre, Francis J. Villinger, Francois Landucci, Gary Forthal, Donald N. Ratcliffe, Sarah Tuero, Iskra Robert-Guroff, Marjorie Polonis, Victoria R. Bilska, Miroslawa Montefiori, David C. Johnson, Welkin E. Ertl, Hildegund C. Ruprecht, Ruth M. TI Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose SO RETROVIROLOGY LA English DT Article DE Macaque model; Heterologous R5 SHIV clade C challenge; SHIVIG; Passive immunization; Enhancement of infection; Non-human primate model ID HIV-1/SIV CHIMERIC VIRUS; CLADE-C INFECTION; NEUTRALIZING ANTIBODIES; HIV-INFECTION; RHESUS MACAQUES; NONNEUTRALIZING ANTIBODIES; REPLICATION-COMPETENT; ENVELOPE GLYCOPROTEIN; MEDIATED ENHANCEMENT; VACCINE DEVELOPMENT AB Background: A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results: SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C'-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion: Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. C1 [Sholukh, Anton M.; Lakhashe, Samir K.; Vyas, Hemant K.; Mukhtar, Muhammad M.; Ruprecht, Ruth M.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78245 USA. [Sholukh, Anton M.; Byrareddy, Siddappa N.; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Lakhashe, Samir K.; Rasmussen, Robert A.; Watkins, Jennifer D.; Vyas, Hemant K.; Thorat, Swati; Brandstoetter, Tania; Mukhtar, Muhammad M.; Yoon, John K.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sholukh, Anton M.; Byrareddy, Siddappa N.; Lakhashe, Samir K.; Rasmussen, Robert A.; Watkins, Jennifer D.; Vyas, Hemant K.; Thorat, Swati; Mukhtar, Muhammad M.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Novembre, Francis J.; Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Novembre, Francis J.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Byrareddy, Siddappa N.; Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Landucci, Gary; Forthal, Donald N.] Univ Calif Irvine, Sch Med, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Ratcliffe, Sarah] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Tuero, Iskra; Robert-Guroff, Marjorie] NCI, Ctr Canc Res, Vaccine Branch, Bethesda, MD 20892 USA. [Polonis, Victoria R.] Walter Reed Army Inst Res, Mil HIV Res Program, Silver Spring, MD USA. [Bilska, Miroslawa; Montefiori, David C.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA. [Johnson, Welkin E.] Boston Coll, Dept Biol, Boston, MA USA. [Ertl, Hildegund C.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Ruprecht, RM (reprint author), Texas Biomed Res Inst, Dept Virol & Immunol, POB 760549, San Antonio, TX 78245 USA. EM rruprecht@txbiomed.org RI Lakhashe, Samir/F-1150-2014; OI Byrareddy, Siddappa /0000-0002-7423-1763; Ratcliffe, Sarah/0000-0002-6644-8284 FU NIH [P01 AI082282, R37 AI034266, R01 DE023049, P01 AI048240, R01 AI083118, HHSN27201100016C]; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense (DOD) [W81XWH-07-2-0067]; Intramural Research Program of the NIH, National Cancer Institute; Office of Research Infrastructure Programs/OD [P51OD11107] FX We thank Dr. J. Mascola for providing mAb VRC01, Dr. S.-L. Hu for providing SHIV-1157ip Env proteins, Dr. W. Marasco for providing mAb Fm-6, Dr. C. Ochsenbauer for providing pNL-LucR.T2A plasmid, P. Ehrenberg for production of the infectious molecular clones (GS 014 and GS 020), Dr. J. Hoxie for providing SupT1.R5 cells, and Juan Esquivel for technical help with the manuscript. This work was supported by NIH grants P01 AI082282 to RMR, SR and HCE, R37 AI034266, R01 DE023049 and P01 AI048240 to RMR, R01 AI083118 to WEJ, and HHSN27201100016C to DCM as well as by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD) to VRP. This project was also funded in part by the Intramural Research Program of the NIH, National Cancer Institute, to MR-G and by the Office of Research Infrastructure Programs/OD P51OD11107 to the YNPRC. The authors have no conflicting financial interests. NR 46 TC 8 Z9 8 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 20 PY 2014 VL 11 AR 8 DI 10.1186/1742-4690-11-8 PG 15 WC Virology SC Virology GA AB3OT UT WOS:000331700800001 PM 24444350 ER PT J AU Canellos, GP Rosenberg, SA Friedberg, JW Lister, TA DeVita, VT AF Canellos, George P. Rosenberg, Saul A. Friedberg, Jonathan W. Lister, T. Andrew DeVita, Vincent T. TI Treatment of Hodgkin Lymphoma: A 50-Year Perspective SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROSPECTIVE CLINICAL-TRIAL; STEM-CELL TRANSPLANTATION; COMBINATION CHEMOTHERAPY; RADIATION-THERAPY; FREE SURVIVAL; FOLLOW-UP; DISEASE; ABVD; RADIOTHERAPY; MOPP C1 [Canellos, George P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rosenberg, Saul A.] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA 94305 USA. [Friedberg, Jonathan W.] Univ Rochester, James P Wilmont Canc Ctr, Rochester, NY USA. [Lister, T. Andrew] Univ London, Barts Canc Inst, London, England. [DeVita, Vincent T.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. RP Canellos, GP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 61 TC 37 Z9 39 U1 2 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 BP 163 EP + DI 10.1200/JCO.2013.53.1194 PG 7 WC Oncology SC Oncology GA 302TN UT WOS:000330627900001 PM 24441526 ER PT J AU Berry, DL Hong, F Halpenny, B Partridge, AH Fann, JR Wolpin, S Lober, WB Bush, NE Parvathaneni, U Back, AL Amtmann, D Ford, R AF Berry, Donna L. Hong, Fangxin Halpenny, Barbara Partridge, Ann H. Fann, Jesse R. Wolpin, Seth Lober, William B. Bush, Nigel E. Parvathaneni, Upendra Back, Anthony L. Amtmann, Dagmar Ford, Rosemary TI Electronic Self-Report Assessment for Cancer and Self-Care Support: Results of a Multicenter Randomized Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; INFORMATION; ASKING AB Purpose The purpose of this trial was to evaluate the effect of a Web-based, self-report assessment and educational intervention on symptom distress during cancer therapy. Patients and Methods A total of 752 ambulatory adult participants were randomly assigned to symptom/quality-of-life (SxQOL) screening at four time points (control) versus screening, targeted education, communication coaching, and the opportunity to track/graph SxQOL over time (intervention). A summary of the participant-reported data was delivered to clinicians at each time point in both groups. All participants used the assessment before a new therapeutic regimen, at 3 to 6 weeks and 6 to 8 weeks later, completing the final assessment at the end of therapy. Change in Symptom Distress Scale-15 (SDS-15) score from pretreatment to end of study was compared using analysis of covariance and regression analysis adjusting for selected variables. Results We detected a significant difference between study groups in mean SDS-15 score change from baseline to end of study: 1.27 (standard deviation [SD], 6.7) in the control group (higher distress) versus -0.04 (SD, 5.8) in the intervention group (lower distress). SDS-15 score was reduced by an estimated 1.21 (95% CI, 0.23 to 2.20; P = .02) in the intervention group. Baseline SDS-15 score (P < .001) and clinical service (P = .01) were predictive. Multivariable analyses suggested an interaction between age and study group (P = .06); in subset analysis, the benefit of intervention was strongest in those age > 50 years (P = .002). Conclusion Web-based self-care support and communication coaching added to SxQOL screening reduced symptom distress in a multicenter sample of participants with various diagnoses during and after active cancer treatment. Participants age > 50 years, in particular, may have benefited from the intervention. (C) 2013 by American Society of Clinical Oncology C1 [Berry, Donna L.; Hong, Fangxin; Halpenny, Barbara; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Berry, Donna L.; Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA. [Fann, Jesse R.; Parvathaneni, Upendra; Back, Anthony L.; Amtmann, Dagmar] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Fann, Jesse R.; Back, Anthony L.; Amtmann, Dagmar; Ford, Rosemary] Seattle Canc Care Alliance, Seattle, WA USA. [Lober, William B.] Univ Washington, Seattle, WA 98195 USA. [Bush, Nigel E.] US Dept Def, Natl Ctr Telehealth & Technol, Tacoma, WA USA. RP Berry, DL (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW-518, Boston, MA 02115 USA. EM donna_berry@dfci.harvard.edu OI Parvathaneni, Upendra/0000-0003-2370-4492 FU National Institute of Nursing Research, National Institutes of Health [R01 NR008726] FX Supported by Grant No. R01 NR008726 (2008-2010) from the National Institute of Nursing Research, National Institutes of Health. NR 17 TC 24 Z9 24 U1 1 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2014 VL 32 IS 3 BP 199 EP + DI 10.1200/JCO.2013.48.6662 PG 9 WC Oncology SC Oncology GA 302TN UT WOS:000330627900007 PM 24344222 ER PT J AU Mostaghel, EA Nelson, PS Lange, P Lin, DW Taplin, ME Balk, S Ellis, W Kantoff, P Marck, B Tamae, D Matsumoto, AM True, LD Vessella, R Penning, T Merrill, RH Gulati, R Montgomery, B AF Mostaghel, Elahe A. Nelson, Peter S. Lange, Paul Lin, Daniel W. Taplin, Mary Ellen Balk, Steven Ellis, William Kantoff, Philip Marck, Brett Tamae, Daniel Matsumoto, Alvin M. True, Lawrence D. Vessella, Robert Penning, Trevor Merrill, Rachel Hunter Gulati, Roman Montgomery, Bruce TI Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; NEOADJUVANT CHEMOTHERAPY; SPLICE VARIANTS; RECEPTOR; CASTRATION; TESTOSTERONE; THERAPY; GROWTH; DIHYDROTESTOSTERONE; ADENOCARCINOMA AB Purpose Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5--reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Patients and Methods Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration. Results Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had 0.2 cm(3) of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group. Conclusion Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer. (C) 2013 by American Society of Clinical Oncology C1 [Mostaghel, Elahe A.; Merrill, Rachel Hunter; Gulati, Roman] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Mostaghel, Elahe A.; Nelson, Peter S.; Lange, Paul; Lin, Daniel W.; Ellis, William; Vessella, Robert; Montgomery, Bruce] Univ Washington, Seattle, WA 98195 USA. [Marck, Brett; Matsumoto, Alvin M.; True, Lawrence D.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Taplin, Mary Ellen; Kantoff, Philip] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Balk, Steven] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tamae, Daniel; Penning, Trevor] Univ Penn, Philadelphia, PA 19104 USA. RP Montgomery, B (reprint author), Univ Washington, Dept Med, Div Oncol, 1959 NE Pacific,Box 356158, Seattle, WA 98195 USA. EM rbmontgo@uw.edu OI Penning, Trevor/0000-0002-3937-1066 FU Prostate Cancer Foundation; Damon Runyon Cancer Research Foundation [CI-40-08]; National Institutes of Health (Pacific Northwest Prostate Cancer SPORE) [P50 CA97186, P01CA085859]; Department of Defense Prostate Cancer Research Program Clinical Consortium (the University of Washington) [W81XWH-07-1-0097]; Department of Defense Prostate Cancer Research Program Clinical Consortium (Dana-Farber Cancer Institute) [W81XWH-06-1-0261]; Congressionally Directed Medical Research Program Award [PC093509]; GlaxoSmithKline FX Supported by the Prostate Cancer Foundation (Career Development Award to E.A.M. and Synergy Award to R.B.M. and P.S.N.); Damon Runyon Cancer Research Foundation (Damon Runyon-Genentech Clinical Investigator Award CI-40-08 to E.A.M.); National Institutes of Health (Pacific Northwest Prostate Cancer SPORE Grants No. P50 CA97186; P01CA085859), Department of Defense Prostate Cancer Research Program Clinical Consortium (the University of Washington: Grant No. W81XWH-07-1-0097; Dana-Farber Cancer Institute: Grant No. W81XWH-06-1-0261) and Congressionally Directed Medical Research Program Award PC093509. GlaxoSmithKline provided dutasteride and research support. AstraZeneca provided goserelin and bicalutamide. NR 32 TC 19 Z9 19 U1 0 U2 2 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 JAN 20 PY 2014 VL 32 IS 3 BP 229 EP + DI 10.1200/JCO.2012.48.6431 PG 13 WC Oncology SC Oncology GA 302TN UT WOS:000330627900011 PM 24323034 ER PT J AU Choi, SH Lee, HJ Jin, YB Jang, J Kang, GY Lee, M Kim, CH Kim, J Yoon, SS Lee, YS Lee, YJ AF Choi, Seo-hyun Lee, Hae-June Jin, Yeung Bae Jang, Junho Kang, Ga-Young Lee, Minyoung Kim, Chun-Ho Kim, Joon Yoon, Sam S. Lee, Yun-Sil Lee, Yoon-Jin TI MMP9 Processing of HSPB1 Regulates Tumor Progression SO PLOS ONE LA English DT Article ID SHOCK-PROTEIN EXPRESSION; MATRIX METALLOPROTEINASES; CANCER-THERAPY; LUNG-CANCER; CELL-DEATH; HSP27; ANGIOGENESIS; INHIBITION; CARCINOMA; SERUM AB Matrix metalloproteinases regulate pathophysiological events by processing matrix proteins and secreted proteins. Previously, we demonstrated that soluble heat shock protein B1 (HSPB1) is released primarily from endothelial cells (ECs) and regulates angiogenesis via direct interaction with vascular endothelial growth factor (VEGF). Here we report that MMP9 can cleave HSPB1 and release anti-angiogenic fragments, which play a key role in tumorprogression. We mapped the cleavage sites and explored their physiological relevance during these processing events. HSPB1 cleavage by MMP9 inhibited VEGF-induced ECs activation and the C-terminal HSPB1 fragment exhibited more interaction with VEGF than did full-length HSPB1. HSPB1 cleavage occurs during B16F10 lung progression in wild-type mice. Also, intact HSPB1 was more detected on tumor endothelium of MMP9 null mice than wild type mice. Finally, we confirmed that secretion of C-terminal HSPB1 fragment was significantly inhibited lung and liver tumor progression of B16F10 melanoma cells and lung tumor progression of CT26 colon carcinoma cells, compared to full-length HSPB1. These data suggest that in vivo MMP9-mediated processing of HSPB1 acts to regulate VEGF-induced ECs activation for tumor progression, releasing anti-angiogenic HSPB1 fragments. Moreover, these findings potentially explain an anti-target effect for the failure of MMP inhibitors in clinical trials, suggesting that MMP inhibitors may have pro-tumorigenic effects by reducing HSPB1 fragmentation. C1 [Choi, Seo-hyun; Lee, Hae-June; Jin, Yeung Bae; Jang, Junho; Lee, Minyoung; Lee, Yoon-Jin] Korea Inst Radiol & Med Sci, Div Radiat Effects, Seoul, South Korea. [Choi, Seo-hyun; Kim, Joon] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. [Kang, Ga-Young; Lee, Yun-Sil] Ewha Womans Univ, Coll Pharm, Seoul, South Korea. [Kang, Ga-Young; Lee, Yun-Sil] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul, South Korea. [Kim, Chun-Ho] Korea Inst Radiol & Med Sci, Lab Tissue Engn, Seoul, South Korea. [Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yoon, Sam S.] Harvard Univ, Sch Med, Boston, MA USA. RP Lee, YS (reprint author), Ewha Womans Univ, Coll Pharm, Seoul, South Korea. EM yslee0425@ewha.ac.kr; yjlee8@kcch.re.kr FU Nuclear Research and Development Program [NRF-2012M2A2A7012483, NRF-2011-0031697, NRF-2013M2A2A7043580]; KIRAMS research project [50520-2013]; Nuclear Research and Development Program; Basic Science Research Program [R1A4A002]; Mid-career Researcher Program of the National Research Foundation of Korea (NRF) [2011-0013364]; Korean Ministry of Education, Science, and Technology (MEST); Ewha Womans University FX This work was supported by the Nuclear Research and Development Program (Grant No. NRF-2012M2A2A7012483, NRF-2011-0031697 and NRF-2013M2A2A7043580) and a KIRAMS research project (Grant No. 50520-2013) funded by the Nuclear Research and Development Program. This work also supported by the Basic Science Research Program (Grant No. R1A4A002), Mid-career Researcher Program (Grant No. 2011-0013364) of the National Research Foundation of Korea (NRF), funded by the Korean Ministry of Education, Science, and Technology (MEST) and the Ewha Global Top5 Grant 2011 of Ewha Womans University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 5 Z9 6 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 20 PY 2014 VL 9 IS 1 AR e85509 DI 10.1371/journal.pone.0085509 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297FH UT WOS:000330240500054 PM 24465581 ER PT J AU McFarland, NR Dimant, H Kibuuka, L Ebrahimi-Fakhari, D Desjardins, CA Danzer, KM Danzer, M Fan, ZY Schwarzschild, MA Hirst, W McLean, PJ AF McFarland, Nikolaus R. Dimant, Hemi Kibuuka, Laura Ebrahimi-Fakhari, Darius Desjardins, Cody A. Danzer, Karin M. Danzer, Michael Fan, Zhanyun Schwarzschild, Michael A. Hirst, Warren McLean, Pamela J. TI Chronic Treatment with Novel Small Molecule Hsp90 Inhibitors Rescues Striatal Dopamine Levels but Not alpha-Synuclein-Induced Neuronal Cell Loss SO PLOS ONE LA English DT Article ID HEAT-SHOCK PROTEINS; UBIQUITIN-PROTEASOME SYSTEM; RAT SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; NIGROSTRIATAL DEGENERATION; INDUCED TOXICITY; AGGREGATION; MODEL; CHAPERONES; GELDANAMYCIN AB Hsp90 inhibitors such as geldanamycin potently induce Hsp70 and reduce cytotoxicity due to alpha-synuclein expression, although their use has been limited due to toxicity, brain permeability, and drug design. We recently described the effects of a novel class of potent, small molecule Hsp90 inhibitors in cells overexpressing alpha-synuclein. Screening yielded several candidate compounds that significantly reduced alpha-synuclein oligomer formation and cytotoxicity associated with Hsp70 induction. In this study we examined whether chronic treatment with candidate Hsp90 inhibitors could protect against alpha-synuclein toxicity in a rat model of parkinsonism. Rats were injected unilaterally in the substantia nigra with AAV8 expressing human alpha-synuclein and then treated with drug for approximately 8 weeks by oral gavage. Chronic treatment with SNX-0723 or the more potent, SNX-9114 failed to reduce dopaminergic toxicity in the substantia nigra compared to vehicle. However, SNX-9114 significantly increased striatal dopamine content suggesting a positive neuromodulatory effect on striatal terminals. Treatment was generally well tolerated, but higher dose SNX-0723 (6-10 mg/kg) resulted in systemic toxicity, weight loss, and early death. Although still limited by potential toxicity, Hsp90 inhibitors tested herein demonstrate oral efficacy and possible beneficial effects on dopamine production in a vertebrate model of parkinsonism that warrant further study. C1 [McFarland, Nikolaus R.] Univ Florida, Dept Neurol, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. [Dimant, Hemi; Kibuuka, Laura; Desjardins, Cody A.; Danzer, Michael; Fan, Zhanyun; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Ebrahimi-Fakhari, Darius] Heidelberg Univ, Childrens Hosp, Univ Heidelberg Hosp, Div Neurol & Inherited Metab Dis, Heidelberg, Germany. [Danzer, Karin M.] Univ Ulm Klinikum, Deparment Neurol, Ulm, Germany. [Hirst, Warren] Pfizer Neurosci Res Unit, Cambridge, MA USA. [McLean, Pamela J.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. RP McFarland, NR (reprint author), Univ Florida, Dept Neurol, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. EM nikolaus.mcfarland@neurology.ufl.edu; mclean.pamela@mayo.edu OI McFarland, Nikolaus/0000-0002-8699-8857 FU NIH [K08-NS067024, K24NS060991, NS063963]; Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grants [T32]; German National Academic Foundation (Studienstiftung des deutschen Volkes e.V.); Parkinson's Disease Foundation; DOD [W81XWH-11-1-0150]; Michael J. Fox Target Validation grant FX N.R.M. is supported by NIH K08-NS067024. H.D. is supported by Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grants (T32). D.E-F. received support from the German National Academic Foundation (Studienstiftung des deutschen Volkes e.V.) and from the Parkinson's Disease Foundation. C.A.D. and M.A.S. were supported by DOD W81XWH-11-1-0150 and NIH K24NS060991. P.J.M. received support from then Michael J. Fox 2008 Target Validation grant and NIH NS063963. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 11 Z9 11 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 20 PY 2014 VL 9 IS 1 AR e86048 DI 10.1371/journal.pone.0086048 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297FH UT WOS:000330240500103 PM 24465863 ER PT J AU Loving, GS Caravan, P AF Loving, Galen S. Caravan, Peter TI Activation and Retention: A Magnetic Resonance Probe for the Detection of Acute Thrombosis SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE disulfide bonds; enzymatic activation; fibrin; imaging agents; magnetic resonance imaging ID PROTEIN-DISULFIDE-ISOMERASE; PLATELET PLASMA-MEMBRANE; CONTRAST AGENTS; FIBRIN; MRI; EP-2104R AB Blood-clot formation that results in the complete occlusion of a blood vessel (thrombosis) often leads to serious life-threatening events, such as strokes and heart attacks. As the composition of a thrombus changes as it matures, new imaging methods that are capable of distinguishing new clots from old clots may yield important diagnostic and prognostic information. To address this need, an activatable magnetic resonance (MR) probe that is responsive to a key biochemical process associated with recently formed clots has been developed. C1 [Loving, Galen S.; Caravan, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Institutes of Health [HL109448, CA009502]; [RR023385]; [EB015896] FX The National Institutes of Health are acknowledged for funding to P.C. (HL109448)) and G.S.L. (CA009502) and instrumentation grants (RR023385, EB015896). Chris Farrar is thanked for help with the MRI experiment. NR 20 TC 8 Z9 8 U1 3 U2 39 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD JAN 20 PY 2014 VL 53 IS 4 BP 1140 EP 1143 DI 10.1002/anie.201308607 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 292CL UT WOS:000329879500043 PM 24338877 ER PT J AU Xu, ZP Dong, YL Wang, H Culley, DJ Marcantonio, ER Crosby, G Tanzi, RE Zhang, YY Xie, ZC AF Xu, Zhipeng Dong, Yuanlin Wang, Hui Culley, Deborah J. Marcantonio, Edward R. Crosby, Gregory Tanzi, Rudolph E. Zhang, Yiying Xie, Zhongcong TI Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice SO SCIENTIFIC REPORTS LA English DT Article ID NECROSIS-FACTOR-ALPHA; AMYLOID BETA-PROTEIN; GENERAL-ANESTHESIA; NONCARDIAC SURGERY; INTERFERON-GAMMA; TRANSGENIC MICE; MOUSE MODEL; A-BETA; DYSFUNCTION; DISEASE AB Post-operative cognitive dysfunction (POCD) is associated with increased cost of care, morbidity, and mortality. However, its pathogenesis remains largely to be determined. Specifically, it is unknown why elderly patients are more likely to develop POCD and whether POCD is dependent on general anesthesia. We therefore set out to investigate the effects of peripheral surgery on the cognition and Alzheimer-related neuropathology in mice with different ages. Abdominal surgery under local anesthesia was established in the mice. The surgery induced post-operative elevation in brain beta-amyloid (A beta) levels and cognitive impairment in the 18 month-old wild-type and 9 month-old Alzheimer's disease transgenic mice, but not the 9 month-old wild-type mice. The A beta accumulation likely resulted from elevation of beta-site amyloid precursor protein cleaving enzyme and phosphorylated eukaryotic translation initiation factor 2 alpha. gamma-Secretase inhibitor compound E ameliorated the surgery-induced brain A beta accumulation and cognitive impairment in the 18 month-old mice. These data suggested that the peripheral surgery was able to induce cognitive impairment independent of general anesthesia, and that the combination of peripheral surgery with aging-or Alzheimer gene mutation-associated A beta accumulation was needed for the POCD to occur. These findings would likely promote more research to investigate the pathogenesis of POCD. C1 [Xu, Zhipeng; Dong, Yuanlin; Wang, Hui; Zhang, Yiying; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Xu, Zhipeng; Dong, Yuanlin; Wang, Hui; Tanzi, Rudolph E.; Zhang, Yiying; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wang, Hui] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing 100020, Peoples R China. [Culley, Deborah J.; Crosby, Gregory] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Culley, Deborah J.; Marcantonio, Edward R.; Crosby, Gregory] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. EM zxie@mgh.harvard.edu FU National Institutes of Health grants (Bethesda, Maryland) [R21 AG029856, R21 AG038994, R01 GM088801, R01 AG041274]; Investigator-Initiated Research Grant from Alzheimer's Association (Chicago, IL); Cure Alzheimer's Fund (Wellesley, MA); Midcareer Investigator Award in Patient-Oriented Research from the National Institute on Aging [K24 AG035075] FX This study was supported by National Institutes of Health grants (Bethesda, Maryland) (R21 AG029856, R21 AG038994, R01 GM088801 and R01 AG041274); Investigator-Initiated Research Grant from Alzheimer's Association (Chicago, IL) and Cure Alzheimer's Fund (Wellesley, MA) to Dr. Zhongcong Xie. Dr. Edward Marcantonio is supported by a Midcareer Investigator Award in Patient-Oriented Research from the National Institute on Aging [K24 AG035075]. The authors would like to thank Dr. Mark Baxter from Mount Sinai School of Medicine for constructive discussion, Dr. Hui Zheng from Massachusetts General Hospital for the help of statistical analysis of the data, and Joshua J. Busscher and Dr. Xin Xin from Massachusetts General Hospital for technical help. NR 41 TC 16 Z9 18 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 20 PY 2014 VL 4 AR 3766 DI 10.1038/srep03766 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291SW UT WOS:000329850900004 PM 24441878 ER PT J AU Ismahil, MA Hamid, T Bansal, SS Patel, B Kingery, JR Prabhu, SD AF Ismahil, Mohamed Ameen Hamid, Tariq Bansal, Shyam S. Patel, Bindiya Kingery, Justin R. Prabhu, Sumanth D. TI Remodeling of the Mononuclear Phagocyte Network Underlies Chronic Inflammation and Disease Progression in Heart Failure SO CIRCULATION RESEARCH LA English DT Article DE dendritic cells; heart failure; inflammation; monocytes; spleen ID PLASMACYTOID DENDRITIC CELLS; EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; ADOPTIVE TRANSFER; STEADY-STATE; KAPPA-B; MONOCYTE; SUBSETS; INFARCTION; SPLEEN; EXPRESSION AB Rationale: The role of mononuclear phagocytes in chronic heart failure (HF) is unknown. Objective: Our aim was to delineate monocyte, macrophage, and dendritic cell trafficking in HF and define the contribution of the spleen to cardiac remodeling. Methods and Results: We evaluated C57Bl/6 mice with chronic HF 8 weeks after coronary ligation. As compared with sham-operated controls, HF mice exhibited: (1) increased proinflammatory CD11b(+)F4/80(+)CD206(-) macrophages and CD11b(+)F4/80(+)Gr-1(hi) monocytes in the heart and peripheral blood, respectively, and reduced CD11b(+)F4/80(+)Gr-1(hi) monocytes in the spleen; (2) significantly increased CD11c(+)B220(-) classical dendritic cells and CD11c(+/low)B220(+) plasmacytoid dendritic cells in both the heart and spleen, and increased classic dendritic cells and plasmacytoid dendritic cells in peripheral blood and bone marrow, respectively; (3) increased CD4(+) helper and CD8(+) cytotoxic T-cells in the spleen; and (4) profound splenic remodeling with abundant white pulp follicles, markedly increased size of the marginal zone and germinal centers, and increased expression of alarmins. Splenectomy in mice with established HF reversed pathological cardiac remodeling and inflammation. Splenocytes adoptively transferred from mice with HF, but not from sham-operated mice, homed to the heart and induced long-term left ventricular dilatation, dysfunction, and fibrosis in naive recipients. Recipient mice also exhibited monocyte activation and splenic remodeling similar to HF mice. Conclusions: Activation of mononuclear phagocytes is central to the progression of cardiac remodeling in HF, and heightened antigen processing in the spleen plays a critical role in this process. Splenocytes (presumably splenic monocytes and dendritic cells) promote immune-mediated injurious responses in the failing heart and retain this memory on adoptive transfer. C1 [Ismahil, Mohamed Ameen; Hamid, Tariq; Bansal, Shyam S.; Patel, Bindiya; Prabhu, Sumanth D.] Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, Birmingham, AL 35294 USA. [Ismahil, Mohamed Ameen; Hamid, Tariq; Bansal, Shyam S.; Patel, Bindiya; Prabhu, Sumanth D.] Birmingham VAMC, Birmingham, AL USA. [Kingery, Justin R.] Univ Louisville, Dept Med, Louisville, KY 40292 USA. RP Prabhu, SD (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, 311 Tinsley Harrison Tower,1900 Univ Blvd, Birmingham, AL 35294 USA. EM sprabhu@uab.edu FU VA Merit Award; National Institutes of Health grants [HL-78825, HL-99014]; American Heart Association SDG award [0835456 N] FX This work was supported by a VA Merit Award (to S.D.P.), National Institutes of Health grants HL-78825 and HL-99014 (to S.D.P.), and an American Heart Association SDG award 0835456 N (to T.H.). NR 47 TC 54 Z9 58 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 17 PY 2014 VL 114 IS 2 BP 266 EP 282 DI 10.1161/CIRCRESAHA.113.301720 PG 17 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA AG7GU UT WOS:000335587100014 PM 24186967 ER PT J AU Liu, WY Lu, DJ Du, XM Sun, JQ Ge, J Wang, RW Wang, R Zou, J Xu, C Ren, J Wen, XF Liu, Y Cheng, SM Tan, X Pekkala, S Munukka, E Wiklund, P Chen, YQ Gu, Q Xia, ZC Liu, JJ Liu, WB Chen, XB Zhang, YM Li, R Borra, RJH Yao, JX Chen, PJ Cheng, SL AF Liu, Wu Yi Lu, Da Jiang Du, Xia Ming Sun, Jian Qin Ge, Jun Wang, Ren Wei Wang, Ru Zou, Jun Xu, Chang Ren, Jie Wen, Xin Fei Liu, Yang Cheng, Shu Mei Tan, Xiao Pekkala, Satu Munukka, Eveliina Wiklund, Petri Chen, Yan Qiu Gu, Qing Xia, Zheng Chang Liu, Jun Jun Liu, Wen Bin Chen, Xue Bo Zhang, Yi Min Li, Rui Borra, Ronald J. H. Yao, Jia Xin Chen, Pei Jie Cheng, Sulin TI Effect of aerobic exercise and low carbohydrate diet on pre-diabetic non-alcoholic fatty liver disease in postmenopausal women and middle aged men - the role of gut microbiota composition: study protocol for the AELC randomized controlled trial SO BMC PUBLIC HEALTH LA English DT Article DE Liver fat content; Glucose metabolism; Lipid metabolism; Gut microbiota; Metabonomics; Human; Clinical setting ID IMPAIRED GLUCOSE-TOLERANCE; DIABETES-MELLITUS; LIFE-STYLE; OBESITY; EPIDEMIOLOGY; PATHOGENESIS; ADULTS; CHINA; MICE AB Background: Pre-diabetes and non-alcoholic fatty liver disease (NAFLD) are associated with an unhealthy lifestyle and pose extremely high costs to the healthcare system. In this study, we aim to explore whether individualized aerobic exercise (AEx) and low carbohydrate diet (LCh) intervention affect hepatic fat content (HFC) in pre-diabetes via modification of gut microbiota composition and other post-interventional effects. Methods/design: A 6-month randomized intervention with 6-month follow-up is conducted from January 2013 to December 2015. The target sample size for intervention is 200 postmenopausal women and middle-aged men aged 50-65 year-old with pre-diabetes and NAFLD. The qualified subjects are randomized into 4 groups with 50 subjects in each group: 1 = AEx, 2 = LCh, 3 = AEx + LCh, and 4 = control. In addition, two age-matched reference groups (5 = pre-diabetes without NAFLD (n = 50) and 6 = Healthy without pre-diabetes or NAFLD (n = 50)) are included. The exercise program consists of progressive and variable aerobic exercise (intensity of 60 to 75% of initial fitness level, 3-5 times/week and 30-60 min/time). The diet program includes dietary consultation plus supplementation with a special lunch meal (40% of total energy intake/day) which aims to reduce the amount of carbohydrate consumption (30%). The control and reference groups are advised to maintain their habitual habits during the intervention. The primary outcome measures are HFC, serum metabolomics and gut microbiota composition. The secondary outcome measures include body composition and cytokines. In addition, socio-psychological aspects, social support, physical activity and diet will be performed by means of questionnaire and interview. Discussion: Specific individualized exercise and diet intervention in this study offers a more efficient approach for liver fat reduction and diabetes prevention via modification of gut microbiota composition. Besides, the study explores the importance of incorporating fitness assessment and exercise in the management of patients with pre-diabetes and fatty liver disorders. If our program is shown to be effective, it will open new strategies to combat these chronic diseases. C1 [Liu, Wu Yi; Lu, Da Jiang; Wang, Ren Wei; Wang, Ru; Zou, Jun; Xu, Chang; Ren, Jie; Wen, Xin Fei; Chen, Pei Jie; Cheng, Sulin] Shanghai Univ Sport, Sch Kinesiol, Shanghai 200438, Peoples R China. [Du, Xia Ming; Ge, Jun; Gu, Qing] Shanghai Shidong Hosp, Shanghai, Peoples R China. [Sun, Jian Qin; Chen, Yan Qiu] Fudan Univ, Huadong Hosp, Clin Nutr Ctr, Shanghai 200433, Peoples R China. [Liu, Yang] Shanghai Univ Sport, Sch Phys Educ & Coaching, Shanghai 200438, Peoples R China. [Liu, Yang] Univ Jyvaskyla, Dept Hlth Sci, Res Ctr Hlth Promot, Jyvaskyla 40014, Finland. [Cheng, Shu Mei; Tan, Xiao; Pekkala, Satu; Munukka, Eveliina; Wiklund, Petri; Cheng, Sulin] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla 40014, Finland. [Xia, Zheng Chang; Liu, Jun Jun] Yanji Hlth Care Serv Ctr, Shanghai, Peoples R China. [Liu, Wen Bin; Chen, Xue Bo] Wujiaochang Hlth Care Serv Ctr, Shanghai, Peoples R China. [Zhang, Yi Min] Beijing Sport Univ, Teaching Expt Ctr, Beijing, Peoples R China. [Li, Rui] Shanghai Municipal Ctr Dis Control & Prevent, Dept Diabet Control, Shanghai, Peoples R China. [Borra, Ronald J. H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Borra, Ronald J. H.] Univ Turku, Dept Diagnost Radiol, Turku, Finland. [Borra, Ronald J. H.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Yao, Jia Xin] Tianjin Univ Sport, Dept Psychol, Tianjin, Peoples R China. RP Chen, PJ (reprint author), Shanghai Univ Sport, Sch Kinesiol, Shanghai 200438, Peoples R China. EM chenpeijie@sus.edu.cn; sulin.cheng@jyu.fi OI Borra, Ronald/0000-0001-8072-1243 FU Ministry of Science and Technology, People's Republic of China [2012BAK21B00, 2012BAK21B03-4]; Shanghai overseas distinguish professor award program; Shanghai Key Lab of Human Sport Competence Development and Maintenance [11DZ2261100]; Science and Education Department of the State General administration of Sports, People's Republic of China [2013B040]; Key Lab of Exercise & Health Sciences, Ministry of Education, People's Republic of China FX The study funding is supported by various sources: The 2012 National Science and Technology Infrastructure Program (Grant No. 2012BAK21B00), project code 2012BAK21B03-4, Ministry of Science and Technology, People's Republic of China; Shanghai overseas distinguish professor award program 2012; Shanghai Key Lab of Human Sport Competence Development and Maintenance (No. 11DZ2261100); Science and Education Department of the State General administration of Sports, People's Republic of China (2013B040); and Key Lab of Exercise & Health Sciences, Ministry of Education, People's Republic of China. NR 37 TC 6 Z9 6 U1 7 U2 56 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD JAN 17 PY 2014 VL 14 AR 48 DI 10.1186/1471-2458-14-48 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA7QQ UT WOS:000331292400003 PM 24438438 ER PT J AU Boufassa, F Lechenadec, J Meyer, L Costagliola, D Hunt, PW Pereyra, F Deeks, S Pancino, G Taulera, O Lichterfeld, M Delobel, P Saez-Cirion, A Lambotte, O AF Boufassa, Faroudy Lechenadec, Jerome Meyer, Laurence Costagliola, Dominique Hunt, Peter W. Pereyra, Florencia Deeks, Steve Pancino, Gianfranco Taulera, Olivier Lichterfeld, Mathias Delobel, Pierre Saez-Cirion, Asier Lambotte, Olivier CA ANRS CO18 HIV Controllers Cohort Cascade Collaboration Eurocoord SCOPE Cohort Int HIV Controllers Study TI Blunted Response to Combination Antiretroviral Therapy in HIV Elite Controllers: An International HIV Controller Collaboration SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LOW-LEVEL VIREMIA; CD4 CELL COUNTS; LONG-TERM; DISEASE PROGRESSION; VIRAL SUPPRESSION; ABSENCE; REPLICATION; INFECTION; DETERMINANTS AB Objective: HIV "elite controllers'' (ECs) spontaneously control viral load, but some eventually require combination antiretroviral treatment (cART), due to a loss of viral control or a decline in CD4 T-cell counts. Here we studied the CD4 T-cell count dynamics after cART initiation among 34 ECs followed in U.S. and European cohorts, by comparison with chronically viremic patients (VIRs). Methods: ECs were defined as patients with at least >= 5 viral load (VL) measurements below 400 copies/mL during at least a 5-year period despite never receiving ART and were selected from the French ANRS CO18 cohort, the U.S. SCOPE cohort, the International HIV Controllers study and the European CASCADE collaboration. VIRs were selected from the ANRS COPANA cohort of recently-diagnosed (< 1 year) ART-naive HIV-1-infected adults. CD4 T-cell count dynamics after cART initiation in both groups were modelled with piecewise mixed linear models. Results: After cART initiation, CD4 T-cell counts showed a biphasic rise in VIRs with: an initial rapid increase during the first 3 months (+0.63 root CD4/month), followed by +0.19 root CD4/month. This first rapid phase was not observed in ECs, in whom the CD4Tc count increased steadily, at a rate similar to that of the second phase observed in VIRs. After cART initiation at a CD4 T-cell count of 300/mm(3), the estimated mean CD4 T-cell gain during the first 12 months was 139/mm(3) in VIRs and 80/mm(3) in ECs (p = 0.048). Conclusions: cART increases CD4 T-cell counts in elite controllers, albeit less markedly than in other patients. C1 [Boufassa, Faroudy; Meyer, Laurence] CESP Ctr Res Epidemiol & Populat Hlth, INSERM, Epidemiol HIV & STI Team, Le Kremlin Bicetre, France. [Boufassa, Faroudy; Lechenadec, Jerome; Meyer, Laurence] Univ Paris 11, Le Kremlin Bicetre, France. [Meyer, Laurence] Hop Bicetre, AP HP, Serv Sante Publ, Le Kremlin Bicetre, France. [Costagliola, Dominique] Univ Paris 06, Paris, France. [Costagliola, Dominique] INSERM, Paris, France. [Hunt, Peter W.; Deeks, Steve] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Hunt, Peter W.; Deeks, Steve] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Hunt, Peter W.; Deeks, Steve] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Pereyra, Florencia] Massachusetts Gen Hosp, Ragon Inst, MIT, Cambridge, MA USA. [Pereyra, Florencia] Harvard Univ, Cambridge, MA 02138 USA. [Taulera, Olivier] Hop St Louis, Paris, France. [Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Delobel, Pierre] Hop Purpan, Serv Malad Infect & Trop, Toulouse, France. [Delobel, Pierre] Fac Med Toulouse, INSERM, F-31073 Toulouse, France. [Saez-Cirion, Asier] Inst Pasteur, Unite Regulat Infect Retrovirales, Paris, France. [Lambotte, Olivier] Hop Bicetre, AP HP, Serv Med Interne, Le Kremlin Bicetre, France. RP Boufassa, F (reprint author), CESP Ctr Res Epidemiol & Populat Hlth, INSERM, Epidemiol HIV & STI Team, Le Kremlin Bicetre, France. EM faroudy.boufassa@inserm.fr RI Delobel, Pierre/K-3166-2014; Costagliola, Dominique/H-5849-2011; OI Delobel, Pierre/0000-0002-2874-3581; Costagliola, Dominique/0000-0003-0765-0869; Saez-Cirion, Asier/0000-0003-2406-7536 FU ANRS (Agence nationale de recherches sur le sida et les hepatites virales); European Union under EuroCoord [260694]; Bill and Melinda Gates Foundation; Harvard University Center for AIDS Research [P-30-AI060354]; National Institutes of Health/National Institute of Allergy and Infectious Diseases [P30 AI027763]; AIDS Healthcare Foundation FX The ANRS CO18 HIV Controllers Cohort was funded by ANRS (Agence nationale de recherches sur le sida et les hepatites virales). The CASCADE Collaboration has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no 260694. The Bill and Melinda Gates Foundation, AIDS Healthcare Foundation and Harvard University Center for AIDS Research (P-30-AI060354) for The International HIV Controllers Study and the SCOPE Cohort is supported by a grant from the National Institutes of Health/National Institute of Allergy and Infectious Diseases: P30 AI027763. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 7 Z9 7 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 17 PY 2014 VL 9 IS 1 AR e85516 DI 10.1371/journal.pone.0085516 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297EA UT WOS:000330237000041 PM 24465584 ER PT J AU Kronke, J Udeshi, ND Narla, A Grauman, P Hurst, SN McConkey, M Svinkina, T Heckl, D Comer, E Li, XY Ciarlo, C Hartman, E Munshi, N Schenone, M Schreiber, SL Carr, SA Ebert, BL AF Kroenke, Jan Udeshi, Namrata D. Narla, Anupama Grauman, Peter Hurst, Slater N. McConkey, Marie Svinkina, Tanya Heckl, Dirk Comer, Eamon Li, Xiaoyu Ciarlo, Christie Hartman, Emily Munshi, Nikhil Schenone, Monica Schreiber, Stuart L. Carr, Steven A. Ebert, Benjamin L. TI Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells SO SCIENCE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; UBIQUITIN LIGASE; IKAROS GENE; TRANSCRIPTION FACTOR; AIOLOS; LYMPHOMA; DIFFERENTIATION; IDENTIFICATION; POMALIDOMIDE; ACTIVATION AB Lenalidomide is a drug with clinical efficacy in multiple myeloma and other B cell neoplasms, but its mechanism of action is unknown. Using quantitative proteomics, we found that lenalidomide causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. IKZF1 and IKZF3 are essential transcription factors in multiple myeloma. A single amino acid substitution of IKZF3 conferred resistance to lenalidomide-induced degradation and rescued lenalidomide-induced inhibition of cell growth. Similarly, we found that lenalidomide-induced interleukin-2 production in T cells is due to depletion of IKZF1 and IKZF3. These findings reveal a previously unknown mechanism of action for a therapeutic agent: alteration of the activity of an E3 ubiquitin ligase, leading to selective degradation of specific targets. C1 [Kroenke, Jan; Narla, Anupama; Grauman, Peter; Hurst, Slater N.; McConkey, Marie; Heckl, Dirk; Ebert, Benjamin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Udeshi, Namrata D.; Svinkina, Tanya; Comer, Eamon; Li, Xiaoyu; Ciarlo, Christie; Hartman, Emily; Schenone, Monica; Schreiber, Stuart L.; Carr, Steven A.; Ebert, Benjamin L.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Munshi, Nikhil] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ebert, BL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM bebert@partners.org FU NIH [R01HL082945, P01 CA108631]; Leukemia and Lymphoma Society Scholar Award; Evans Foundation grant; Starr Cancer Consortium; SPARC consortium; National Human Genome Research Institute [RL1-HG004671]; German Research Foundation (DFG) [Kr-3886/1-1]; German Cancer Aid; Celgene FX We thank Y.-T. Tai (Dana-Faber Cancer Institute) for technical assistance with primary multiple myeloma samples. This work was supported by funding from the NIH (R01HL082945, P01 CA108631), a Leukemia and Lymphoma Society Scholar Award, an Evans Foundation grant, and a grant from the Starr Cancer Consortium to B. L. E. In addition, the work was supported by a grant from the SPARC consortium and by an National Human Genome Research Institute (RL1-HG004671) initiative in genome-based drug discovery. J.K. was supported by the German Research Foundation (DFG, Kr-3886/1-1). D. H. was supported by the German Cancer Aid. B. L. E. and N.M. have received consulting fees from Celgene. The authors (J.K., N.D.U., S. A. C., and B. L. E.) and the Broad Institute have filed a patent application (number 61/902,066) pertaining to the prediction of therapeutic response to lenalidomide and related compounds. NR 27 TC 209 Z9 215 U1 8 U2 53 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 17 PY 2014 VL 343 IS 6168 BP 301 EP 305 DI 10.1126/science.1244851 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289YN UT WOS:000329718600037 PM 24292625 ER PT J AU Lu, G Middleton, RE Sun, HH Naniong, M Ott, CJ Mitsiades, CS Wong, KK Bradner, JE Kaelin, WG AF Lu, Gang Middleton, Richard E. Sun, Huahang Naniong, MarkVic Ott, Christopher J. Mitsiades, Constantine S. Wong, Kwok-Kin Bradner, James E. Kaelin, William G., Jr. TI The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins SO SCIENCE LA English DT Article ID B-CELL LYMPHOMA; MULTIPLE-MYELOMA; MAMMALIAN-CELLS; EXPRESSION; POMALIDOMIDE; DIFFERENTIATION; THALIDOMIDE; IDENTIFICATION; SURVIVAL; TARGET AB Thalidomide-like drugs such as lenalidomide are clinically important treatments for multiple myeloma and show promise for other B cell malignancies. The biochemical mechanisms underlying their antitumor activity are unknown. Thalidomide was recently shown to bind to, and inhibit, the cereblon ubiquitin ligase. Cereblon loss in zebrafish causes fin defects reminiscent of the limb defects seen in children exposed to thalidomide in utero. Here we show that lenalidomide-bound cereblon acquires the ability to target for proteasomal degradation two specific B cell transcription factors, Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). Analysis of myeloma cell lines revealed that loss of IKZF1 and IKZF3 is both necessary and sufficient for lenalidomide's therapeutic effect, suggesting that the antitumor and teratogenic activities of thalidomide-like drugs are dissociable. C1 [Lu, Gang; Middleton, Richard E.; Sun, Huahang; Naniong, MarkVic; Ott, Christopher J.; Mitsiades, Constantine S.; Wong, Kwok-Kin; Bradner, James E.; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Middleton, Richard E.; Sun, Huahang; Naniong, MarkVic; Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM william_kaelin@dfci.harvard.edu OI wong, kwok kin/0000-0001-6323-235X FU NIH; Leukemia and Lymphoma Society; Multiple Myeloma Research Foundation; Celgene, the manufacturer of lenalidomide and pomalidomide FX We thank M. Vidal and A. MacWilliams at Dana-Farber Cancer Institute for the ORF cDNA collection and for help with recombination cloning. This work was supported by a grant (W. G. K.) and F32 fellowship (G. L.) from NIH. C.J.O. is supported by a Leukemia and Lymphoma Society Fellowship award, and J.E.B. and C. S. M. are supported by the Multiple Myeloma Research Foundation. W. G. K. is a Howard Hughes Medical Institute Investigator. C. S. M. has received consulting fees from Celgene, the manufacturer of lenalidomide and pomalidomide. The primary and secondary luciferase screen data are presented in the supplementary materials. NR 29 TC 191 Z9 197 U1 7 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 17 PY 2014 VL 343 IS 6168 BP 305 EP 309 DI 10.1126/science.1244917 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289YN UT WOS:000329718600038 PM 24292623 ER PT J AU Celli, JP Rizvi, I Blanden, AR Massodi, I Glidden, MD Pogue, BW Hasan, T AF Celli, Jonathan P. Rizvi, Imran Blanden, Adam R. Massodi, Iqbal Glidden, Michael D. Pogue, Brian W. Hasan, Tayyaba TI An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models SO SCIENTIFIC REPORTS LA English DT Article ID EPITHELIAL OVARIAN-CANCER; PHOTODYNAMIC THERAPY; MALIGNANT BREAST; NUCLEAR-ORGANIZATION; TISSUE STRUCTURE; GENE-EXPRESSION; SOLID TUMORS; GEMCITABINE; RESISTANCE; APOPTOSIS AB While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls for reliable quantification of fluorescence signal. This streamlined methodology reads out the high density of information embedded in 3D culture systems, while maintaining a level of speed and efficiency traditionally achieved with global colorimetric reporters in order to facilitate broader implementation of 3D tumour models in therapeutic screening. C1 [Celli, Jonathan P.; Rizvi, Imran; Blanden, Adam R.; Massodi, Iqbal; Glidden, Michael D.; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Celli, Jonathan P.; Rizvi, Imran; Blanden, Adam R.; Massodi, Iqbal; Glidden, Michael D.; Hasan, Tayyaba] Harvard Univ, Sch Med, Boston, MA USA. [Celli, Jonathan P.; Glidden, Michael D.] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. [Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu FU National Cancer Institute (NIH/NCI) [P01CA084203-06, 1RC1CA146337, R01CA158415, R01CA1609998, K99CA155045, R00CA155045] FX We gratefully acknowledge constructive input from Dr. Bryan Spring, Dr. Adnan Abu-Yousif and Dr. Conor Evans, of the Wellman Center for Photomedicine, arising from discussions about the image analysis routines described herein. Dr. Hasan, Dr. Pogue and Dr. Celli wish to acknowledge support from the National Cancer Institute (NIH/NCI) P01CA084203-06 (T.H., B.W.P.) 1RC1CA146337 (T.H.), R01CA158415 (T.H.), R01CA1609998 (T.H.), K99CA155045 (J.P.C.) and R00CA155045 (J.P.C.). NR 47 TC 30 Z9 30 U1 3 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 17 PY 2014 VL 4 AR 3751 DI 10.1038/srep03751 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291SH UT WOS:000329849100017 PM 24435043 ER PT J AU Ong, QR Chan, ES Lim, ML Cole, GM Wong, BS AF Ong, Qi-Rui Chan, Elizabeth S. Lim, Mei-Li Cole, Gregory M. Wong, Boon-Seng TI Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice SO SCIENTIFIC REPORTS LA English DT Article ID CEREBRAL GLUCOSE-METABOLISM; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; SYNAPTIC PLASTICITY; APOE EPSILON-4; MOUSE MODEL; SIGNALING PATHWAY; TRANSPORT PROTEIN; TRANSGENIC MICE AB Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content. C1 [Ong, Qi-Rui; Chan, Elizabeth S.; Lim, Mei-Li; Wong, Boon-Seng] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore. [Cole, Gregory M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Cole, Gregory M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Cole, Gregory M.] Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res & Clin Ctr, North Hills, CA USA. RP Ong, QR (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore. EM bswong@nus.edu.sg RI Wong, Boon-Seng/G-2759-2012 OI Wong, Boon-Seng/0000-0002-7118-8077 FU National Medical Research Council [NMRC/1148/2008]; Biomedical Research Council [BMRC/05/1/21/19/401]; Singapore Ministry of Education FX This work was supported by grants to B.S.W. from the National Medical Research Council (NMRC/1148/2008) and the Biomedical Research Council (BMRC/05/1/21/19/401). Q.R.O. and E.S.C. were supported by graduate scholarships from Singapore Ministry of Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 5 Z9 5 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 17 PY 2014 VL 4 AR 3754 DI 10.1038/srep03754 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291SH UT WOS:000329849100020 PM 24435134 ER PT J AU McDougal, WS Lee, RJ Efstathiou, JA Harisinghani, M Wu, CL AF McDougal, W. Scott Lee, Richard J. Efstathiou, Jason A. Harisinghani, Mukesh Wu, Chin-Lee TI Case 2-2014-A 44-Year-Old Man with a Lesion on the Penis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; CANCER; LYMPHADENECTOMY; SURGERY; CHEMOTHERAPY; RADIOTHERAPY; EXPERIENCE; MANAGEMENT; CISPLATIN; SKIN AB A 44-year-old man was seen in the urology clinic because of a penile lesion that had been enlarging for 6 months. Examination and imaging revealed an ulcerated mass and enlarged inguinal lymph nodes. A diagnostic procedure was performed, and management decisions were made. Presentation of Case A 44-year-old man was seen in the urology clinic at this hospital because of a lesion on the penis. The patient had been in good health until 6 months earlier when, while visiting another country, a sports-related injury to his groin occurred, after which he noted a small, dark area on the distal penis and slight hematuria. The next day, he saw a physician at a local hospital who made a diagnosis of hematoma. The lesion persisted, and 2 months later, a small, firm nodule developed at the site. During the next 2.5 months, the nodule enlarged, ... C1 [McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Lee, Richard J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Harisinghani, Mukesh] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [McDougal, W. Scott] Harvard Univ, Sch Med, Dept Urol, Boston, MA USA. [Lee, Richard J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Efstathiou, Jason A.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Harisinghani, Mukesh] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 22 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 16 PY 2014 VL 370 IS 3 BP 263 EP 271 DI 10.1056/NEJMcpc1310005 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 294HK UT WOS:000330035600013 PM 24428472 ER PT J AU Abel, GA Klaassen, R Lee, SJ Young, NL Cannella, L Steensma, DP Efficace, F AF Abel, Gregory A. Klaassen, Robert Lee, Stephanie J. Young, Nancy L. Cannella, Laura Steensma, David P. Efficace, Fabio TI Patient-reported outcomes for the myelodysplastic syndromes: a new MDS-specific measure of quality of life SO BLOOD LA English DT Letter C1 [Abel, Gregory A.] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02215 USA. [Abel, Gregory A.; Steensma, David P.] Dana Farber Canc Inst, Ctr Leukemia, Dept Med Oncol, Boston, MA 02215 USA. [Klaassen, Robert] Childrens Hosp Eastern Ontario, Dept Pediat, Ottawa, ON K1H 8L1, Canada. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Young, Nancy L.] Laurentian Univ, Sch Rural & Northern Hlth, Sudbury, ON P3E 2C6, Canada. [Cannella, Laura; Efficace, Fabio] Italian Grp Adult Hematol Dis, Ctr Data, Rome, Italy. [Cannella, Laura; Efficace, Fabio] Hlth Outcomes Res Unit, Rome, Italy. RP Abel, GA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM gregory_abel@dfci.harvard.edu RI Young, Nancy/G-3934-2011 OI Young, Nancy/0000-0002-1739-3299 NR 10 TC 7 Z9 7 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 16 PY 2014 VL 123 IS 3 BP 451 EP 452 DI 10.1182/blood-2013-11-540021 PG 2 WC Hematology SC Hematology GA 290IP UT WOS:000329748700025 PM 24434998 ER PT J AU Rosen, ED Spiegelman, BM AF Rosen, Evan D. Spiegelman, Bruce M. TI What We Talk About When We Talk About Fat SO CELL LA English DT Review ID BROWN ADIPOSE-TISSUE; ACTIVATED-RECEPTOR-GAMMA; DIET-INDUCED OBESITY; REGULATORY T-CELLS; MITOCHONDRIAL UNCOUPLING PROTEIN; INDUCED INSULIN-RESISTANCE; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR 21; PPAR-GAMMA; WHITE FAT AB There has been an upsurge of interest in the adipocyte coincident with the onset of the obesity epidemic and the realization that adipose tissue plays a major role in the regulation of metabolic function. The past few years, in particular, have seen significant changes in the way that we classify adipocytes and how we view adipose development and differentiation. We have new perspective on the roles played by adipocytes in a variety of homeostatic processes and on the mechanisms used by adipocytes to communicate with other tissues. Finally, there has been significant progress in understanding how these relationships are altered during metabolic disease and how they might be manipulated to restore metabolic health. C1 [Rosen, Evan D.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. [Rosen, Evan D.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Rosen, Evan D.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. [Rosen, Evan D.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Rosen, ED (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. EM erosen@bidmc.harvard.edu; bruce_spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [R01 DK085171, R01 DK087092] NR 302 TC 309 Z9 312 U1 25 U2 148 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 16 PY 2014 VL 156 IS 1-2 BP 20 EP 44 DI 10.1016/j.cell.2013.12.012 PG 25 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292OS UT WOS:000329912200009 PM 24439368 ER PT J AU Wu, H Zhang, Y AF Wu, Hao Zhang, Yi TI Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions SO CELL LA English DT Review ID EMBRYONIC STEM-CELLS; PRIMORDIAL GERM-CELLS; MEDIATED 5-METHYLCYTOSINE OXIDATION; MOUSE PREIMPLANTATION DEVELOPMENT; DOMAIN-CONTAINING PROTEINS; ZYGOTIC PATERNAL GENOME; ACUTE MYELOID-LEUKEMIA; BASE EXCISION-REPAIR; DE-NOVO METHYLATION; CPG BINDING DOMAIN AB Methylation of cytosines in the mammalian genome represents a key epigenetic modification and is dynamically regulated during development. Compelling evidence now suggests that dynamic regulation of DNA methylation is mainly achieved through a cyclic enzymatic cascade comprised of cytosine methylation, iterative oxidation of methyl group by TET dioxygenases, and restoration of unmodified cytosines by either replication-dependent dilution or DNA glycosylase-initiated base excision repair. In this review, we discuss the mechanism and function of DNA demethylation in mammalian genomes, focusing particularly on how developmental modulation of the cytosine-modifying pathway is coupled to active reversal of DNA methylation in diverse biological processes. C1 [Wu, Hao; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Wu, Hao; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wu, Hao; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Wu, Hao; Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu RI Wu, Hao/G-4145-2013 OI Wu, Hao/0000-0002-1256-6891 FU NIH [GM68804, U01DK089565]; Jane Coffin Childs Memorial Fund for Medical Research FX We thank members of the Zhang Lab for their comments on the manuscript. We apologize to colleagues whose work cannot be cited owing to space constrains. This work was supported by NIH grants GM68804 and U01DK089565 (to Y.Z.). H.W. is supported by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. Y.Z. is an Investigator of the Howard Hughes Medical Institute. NR 214 TC 257 Z9 263 U1 25 U2 234 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 16 PY 2014 VL 156 IS 1-2 BP 45 EP 68 DI 10.1016/j.cell.2013.12.019 PG 24 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292OS UT WOS:000329912200010 PM 24439369 ER PT J AU Graff, J Joseph, NF Hom, ME Samiei, A Meng, J Seo, J Rei, D Bero, AW Phan, TX Wagner, F Holson, E Xu, JB Sun, J Neve, RL Mach, RH Haggarty, SJ Tsai, LH AF Graeff, Johannes Joseph, Nadine F. Hom, Meryl E. Samiei, Alireza Meng, Jia Seo, Jinsoo Rei, Damien Bero, Adam W. Phan, Trongha X. Wagner, Florence Holson, Edward Xu, Jinbin Sun, Jianjun Neve, Rachael L. Mach, Robert H. Haggarty, Stephen J. Tsai, Li-Huei TI Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories SO CELL LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; CONTEXTUAL FEAR; SPONTANEOUS-RECOVERY; SYNAPTIC PLASTICITY; RETROGRADE-AMNESIA; PROTEIN-SYNTHESIS; CONDITIONED FEAR; EXTINCTION; RETRIEVAL; GENE AB Traumatic events generate some of the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that, in mice, successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that, whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes, which is accompanied by higher metabolic, synaptic, and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata. C1 [Graeff, Johannes; Joseph, Nadine F.; Hom, Meryl E.; Samiei, Alireza; Meng, Jia; Seo, Jinsoo; Rei, Damien; Bero, Adam W.; Phan, Trongha X.; Neve, Rachael L.; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Graeff, Johannes; Joseph, Nadine F.; Hom, Meryl E.; Meng, Jia; Seo, Jinsoo; Rei, Damien; Bero, Adam W.; Phan, Trongha X.; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Graeff, Johannes; Joseph, Nadine F.; Wagner, Florence; Holson, Edward; Haggarty, Stephen J.; Tsai, Li-Huei] Broad Inst Harvard Univ & MIT, Cambridge, MA 02142 USA. [Xu, Jinbin; Sun, Jianjun; Mach, Robert H.] Washington Univ, Sch Med, Dept Radiol, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Tsai, LH (reprint author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. EM lhtsai@mit.edu OI Graff, Johannes/0000-0002-3219-3578; Meng, Jia/0000-0003-3455-205X; Haggarty, Stephen J./0000-0002-7872-168X FU NIH NINDS/NIA [NS078839]; NIH/NIDA [R01DA028301]; Picower Neurological Disorder Fund (PNDRF); Stanley Medical Foundation, HHMI, and a Bard Richmond fellowship FX We thank MIT's BioMicroCenter for the RNA sequencing, Martin Kahn for help with the qRT-PCR and IHC experiments, and Theo Elfers for critical comments on the manuscript. This work was partially supported by NIH NINDS/NIA (NS078839) to L.-H.T. and NIH/NIDA (R01DA028301) to S.J.H., the Picower Neurological Disorder Fund (PNDRF), the Stanley Medical Foundation, HHMI, and a Bard Richmond fellowship to J.G. NR 70 TC 75 Z9 77 U1 3 U2 65 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 16 PY 2014 VL 156 IS 1-2 BP 261 EP 276 DI 10.1016/j.cell.2013.12.020 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292OS UT WOS:000329912200026 PM 24439381 ER PT J AU Cohen, P Levy, JD Zhang, YY Frontini, A Kolodin, DP Svensson, KJ Lo, JC Zeng, X Ye, L Khandekar, MJ Wu, J Gunawardana, SC Banks, AS Camporez, JPG Jurczak, MJ Kajimura, S Piston, DW Mathis, D Cinti, S Shulman, GI Seale, P Spiegelman, BM AF Cohen, Paul Levy, Julia D. Zhang, Yingying Frontini, Andrea Kolodin, Dmitriy P. Svensson, Katrin J. Lo, James C. Zeng, Xing Ye, Li Khandekar, Melin J. Wu, Jun Gunawardana, Subhadra C. Banks, Alexander S. Camporez, Joao Paulo G. Jurczak, Michael J. Kajimura, Shingo Piston, David W. Mathis, Diane Cinti, Saverio Shulman, Gerald I. Seale, Patrick Spiegelman, Bruce M. TI Ablation of PRDM16 and Beige Adipose Causes Metabolic Dysfunction and a Subcutaneous to Visceral Fat Switch SO CELL LA English DT Article ID INSULIN-RESISTANCE; BROWN-FAT; PPAR-GAMMA; TRANSCRIPTIONAL CONTROL; GLUCOSE-INTOLERANCE; ENERGY HOMEOSTASIS; MESSENGER-RNA; WILMS-TUMOR; OBESITY; TISSUE AB A clear relationship exists between visceral obesity and type 2 diabetes, whereas subcutaneous obesity is comparatively benign. Here, we show that adipocyte- specific deletion of the coregulatory protein PRDM16 caused minimal effects on classical brown fat but markedly inhibited beige adipocyte function in subcutaneous fat following cold exposure or beta 3-agonist treatment. These animals developed obesity on a high-fat diet, with severe insulin resistance and hepatic steatosis. They also showed altered fat distribution with markedly increased subcutaneous adiposity. Subcutaneous adipose tissue in mutant mice acquired many key properties of visceral fat, including decreased thermogenic and increased inflammatory gene expression and increased macrophage accumulation. Transplantation of subcutaneous fat into mice with diet-induced obesity showed a loss of metabolic benefit when tissues were derived from PRDM16 mutant animals. These findings indicate that PRDM16 and beige adipocytes are required for the "browning'' of white fat and the healthful effects of subcutaneous adipose tissue. C1 [Cohen, Paul; Levy, Julia D.; Zhang, Yingying; Svensson, Katrin J.; Lo, James C.; Zeng, Xing; Ye, Li; Khandekar, Melin J.; Wu, Jun; Banks, Alexander S.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Cohen, Paul; Levy, Julia D.; Zhang, Yingying; Svensson, Katrin J.; Lo, James C.; Zeng, Xing; Ye, Li; Khandekar, Melin J.; Wu, Jun; Banks, Alexander S.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. [Cohen, Paul; Lo, James C.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Frontini, Andrea; Cinti, Saverio] Univ Politecn Marche, Dept Expt & Clin Med, I-60020 Ancona, Italy. [Kolodin, Dmitriy P.; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunolbiol, Div Immunol, Boston, MA 02115 USA. [Gunawardana, Subhadra C.; Piston, David W.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Camporez, Joao Paulo G.; Jurczak, Michael J.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06519 USA. [Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06519 USA. [Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06519 USA. [Kajimura, Shingo] Univ Calif San Francisco, UCSF Diabet Ctr, San Francisco, CA 94143 USA. [Kajimura, Shingo] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. [Seale, Patrick] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. EM bruce_spiegelman@dfci.harvard.edu RI Camporez, Joao Paulo/B-9122-2015; Banks, Alexander/B-4832-2012; OI Banks, Alexander/0000-0003-1787-6925; Svensson, Katrin J/0000-0001-5376-5128; Jurczak, Michael/0000-0002-6335-6915; Gunawardana, Suba/0000-0003-4211-982X FU American Heart Association grant [11FTF7510004]; National Science Foundation Graduate Research Fellowship; NIH [DK040936, DK045735, DK059635, DK092541, DK031405]; JPB foundation FX We thank Dr. Evan Rosen (Beth Israel Deaconess Medical Center) for providing Adiponectin-Cre mice, Dr. Vicki Huff (MD Anderson) for providing Wt1lox/lox mice, and the Nikon Imaging Center at Harvard Medical School for use of microscopy equipment. We thank Dr. Vamsi Mootha (Massachusetts General Hospital) for guidance on data analysis and Drs. Rana Gupta, Pere Puigserver, Evan Rosen, and members of the Spiegelman lab for helpful discussions. P.C. was supported by the American Heart Association grant 11FTF7510004. D.P.K. was supported by a National Science Foundation Graduate Research Fellowship. This work was supported by NIH grants DK040936, DK045735, DK059635 (G.I.S.); NIH grant DK092541 (D.M.); and by NIH grant DK031405 and the JPB foundation (B.M.S.). NR 57 TC 174 Z9 184 U1 7 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 16 PY 2014 VL 156 IS 1-2 BP 304 EP 316 DI 10.1016/j.cell.2013.12.021 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292OS UT WOS:000329912200029 PM 24439384 ER PT J AU Morrison, SJ Scadden, DT AF Morrison, Sean J. Scadden, David T. TI The bone marrow niche for haematopoietic stem cells SO NATURE LA English DT Review ID SELF-RENEWAL; PROGENITOR CELLS; N-CADHERIN; ENDOTHELIAL-CELLS; STROMAL CELLS; STEM/PROGENITOR CELLS; MICE LACKING; IN-VIVO; STIMULATING FACTOR; IRRADIATED MICE AB Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their niches, but the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Recent progress has been made in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum and functional heterogeneity among perivascular microenvironments. C1 [Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Childrens Res Inst, Dept Pediat, Dallas, TX 75390 USA. [Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Cambridge, MA 02138 USA. [Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Morrison, SJ (reprint author), Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Childrens Res Inst, Dept Pediat, Dallas, TX 75390 USA. EM Sean.Morrison@UTSouthwestern.edu; David_Scadden@Harvard.edu FU National Heart, Lung and Blood Institute [HL097760]; Howard Hughes Medical Institute; Mary McDermott Cook Chair in Pediatric Genetics; National Institutes of Health [HL044851, HL096372, EB014703]; Gerald and Darlene Jordan Chair in Medicine FX S.J.M. was supported by the National Heart, Lung and Blood Institute (HL097760), the Howard Hughes Medical Institute, and the Mary McDermott Cook Chair in Pediatric Genetics. D.T.S. was supported by the National Institutes of Health (HL044851, HL096372, EB014703) and the Gerald and Darlene Jordan Chair in Medicine. We apologize to authors whose work could not be cited because of space limitations. NR 125 TC 394 Z9 408 U1 20 U2 172 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 16 PY 2014 VL 505 IS 7483 BP 327 EP 334 DI 10.1038/nature12984 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 288OR UT WOS:000329621800030 PM 24429631 ER PT J AU Ferrari, F Apostolou, E Park, PJ Hochedlinger, K AF Ferrari, Francesco Apostolou, Effie Park, Peter J. Hochedlinger, Konrad TI Rearranging the chromatin for pluripotency SO CELL CYCLE LA English DT Editorial Material ID ORGANIZATION; GENOMES; LOCUS C1 [Ferrari, Francesco; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Apostolou, Effie; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Apostolou, Effie; Hochedlinger, Konrad] Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA USA. [Apostolou, Effie; Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Apostolou, Effie; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Apostolou, Effie; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. [Park, Peter J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. RP Park, PJ (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. EM peter_park@harvard.edu; khochedlinger@helix.mgh.harvard.edu RI Ferrari, Francesco/H-5007-2012 OI Ferrari, Francesco/0000-0002-9811-3753 NR 8 TC 2 Z9 2 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2014 VL 13 IS 2 BP 167 EP 168 DI 10.4161/cc.27028 PG 2 WC Cell Biology SC Cell Biology GA AI2AM UT WOS:000336658200001 PM 24241209 ER PT J AU Ning, JF Wakimoto, H Rabkin, SD AF Ning, Jianfang Wakimoto, Hiroaki Rabkin, Samuel D. TI Immunovirotherapy for glioblastoma SO CELL CYCLE LA English DT Editorial Material ID STEM-CELLS; VIRUS; MODEL C1 [Ning, Jianfang; Wakimoto, Hiroaki; Rabkin, Samuel D.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Boston, MA 02114 USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Boston, MA 02114 USA. EM rabkin@helix.mgh.harvard.edu OI rabkin, samuel/0000-0003-2344-2795 FU NCI NIH HHS [R01 CA160762]; NINDS NIH HHS [R01 NS032677] NR 8 TC 4 Z9 4 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2014 VL 13 IS 2 BP 175 EP 176 DI 10.4161/cc.27039 PG 2 WC Cell Biology SC Cell Biology GA AI2AM UT WOS:000336658200005 PM 24241205 ER PT J AU Aird, KM Li, H Xin, F Konstantinopoulos, PA Zhang, RG AF Aird, Katherine M. Li, Hua Xin, Frances Konstantinopoulos, Panagiotis A. Zhang, Rugang TI Identification of ribonucleotide reductase M2 as a potential target for pro-senescence therapy in epithelial ovarian cancer SO CELL CYCLE LA English DT Article DE epithelial ovarian cancer; cellular senescence; ribonucleotide reductase M2 (RRM2); DNA damage response; cell proliferation ID ONCOGENE-INDUCED SENESCENCE; PRIMARY HUMAN-CELLS; 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE; DNA-DAMAGE; HETEROCHROMATIN FOCI; CELLULAR SENESCENCE; SUBUNIT M2; IN-VIVO; PHASE-I; INHIBITORS AB Epithelial ovarian cancer (EOC) is the leading cause of gynecological-related cancer deaths in the United States. There is, therefore, an urgent need to develop novel therapeutic strategies for this devastating disease. Cellular senescence is a state of stable cell growth arrest that acts as an important tumor suppression mechanism. Ribonucleotide reductase M2 (RRM2) plays a key role in regulating the senescence-associated cell growth arrest by controlling biogenesis of 2'-deoxyribonucleoside 5'-triphosphates (dNTPs). The role of RRM2 in EOC remains poorly understood. Here we show that RRM2 is expressed at higher levels in EOCs compared with either normal ovarian surface epithelium (P < 0.001) or fallopian tube epithelium (P < 0.001). RRM2 expression significantly correlates with the expression of Ki67, a marker of cell proliferation (P < 0.001). Moreover, RRM2 expression positively correlates with tumor grade and stage, and high RRM2 expression independently predicts a shorter overall survival in EOC patients (P < 0.001). To delineate the functional role of RRM2 in EOC, we knocked down RRM2 expression in a panel of EOC cell lines. Knockdown of RRM2 expression inhibits the growth of human EOC cells. Mechanistically, RRM2 knockdown triggers cellular senescence in these cells. Notably, this correlates with the induction of the DNA damage response, a known mediator of cellular senescence. These data suggest that targeting RRM2 in EOCs by suppressing its activity is a novel pro-senescence therapeutic strategy that has the potential to improve survival of EOC patients. C1 [Aird, Katherine M.; Li, Hua; Zhang, Rugang] Wistar Inst Anat & Biol, Ctr Canc, Gene Express & Regulat Program, Philadelphia, PA 19104 USA. [Xin, Frances] Univ Penn, Sch Med, Cell & Mol Biol Grad Program, Philadelphia, PA 19104 USA. [Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Gynecol Oncol Program, Boston, MA 02115 USA. RP Zhang, RG (reprint author), Wistar Inst Anat & Biol, Ctr Canc, Gene Express & Regulat Program, Philadelphia, PA 19104 USA. EM panagiotisa_konstantinopoulos@dfci.harvard.edu; rzhang@wistar.org FU NIH/NCI [R01CA160331, R01CA163377, T32CA9171-35]; DoD Ovarian Cancer Academy [OC093420]; Cancer Center Support Grant (CCSG) [CA010815] FX NIH/NCI grants (R01CA160331 and R01CA163377 to RZ), a DoD Ovarian Cancer Academy Award (OC093420 to RZ), and a NIH/NCI training grant (T32CA9171-35 to KMA).; Support of Core Facilities used in this study was provided by Cancer Center Support Grant (CCSG) CA010815 to The Wistar Institute. NR 50 TC 6 Z9 7 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2014 VL 13 IS 2 BP 199 EP 207 DI 10.4161/cc.26953 PG 9 WC Cell Biology SC Cell Biology GA AI2AM UT WOS:000336658200012 PM 24200970 ER PT J AU Menendez, ME Neuhaus, V Bot, AGJ Ring, D Cha, TD AF Menendez, Mariano E. Neuhaus, Valentin Bot, Arjan G. J. Ring, David Cha, Thomas D. TI Psychiatric Disorders and Major Spine Surgery Epidemiology and Perioperative Outcomes SO SPINE LA English DT Article DE spinal fusion; laminectomy; depression; anxiety; schizophrenia; dementia; perioperative; complications; risk factors; mortality; discharge; epidemiology ID UNITED-STATES TRENDS; QUALITY-OF-LIFE; MEDICARE BENEFICIARIES; DEPRESSIVE SYMPTOMS; METABOLIC SYNDROME; GLOBAL PREVALENCE; FUSION SURGERY; PRIMARY-CARE; RISK-FACTORS; MORTALITY AB Study Design. Analysis of the National Hospital Discharge Survey database from 1990 to 2007. Objective. To evaluate the influence of preoperative depression, anxiety, schizophrenia, or dementia on in-hospital (1) adverse events, (2) mortality, and (3) nonroutine discharge in patients undergoing major spine surgery. Summary of Background Data. Psychiatric comorbidity is a known risk factor for impaired health-related quality of life and poor long-term outcomes after spine surgery, yet little is known about its impact in the perioperative spine surgery setting. Methods. Using the National Hospital Discharge Survey database, all patients undergoing either spinal fusion or laminectomy between 1990 and 2007 were identified and separated into groups with and without psychiatric disorders. Multivariable regression analysis was performed for each of the outcome variables. Results. Between 1990 and 2007, a total estimated number of 5,382,343 spinal fusions and laminectomies were performed. The prevalence of diagnosed depression, anxiety, and schizophrenia among the study population increased significantly over time. Depression, anxiety, schizophrenia, and dementia were associated with higher rates of nonroutine discharge. Depression, schizophrenia, and dementia were associated with higher rates of adverse events. Dementia was the only psychiatric disorder associated with a higher risk of in-hospital mortality. Conclusion. Patients with preoperative psychiatric disorders undergoing major spine surgery are at increased risk for perioperative adverse events and posthospitalization care, but its effect in perioperative mortality is more limited. Presurgical psychological screening of candidates undergoing spine surgery might ultimately lead to the enhancement of perioperative outcomes in this growing segment of the US population. C1 [Menendez, Mariano E.; Neuhaus, Valentin; Bot, Arjan G. J.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Cha, Thomas D.] Orthopaed Spine Serv, Boston, MA USA. RP Cha, TD (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Spine Serv, Ste 3A,55 Fruit St, Boston, MA 02114 USA. EM tcha@partners.org NR 51 TC 24 Z9 24 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JAN 15 PY 2014 VL 39 IS 2 BP E111 EP E122 DI 10.1097/BRS.0000000000000064 PG 12 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AH5ZQ UT WOS:000336210800007 PM 24108288 ER PT J AU Treebak, JT Pehmoller, C Kristensen, JM Kjobsted, R Birk, JB Schjerling, P Richter, EA Goodyear, LJ Wojtaszewski, JFP AF Treebak, Jonas T. Pehmoller, Christian Kristensen, Jonas M. Kjobsted, Rasmus Birk, Jesper B. Schjerling, Peter Richter, Erik A. Goodyear, Laurie J. Wojtaszewski, Jorgen F. P. TI Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID STIMULATED GLUT4 TRANSLOCATION; SITE-SPECIFIC PHOSPHORYLATION; INDUCED GLUCOSE-TRANSPORT; AS160 PHOSPHORYLATION; GLYCOGEN-SYNTHASE; 14-3-3 BINDING; INDUCED INCREASE; PLASMA-MEMBRANE; REGULATE AS160; DOMAIN FAMILY AB We investigated the phosphorylation signatures of two Rab-GTPase activating proteins TBC1D1 and TBC1D4 in human skeletal muscle in response to physical exercise and physiological insulin levels induced by a carbohydrate rich meal using a paired experimental design. Eight healthy male volunteers exercised in the fasted or fed state and muscle biopsies were taken before and immediately after exercise. We identified TBC1D1/4 phospho-sites that (1) did not respond to exercise or postprandial increase in insulin (TBC1D4: S666), (2) responded to insulin only (TBC1D4: S318), (3) responded to exercise only (TBC1D1: S237, S660, S700; TBC1D4: S588, S751), and (4) responded to both insulin and exercise (TBC1D1: T596; TBC1D4: S341, T642, S704). In the insulin-stimulated leg, Akt phosphorylation of both T308 and S473 correlated significantly with multiple sites on both TBC1D1 (T596) and TBC1D4 (S318, S341, S704). Interestingly, in the exercised leg in the fasted state TBC1D1 phosphorylation (S237, T596) correlated significantly with the activity of the alpha 2/beta 2/gamma 3 AMPK trimer, whereas TBC1D4 phosphorylation (S341, S704) correlated with the activity of the alpha 2/beta 2/gamma 1 AMPK trimer. Our data show differential phosphorylation of TBC1D1 and TBC1D4 in response to physiological stimuli in human skeletal muscle and support the idea that Akt and AMPK are upstream kinases. TBC1D1 phosphorylation signatures were comparable between in vitro contracted mouse skeletal muscle and exercised human muscle, and we show that AMPK regulated phosphorylation of these sites in mouse muscle. Contraction and exercise elicited a different phosphorylation pattern of TBC1D4 in mouse compared with human muscle, and although different circumstances in our experimental setup may contribute to this difference, the observation exemplifies that transferring findings between species is problematic. C1 [Treebak, Jonas T.; Pehmoller, Christian; Kristensen, Jonas M.; Kjobsted, Rasmus; Birk, Jesper B.; Richter, Erik A.; Wojtaszewski, Jorgen F. P.] Univ Copenhagen, Sect Mol Physiol, Dept Nutr Exercise & Sports, August Krogh Ctr, DK-2100 Copenhagen, Denmark. [Schjerling, Peter] Bispebjerg Hosp, Dept Orthoped Surg M, Inst Sports Med, DK-2400 Copenhagen, Denmark. [Schjerling, Peter] Univ Copenhagen, Fac Hlth & Med Sci, Ctr Healthy Aging, DK-2200 Copenhagen, Denmark. [Goodyear, Laurie J.] Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Wojtaszewski, JFP (reprint author), Univ Copenhagen, Sect Mol Physiol, Dept Nutr Exercise & Sports, August Krogh Ctr, Univ Pk 13, DK-2100 Copenhagen, Denmark. EM jwojtaszewski@ifi.ku.dk RI Wojtaszewski, Jorgen /P-6583-2014; Birk, Jesper/D-3523-2015; Treebak, Jonas/B-4521-2017; OI Wojtaszewski, Jorgen /0000-0001-9785-6830; Birk, Jesper/0000-0001-9775-4789; Treebak, Jonas/0000-0003-1488-7012; Schjerling, Peter/0000-0001-7138-3211 FU Danish Medical Research Council; Novo Nordisk Research Foundation; Lundbeck Foundation; Danish Ministry of Food, Agriculture and Fisheries; European Union [LSHMCT-2004-005272]; NIH [R0142238]; Danish Ministry of Science, Technology and Innovation; Danish Agency for Science, Technology and Innovation; Novo Nordisk Foundation Center for Basic Metabolic Research; Novo Nordisk Foundation FX This study was supported by grants from the Danish Medical Research Council, The Novo Nordisk Research Foundation, The Lundbeck Foundation, and Danish Ministry of Food, Agriculture and Fisheries, an integrated project funded by the European Union (LSHMCT-2004-005272), and NIH R0142238 (LJG). This work was carried out as part of the research program of the UNIK: Food, Fitness and Pharma for Health and Disease (www.foodfitnesspharma.ku.dk). The UNIK project is supported by the Danish Ministry of Science, Technology and Innovation. Jonas T. Treebak was supported by a postdoctoral fellowship from The Danish Agency for Science, Technology and Innovation, and by the Novo Nordisk Foundation Center for Basic Metabolic Research. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center, based at the University of Copenhagen, Denmark and partially funded by an unconditional donation from the Novo Nordisk Foundation (http://metabol.ku.dk). NR 73 TC 24 Z9 24 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 15 PY 2014 VL 592 IS 2 BP 351 EP 375 DI 10.1113/jphysiol.2013.266338 PG 25 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA AE2OQ UT WOS:000333813200013 PM 24247980 ER PT J AU Lim, YH Ovejero, D Sugarman, JS DeKlotz, CMC Maruri, A Eichenfield, LF Kelley, PK Juppner, H Gottschalk, M Tifft, CJ Gafni, RI Boyce, AM Cowen, EW Bhattacharyya, N Guthrie, LC Gahl, WA Golas, G Loring, EC Overton, JD Mane, SM Lifton, RP Levy, ML Collins, MT Choate, KA AF Lim, Young H. Ovejero, Diana Sugarman, Jeffrey S. DeKlotz, Cynthia M. C. Maruri, Ann Eichenfield, Lawrence F. Kelley, Patrick K. Jueppner, Harald Gottschalk, Michael Tifft, Cynthia J. Gafni, Rachel I. Boyce, Alison M. Cowen, Edward W. Bhattacharyya, Nisan Guthrie, Lori C. Gahl, William A. Golas, Gretchen Loring, Erin C. Overton, John D. Mane, Shrikant M. Lifton, Richard P. Levy, Moise L. Collins, Michael T. Choate, Keith A. TI Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia SO HUMAN MOLECULAR GENETICS LA English DT Article ID EPIDERMAL NEVUS-SYNDROME; D-RESISTANT RICKETS; MCCUNE-ALBRIGHT-SYNDROME; FIBROBLAST GROWTH FACTOR-23; FAMILIAL TUMORAL CALCINOSIS; HYPEROSTOSIS-HYPERPHOSPHATEMIA SYNDROME; CONGENITAL MELANOCYTIC NEVI; N-RAS GENE; IN-VIVO; PHOSPHATE HOMEOSTASIS AB Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23. C1 [Lim, Young H.; Choate, Keith A.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Loring, Erin C.; Overton, John D.; Mane, Shrikant M.; Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Lifton, Richard P.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Ovejero, Diana; Gafni, Rachel I.; Boyce, Alison M.; Bhattacharyya, Nisan; Guthrie, Lori C.; Collins, Michael T.] Natl Inst Dental & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Tifft, Cynthia J.; Gahl, William A.; Golas, Gretchen] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ovejero, Diana] Univ Autonoma Barcelona, Dept Med, Bellaterra, Spain. [Sugarman, Jeffrey S.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 95403 USA. [Sugarman, Jeffrey S.] Univ Calif San Francisco, Dept Family Med, San Francisco, CA 95403 USA. [DeKlotz, Cynthia M. C.; Eichenfield, Lawrence F.] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Gottschalk, Michael] Rady Childrens Hosp, San Diego, CA USA. [DeKlotz, Cynthia M. C.; Eichenfield, Lawrence F.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92123 USA. [DeKlotz, Cynthia M. C.; Eichenfield, Lawrence F.] Univ Calif San Diego, Dept Med Dermatol, San Diego, CA 92123 USA. [Maruri, Ann; Gottschalk, Michael] Pediat Care Ogden, Ogden, UT USA. [Maruri, Ann] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Kelley, Patrick K.] Dell Childrens Med Ctr Cent Texas, Univ Med Ctr Brackenridge, Seton Inst Reconstruct Plast Surg, Austin, TX 78723 USA. [Jueppner, Harald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Tifft, Cynthia J.; Gahl, William A.; Golas, Gretchen] NIH Common Fund, NIH Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Boyce, Alison M.] Childrens Natl Med Ctr, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC 20010 USA. [Loring, Erin C.; Overton, John D.; Mane, Shrikant M.; Lifton, Richard P.] Yale Ctr Mendelian Genom, New Haven, CT 06510 USA. [Levy, Moise L.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA. [Levy, Moise L.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Levy, Moise L.] Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. RP Collins, MT (reprint author), Natl Inst Dental & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. EM mcollins@dir.nidcr.nih.gov; keith.choate@yale.edu OI DeKlotz, Cynthia/0000-0002-6410-8710 FU Doris Duke Charitable Foundation; Yale Center for Mendelian Genomics (NIH) [U54 HG006504]; Yale University School of Medicine; "la Caixa" Fellowship Program; Division of Intramural Research, National Institutes of Dental and Craniofacial Research, NIH FX This work was supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award to K. A. C. and by the Yale Center for Mendelian Genomics (NIH U54 HG006504). Y.H.L. was supported by the Paul H. Lavietes, M. D. Student Research Fellowship from the Yale University School of Medicine. D.O. was supported by the "la Caixa" Fellowship Program. M. T. C. and R. I. G. were supported by the Division of Intramural Research, National Institutes of Dental and Craniofacial Research, NIH. NR 117 TC 18 Z9 18 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2014 VL 23 IS 2 BP 397 EP 407 DI 10.1093/hmg/ddt429 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AA1EX UT WOS:000330840400010 PM 24006476 ER PT J AU Selhub, EM Logan, AC Bested, AC AF Selhub, Eva M. Logan, Alan C. Bested, Alison C. TI Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry SO JOURNAL OF PHYSIOLOGICAL ANTHROPOLOGY LA English DT Review ID MAJOR DEPRESSIVE DISORDER; LACTIC-ACID BACTERIA; HIGH-FAT-DIET; MILK-DERIVED LACTOFERRIN; CHRONIC-FATIGUE-SYNDROME; ANXIETY-LIKE BEHAVIOR; GUT MICROBIOTA; INTESTINAL PERMEABILITY; BIFIDOBACTERIUM-LONGUM; RICE BRAN AB The purposeful application of fermentation in food and beverage preparation, as a means to provide palatability, nutritional value, preservative, and medicinal properties, is an ancient practice. Fermented foods and beverages continue to make a significant contribution to the overall patterns of traditional dietary practices. As our knowledge of the human microbiome increases, including its connection to mental health (for example, anxiety and depression), it is becoming increasingly clear that there are untold connections between our resident microbes and many aspects of physiology. Of relevance to this research are new findings concerning the ways in which fermentation alters dietary items pre-consumption, and in turn, the ways in which fermentation-enriched chemicals (for example, lactoferrin, bioactive peptides) and newly formed phytochemicals (for example, unique flavonoids) may act upon our own intestinal microbiota profile. Here, we argue that the consumption of fermented foods may be particularly relevant to the emerging research linking traditional dietary practices and positive mental health. The extent to which traditional dietary items may mitigate inflammation and oxidative stress may be controlled, at least to some degree, by microbiota. It is our contention that properly controlled fermentation may often amplify the specific nutrient and phytochemical content of foods, the ultimate value of which may associated with mental health; furthermore, we also argue that the microbes (for example, Lactobacillus and Bifidobacteria species) associated with fermented foods may also influence brain health via direct and indirect pathways. C1 [Selhub, Eva M.] Harvard Univ, Sch Med, Waltham, MA 02453 USA. [Selhub, Eva M.] Massachusetts Gen Hosp, Waltham, MA 02453 USA. [Logan, Alan C.] CAMNR, Calabasas, CA 91302 USA. [Bested, Alison C.] BC Womens Hosp & Hlth Ctr, Complex Chron Dis Program, Vancouver, BC V6H 3N1, Canada. RP Selhub, EM (reprint author), Harvard Univ, Sch Med, 40 Crescent St,Suite 201, Waltham, MA 02453 USA. EM eselhub@partners.org FU Genuine Health, Toronto, Canada FX ACL has received consulting fees from Genuine Health, Toronto, Canada. EMS and ACB have no competing interests. NR 166 TC 21 Z9 23 U1 15 U2 106 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1880-6791 EI 1880-6805 J9 J PHYSIOL ANTHROPOL JI J. Physiol. Anthropol. PD JAN 15 PY 2014 VL 33 AR 2 DI 10.1186/1880-6805-33-2 PG 12 WC Physiology SC Physiology GA AA9XS UT WOS:000331447000001 PM 24422720 ER PT J AU Dangas, GD Kini, AS Sharma, SK Henriques, JPS Claessen, BE Dixon, SR Massaro, JM Palacios, I Popma, JJ Ohman, EM Stone, GW O'Neill, WW AF Dangas, George D. Kini, Annapoorna S. Sharma, Samin K. Henriques, Jose P. S. Claessen, Bimmer E. Dixon, Simon R. Massaro, Joseph M. Palacios, Igor Popma, Jeffrey J. Ohman, E. Magnus Stone, Gregg W. O'Neill, William W. TI Impact of Hemodynamic Support With Impella 2.5 Versus Intra-Aortic Balloon Pump on Prognostically Important Clinical Outcomes in Patients Undergoing High-Risk Percutaneous Coronary Intervention (from the PROTECT II Randomized Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERIPROCEDURAL MYOCARDIAL-INFARCTION; KINASE-MB ELEVATION; STENT TRIALS; REGISTRY; DEFINITIONS; MORTALITY; FREQUENCY; SURVIVAL; SOCIETY; DEVICE AB A periprocedural myocardial infarction, defined as the advent of new Q-waves or a creatine kinase-MB elevation >8 x normal has been previously validated as predictive of subsequent mortality. We examined the effects of using this clinically relevant definition of periprocedural myocardial infarction instead of the original protocol definition on outcomes in the recent PROTECT II [A Prospective, Multi-center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump (IABP) in Patients Undergoing Non Emergent High Risk PCI] trial. In this trial, patients who were undergoing high-risk percutaneous coronary intervention (PCI) were randomized to either an intra-aortic balloon pump (IABP, n = 211) or a left ventricular assist device (Impella, n = 216). All eligible patients per study protocol were included in the analysis. Patient outcomes were compared up to 90 days, the longest available follow-up, on the composite end points of major adverse events (MAE) and major adverse cardiac and cerebral events (MACCE = death, stroke, myocardial infarction, and repeat revascularization). At 90 days, the rates of both composite end points were lower in the Impella group compared with the IABP group (MAE, 37% vs 49%, p = 0.014 respectively; MACCE, 22% vs 31%, p = 0.034 respectively). There were no differences in death or large myocardial infarction between the 2 arms. By multivariable analysis, treatment with Impella as opposed to IABP was an independent predictor for freedom from MAE (odds ratio = 0.75 [95% confidence interval 0.61 to 0.92], p = 0.007) and MACCE (odds ratio = 0.76 [95% confidence interval 0.61 to 0.96], p = 0.020) at 90 days postprocedure. In conclusion, hemodynamic support with Impella compared with IABP during high-risk PCI in the PROTECT-II trial resulted in improved event-free survival at 3-month follow-up; this finding was further supported by multivariate analyses. (C) 2014 Elsevier Inc. All rights reserved. C1 [Dangas, George D.; Kini, Annapoorna S.; Sharma, Samin K.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Henriques, Jose P. S.; Claessen, Bimmer E.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Dixon, Simon R.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Massaro, Joseph M.] Harvard Clin Res Inst, Boston, MA USA. [Palacios, Igor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Popma, Jeffrey J.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Ohman, E. Magnus] Duke Univ, Med Ctr, Durham, NC USA. [Stone, Gregg W.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [O'Neill, William W.] Henry Ford Med Ctr, Detroit, MI USA. RP Dangas, GD (reprint author), Mt Sinai Med Ctr, New York, NY 10029 USA. EM gdangas@crf.org FU Abiomed; Harvard Clinical Research Institute FX Drs. George Dangas, Annapoorna S. Kini, Samin K. Sharma, Neal Kleiman, Simon Dixon, and William O'Neill have no conflict of interest to report for this study. Dr. Henriques reported that his institution has received research funding from Abiomed as an investigator site for other Impel la trials. Dr. Henriques received modest speaker honoraria from Abiomed. Dr. Claessen reported that his institution has received research funding from Abiomed as investigator site for other Impel la trials. Dr. Joseph Massaro reported that he has received funding for the study through Harvard Clinical Research Institute for biostatistics, trial design, and analyses. Dr. Igor Palacios reported that he has received modest speaker honoraria from Abiomed. Dr. Popma reported that his institution (angiographic core laboratory) has received a research grant from Abiomed for the angiographic analysis of the study. He has also received modest funding for participation in some advisory board meetings. Dr. Magnus Ohman reported that he has received grants from Daiichi Sankyo, Maquet (formerly Datascope), and Eli Lilly. Dr. Gregg Stone has served as a consultant for Boston Scientific Corp. and Thoratec. NR 27 TC 25 Z9 27 U1 1 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2014 VL 113 IS 2 BP 222 EP 228 DI 10.1016/j.amjcard.2013.09.008 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 297KI UT WOS:000330253900005 PM 24527505 ER PT J AU Weinberg, I Abtahian, F DeBiasi, R Cefalo, P MacKay, C Hawkins, BM Jaff, MR AF Weinberg, Ido Abtahian, Farhad DeBiasi, Ralph Cefalo, Philip MacKay, Cheryl Hawkins, Beau M. Jaff, Michael R. TI Effect of Delayed Inferior Vena Cava Filter Retrieval After Early Initiation of Anticoagulation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM; TRAUMA PATIENTS; PLACEMENT; OUTCOMES; RATES; COMPLICATIONS; MULTICENTER; POPULATION; GUIDELINES AB Retrievable inferior vena cava filters (IVCFs) were designed to provide temporary protection from pulmonary embolism in high-risk situations. However, little is known about their effectiveness, and many remain permanently implanted, leading to potential complications. The aim of this study was to determine patient characteristics, indications for IVCF placement, retrieval rates, complications, and post-IVCF anticoagulation (AC) practices in patients who have received IVCFs. A retrospective review of IVCF use by 3 specialty groups from January 1, 2009, to December 31, 2011, was conducted at a tertiary referral center. Indications for IVCF, procedural success and complications, post-IVCF AC practices, and patient outcomes were assessed. Seven hundred fifty-eight IVCFs were placed. Follow-up was available for 688 patients (90.7%) at a median of 342.0 days (interquartile range 81.5 to 758.0). Indications for IVCF placement included contraindication to AC in the presence of acute venous thromboembolism (n = 287 [41.7%]) and prophylaxis (n = 235 [34.2%]). Insertion-related complications occurred in 28 patients (4.1%). After IVCF placement, adequate AC was initiated in 454 patients (66.0%) <3.0 days (interquartile range 0 to 13.0) after insertion, but the overall retrieval rate was only 252 of 688 (36.6%) within a median of 134.0 days (interquartile range 72.50 to 205.8). Significant IVCF-related complications occurred in 122 patients (17.7%) within 32 days (interquartile range 13.0 to 116.8). The most common complication (72 of 131 [55.0%]) was deep vein thrombosis. In conclusion, in a large, modern cohort of patients receiving retrievable IVCFs for a variety of indications by various specialties, IVCF insertion remains safe. However, many patients have IVCF-related complications, and often, even when IVCFs are retrieved, there is a delay between AC and retrieval. Quality improvement initiatives that facilitate the expeditious retrieval of IVCF are needed. (C) 2014 Elsevier Inc. All rights reserved. C1 [Weinberg, Ido; MacKay, Cheryl; Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Abtahian, Farhad] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [DeBiasi, Ralph] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Cefalo, Philip] Spaulding Rehabil Hosp, Dept Med, Boston, MA USA. [Hawkins, Beau M.] Univ Oklahoma, Hlth Sci Ctr, Div Cardiol, Oklahoma City, OK USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. EM iweinberg@partners.org OI Jaff, Michael R/0000-0002-3772-5887 NR 30 TC 7 Z9 7 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2014 VL 113 IS 2 BP 389 EP 394 DI 10.1016/j.amjcard.2013.08.053 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 297KI UT WOS:000330253900032 PM 24176068 ER PT J AU Otero, JJ Kalaszczynska, I Michowski, W Wong, M Gygli, PE Gokozan, HN Griveau, A Odajima, J Czeisler, C Catacutan, FP Murnen, A Schuller, U Sicinski, P Rowitch, D AF Otero, Jose Javier Kalaszczynska, Ilona Michowski, Wojciech Wong, Michael Gygli, Patrick Edwin Gokozan, Hamza Numan Griveau, Amelie Odajima, Junko Czeisler, Catherine Catacutan, Fay Patsy Murnen, Alice Schueller, Ulrich Sicinski, Piotr Rowitch, David TI Cerebellar cortical lamination and foliation require cyclin A2 SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Cyclin A2; External granule layer; Cyclin A1; Nestin; Cyclin E1; CNS development; DNA repair; Cell cycle; Brain malformation ID GRANULE NEURON PRECURSORS; CELL-CYCLE PROGRESSION; SONIC HEDGEHOG; POSTNATAL-DEVELOPMENT; MOUSE CEREBELLUM; BRAIN-INJURY; N-MYC; MEDULLOBLASTOMA; PROLIFERATION; EXPRESSION AB The mammalian genome encodes two A-type cyclins, which are considered potentially redundant yet essential regulators of the cell cycle. Here, we tested requirements for cyclin A1 and cyclin A2 function in cerebellar development. Compound conditional loss of cyclin A1/A2 in neural progenitors resulted in severe cerebellar hypoplasia, decreased proliferation of cerebellar granule neuron progenitors (CGNP), and Purkinje (PC) neuron dyslamination. Deletion of cyclin A2 alone showed an identical phenotype, demonstrating that cyclin A1 does not compensate for cyclin A2 loss in neural progenitors. Cyclin A2 loss lead to increased apoptosis at early embryonic time points but not at post-natal time points. In contrast, neural progenitors of the VZ/SVZ did not undergo increased apoptosis, indicating that VZ/SVZ-derived and rhombic lip-derived progenitor cells show differential requirements to cyclin A2. Conditional knockout of cyclin A2 or the SHH proliferative target Nmyc in CGNP also resulted in PC neuron dyslamination. Although cyclin E1 has been reported to compensate for cyclin A2 function in fibroblasts and is upregulated in cyclin A2 null cerebella, cyclin El expression was unable to compensate for loss-of cyclin A2 function. (C) 2013 Elsevier Inc. All rights reserved. C1 [Otero, Jose Javier; Gygli, Patrick Edwin; Gokozan, Hamza Numan; Czeisler, Catherine; Catacutan, Fay Patsy] Ohio State Univ, Div Neuropathol, Dept Pathol, Coll Med, Columbus, OH 43210 USA. [Otero, Jose Javier] Univ Calif San Francisco, San Francisco Dept Pathol, Div Neuropathol, San Francisco, CA USA. [Wong, Michael; Griveau, Amelie; Murnen, Alice; Rowitch, David] Univ Calif San Francisco, San Francisco Dept Pediat, San Francisco, CA USA. [Kalaszczynska, Ilona; Michowski, Wojciech; Odajima, Junko; Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Cambridge, MA 02138 USA. [Kalaszczynska, Ilona; Michowski, Wojciech; Odajima, Junko; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Schueller, Ulrich] Univ Munich, Munich, Germany. [Kalaszczynska, Ilona] Med Univ Warsaw, Ctr Biostruct Res, Dept Histol & Embryol, Tissue Engn Lab, Warsaw, Poland. RP Otero, JJ (reprint author), Ohio State Univ, Div Neuropathol, Dept Pathol, Coll Med, 4169 Graves Hall,333 10th Ave, Columbus, OH 43210 USA. EM jose.otero@osumc.edu RI Otero, Jose/B-8955-2013; OI Kalaszczynska, Ilona/0000-0001-6698-1372 FU California Institute for Regenerative Medicine [TG2-01153]; NIH/NCRR [UL1RR024131]; Foundation for Polish Science, American Brain Tumor Association; German Cancer Aid; NIH [R01NS40511, R01 CA132740] FX J.J.O acknowledges support from The California Institute for Regenerative Medicine (Grant number TG2-01153) and NIH/NCRR (Grant number UL1RR024131). W.M., A.G., and US were supported by the Foundation for Polish Science, American Brain Tumor Association, and the German Cancer Aid, respectively. This work was funded by NIH Grants R01NS40511 (to D.H.R.) and R01 CA132740 (to P.S.). D.H.R. is a Howard Hughes Medical Institute Investigator. NR 57 TC 7 Z9 7 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2014 VL 385 IS 2 BP 328 EP 339 DI 10.1016/j.ydbio.2013.10.019 PG 12 WC Developmental Biology SC Developmental Biology GA 296SM UT WOS:000330205700017 PM 24184637 ER PT J AU Shaik, JSB Miller, TM Graham, SH Manole, MD Poloyac, SM AF Shaik, Jafar Sadik B. Miller, Tricia M. Graham, Steven H. Manole, Mioara D. Poloyac, Samuel M. TI Rapid and simultaneous quantitation of prostanoids by UPLC-MS/MS in rat brain SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Arachidonic acid; Cyclooxygenase; Eicosanoids; Ischemic stroke; Prostanoids; UPLC-MS/MS ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; FOCAL CEREBRAL-ISCHEMIA; SOLID-PHASE EXTRACTION; PGE(2) EP2 RECEPTOR; ARACHIDONIC-ACID; CARDIOVASCULAR ACTIONS; HUMAN PLASMA; PROSTAGLANDINS; PROSTACYCLIN AB The metabolites of arachidonic acid (AA) produced from the cyclooxygenase (COX) pathway, collectively termed as prostanoids, and from the CYP 450 pathway, eicosanoids, have been implicated in various neuro-degenerative and neuroinflammatory diseases. This study developed a quantitative UPLC-MS/MS method to simultaneously measure 11 prostanoids including prostaglandins and cyclopentenone metabolites in the rat brain cortical tissue. Linear calibration curves ranging from 0.104 to 33.3 ng/ml were validated. The inter-day and intra-day variance for all metabolites was less than 15%. The extraction recovery efficiency and matrix (deionized water) effects measured at 12.5 ng/ml (750 pg on column) ranged from 88 to 100% and 3 to 14%, respectively, with CV% values below 20%. Additionally, applying the processing and extraction conditions of this method to our previous CYP450 eicosanoids method resulted in overall improvement in extraction recovery and reduction in matrix effects at low (0.417 ng/ml) and high (8.33 ng/ml) concentrations. In rat brain cortical tissue samples, concentrations of prostanoids ranged from 10.2 to 937 pmol/g wet tissue and concentration of eicosanoids ranged from 2.23 to 793 pmol/g wet tissue. These data demonstrate that the successive measurement of prostanoids and eicosanoids from a single extracted sample of rat brain tissue can be achieved with a UPLC-MS/MS system and that this method is necessary for evaluation of these metabolites to delineate their role in various neuroinflammatory and cerebrovascular disorders. (C) 2013 Elsevier BM. All rights reserved. C1 [Shaik, Jafar Sadik B.; Miller, Tricia M.; Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Graham, Steven H.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Manole, Mioara D.] Childrens Hosp Pittsburgh, Div Pediat Emergency Med, Dept Pediat, Pittsburgh, PA 15261 USA. [Manole, Mioara D.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15261 USA. RP Poloyac, SM (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 807 Salk Hall, Pittsburgh, PA 15261 USA. EM poloyac@pitt.edu RI SHAIK, JAFAR SADIK/A-9638-2010 OI SHAIK, JAFAR SADIK/0000-0001-5776-3138 FU AHA [10BGIA3580040]; NIH [R01HD075760]; [R01NS37459]; [S10RR023461] FX This work was funded by R01NS37459 (SHG), AHA 10BGIA3580040 (MDM), NIH R01HD075760 (MDM), S10RR023461 (SMP). NR 46 TC 6 Z9 6 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 EI 1873-376X J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 15 PY 2014 VL 945 BP 207 EP 216 DI 10.1016/j.jchromb.2013.11.041 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 295WS UT WOS:000330147700029 PM 24355215 ER PT J AU Shoup, TM McCauley, JP Lee, DF Chen, R Normandin, MD Bonab, AA El Fakhri, G Vasdev, N AF Shoup, Timothy M. McCauley, John P. Lee, David F., Jr. Chen, Rui Normandin, Marc D. Bonab, Ali A. El Fakhri, Georges Vasdev, Neil TI Synthesis of the dopamine D-2/D-3 receptor agonist (+)-PHNO via supercritical fluid chromatography: preliminary PET imaging study with [3-C-11]-(+)PHNO SO TETRAHEDRON LETTERS LA English DT Article DE PHNO; Carbon-11; Dopamine D-3 agonist; [C-11]methyl iodide; Brown fat ID BROWN ADIPOSE-TISSUE; HIGH-AFFINITY STATE; RADIOSYNTHESIS; THERMOGENESIS; RADIOTRACER AB Carbon-11 labeled (+)-4-[1-C-11]propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([1-(11)]-(+)-PHNO) is a dopamine D-3-preferring agonist radiopharmaceutical used for medical imaging by positron emission tomography (PET). We report the synthesis of (+)-PHNO using supercritical fluid chromatography for enantiomeric resolution of its norpropyl derivative, HNO, followed by propylation. (+)-HNO was used to prepare the radiolabeling precursor, (+)-trans-4-acetyl-9-triisopropylsilyloxy-2,3,4a,5,6,10b-hexahydro-4H-naphth[1,2b)][1,4]oxazine, in 12 steps. Modifications to the labeling procedure were made to ensure consistent preparation of [3-C-11]-(+)-PHNO via [C-11[CH3I. A preliminary PET imaging study was carried out with this tracer in an attempt to image dopamine receptors in brown adipose tissue (brown fat) in vivo. Published by Elsevier Ltd. C1 [Shoup, Timothy M.; Lee, David F., Jr.; Normandin, Marc D.; Bonab, Ali A.; El Fakhri, Georges; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Shoup, Timothy M.; Lee, David F., Jr.; Normandin, Marc D.; Bonab, Ali A.; El Fakhri, Georges; Vasdev, Neil] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Shoup, Timothy M.; Normandin, Marc D.; Bonab, Ali A.; El Fakhri, Georges; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [McCauley, John P.; Chen, Rui] Waters Corp, SFC Div, New Castle, DE 19720 USA. RP Vasdev, N (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, 55 Fruit St,White 427, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu RI Normandin, Marc/C-6728-2015 OI Normandin, Marc/0000-0003-1645-523X NR 19 TC 3 Z9 3 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JAN 15 PY 2014 VL 55 IS 3 BP 682 EP 685 DI 10.1016/j.tetlet.2013.11.113 PG 4 WC Chemistry, Organic SC Chemistry GA 295YT UT WOS:000330153000025 ER PT J AU Blackwell, TS Tager, AM Borok, Z Moore, BB Schwartz, DA Anstrom, KJ Bar-Joseph, Z Bitterman, P Blackburn, MR Bradford, W Brown, KK Chapman, HA Collard, HR Cosgrove, GP Deterding, R Doyle, R Flaherty, KR Garcia, CK Hagood, JS Henke, CA Herzog, E Hogaboam, CM Horowitz, JC King, TE Loyd, JE Lawson, WE Marsh, CB Noble, PW Noth, I Sheppard, D Olsson, J Ortiz, LA O'Riordan, TG Oury, TD Raghu, G Roman, J Sime, PJ Sisson, TH Tschumperlin, D Violette, SM Weaver, TE Wells, RG White, ES Kaminski, N Martinez, FJ Wynn, TA Thannickal, VJ Eu, JP AF Blackwell, Timothy S. Tager, Andrew M. Borok, Zea Moore, Bethany B. Schwartz, David A. Anstrom, Kevin J. Bar-Joseph, Ziv Bitterman, Peter Blackburn, Michael R. Bradford, William Brown, Kevin K. Chapman, Harold A. Collard, Harold R. Cosgrove, Gregory P. Deterding, Robin Doyle, Ramona Flaherty, Kevin R. Garcia, Christine Kim Hagood, James S. Henke, Craig A. Herzog, Erica Hogaboam, Cory M. Horowitz, Jeffrey C. King, Talmadge E., Jr. Loyd, James E. Lawson, William E. Marsh, Clay B. Noble, Paul W. Noth, Imre Sheppard, Dean Olsson, Julie Ortiz, Luis A. O'Riordan, Thomas G. Oury, Tim D. Raghu, Ganesh Roman, Jesse Sime, Patricia J. Sisson, Thomas H. Tschumperlin, Daniel Violette, Shelia M. Weaver, Timothy E. Wells, Rebecca G. White, Eric S. Kaminski, Naftali Martinez, Fernando J. Wynn, Thomas A. Thannickal, Victor J. Eu, Jerry P. TI Future Directions in Idiopathic Pulmonary Fibrosis Research SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE idiopathic pulmonary fibrosis; alveolar epithelial cells; extracellular matrix; interstitial lung disease; inflammation ID MUC5B PROMOTER POLYMORPHISM; SURFACTANT PROTEIN-C; GROWTH-FACTOR-BETA; ENDOPLASMIC-RETICULUM STRESS; GENOME-WIDE ASSOCIATION; SERUM AMYLOID P; LUNG FIBROSIS; MESENCHYMAL TRANSITION; CIRCULATING FIBROCYTES; LIVER FIBROSIS AB The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U. S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI. C1 [Blackwell, Timothy S.; Loyd, James E.; Lawson, William E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Tager, Andrew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Borok, Zea] Univ So Calif, Los Angeles, CA USA. [Moore, Bethany B.; Flaherty, Kevin R.; Hogaboam, Cory M.; Horowitz, Jeffrey C.; Sisson, Thomas H.; White, Eric S.; Martinez, Fernando J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Schwartz, David A.; Brown, Kevin K.; Cosgrove, Gregory P.; Deterding, Robin] Natl Jewish Hlth, Denver, CO USA. [Schwartz, David A.; Brown, Kevin K.; Cosgrove, Gregory P.; Deterding, Robin] Univ Colorado, Denver, CO 80202 USA. [Anstrom, Kevin J.] Duke Clin Res Inst, Durham, NC USA. [Bar-Joseph, Ziv; Kaminski, Naftali] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Bitterman, Peter; Henke, Craig A.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Blackburn, Michael R.] Univ Texas Houston, Med Sch Houston, Houston, TX USA. [Bradford, William] InterMune Inc, Brisbane, CA USA. [Chapman, Harold A.; Collard, Harold R.; King, Talmadge E., Jr.; Sheppard, Dean] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Doyle, Ramona; Olsson, Julie] Genentech Roche, San Francisco, CA USA. [Garcia, Christine Kim] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Hagood, James S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Herzog, Erica] Yale Univ, Sch Med, New Haven, CT USA. [Marsh, Clay B.] Ohio State Univ, Columbus, OH 43210 USA. [Noble, Paul W.] Cedars Sinai Med Ctr, Los Angeles, CA USA. [Noth, Imre] Univ Chicago, Chicago, IL 60637 USA. [Ortiz, Luis A.; Oury, Tim D.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [O'Riordan, Thomas G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Raghu, Ganesh] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Roman, Jesse] Univ Louisville, Louisville, KY 40292 USA. [Sime, Patricia J.] Univ Rochester, Sch Med, Rochester, NY USA. [Tschumperlin, Daniel] Harvard Sch Publ Hlth, Boston, MA USA. [Violette, Shelia M.] Biogen Idec Inc, Cambridge, MA USA. [Weaver, Timothy E.] Cincinnati Childrens Res Fdn, Cincinnati, OH USA. [Wells, Rebecca G.] Univ Penn, Philadelphia, PA 19104 USA. [Wynn, Thomas A.] NIAID, Bethesda, MD 20892 USA. [Thannickal, Victor J.] Univ Alabama Birmingham, Birmingham, AL USA. [Eu, Jerry P.] NHLBI, Bethesda, MD 20892 USA. RP Eu, JP (reprint author), NHLBI, Natl Inst Hlth, Div Lung Dis, 6701 Rockledge Dr,Rockledge Ctr II,Room 10042, Bethesda, MD 20892 USA. EM jerry.eu@nih.gov RI ortiz, luis/H-9851-2013; hogaboam, cory /M-3578-2014 FU NHLBI; National Institutes of Health FX Supported by NHLBI, National Institutes of Health. NR 113 TC 59 Z9 61 U1 0 U2 33 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2014 VL 189 IS 2 BP 214 EP 222 DI 10.1164/rccm.201306-1141WS PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 290VG UT WOS:000329785900015 PM 24160862 ER PT J AU Deschenes-Simard, X Kottakis, F Meloche, S Ferbeyre, G AF Deschenes-Simard, Xavier Kottakis, Filippos Meloche, Sylvain Ferbeyre, Gerardo TI ERKs in Cancer: Friends or Foes? SO CANCER RESEARCH LA English DT Review ID ONCOGENE-INDUCED SENESCENCE; PANCREATIC DUCTAL ADENOCARCINOMA; KINASE KINASE-1/2 INHIBITOR; K-RAS; MEK INHIBITION; LUNG-CANCER; PHASE-II; TUMOR PROGRESSION; NEUROFIBROMATOSIS TYPE-1; AZD6244 ARRY-142886 AB The extracellular signal-regulated kinase ERK1 and ERK2 (ERK1/2) cascade regulates a variety of cellular processes by phosphorylating multiple target proteins. The outcome of its activation ranges from stimulation of cell survival and proliferation to triggering tumor suppressor responses such as cell differentiation, cell senescence, and apoptosis. This pathway is intimately linked to cancer as several of its upstream activators are frequently mutated in human disease and are shown to accelerate tumorigenesis when engineered in the mouse genome. However, measurement of activated ERKs in human cancers or mouse models does not always support a role in tumorigenesis, and data consistent with a role in tumor suppression have been reported as well. The intensity of ERK signaling, negative feedback loops that regulate the pathway, and cross-talks with other signaling pathways, seem to be of primary importance in determining the final cellular outcome. Cell senescence, a putative tumor-suppression mechanism, depends on high-intensity ERK signals that trigger phosphorylation-dependent protein degradation of multiple proteins required for cell-cycle progression. This response may be circumvented during carcinogenesis by a variety of mechanisms, some of them yet to be discovered, which in essence turn ERK functions from tumor suppression to tumor promotion. The use of pharmacologic inhibitors targeting this pathway must be carefully evaluated so they are applied to cases in which ERKs are mainly oncogenic. (C) 2014 AACR. C1 [Deschenes-Simard, Xavier; Ferbeyre, Gerardo] Univ Montreal, Dept Biochim & Med Mol, Inst Rech Immunol & Cancerol, Montreal, PQ H3C 3J7, Canada. [Meloche, Sylvain] Univ Montreal, Dept Pharmacol, Inst Rech Immunol & Cancerol, Montreal, PQ H3C 3J7, Canada. [Meloche, Sylvain] Univ Montreal, Program Mol Biol, Inst Rech Immunol & Cancerol, Montreal, PQ H3C 3J7, Canada. [Deschenes-Simard, Xavier; Kottakis, Filippos] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Ferbeyre, G (reprint author), Univ Montreal, 2900 Edouard Montpetit,Roger Gaudry E515, Montreal, PQ H3C 3J7, Canada. EM g.ferbeyre@umontreal.ca OI Deschenes-Simard, Xavier/0000-0002-4689-886X FU Canadian Institute of Health and Research (CIHR) FX G. Ferbeyre and S. Meloche are supported by grants from the Canadian Institute of Health and Research (CIHR). NR 81 TC 69 Z9 70 U1 1 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2014 VL 74 IS 2 BP 412 EP 419 DI 10.1158/0008-5472.CAN-13-2381 PG 8 WC Oncology SC Oncology GA 294HB UT WOS:000330034200002 PM 24408923 ER PT J AU Carstens, JL Shahi, P Van Tsang, S Smith, B Creighton, CJ Zhang, YQ Seamans, A Seethammagari, M Vedula, I Levitt, JM Ittmann, MM Rowley, DR Spencer, DM AF Carstens, Julienne L. Shahi, Payam Van Tsang, Susan Smith, Billie Creighton, Chad J. Zhang, Yiqun Seamans, Amber Seethammagari, Mamatha Vedula, Indira Levitt, Jonathan M. Ittmann, Michael M. Rowley, David R. Spencer, David M. TI FGFR1-WNT-TGF-beta Signaling in Prostate Cancer Mouse Models Recapitulates Human Reactive Stroma SO CANCER RESEARCH LA English DT Article ID LARGE GENE LISTS; IN-VITRO; WNT/BETA-CATENIN; PRIMITIVE STREAK; GROWTH-FACTORS; ACTIVATION; CELLS; WNT; TUMORIGENESIS; EXPRESSION AB The reactive stroma surrounding tumor lesions performs critical roles ranging from supporting tumor cell proliferation to inducing tumorigenesis and metastasis. Therefore, it is critical to understand the cellular components and signaling control mechanisms that underlie the etiology of reactive stroma. Previous studies have individually implicated fibroblast growth factor receptor 1 (FGFR1) and canonical WNT/beta-catenin signaling in prostate cancer progression and the initiation and maintenance of a reactive stroma; however, both pathways are frequently found to be coactivated in cancer tissue. Using autochthonous transgenic mouse models for inducible FGFR1 (JOCK1) and prostate-specific and ubiquitously expressed inducible beta-catenin (Pro-Cat and Ubi-Cat, respectively) and bigenic crosses between these lines (Pro-Cat x JOCK1 and Ubi-Cat x JOCK1), we describe WNT-induced synergistic acceleration of FGFR1-driven adenocarcinoma, associated with a pronounced fibroblastic reactive stroma activation surrounding prostatic intraepithelial neoplasia (mPIN) lesions found both in in situ and reconstitution assays. Both mouse and human reactive stroma exhibited increased transforming growth factor-beta (TGF-beta) signaling adjacent to pathologic lesions likely contributing to invasion. Furthermore, elevated stromal TGF-beta signaling was associated with higher Gleason scores in archived human biopsies, mirroring murine patterns. Our findings establish the importance of the FGFR1-WNT-TGF-beta signaling axes as driving forces behind reactive stroma in aggressive prostate adenocarcinomas, deepening their relevance as therapeutic targets. C1 [Carstens, Julienne L.; Shahi, Payam; Seethammagari, Mamatha; Vedula, Indira; Levitt, Jonathan M.; Rowley, David R.; Spencer, David M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Van Tsang, Susan; Ittmann, Michael M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Carstens, Julienne L.; Smith, Billie; Creighton, Chad J.; Zhang, Yiqun; Seamans, Amber; Ittmann, Michael M.; Rowley, David R.; Spencer, David M.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Ittmann, Michael M.] Dept Vet Affairs Med Ctr, Houston, TX USA. RP Spencer, DM (reprint author), Baylor Coll Med, 1 Baylor Plaza,MS245, Houston, TX 77030 USA. EM drowley@bcm.edu; dspencer@bcm.edu FU mouse models for human cancer consortium (MMHCC) [U01-CA84296, NIH R01 CA58093]; NIH [AI036211, CA125123, RR024574]; National Cancer Institute P30 Cancer Center [P30 CA125123] FX This work was financially supported by the mouse models for human cancer consortium (MMHCC) grant U01-CA84296, NIH R01 CA58093; the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH (AI036211, CA125123, and RR024574); and the National Cancer Institute P30 Cancer Center support grant (P30 CA125123) for support of the Human Tissue Acquisition and Pathology and Genetically Engineered Mouse Cores. NR 47 TC 11 Z9 11 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2014 VL 74 IS 2 BP 609 EP 620 DI 10.1158/0008-5472.CAN-13-1093 PG 12 WC Oncology SC Oncology GA 294HB UT WOS:000330034200020 PM 24305876 ER PT J AU Duraiswamy, J Freeman, GJ Coukos, G AF Duraiswamy, Jaikumar Freeman, Gordon J. Coukos, George TI Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors-Response SO CANCER RESEARCH LA English DT Letter ID CANCER; THERAPY C1 [Duraiswamy, Jaikumar] Univ Penn, Philadelphia, PA 19104 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Coukos, George] Ludwig Inst Canc Res, Lausanne, Switzerland. RP Coukos, G (reprint author), Ludwig Inst Canc Res, Chemin Boveresses 155, CH-1066 Epalinges, Switzerland. EM george.coukos@chuv.ch FU NCI NIH HHS [P50 CA083638] NR 10 TC 10 Z9 10 U1 3 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2014 VL 74 IS 2 BP 633 EP 634 DI 10.1158/0008-5472.CAN-13-2752 PG 2 WC Oncology SC Oncology GA 294HB UT WOS:000330034200023 PM 24408920 ER PT J AU Proia, DA Zhang, CH Sequeira, M Jimenez, JP He, SQ Spector, N Shapiro, GI Tolaney, S Nagai, M Acquaviva, J Smith, DL Sang, J Bates, RC El-Hariry, I AF Proia, David A. Zhang, Chaohua Sequeira, Manuel Jimenez, John-Paul He, Suqin Spector, Neil Shapiro, Geoffrey I. Tolaney, Sara Nagai, Masazumi Acquaviva, Jaime Smith, Donald L. Sang, Jim Bates, Richard C. El-Hariry, Iman TI Preclinical Activity Profile and Therapeutic Efficacy of the HSP90 Inhibitor Ganetespib in Triple-Negative Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; POTENT ANTITUMOR-ACTIVITY; TOPOISOMERASE-II POISONS; IN-VIVO; MOLECULAR PORTRAITS; MITOTIC CATASTROPHE; DNA-DAMAGE; PHASE-II; EXPRESSION; TUMORS AB Purpose: Treatment options for patients with triple-negative breast cancer (TNBC) are largely limited to systemic chemotherapies, which have shown disappointing efficacy in the metastatic setting. Here, we undertook a comprehensive evaluation of the activity of ganetespib, a potent inhibitor of HSP90, in this malignancy. Experimental Design: The antitumor and antimetastatic activity of ganetespib was investigated using TNBC cell lines and xenograft models. Combinatorial drug analyses were performed with chemotherapeutic agents and concomitant effects on DNA damage and cell-cycle disruption were assessed in vitro; antitumor efficacy was assessed in vivo. Metabolic and objective tumor responses were evaluated in patients with metastatic TNBC undergoing ganetespib treatment. Results: Ganetespib simultaneously deactivated multiple oncogenic pathways to potently reduce cell viability in TNBC cell lines, and suppressed lung metastases in experimental models. Ganetespib potentiated the cytotoxic activity of doxorubicin via enhanced DNA damage and mitotic arrest, conferring superior efficacy to the doxorubicin-cyclophosphamide regimen in TNBC xenografts. Ganetespib also promoted mitotic catastrophe and apoptosis in combination with taxanes in vitro, and these effects translated to significantly improved combinatorial activity in vivo. Marked tumor shrinkage of metastatic lung and lymphatic lesions were seen in patients on ganetespib monotherapy. Conclusion: The preclinical activity profile and clinical evidence of tumor regression suggest that ganetespib offers considerable promise as a new therapeutic candidate to target TNBC. (C) 2013 AACR. C1 [Proia, David A.; Zhang, Chaohua; Sequeira, Manuel; Jimenez, John-Paul; He, Suqin; Nagai, Masazumi; Acquaviva, Jaime; Smith, Donald L.; Sang, Jim; Bates, Richard C.; El-Hariry, Iman] Synta Pharmaceut Corp, Lexington, MA 02421 USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. [Tolaney, Sara] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. [Spector, Neil] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Proia, DA (reprint author), Synta Pharmaceut Corp, 125 Hartwell Ave, Lexington, MA 02421 USA. EM dproia@syntapharma.com FU Synta Pharmaceuticals Corp. FX This study was funded by Synta Pharmaceuticals Corp. NR 50 TC 10 Z9 10 U1 0 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2014 VL 20 IS 2 BP 413 EP 424 DI 10.1158/1078-0432.CCR-13-2166 PG 12 WC Oncology SC Oncology GA 292QZ UT WOS:000329918600016 PM 24173541 ER PT J AU Terunuma, M Revilla-Sanchez, R Quadros, IM Deng, QD Deeb, TZ Lumb, M Sicinski, P Haydon, PG Pangalos, MN Moss, SJ AF Terunuma, Miho Revilla-Sanchez, Raquel Quadros, Isabel M. Deng, Qiudong Deeb, Tarek Z. Lumb, Michael Sicinski, Piotr Haydon, Philip G. Pangalos, Menelas N. Moss, Stephen J. TI Postsynaptic GABA(B) Receptor Activity Regulates Excitatory Neuronal Architecture and Spatial Memory SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LONG-TERM-MEMORY; DEPENDENT PROTEIN-KINASE; GAMMA-AMINOBUTYRIC-ACID; MEDIATED ACTIN DYNAMICS; SYNAPTIC PLASTICITY; FUNCTIONAL MODULATION; NMDA RECEPTORS; ARC/ARG3.1; MICE; EXPRESSION AB Cognitive dysfunction is a common symptom in many neuropsychiatric disorders and directly correlates with poor patient outcomes. The majority of prolonged inhibitory signaling in the brain is mediated via GABA(B) receptors (GABA(B)Rs), but the molecular function of these receptors in cognition is ill defined. To explore the significance of GABA(B)Rs in neuronal activity and cognition, we created mice with enhanced postsynaptic GABA(B)R signaling by mutating the serine 783 in receptor R2 subunit (S783A), which decreased GABA(B)R degradation. Enhanced GABA(B)R activity reduced the expression of immediate-early gene-encoded protein Arc/Arg3.1, effectors that are critical for long-lasting memory. Intriguingly, S783A mice exhibited increased numbers of excitatory synapses and surface AMPA receptors, effects that are consistent with decreased Arc/Arg3.1 expression. These deficits in Arc/Arg3.1 and neuronal morphology lead to a deficit in spatial memory consolidation. Collectively our results suggest a novel and unappreciated role for GABA(B)R activity in determining excitatory neuronal architecture and spatial memory via their ability to regulate Arc/Arg3.1. C1 [Terunuma, Miho; Revilla-Sanchez, Raquel; Quadros, Isabel M.; Deng, Qiudong; Deeb, Tarek Z.; Haydon, Philip G.; Moss, Stephen J.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Lumb, Michael; Moss, Stephen J.] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England. [Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Pangalos, Menelas N.] AstraZeneca, Innovat Med, Macclesfield SK10 4TG, Cheshire, England. RP Terunuma, M (reprint author), Univ Leicester, Coll Med Biol Sci & Psychol, Dept Cell Physiol & Pharmacol, Univ Rd, Leicester LE1 9HN, Leics, England. EM mt304@le.ac.uk; Stephen.Moss@tufts.edu FU National Scientist Development Grant from the American Heart Association [09SDG2260557]; NIH-National Institute of Neurological Disorders and Stroke [NS051195, NS056359, NS081735, MH097446]; Citizens United for Research in Epilepsy [PV0178]; Simons Foundation [PV0138] FX M.T. was a recipient of a National Scientist Development Grant (09SDG2260557) from the American Heart Association. S.J.M. is supported by NIH-National Institute of Neurological Disorders and Stroke Grants NS051195, NS056359, NS081735, and MH097446; and by Citizens United for Research in Epilepsy (PV0178) and the Simons Foundation (PV0138). We thank to the members of the Moss Laboratory for discussions during the course of this study and Dr. M. Ericsson for help and advice. NR 44 TC 16 Z9 17 U1 0 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 2014 VL 34 IS 3 BP 804 EP 816 DI 10.1523/JNEUROSCI.3320-13.2013 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 292QH UT WOS:000329916600014 PM 24431439 ER PT J AU Mukamel, EA Pirondini, E Babadi, B Wong, KFK Pierce, ET Harrell, PG Walsh, JL Salazar-Gomez, AF Cash, SS Eskandar, EN Weiner, VS Brown, EN Purdon, PL AF Mukamel, Eran A. Pirondini, Elvira Babadi, Behtash Wong, Kin Foon Kevin Pierce, Eric T. Harrell, P. Grace Walsh, John L. Salazar-Gomez, Andres F. Cash, Sydney S. Eskandar, Emad N. Weiner, Veronica S. Brown, Emery N. Purdon, Patrick L. TI A Transition in Brain State during Propofol-Induced Unconsciousness SO JOURNAL OF NEUROSCIENCE LA English DT Article DE alpha rhythm; anesthesia; cross-frequency coupling; propofol; Slow oscillation; unconsciousness ID NEURONAL OSCILLATIONS; CORTICAL SURFACE; GENERAL-ANESTHESIA; BURST-SUPPRESSION; CONSCIOUSNESS; SLEEP; EEG; COMPONENTS; RESOLUTION; AWARENESS AB Rhythmic oscillations shape cortical dynamics during active behavior, sleep, and general anesthesia. Cross-frequency phase-amplitude coupling is a prominent feature of cortical oscillations, but its role in organizing conscious and unconscious brain states is poorly understood. Using high-density EEG and intracranial electrocorticography during gradual induction of propofol general anesthesia in humans, we discovered a rapid drug-induced transition between distinct states with opposite phase-amplitude coupling and different cortical source distributions. One state occurs during unconsciousness and may be similar to sleep slow oscillations. A second state occurs at the loss or recovery of consciousness and resembles an enhanced slow cortical potential. These results provide objective electrophysiological land marks of distinct unconscious brain states, and could be used to help improve EEG-based monitoring for general anesthesia. C1 [Mukamel, Eran A.] Harvard Univ, Swartz Program Theoret Neurosci, Cambridge, MA 02138 USA. [Mukamel, Eran A.] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA. [Mukamel, Eran A.] Salk Inst Biol Studies, Computat Neurobiol Lab, San Diego, CA 92037 USA. [Pirondini, Elvira; Babadi, Behtash; Wong, Kin Foon Kevin; Pierce, Eric T.; Harrell, P. Grace; Walsh, John L.; Salazar-Gomez, Andres F.; Brown, Emery N.; Purdon, Patrick L.] Massachusetts Gen Hosp, Department Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Weiner, Veronica S.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.; Purdon, Patrick L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Brown, Emery N.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Purdon, PL (reprint author), Dept Anesthesia Crit Care & Pain Med, Bldg 149,13th St,Room 4012, Charlestown, MA 02129 USA. EM patrickp@nmr.mgh.harvard.edu RI Wong, Kin Foon Kevin/C-7896-2014 FU Swartz Fellowship in Theoretical Neuroscience; University of California-San Diego Center for Biological Physics; National Institutes of Health [K99NS080911, DP2-OD006454, K25-NS057580, DP1-OD003646-01, R01-EB006385, R01-MH071847] FX This work was supported by a Swartz Fellowship in Theoretical Neuroscience (E.A.M.), the University of California-San Diego Center for Biological Physics (E.A.M.), and National Institutes of Health Grants K99NS080911 (E.A.M.), DP2-OD006454 (P.L.P.), K25-NS057580 (P.L.P.), DP1-OD003646-01 (E.N.B.), R01-EB006385 (E.N.B., P.L.P.), and R01-MH071847 (E.N.B.). NR 37 TC 17 Z9 18 U1 0 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 2014 VL 34 IS 3 BP 839 EP 845 DI 10.1523/JNEUROSCI.5813-12.2014 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 292QH UT WOS:000329916600017 PM 24431442 ER PT J AU Aizer, AA Ancukiewicz, M Nguyen, PL Shih, HA Loeffler, JS Oh, KS AF Aizer, Ayal A. Ancukiewicz, Marek Nguyen, Paul L. Shih, Helen A. Loeffler, Jay S. Oh, Kevin S. TI Underutilization of Radiation Therapy in Patients With Glioblastoma Predictive Factors and Outcomes SO CANCER LA English DT Article DE glioblastoma; omission; radiation; risk factors; survival ID LOW-INCOME WOMEN; BREAST-CANCER; CLINICAL-TRIAL; MARITAL-STATUS; UNITED-STATES; RADIOTHERAPY; SURVIVAL; CARE; STAGE; RACE/ETHNICITY AB BACKGROUNDRandomized trials have demonstrated that radiation improves survival in patients with glioblastoma. The purpose of this study was to characterize the risk factors and impact of omission of radiation therapy in such patients. METHODSThe Surveillance, Epidemiology, and End Results (SEER) program was used to identify 22,777 patients diagnosed with glioblastoma between 1988 and 2007. Multivariable logistic regression was employed to identify predictors associated with omission of radiation. Cox regression was used to characterize the impact of omitting radiation on all-cause mortality. RESULTSAmong the entire cohort, 16,863 of 22,777 patients (74%) received radiation, whereas 5914 of 22,777 patients (26%) did not. Factors associated with omission of radiation included older age (OR=1.048 per year increase, 95% CI=1.046-1.051, P<.001), lower annual income (OR=0.93 per $10,000 increase, 95% CI=0.90-0.96, P<.001), African American race (reference=white, OR=1.19, 95% CI=1.03-1.37, P=.02), Hispanic race (OR=1.34, 95% CI=1.19-1.50, P<.001), Asian American race (OR=1.24, 95% CI=1.04-1.48, P<.001), unmarried status (OR=1.71, 95% CI=1.60-1.83, P<.001), and subtotal resection/biopsy (OR=1.82, 95% CI=1.69-1.96, P<.001). The use of radiation was significantly associated with improved overall survival (2-year survival: 14.6% versus 4.2%, P<.001; adjusted HR=2.09, 95% CI=2.02-2.16, P<.001). When the population was restricted to patients <50 years old, these findings remained largely unchanged. CONCLUSIONSRadiation therapy is associated with survival benefit in patients with glioblastoma, and sociodemographic factors play a significant role in the underutilization of radiation. The underlying causes for these disparities in care require further research. Cancer 2014;120:238-243. (c) 2013 American Cancer Society. Omission of radiation therapy in patients with glioblastoma occurs frequently and is driven in part by sociodemographic factors. Radiation therapy is associated with a survival benefit in most patients with glioblastoma, and clinicians should be aware of patients at risk for its omission. C1 [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA USA. [Ancukiewicz, Marek] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Biostat & Biomath, Boston, MA 02114 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shih, Helen A.; Loeffler, Jay S.; Oh, Kevin S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Oh, KS (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM koh2@partners.org FU Varian FX Dr. Nguyen has received research funding from Varian and consulted for Ferring Inc., Astellas Pharmaceuticals, and Medivation. All other authors made no disclosure. NR 27 TC 2 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2014 VL 120 IS 2 BP 238 EP 243 DI 10.1002/cncr.28398 PG 6 WC Oncology SC Oncology GA 284QC UT WOS:000329334000014 PM 24122361 ER PT J AU Brinkman, TM Zhang, N Recklitis, CJ Kimberg, C Zeltzer, LK Muriel, AC Stovall, M Srivastava, DK Sklar, CA Robison, LL Krull, KR AF Brinkman, Tara M. Zhang, Nan Recklitis, Christopher J. Kimberg, Cara Zeltzer, Lonnie K. Muriel, Anna C. Stovall, Marilyn Srivastava, Deo Kumar Sklar, Charles A. Robison, Leslie L. Krull, Kevin R. TI Suicide Ideation and Associated Mortality in Adult Survivors of Childhood Cancer SO CANCER LA English DT Article DE childhood cancer; survivorship; suicide; mortality; late effects ID 5-YEAR SURVIVORS; COMPETING RISK; PREVALENCE; VALIDITY; OUTCOMES; COHORT AB BACKGROUNDAdult survivors of childhood cancer are at risk for suicide ideation, although longitudinal patterns and rates of recurrent suicide ideation are unknown. This study investigated the prevalence of late report (ie, after initial assessment) and recurrent suicide ideation in adult survivors of childhood cancer, identified predictors of suicide ideation, and examined associations among suicide ideation and mortality. METHODSParticipants included 9128 adult survivors of childhood cancer and 3082 sibling controls enrolled in the Childhood Cancer Survivor Study who completed a survey question assessing suicide ideation on one or more occasions between 1994 and 2010. Suicide ideation was assessed using the Brief Symptom Inventory-18 instrument. Mortality data was ascertained from the National Death Index. RESULTSSurvivors were more likely to report late (odds ratio [OR]=1.9, 95% confidence interval [CI]=1.5-2.5) and recurrent suicide ideation (OR=2.6, 95% CI=1.8-3.8) compared to siblings. Poor physical health status was associated with increased risk of suicide ideation in survivors (late report: OR=1.9, 95% CI=1.3-2.7; recurrent: OR=1.9, 95% CI=1.2-2.9). Suicide ideation was associated with increased risk for all-cause mortality (hazard ratio=1.3, 95% CI=1.03-1.6) and death by external causes (hazard ratio=2.4, 95% CI=1.4-4.1). CONCLUSIONSAdult survivors of childhood cancer are at risk for late-report and recurrent suicide ideation, which is associated with increased risk of mortality. Routine screening for psychological distress in adult survivors appears warranted, especially for survivors who develop chronic physical health conditions. Cancer 2014;120:271-277. (c) 2013 American Cancer Society. Adult survivors of childhood cancer are at risk for late and recurrent suicide ideation. Suicide ideation in survivors is associated with increased risk of mortality. C1 [Brinkman, Tara M.; Kimberg, Cara; Robison, Leslie L.; Krull, Kevin R.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Zhang, Nan; Srivastava, Deo Kumar] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. [Zeltzer, Lonnie K.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Dept Pediat, Los Angeles, CA 90095 USA. [Muriel, Anna C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Brinkman, TM (reprint author), St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 262 Danny Thomas Pl,MS 735, Memphis, TN 38105 USA. EM tara.brinkman@stjude.org OI Zeltzer, Lonnie/0000-0001-9306-9450 FU National Cancer Institute [U24 CA 055727]; Cancer Center Support (CORE) [CA21765]; ALSAC FX This work was supported by grant U24 CA 055727 (to Dr. Robison) from the National Cancer Institute, with additional support provided to St. Jude Children's Research Hospital by the Cancer Center Support (CORE) grant CA21765 and by ALSAC. NR 28 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2014 VL 120 IS 2 BP 271 EP 277 DI 10.1002/cncr.28385 PG 7 WC Oncology SC Oncology GA 284QC UT WOS:000329334000018 PM 24122148 ER PT J AU El-Jawahri, A Traeger, L Park, ER Greer, JA Pirl, WF Lennes, IT Jackson, VA Gallagher, ER Temel, JS AF El-Jawahri, Areej Traeger, Lara Park, Elyse R. Greer, Joseph A. Pirl, William F. Lennes, Inga T. Jackson, Vicki A. Gallagher, Emily R. Temel, Jennifer S. TI Associations Among Prognostic Understanding, Quality of Life, and Mood in Patients With Advanced Cancer SO CANCER LA English DT Article DE supportive care; prognostic understanding; quality of life; mood; advanced cancer; illness understanding ID CELL LUNG-CANCER; EARLY PALLIATIVE CARE; GALLBLADDER CANCER; BILIARY-TRACT; NEAR-DEATH; CHEMOTHERAPY; PREFERENCES; END; COMMUNICATION; DISCUSSIONS AB BACKGROUNDPatients' perception of their prognosis has an impact on their decisions about medical care. However, the relations between prognostic understanding and quality of life (QoL) and mood are unknown. The objectives of this study were to assess perceptions of prognosis and preferences for prognostic information among patients with advanced cancer and to explore the associations of prognostic understanding with QoL and mood. METHODSFifty patients were assessed within 6 to 12 weeks of initiating chemotherapy for advanced gastrointestinal cancers. A 13-item questionnaire was used to assess patients' information preferences, perceptions of their prognosis and goal of therapy, and communication about end-of-life care. The Functional Assessment of Cancer Therapy-General and the Hospital Anxiety and Depression Scale were used to assess QoL and mood, respectively. RESULTSFifty of 62 (80%) consecutive, eligible patients were enrolled. Thirty-eight of 50 patients (75%) wanted to know as many details as possible about their cancer diagnosis and treatment. However, 25 of 50 patients (50%) stated that the goal of therapy was to cure their cancer, and only 10 of 49 patients (22%) reported having a discussion about end-of-life preferences with their oncologist. Patients who acknowledged their illness as terminal reported lower QoL (P=.005) and higher anxiety (P=.003) compared with those who did not perceive themselves as being terminally ill. CONCLUSIONSAlthough patients desired detailed information about their illness, half incorrectly perceived their cancer as curable. Accurate prognostic understanding was associated with lower QoL and worse anxiety. Interventions to improve patients' prognostic understanding while providing adequate psychosocial support are warranted. Cancer 2014;120:278-285. (c) 2013 American Cancer Society. Patients with advanced cancer often have an inaccurate understanding of their illness and prognosis. In these patients, an accurate prognostic understanding is associated with lower quality of life and worse anxiety. C1 [El-Jawahri, Areej; Park, Elyse R.; Lennes, Inga T.; Gallagher, Emily R.; Temel, Jennifer S.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Traeger, Lara; Pirl, William F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greer, Joseph A.; Jackson, Vicki A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP El-Jawahri, A (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 55 Fruit St,Yawkey 10B, Boston, MA 02114 USA. EM ael-jawhari@partners.org FU Golf Fights Cancer; Joanne Hill Monahan Fund FX This work was supported by Golf Fights Cancer and by the Joanne Hill Monahan Fund. NR 34 TC 25 Z9 25 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2014 VL 120 IS 2 BP 278 EP 285 DI 10.1002/cncr.28369 PG 8 WC Oncology SC Oncology GA 284QC UT WOS:000329334000019 PM 24122784 ER PT J AU James, AE Gellad, WF Primack, BA AF James, A. Everette, III Gellad, Walid F. Primack, Brian A. TI Implications of New Insurance Coverage for Access to Care, Cost-Sharing, and Reimbursement SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [James, A. Everette, III] Univ Pittsburgh, Sch Hlth Sci, Hlth Policy Inst, Pittsburgh, PA 15261 USA. [James, A. Everette, III] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Gellad, Walid F.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gellad, Walid F.] RAND Corp, Pittsburgh, PA USA. [Primack, Brian A.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15261 USA. RP James, AE (reprint author), Univ Pittsburgh, Hlth Policy Inst, 3550 Terrace St,S306 Scaife Hall, Pittsburgh, PA 15261 USA. EM aejames@pitt.edu NR 8 TC 5 Z9 5 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 15 PY 2014 VL 311 IS 3 BP 241 EP 242 DI 10.1001/jama.2013.283150 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 287TZ UT WOS:000329566400012 PM 24337312 ER PT J AU Florez, JC AF Florez, Jose C. TI Insights From Monogenic Diabetes and Glycemic Treatment Goals for Common Types of Diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID BLOOD-GLUCOSE CONTROL; CARDIOVASCULAR-DISEASE; EUROPEAN-ASSOCIATION; CONSENSUS ALGORITHM; INTENSIVE TREATMENT; MELLITUS; COMPLICATIONS; HYPERGLYCEMIA; GLUCOKINASE; THERAPY C1 [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, 185 Cambridge St,Simches Res Bldg CPZN 5-250, Boston, MA 02114 USA. EM jcflorez@mgh.harvard.edu NR 22 TC 0 Z9 0 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 15 PY 2014 VL 311 IS 3 BP 249 EP 251 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 287TZ UT WOS:000329566400016 PM 24430318 ER PT J AU Bedair, H Cha, TD Hansen, VJ AF Bedair, Hany Cha, Thomas D. Hansen, Viktor J. TI Economic Benefit to Society at Large of Total Knee Arthroplasty in Younger Patients A Markov Analysis SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID DIRECT MEDICAL COSTS; QUALITY-OF-LIFE; TOTAL HIP; UNITED-STATES; REPORTED ACTIVITY; OSTEOARTHRITIS; REPLACEMENT; OUTCOMES; HEALTH; METAANALYSIS AB Background: To our knowledge, the economic implications of total knee arthroplasty to society at large have not been assessed with specific consideration of the young working population with osteoarthritis of the knee. The goal of the present study was to use a Markov analysis to estimate the overall average cost to society in terms of medical expenses and lost wages of delaying early total knee arthroplasty in favor of nonoperative treatment for end-stage knee osteoarthritis in a hypothetical fifty-year-old patient. Methods: A Markov state-transition decision model was constructed to compare the overall average cost over thirty years of total knee arthroplasty with the average thirty-year cost of nonoperative treatment for a fifty-year-old patient with end-stage osteoarthritis. Earned income, lost wages, and direct medical costs related to nonoperative treatment and to total knee arthroplasty, including revisions and complications, were considered. A sensitivity analysis was performed to assess the effect that variation of key model parameters had on the overall outcome of the model. Results: This Markov model favored early total knee arthroplasty over nonoperative treatment across all plausible values for most input parameters assessed during one-way sensitivity analysis. Total knee arthroplasty was more expensive during the first 3.5 years because of higher initial costs, but over thirty years the cost benefit of total knee arthroplasty was $69,800 (2012 U.S. dollars). Only when lost wages were <17.7 equivalent work days per year for patients treated nonoperatively or when the rate of returning to work after total knee arthroplasty was <81% did the model favor nonoperative treatment. Conclusions: The results of the current study demonstrated that the total economic cost to society for treatment of severe knee osteoarthritis in a relatively young working person is markedly lower with total knee arthroplasty than it is with nonoperative treatment. The increasing financial restrictions on health-care providers in the U.S. necessitate careful consideration of the economic impact of different treatment options from the societal perspective. C1 [Bedair, Hany] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Bedair, H (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, 55 Fruit St,Yawkey Suite 3B, Boston, MA 02114 USA. EM hbedair@gmail.com NR 60 TC 13 Z9 13 U1 0 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN 15 PY 2014 VL 96A IS 2 BP 119 EP 126 DI 10.2106/JBJS.L.01736 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 288HP UT WOS:000329602900006 PM 24430411 ER PT J AU Kobzik, L Swirski, FK AF Kobzik, Lester Swirski, Filip K. TI MARCOing Monocytes for Elimination SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID SUBSETS; MACROPHAGES; PARTICLES; RECEPTOR AB Eliminating infammatory monocytes using microparticles that bind to the MARCO receptor represents a promising strategy to reduce inf ammation and injury (Getts et al., this issue). C1 [Kobzik, Lester] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02114 USA. [Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kobzik, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02114 USA. EM lkobzik@hsph.harvard.edu; fswirski@mgh.harvard.edu FU NHLBI NIH HHS [R01-HL095612, R01 HL115778, HL115778, R01 HL095612]; NIAID NIH HHS [R56-AI104695, R56 AI104695]; NIEHS NIH HHS [ES00002, P30 ES000002] NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 15 PY 2014 VL 6 IS 219 AR 219fs4 DI 10.1126/scitranslmed.3008448 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 292OY UT WOS:000329912800002 PM 24431109 ER PT J AU Chauhan, SK Saban, DR Dohlman, TH Dana, R AF Chauhan, Sunil K. Saban, Daniel R. Dohlman, Thomas H. Dana, Reza TI CCL-21 Conditioned Regulatory T Cells Induce Allotolerance through Enhanced Homing to Lymphoid Tissue SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; TRANSPLANTATION TOLERANCE; ALLOGRAFT-REJECTION; CCR7; MIGRATION; LIGANDS; CD25(+); LYMPHOCYTES; PHENOTYPE; NODES AB Regulatory T cells (Tregs) are instrumental in the induction and maintenance of tolerance, including in transplantation. Tregs induce allotolerance by interacting with APCs and T cells, interactions that require their proper homing to the lymphoid tissues. Using a well-characterized model of corneal allotransplantation, we demonstrate in this study that Tregs in the draining lymph nodes (LN) of allograft acceptors, but not rejectors, colocalize with APCs in the paracortical areas and express high levels of CCR7. In addition, we show that Treg expression of CCR7 is important not only for Treg homing to the draining LN, but also for optimal Treg suppressive function. Finally, we show that Tregs augmented for CCR7 expression by their ex vivo stimulation with the CCR7 ligand CCL21 show enhanced homing to the draining LN of allograft recipients and promote transplant survival. Together, these findings suggest that CCR7 expression is critical for Treg function and migration and that conditioning of Treg for maximal CCR7 expression may be a viable strategy for promoting allograft survival. C1 [Chauhan, Sunil K.; Saban, Daniel R.; Dohlman, Thomas H.; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02144 USA. RP Chauhan, SK (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM Sunil_Chauhan@meei.harvard.edu FU Eye Bank Association of America; National Institutes of Health [NEI-12963] FX This work was supported in part by a grant from the Eye Bank Association of America (to S.K.C.) and National Institutes of Health Grant NEI-12963 (to R.D.). NR 28 TC 9 Z9 10 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2014 VL 192 IS 2 BP 817 EP 823 DI 10.4049/jimmunol.1203469 PG 7 WC Immunology SC Immunology GA 283DA UT WOS:000329224000028 PM 24337379 ER PT J AU Rost, NS Sadaghiani, S Biffi, A Fitzpatrick, KM Cloonan, L Rosand, J Shibata, DK Mosley, TH AF Rost, Natalia S. Sadaghiani, Saloomeh Biffi, Alessandro Fitzpatrick, Kaitlin M. Cloonan, Lisa Rosand, Jonathan Shibata, Dean K. Mosley, Thomas H., Jr. TI Setting a gold standard for quantification of leukoaraiosis burden in patients with ischemic stroke: The Atherosclerosis Risk in Communities Study SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE All cerebrovascular disease/stroke; Volumetric MRI; White matter hyperintensity; Leukoaraiosis; Small vessel stroke ID WHITE-MATTER LESIONS; CEREBRAL AMYLOID ANGIOPATHY; CARDIOVASCULAR-DISEASE; HYPERINTENSITY VOLUME; MRI; SEVERITY; DEMENTIA; BRAIN; SUSCEPTIBILITY; PROGRESSION AB Background: Accurate and reliable measurement of leukoaraiosis, or MR-detected white, matter hyperintensity (WMH) burden in subjects with acute ischemic stroke (AIS) is important for, ongoing research studies and future models of risk and outcome prediction, but the presence of a, cerebral infarct may complicate measurement. We sought to assess accuracy of a volumetric method, designed to measure WMH in AIS subjects as compared to the previously validated protocol. New method: We randomly selected and equally sampled 120 brain scans from the Atherosclerosis, Risk in Communities (ARIC) MRI Study individuals within designated mild, moderate, and severe, tertiles of WMH volume (WMHV). T2 FLAIR axial images were analyzed using the AIS WMH volumetric, protocol and compared with the ARIC (gold standard) method. Pearson correlation coefficients, linear, concordance correlation coefficient, and Blant-Altman procedures were used to assess measurement, agreements between the two procedures. Results: Median WMHV determined by using the ARIC method was 7.8 cm(3) (IQR 5.7-13.55) vs. 3.54 cm(3), (IQR 2.1-7.2) using the AIS WMH method. There was good correlation between the two measurements, (r = 0.52, 0.67, and 0.9 for tertiles 1, 2, and 3 respectively) (p < 0.001). Comparison with existing method: The AIS WMH protocol was specific for leukoaraiosis in ischemic, stroke, but it appeared to underestimate WMHV compared to the gold standard method. Conclusions: Estimates of MR-detectable WMH burden using a volumetric protocol designed for, analysis of clinical scans correlate strongly with gold standard measurements. These findings will, facilitate future studies of WMH in normal aging and in patients with stroke and other cerebrovascular, disease. (C) 2013 Elsevier B.V. All rights reserved. C1 [Rost, Natalia S.; Sadaghiani, Saloomeh; Biffi, Alessandro; Fitzpatrick, Kaitlin M.; Cloonan, Lisa] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rosand, Jonathan; Shibata, Dean K.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Mosley, Thomas H., Jr.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Mosley, Thomas H., Jr.] Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]; NIH [R01-HL70825]; NINDS [K23NS064052]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research; MGH Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; National Institute of Neurological Disorders and Stroke [K23NS064052, R01 NS082285]; American Heart Association Bugher Foundation; National Institute of Health [R01-HL70825] FX The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. This work was also supported by NIH R01-HL70825 (T.M.), NINDS K23NS064052 (N.S.R.), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research, and the MGH Deane Institute for Integrative Study of Atrial Fibrillation and Stroke.; Dr. Natalia Rost is supported by the National Institute of Neurological Disorders and Stroke (K23NS064052 and R01 NS082285). Dr. Alessandro Biffi is supported by the American Heart Association Bugher Foundation. Dr. Thomas Mosley is supported by the National Institute of Health (R01-HL70825). NR 37 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 15 PY 2014 VL 221 BP 196 EP 201 DI 10.1016/j.jneumeth.2013.10.009 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 282AZ UT WOS:000329143800024 PM 24459720 ER PT J AU Becker, JR Chatterjee, S Robinson, TY Bennett, JS Panakova, D Galindo, CL Zhong, L Shin, JT Coy, SM Kelly, AE Roden, DM Lim, CC MacRae, CA AF Becker, Jason R. Chatterjee, Sneha Robinson, Tamara Y. Bennett, Jeffrey S. Panakova, Daniela Galindo, Cristi L. Zhong, Lin Shin, Jordan T. Coy, Shannon M. Kelly, Amy E. Roden, Dan M. Lim, Chee Chew MacRae, Calum A. TI Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development SO DEVELOPMENT LA English DT Article DE ANP; BNP; Npr3; Cardiomyocyte proliferation; Heart development; Natriuretic peptides ID CLEARANCE RECEPTOR; CARDIAC-HYPERTROPHY; G-PROTEIN; NPR-C; HEART; EXPRESSION; MICE; ZEBRAFISH; BRAIN; HYPERTENSION AB Organ development is a highly regulated process involving the coordinated proliferation and differentiation of diverse cellular populations. The pathways regulating cell proliferation and their effects on organ growth are complex and for many organs incompletely understood. In all vertebrate species, the cardiac natriuretic peptides (ANP and BNP) are produced by cardiomyocytes in the developing heart. However, their role during cardiogenesis is not defined. Using the embryonic zebrafish and neonatal mammalian cardiomyocytes we explored the natriuretic peptide signaling network during myocardial development. We observed that the cardiac natriuretic peptides ANP and BNP and the guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2 are functionally redundant during early cardiovascular development. In addition, we demonstrate that low levels of the natriuretic peptides preferentially activate Npr3, a receptor with Gi activator sequences, and increase cardiomyocyte proliferation through inhibition of adenylate cyclase. Conversely, high concentrations of natriuretic peptides reduce cardiomyocyte proliferation through activation of the particulate guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2, and activation of protein kinase G. These data link the cardiac natriuretic peptides in a complex hierarchy modulating cardiomyocyte numbers during development through opposing effects on cardiomyocyte proliferation mediated through distinct cyclic nucleotide signaling pathways. C1 [Becker, Jason R.; Chatterjee, Sneha; Robinson, Tamara Y.; Galindo, Cristi L.; Zhong, Lin; Lim, Chee Chew] Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Nashville, TN 37235 USA. [Bennett, Jeffrey S.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37235 USA. [Panakova, Daniela; Coy, Shannon M.; Kelly, Amy E.; MacRae, Calum A.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Panakova, Daniela; Coy, Shannon M.; Kelly, Amy E.; MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02215 USA. [Shin, Jordan T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Shin, Jordan T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Roden, Dan M.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37235 USA. [Roden, Dan M.] Vanderbilt Univ, Dept Pharmacol, Sch Med, Nashville, TN 37235 USA. RP Becker, JR (reprint author), Vanderbilt Univ, Sch Med, Div Cardiovasc Med, 221 Kirkland Hall, Nashville, TN 37235 USA. EM jason.becker@vanderbilt.edu FU National Institutes of Health (NIH) [R01HL109264, T32HL007208, K08HL116803, T32GM07347]; Vanderbilt Physician Scientist Development Program FX This work was supported by grants from the National Institutes of Health (NIH) [R01HL109264 to J.R.B. and C. A. M.; T32HL007208 to J.R.B.; K08HL116803 to J.R.B.; T32GM07347 to J.S.B.]; and the Vanderbilt Physician Scientist Development Program (J.R.B.). Deposited in PMC for release after 12 months. NR 35 TC 12 Z9 12 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD JAN 15 PY 2014 VL 141 IS 2 BP 335 EP 345 DI 10.1242/dev.100370 PG 11 WC Developmental Biology SC Developmental Biology GA 282JI UT WOS:000329166700011 PM 24353062 ER PT J AU Hooper, DC Hirsch, MS AF Hooper, David C. Hirsch, Martin S. TI Novel Clostridium botulinum Toxin and Dual Use Research of Concern Issues SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE Clostridium botulinum; DURC ID H5N1 C1 [Hooper, David C.; Hirsch, Martin S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM dhooper@partners.org NR 2 TC 7 Z9 8 U1 1 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2014 VL 209 IS 2 BP 167 EP 167 DI 10.1093/infdis/jit528 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 282GA UT WOS:000329157200001 PM 24106293 ER PT J AU Boas, DA Elwell, CE Ferrari, M Taga, G AF Boas, David A. Elwell, Clare E. Ferrari, Marco Taga, Gentaro TI Twenty years of functional near-infrared spectroscopy: introduction for the special issue SO NEUROIMAGE LA English DT Editorial Material DE fNIRS; Functional near-infrared spectroscopy; Optical imaging; Brain imaging; Cognitive neuroscience; Neuroscience; Neuro-development; Hemoglobin; Neurovascular coupling; Brain function ID BRAIN AB Papers from four different groups were published in 1993 demonstrating the ability of functional near infrared spectroscopy (fNIRS) to non-invasively measure hemoglobin concentration responses to brain function in humans. This special issue commemorates the first 20 years of fNIRS research. The 9 reviews and 49 contributed papers provide a comprehensive survey of the exciting advances driving the field forward and of the myriad of applications that will benefit from fNIRS. (C) 2013 Elsevier Inc. All rights reserved. C1 [Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Elwell, Clare E.] UCL, Dept Med Phys & Bioengn, London WC1E 6BT, England. [Ferrari, Marco] Univ Laquila, Dept Life Hlth & Environm Sci, Laquila, Italy. [Taga, Gentaro] Univ Tokyo, Grad Sch Educ, Tokyo 1130033, Japan. RP Boas, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. FU NCRR NIH HHS [P41 RR014075] NR 69 TC 61 Z9 64 U1 5 U2 47 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2014 VL 85 SI SI BP 1 EP 5 DI 10.1016/j.neuroimage.2013.11.033 PN 1 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DQ UT WOS:000328869700001 PM 24321364 ER PT J AU Gagnon, L Yuecel, MA Boas, DA Cooper, RJ AF Gagnon, Louis Yuecel, Meryem A. Boas, David A. Cooper, Robert J. TI Further improvement in reducing superficial contamination in NIRS using double short separation measurements SO NEUROIMAGE LA English DT Article DE Near-Infrared Spectroscopy; Systemic interference; Short optode separations; Kalman filtering; State-space analysis ID NEAR-INFRARED SPECTROSCOPY; BRAIN ACTIVATION; ADULT HUMANS; RESPONSES; MODEL; FMRI; HEMODYNAMICS; OXYGENATION; ACCURACY; TASK AB Near-Infrared Spectroscopy (NIRS) allows the recovery of the evoked hemodynamic response to brain activation. In adult human populations, the NIRS signal is strongly contaminated by systemic interference occurring in the superficial layers of the head. An approach to overcome this difficulty is to use additional NIRS measurements with short optode separations to measure the systemic hemodynamic fluctuations occurring in the superficial layers. These measurements can then be used as regressors in the post-experiment analysis to remove the systemic contamination and isolate the brain signal. In our previous work, we showed that the systemic interference measured in NIRS is heterogeneous across the surface of the scalp. As a consequence, the short separation measurement used in the regression procedure must be located close to the standard NIRS channel from which the evoked hemodynamic response of the brain is to be recovered. Here, we demonstrate that using two short separation measurements, one at the source optode and one at the detector optode, further increases the performance of the short separation regression method compared to using a single short separation measurement. While a single short separation channel produces an average reduction in noise of 33% for HbO, using a short separation channel at both source and detector reduces noise by 59% compared to the standard method using a general linear model (GLM) without short separation. For HbR, noise reduction of 3% is achieved using a single short separation and this number goes to 47% when two short separations are used. Our work emphasizes the importance of integrating short separation measurements both at the source and at the detector optode of the standard channels from which the hemodynamic response is to be recovered. While the implementation of short separation sources presents some difficulties experimentally, the improvement in noise reduction is significant enough to justify the practical challenges. (C) 2013 Elsevier Inc. All rights reserved. C1 [Gagnon, Louis; Yuecel, Meryem A.; Boas, David A.; Cooper, Robert J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Gagnon, Louis; Boas, David A.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. [Cooper, Robert J.] UCL, Dept Med Phys & Bioengn, London, England. RP Gagnon, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. EM Igagnon@nmr.mgh.harvard.edu OI Cooper, Robert/0000-0001-6696-8020 FU NIH [P41-RR14075, R01-EB006385, R01-EB000790, R90-DA023427]; Advanced Multimodal Neurolmaging Training Program at MIT FX This work was supported by NIH grants P41-RR14075, R01-EB006385, R01-EB000790 and R90-DA023427. L Gagnon was supported by the Advanced Multimodal Neurolmaging Training Program at MIT. NR 35 TC 44 Z9 46 U1 3 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2014 VL 85 SI SI BP 127 EP 135 DI 10.1016/j.neuroimage.2013.01.073 PN 1 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DQ UT WOS:000328869700010 PM 23403181 ER PT J AU Strangman, GE Zhang, Q Li, Z AF Strangman, Gary E. Zhang, Quan Li, Zhi TI Scalp and skull influence on near infrared photon propagation in the Colin27 brain template SO NEUROIMAGE LA English DT Article DE Near-infrared spectroscopy; NIRS; Monte Carlo simulation; Scalp thickness; Skull thickness ID ADULT HEAD MODEL; LIGHT-PROPAGATION; SUPERFICIAL TISSUE; SPECTROSCOPY; THICKNESS; SCATTERING; SENSITIVITY; INTERFERENCE; OXYGENATION; PARAMETERS AB Near-infrared neuromonitoring (NIN) is based on near-infrared spectroscopy (NIRS) measurements performed through the intact scalp and skull. Despite the important effects of overlying tissue layers on the measurement of brain hemodynamics, the influence of scalp and skull on NIN sensitivity are not well characterized. Using 3555 Monte Carlo simulations, we estimated the sensitivity of individual continuous-wave NIRS measurements to brain activity over the entire adult human head by introducing a small absorption perturbation to brain gray matter and quantifying the influence of scalp and skull thickness on this sensitivity. After segmenting the Colin27 template into five tissue types (scalp, skull, cerebrospinal fluid, gray matter and white matter), the average scalp thickness was 6.9 +/- 3.6 mm (range: 3.6-11.2 mm), while the average skull thickness was 6.0 +/- 1.9 mm (range: 2.5-10.5 mm). Mean NIN sensitivity - defined as the partial path length through gray matter divided by the total photon path length - ranged from 0.06 (i.e., 6% of total path length) at a 20 mm source-detector separation, to over 0.19 at 50 mm separations. NIN sensitivity varied substantially around the head, with occipital pole exhibiting the highest NIRS sensitivity to gray matter, whereas inferior frontal regions had the lowest sensitivity. Increased scalp and skull thickness were strongly associated with decreased sensitivity to brain tissue. Scalp thickness always exhibited a slightly larger effect on sensitivity than skull thickness, but the effect of both varied with SD separation. We quantitatively characterize sensitivity around the head as well as the effects of scalp and skull, which can be used to interpret NIN brain activation studies as well as guide the design, development and optimization of NIRS devices and sensors. (C) 2013 Elsevier Inc. All rights reserved. C1 [Strangman, Gary E.; Zhang, Quan; Li, Zhi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA. RP Strangman, GE (reprint author), Neural Syst Grp, 149 13th St,Psychiat Rm 2651, Charlestown, MA 02129 USA. EM strang@nmr.mgh.harvard.edu FU National Space Biomedical Research Institute through NASA [NCC 9-58] FX This work was supported by the National Space Biomedical Research Institute through NASA NCC 9-58. NR 46 TC 29 Z9 29 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2014 VL 85 SI SI BP 136 EP 149 DI 10.1016/j.neuroimage.2013.04.090 PN 1 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DQ UT WOS:000328869700011 PM 23660029 ER PT J AU Brigadoi, S Ceccherini, L Cutini, S Scarpa, F Scatturin, P Selb, J Gagnon, L Boas, DA Cooper, RJ AF Brigadoi, Sabrina Ceccherini, Lisa Cutini, Simone Scarpa, Fabio Scatturin, Pietro Selb, Juliette Gagnon, Louis Boas, David A. Cooper, Robert J. TI Motion artifacts in functional near-infrared spectroscopy: A comparison of motion correction techniques applied to real cognitive data SO NEUROIMAGE LA English DT Article DE Functional near-infrared spectroscopy; fNIRS; Motion artifact; Hemodynamic response; Motion correction ID NIRS; ACTIVATION; INFANTS; OXYGENATION; STIMULI; STROKE; TISSUE; FNIRS; BRAIN AB Motion artifacts are a significant source of noise in many functional near-infrared spectroscopy (fNIRS) experiments. Despite this, there is no well-established method for their removal. Instead, functional trials of fNIRS data containing a motion artifact are often rejected completely. However, in most experimental circumstances the number of trials is limited, and multiple motion artifacts are common, particularly in challenging populations. Many methods have been proposed recently to correct for motion artifacts, including principle component analysis, spline interpolation, Kalman filtering, wavelet filtering and correlation-based signal improvement. The performance of different techniques has been often compared in simulations, but only rarely has it been assessed on real functional data. Here, we compare the performance of these motion correction techniques on real functional data acquired during a cognitive task, which required the participant to speak aloud, leading to a low-frequency, low-amplitude motion artifact that is correlated with the hemodynamic response. To compare the efficacy of these methods, objective metrics related to the physiology of the hemodynamic response have been derived. Our results show that it is always better to correct for motion artifacts than reject trials, and that wavelet filtering is the most effective approach to correcting this type of artifact, reducing the area under the curve where the artifact is present in 93% of the cases. Our results therefore support previous studies that have shown wavelet filtering to be the most promising and powerful technique for the correction of motion artifacts in fNIRS data. The analyses performed here can serve as a guide for others to objectively test the impact of different motion correction algorithms and therefore select the most appropriate for the analysis of their own fNIRS experiment. (C) 2013 Elsevier Inc. All rights reserved. C1 [Brigadoi, Sabrina; Ceccherini, Lisa; Scarpa, Fabio; Scatturin, Pietro] Univ Padua, Dept Dev Psychol, I-35100 Padua, Italy. [Cutini, Simone] Univ Padua, Dept Gen Psychol, I-35100 Padua, Italy. [Selb, Juliette; Gagnon, Louis; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA. [Cooper, Robert J.] UCL, Dept Med Phys & Bioeng, Biomed Opt Res Lab, London WC1E 6BT, England. RP Brigadoi, S (reprint author), Univ Padua, Dept Dev Psychol DPSS, Via Venezia 8, I-35131 Padua, Italy. EM sabrina.brigadoi@studenti.unipd.it RI Scarpa, Fabio/I-7864-2014; OI Scarpa, Fabio/0000-0002-8093-9047; Cooper, Robert/0000-0001-6696-8020; Brigadoi, Sabrina/0000-0003-3032-7381 FU NIH [P41-RR14075] FX This work is supported by NIH grant P41-RR14075 to David A. Boas. NR 33 TC 47 Z9 50 U1 7 U2 40 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2014 VL 85 SI SI BP 181 EP 191 DI 10.1016/j.neuroimage.2013.04.082 PN 1 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DQ UT WOS:000328869700014 PM 23639260 ER PT J AU Yucel, MA Selb, J Boas, DA Cash, SS Cooper, RJ AF Yuecel, Meryem A. Selb, Juliette Boas, David A. Cash, Sydney S. Cooper, Robert J. TI Reducing motion artifacts for long-term clinical NIRS monitoring using collodion-fixed prism-based optical fibers SO NEUROIMAGE LA English DT Article DE Near-infrared spectroscopy; Motion artifact; Epilepsy ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL BLOOD; SIMULTANEOUS EEG; BRAIN; OXYGENATION; TIME; FLOW; STIMULATION; TOMOGRAPHY; DIAGNOSIS AB As the applications of near-infrared spectroscopy (NIRS) continue to broaden and long-term clinical monitoring becomes more common, minimizing signal artifacts due to patient movement becomes more pressing. This is particularly true in applications where clinically and physiologically interesting events are intrinsically linked to patient movement, as is the case in the study of epileptic seizures. In this study, we apply an approach common in the application of EEG electrodes to the application of specialized NIRS optical fibers. The method provides improved optode-scalp coupling through the use of miniaturized optical fiber tips fixed to the scalp using collodion, a clinical adhesive. We investigate and quantify the performance of this new method in minimizing motion artifacts in healthy subjects, and apply the technique to allow continuous NIRS monitoring throughout epileptic seizures in two epileptic in-patients. Using collodion-fixed fibers reduces the percent signal change of motion artifacts by 90% and increases the SNR by 6 and 3 fold at 690 and 830 nm wavelengths respectively when compared to a standard Velcro-based array of optical fibers. The SNR has also increased by 2 fold during rest conditions without motion with the new probe design because of better light coupling between the fiber and scalp. The change in both HbO and HbR during motion artifacts is found to be statistically lower for the collodion-fixed fiber probe. The collodion-fixed optical fiber approach has also allowed us to obtain good quality NIRS recording of three epileptic seizures in two patients despite excessive motion in each case. (C) 2013 Elsevier Inc. All rights reserved. C1 [Yuecel, Meryem A.; Selb, Juliette; Boas, David A.; Cooper, Robert J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MIT Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Yuecel, Meryem A.; Selb, Juliette; Boas, David A.; Cooper, Robert J.] Harvard Univ, Sch Med, Charlestown, MA USA. [Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cooper, Robert J.] UCL, Dept Med Phys & Bioengn, London, England. RP Yuecel, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MIT Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM mayucel@nmr.mgh.harvard.edu OI Cooper, Robert/0000-0001-6696-8020 FU NIH [P41-RR14075, R01-EB006385, R90-DA023427] FX This work was supported by NIH grants P41-RR14075, R01-EB006385 and R90-DA023427. We would like to thank Andres Salom, Kara Houghton and Kristy Nordstrom at the Epilepsy Monitoring Unit of Massachusetts General Hospital and Sabrina Brigadoi at Martinos Center for Biomedical Imaging for all their help. NR 47 TC 15 Z9 15 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2014 VL 85 SI SI BP 192 EP 201 DI 10.1016/j.neuroimage.2013.06.054 PN 1 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DQ UT WOS:000328869700015 PM 23796546 ER PT J AU Roche-Labarbe, N Fenoglio, A Radhakrishnan, H Kocienski-Filip, M Carp, SA Dubb, J Boas, DA Grant, PE Franceschini, MA AF Roche-Labarbe, Nadege Fenoglio, Angela Radhakrishnan, Harsha Kocienski-Filip, Marcia Carp, Stefan A. Dubb, Jay Boas, David A. Grant, P. Ellen Franceschini, Maria Angela TI Somatosensory evoked changes in cerebral oxygen consumption measured non-invasively in premature neonates SO NEUROIMAGE LA English DT Article DE Oxygen metabolism; Functional activation; Premature neonates; Somatosensory cortex; Near infrared spectroscopy; Diffusion correlation spectroscopy ID NEAR-INFRARED SPECTROSCOPY; RAT FOREPAW STIMULATION; MEAN TRANSIT-TIME; BLOOD-FLOW; FUNCTIONAL ACTIVATION; HEMODYNAMIC-RESPONSES; OXIDATIVE-METABOLISM; NEWBORN-INFANTS; PRETERM INFANTS; DYNAMIC CHANGES AB The hemodynamic functional response is used as a reliable marker of neuronal activity in countless studies of brain function and cognition. In newborns and infants, however, conflicting results have appeared in the literature concerning the typical response, and there is little information on brain metabolism and functional activation. Measurement of all hemodynamic components and oxygen metabolism is critical for understanding neurovascular coupling in the developing brain. To this end, we combined multiple near infrared spectroscopy techniques to measure oxy- and deoxy-hemoglobin concentrations, cerebral blood volume (CBV), and relative cerebral blood flow (CBF) in the somatosensoty cortex of 6 preterm neonates during passive tactile stimulation of the hand. By combining these measures we estimated relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO(2)). CBF starts increasing immediately after stimulus onset, and returns to baseline before blood volume. This is consistent with the model of pre-capillary arteriole active dilation driving the CBF response, with a subsequent CBV increase influenced by capillaries and veins dilating passively to accommodate the extra blood. rCMRO(2) estimated using the steady-state formulation shows a biphasic pattern: an increase immediately after stimulus onset, followed by a post-stimulus undershoot due to blood flow returning faster to baseline than oxygenation. However, assuming a longer mean transit time from the arterial to the venous compartment, due to the immature vascular system of premature infants, reduces the post-stimulus undershoot and increases the flow/consumption ratio to values closer to adult values reported in the literature. We are the first to report changes in local rCBF and rCMRO(2) during functional activation in preterm infants. The ability to measure these variables in addition to hemoglobin concentration changes is critical for understanding neurovascular coupling in the developing brain, and for using this coupling as a reliable functional imaging marker in neonates. (C) 2013 Elsevier Inc. All rights reserved. C1 [Roche-Labarbe, Nadege; Radhakrishnan, Harsha; Carp, Stefan A.; Dubb, Jay; Boas, David A.; Franceschini, Maria Angela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Roche-Labarbe, Nadege] Univ Caen Basse Normandie, Lab Psychol Act Langagieres & Motrices, Caen, France. [Fenoglio, Angela; Grant, P. Ellen] Childrens Hosp Boston, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. [Kocienski-Filip, Marcia; Grant, P. Ellen] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Roche-Labarbe, N (reprint author), Univ Caen, Lab PALM, MRSH, SH018, Campus 1, F-14000 Caen, France. EM nadege.roche@unicaen.fr RI Roche-Labarbe, Nadege/N-9101-2015 OI Roche-Labarbe, Nadege/0000-0002-5010-0400 FU NIH [R01 HD042908, P41-RR14075, R21-HD058725]; National Center for Research Resources [UL1RR025758] FX This work was supported by NIH grants R01 HD042908, P41-RR14075 and R21-HD058725 and by the Clinical Translational Science Award UL1RR025758 to Harvard University and Brigham and Women's Hospital from the National Center for Research Resources. 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. David A. Boas is an inventor of a technology licensed to TechEn, used in the CWNIRS system in this study. DAB's interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. NR 59 TC 22 Z9 22 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2014 VL 85 SI SI BP 279 EP 286 DI 10.1016/j.neuroimage.2013.01.035 PN 1 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DQ UT WOS:000328869700023 PM 23370052 ER PT J AU Wilcox, T Hirshkowitz, A Hawkins, L Boas, DA AF Wilcox, Teresa Hirshkowitz, Amy Hawkins, Laura Boas, David A. TI The effect of color priming on infant brain and behavior SO NEUROIMAGE LA English DT Article DE Object processing; Color priming; Temporal cortex; Infants; Near-infrared spectroscopy ID OBJECT INDIVIDUATION; SPATIOTEMPORAL INFORMATION; ACQUIRED DISTINCTIVENESS; TEMPORAL CORTEX; EQUIVALENCE; EXPLORATION; PERCEPTION; ACTIVATION; CATEGORIES; PATTERN AB Behavioral studies have identified select experiences that can prime infants to attend to color information as the basis for individuating objects prior to the time they do so spontaneously. For example, viewing pretest events in which the color of an object predicts the function in which it will engage leads 9-month-olds (who typically do not attend to color differences) to demonstrate increased sensitivity to color information in a subsequent individuation task (Wilcox and Chapa, 2004). In contrast, viewing pretest events in which the color of an object predicts distinct object motions, but the motions are not functionally relevant, does not produce color priming. The purpose of the present research was to identify the cortical underpinnings of these behavioral effects. Infants aged 8 and 9 months viewed function or motion pretest events and then their capacity to individuate-by-color was assessed in an object individuation task. Behavioral and neuroimaging data were collected. Two main findings emerged. First, as predicted, the infants who viewed the function but not the motion pretest events showed prolonged looking to the test event, a behavioral indicator of object individuation. In addition, they evidenced increased activation in anterior temporal cortex, thought to be a cortical signature of object individuation. A second and unexpected finding was that viewing either type of pretest events led to increased activation in the posterior temporal cortex, as compared to infants who did not see pretest events, revealing that prior exposure to the motion pretest events does influence infants' processing of the test event, even though it is not evident in the behavioral results. The cognitive processes involved, and the cortical structures that mediate these processes, are discussed. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wilcox, Teresa; Hirshkowitz, Amy; Hawkins, Laura] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Wilcox, T (reprint author), Texas A&M Univ, Dept Psychol, 4235 TAMU, College Stn, TX 77843 USA. EM twilcox@tamu.edu FU [BCS-0642996]; [R01-HD057999]; [P41-RR14075] FX We thank Tracy Smith Brower, Jennifer Armstrong Haslup, Mariam Massoud, Jennifer Moore Norvell, Jessica Stubbs, Kayla Boone Upshaw, Lesley Wheeler, and the staff of the Infant Cognition Lab at Texas A&M University for the help with data collection and management and the infants and parents who so graciously participated in the research. This work was supported by grants BCS-0642996 and R01-HD057999 to TW and grant P41-RR14075 to DAB. DAB is an inventor on a technology licensed to TechEn, a company whose medical pursuits focus on noninvasive, optical brain monitoring. DAB's interests were reviewed and managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. NR 43 TC 12 Z9 12 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2014 VL 85 SI SI BP 302 EP 313 DI 10.1016/j.neuroimage.2013.08.045 PN 1 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DQ UT WOS:000328869700026 PM 24007805 ER PT J AU Buss, AT Fox, N Boas, DA Spencer, JP AF Buss, Aaron T. Fox, Nicholas Boas, David A. Spencer, John P. TI Probing the early development of visual working memory capacity with functional near-infrared spectroscopy SO NEUROIMAGE LA English DT Article DE Visual working memory; Functional neuroimaging; Development; Working memory capacity; Near-infrared spectroscopy ID SHORT-TERM-MEMORY; POSTERIOR PARIETAL CORTEX; BRAIN ACTIVITY; CHILDREN; ACTIVATION; CHILDHOOD; SCHIZOPHRENIA; INTELLIGENCE; CONJUNCTIONS; MAINTENANCE AB Visual working memory (VWM) is a core cognitive system with a highly limited capacity. The present study is the first to examine VWM capacity limits in early development using functional neuroimaging. We recorded optical neuroimaging data while 3- and 4-year-olds completed a change detection task where they detected changes in the shapes of objects after a brief delay. Near-infrared sources and detectors were placed over the following 10-20 positions: F3 and F5 in left frontal cortex, F4 and F6 in right frontal cortex, P3 and P5 in left parietal cortex, and P4 and P6 in right parietal cortex. The first question was whether we would see robust task-specific activation of the frontal-parietal network identified in the adult fMRI literature. This was indeed the case: three left frontal channels and 11 of 12 parietal channels showed a statistically robust difference between the concentration of oxygenated and deoxygenated hemoglobin following the presentation of the sample array. Moreover, four channels in the left hemisphere near P3, P5, and F5 showed a robust increase as the working memory load increased from 1 to 3 items. Notably, the hemodynamic response did not asymptote at 1-2 items as expected from previous fMRI studies with adults. Finally, 4-year-olds showed a more robust parietal response relative to 3-year-olds, and an increasing sensitivity to the memory load manipulation. These results demonstrate that fNIRS is an effective tool to study the neural processes that underlie the early development of VWM capacity. (C) 2013 Elsevier Inc. All rights reserved. C1 [Buss, Aaron T.; Fox, Nicholas; Spencer, John P.] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Buss, Aaron T.; Fox, Nicholas; Spencer, John P.] Univ Iowa, Delta Ctr, Iowa City, IA 52242 USA. [Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Spencer, JP (reprint author), Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. EM john-spencer@uiowa.edu FU Office of the Executive Vice President and Provost; Office of the Vice President for Research; College of Liberal Arts and Sciences; Department of Psychology; Department of Communication Sciences and Disorders at the University of Iowa; NIH [P41-14075] FX This is the first study reporting data collected using the Delta Center's CHILDS (CHild Imaging Laboratory in Development Science) facility. Thus, we would like to thank the Office of the Executive Vice President and Provost, the Office of the Vice President for Research, the College of Liberal Arts and Sciences, the Department of Psychology, and the Department of Communication Sciences and Disorders at the University of Iowa for their generous support. In addition, we thank the CHILDS facility Director Larissa Samuelson for her immense assistance, Qianqian Fang for generating the digitized image of the head used herein, Jay Dubb for assistance with Homer2, and Vincent Magnotta for consultation on the fNIRS analyses. Sammy Perone, Sobana Wijeakumar, and Kevin Bohache provided helpful comments on earlier versions of this manuscript. Finally, we thank the parents and children who participated in the study, and the undergraduate research assistants in the SPAM lab. DAB acknowledges support from NIH P41-14075. Note that DAB is an inventor on a technology licensed to TechEn, a company whose medical pursuits focus on noninvasive, optical brain monitoring. DAB's interests were reviewed and are managed by Massachusetts General Hospital and Partners Health Care in accordance with their conflict of interest policies. NR 60 TC 14 Z9 14 U1 4 U2 27 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2014 VL 85 SI SI BP 314 EP 325 DI 10.1016/j.neuroimage.2013.05.034 PN 1 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DQ UT WOS:000328869700027 PM 23707803 ER PT J AU Berger, AH Duke, F Imielinski, M Kaplan, N Wala, J Shi, GX Andres, DA Meyerson, M AF Berger, Alice H. Duke, Fujiko Imielinski, Marcin Kaplan, Nathan Wala, Jeremiah Shi, Geng-Xian Andres, Douglas A. Meyerson, Matthew TI Recurrent oncogenic mutations in the small GTPase RIT1 activate PI3K and MEK. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer CY JAN 06-09, 2014 CL San Diego, CA SP Amer Assoc Canc Res, IASLC C1 [Berger, Alice H.; Duke, Fujiko; Imielinski, Marcin; Wala, Jeremiah] Broad Inst, Cambridge, MA USA. [Kaplan, Nathan; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shi, Geng-Xian; Andres, Douglas A.] Univ Kentucky, Coll Med, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2014 VL 20 SU 2 MA PR02 DI 10.1158/1078-0432.14AACRIASLC-PR02 PG 1 WC Oncology SC Oncology GA CR5LV UT WOS:000361385000068 ER PT J AU Berger, AH Duke, F Imielinski, M Kaplan, N Wala, J Shi, GX Andres, DA Meyerson, M AF Berger, Alice H. Duke, Fujiko Imielinski, Marcin Kaplan, Nathan Wala, Jeremiah Shi, Geng-Xian Andres, Douglas A. Meyerson, Matthew TI Recurrent oncogenic mutations in the small GTPase RIT1 activate PI3K and MEK. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer CY JAN 06-09, 2014 CL San Diego, CA SP Amer Assoc Canc Res, IASLC C1 [Berger, Alice H.; Duke, Fujiko; Imielinski, Marcin; Wala, Jeremiah] Broad Inst, Cambridge, MA USA. [Kaplan, Nathan; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shi, Geng-Xian; Andres, Douglas A.] Univ Kentucky, Coll Med, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2014 VL 20 SU 2 MA A04 DI 10.1158/1078-0432.14AACRIASLC-A04 PG 1 WC Oncology SC Oncology GA CR5LV UT WOS:000361385000004 ER PT J AU Garon, EB Balmanoukian, A Hamid, O Hui, R Gandhi, L Leighl, N Gubens, M Goldman, JW Lubiniecki, GM Emancipator, K Dolled-Filhart, M Lunceford, J Gergich, K Rizvi, NA AF Garon, Edward B. Balmanoukian, Ani Hamid, Omid Hui, Rina Gandhi, Leena Leighl, Natasha Gubens, Matthew Goldman, Jonathan W. Lubiniecki, Gregory M. Emancipator, Kenneth Dolled-Filhart, Marisa Lunceford, Jared Gergich, Kevin Rizvi, Naiyer A. TI MK-3475 monotherapy for previously treated non-small cell lung cancer (NSCLC): Preliminary safety and clinical activity. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer CY JAN 06-09, 2014 CL San Diego, CA SP Amer Assoc Canc Res, IASLC C1 [Garon, Edward B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Balmanoukian, Ani; Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Hui, Rina] Crown Princess Mary Canc Ctr Westmead, Westmead, NSW, Australia. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Leighl, Natasha] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Gubens, Matthew] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goldman, Jonathan W.] Univ Calif Los Angeles, Los Angeles, CA USA. [Lubiniecki, Gregory M.; Gergich, Kevin] Merck & Co Inc, N Wales, PA USA. [Emancipator, Kenneth; Dolled-Filhart, Marisa; Lunceford, Jared] Merck & Co Inc, Rahway, NJ 07065 USA. [Rizvi, Naiyer A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. OI Gandhi, Leena/0000-0002-2398-9179 NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2014 VL 20 SU 2 MA A20 DI 10.1158/1078-0432.14AACRIASLC-A20 PG 2 WC Oncology SC Oncology GA CR5LV UT WOS:000361385000015 ER PT J AU Hammerman, PS AF Hammerman, Peter S. TI Squamous cell lung cancer 2014. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer CY JAN 06-09, 2014 CL San Diego, CA SP Amer Assoc Canc Res, IASLC C1 [Hammerman, Peter S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2014 VL 20 SU 2 MA IA39 DI 10.1158/1078-0432.14AACRIASLC-IA39 PG 1 WC Oncology SC Oncology GA CR5LV UT WOS:000361385000066 ER PT J AU Ostroff, R Mehan, MR Williams, S Brody, E Pass, H Rom, W Siegfried, J Muley, T Franklin, W Merrick, D van Bokhoven, A Wolf, H Feser, W Baron, AE Miller, Y AF Ostroff, Rachel Mehan, Michael R. Williams, Stephen Brody, Edward Pass, Harvey Rom, William Siegfried, Jill Muley, Thomas Franklin, Wilbur Merrick, Dan van Bokhoven, Adrie Wolf, Holly Feser, William Baron, Anna E. Miller, York TI Distinctive squamous cell carcinoma protein signatures. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer CY JAN 06-09, 2014 CL San Diego, CA SP Amer Assoc Canc Res, IASLC C1 [Ostroff, Rachel; Mehan, Michael R.; Williams, Stephen; Brody, Edward] SomaLogic, Boulder, CO USA. [Pass, Harvey; Rom, William] NYU, Langone Med & Canc Ctr, New York, NY USA. [Siegfried, Jill] Univ Minnesota, Minneapolis, MN USA. [Muley, Thomas] Univ Heidelberg Hosp, Heidelberg, Germany. [Franklin, Wilbur; van Bokhoven, Adrie; Wolf, Holly; Feser, William; Baron, Anna E.] Univ Colorado, Ctr Canc, Denver, CO USA. [Merrick, Dan; Miller, York] Univ Colorado, Ctr Canc, Denver, CO 80202 USA. [Merrick, Dan; Miller, York] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2014 VL 20 SU 2 MA PR04 DI 10.1158/1078-0432.14AACRIASLC-PR04 PG 1 WC Oncology SC Oncology GA CR5LV UT WOS:000361385000070 ER PT J AU Ullal, AV Peterson, V Agasti, SS Tuang, S Juric, D Castro, CM Weissleder, R AF Ullal, Adeeti V. Peterson, Vanessa Agasti, Sarit S. Tuang, Suan Juric, Dejan Castro, Cesar M. Weissleder, Ralph TI Cancer Cell Profiling by Barcoding Allows Multiplexed Protein Analysis in Fine-Needle Aspirates SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID NEXT-GENERATION; SINGLE CELLS; LUNG-CANCER; EXPRESSION; MUTATIONS; CYTOMETRY; DISEASES; THERAPY; GENE AB Immunohistochemistry-based clinical diagnoses require invasive core biopsies and use a limited number of protein stains to identify and classify cancers. We introduce a technology that allows analysis of hundreds of proteins from minimally invasive fine-needle aspirates (FNAs), which contain much smaller numbers of cells than core biopsies. The method capitalizes on DNA-barcoded antibody sensing, where barcodes can be photocleaved and digitally detected without any amplification steps. After extensive benchmarking in cell lines, this method showed high reproducibility and achieved single-cell sensitivity. We used this approach to profile similar to 90 proteins in cells from FNAs and subsequently map patient heterogeneity at the protein level. Additionally, we demonstrate how the method could be used as a clinical tool to identify pathway responses to molecularly targeted drugs and to predict drug response in patient samples. This technique combines specificity with ease of use to offer a new tool for understanding human cancers and designing future clinical trials. C1 [Ullal, Adeeti V.; Peterson, Vanessa; Agasti, Sarit S.; Tuang, Suan; Castro, Cesar M.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Juric, Dejan; Castro, Cesar M.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NSF fellowship; [U54 CA151884] FX This work was funded in part by U54 CA151884. A.V.U. was funded by an NSF fellowship and U54 CA151884. NR 26 TC 24 Z9 24 U1 1 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 15 PY 2014 VL 6 IS 219 AR 219ra9 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 292OY UT WOS:000329912800009 PM 24431113 ER PT J AU Choueiri, TK Je, YJ Cho, E AF Choueiri, Toni K. Je, Youjin Cho, Eunyoung TI Analgesic use and the risk of kidney cancer: A meta-analysis of epidemiologic studies SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE analgesics; aspirin; non-aspirin non-steroidal anti-inflammatory drugs; acetaminophen; kidney cancer ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RENAL-CELL CANCER; LONG-TERM USE; BLADDER-CANCER; BREAST-CANCER; UNITED-STATES; LARGE COHORT; ASPIRIN USE; ACETAMINOPHEN; POPULATION AB Analgesics are the most commonly used over-the-counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta-analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case-control or cohort studies published in English until June 2012 for three categories of analgesics: acetaminophen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random-effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin and five with other NSAIDs) that were performed in six countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non-aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR: 1.28; 95% CI: 1.15-1.44 and 1.25; 95% CI: 1.06-1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR: 1.10; 95% CI: 0.95-1.28), except for non-US studies (five studies, pooled RR: 1.17; 95% CI: 1.04-1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta-analysis to date, we found that acetaminophen and non-aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings. C1 [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Choueiri, Toni K.; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA. [Je, Youjin] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Cho, Eunyoung] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. RP Cho, E (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu FU National Institutes of Health; Kidney Cancer Association; Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Programs of Research Excellence (SPORE) [NIH P50CA101942, CA137764]; Trust Family Research Fund for Kidney Cancer at Dana-Farber Cancer Institute FX Grant sponsors: National Institutes of Health, Kidney Cancer Association, Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Programs of Research Excellence (SPORE); Grant number: NIH P50CA101942; CA137764; Grant sponsors: Trust Family Research Fund for Kidney Cancer at Dana-Farber Cancer Institute NR 43 TC 4 Z9 6 U1 4 U2 41 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JAN 15 PY 2014 VL 134 IS 2 BP 384 EP 396 DI 10.1002/ijc.28093 PG 13 WC Oncology SC Oncology GA 247VA UT WOS:000326649300065 PM 23400756 ER PT J AU Castiglioni, A Hettmer, S Lynes, MD Rao, TN Tchessalova, D Sinha, I Lee, BT Tseng, YH Wagers, AJ AF Castiglioni, Alessandra Hettmer, Simone Lynes, Matthew D. Rao, Tata Nageswara Tchessalova, Daria Sinha, Indranil Lee, Bernard T. Tseng, Yu-Hua Wagers, Amy J. TI Isolation of Progenitors that Exhibit Myogenic/Osteogenic Bipotency In Vitro by Fluorescence-Activated Cell Sorting from Human Fetal Muscle SO STEM CELL REPORTS LA English DT Article ID HUMAN SKELETAL-MUSCLE; HEMATOPOIETIC STEM-CELLS; SATELLITE CELLS; MYOGENIC PROGENITORS; SELF-RENEWAL; MOUSE; DIFFERENTIATION; PAX7; TRANSPLANTATION; REGENERATION AB Fluorescence-activated cell sorting (FACS) strategies to purify distinct cell types from the pool of fetal human myofiber-associated (hMFA) cells were developed. We demonstrate that cells expressing the satellite cell marker PAX7 are highly enriched within the subset of CD45(-)CD11b(-)GlyA(-)CD31(-)CD34(-)CD56(int)ITGA7(hi) hMFA cells. These CD45(-)CD11b(-)GlyA(-)CD31(-)CD34(-)CD56(int)ITGA7(hi) cells lack adipogenic capacity but exhibit robust, bipotent myogenic and osteogenic activity in vitro and engraft myofibers when transplanted into mouse muscle. In contrast, CD45(-)CD11b(-)GlyA(-)CD31(-)CD34(+) fetal hMFA cells represent stromal constituents of muscle that do not express PAX7, lack myogenic function, and exhibit adipogenic and osteogenic capacity in vitro. Adult muscle likewise contains PAX7(+) CD45(-)CD11b(-)GlyA(-)CD31(-)CD34(-)CD56(int)ITGA7(hi) hMFA cells with in vitro myogenic and osteogenic activity, although these cells are present at lower frequency in comparison to their fetal counterparts. The ability to directly isolate functionally distinct progenitor cells from human muscle will enable novel insights into muscle lineage specification and homeostasis. C1 [Castiglioni, Alessandra; Hettmer, Simone; Rao, Tata Nageswara; Tchessalova, Daria; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Castiglioni, Alessandra; Hettmer, Simone; Lynes, Matthew D.; Rao, Tata Nageswara; Tchessalova, Daria; Tseng, Yu-Hua; Wagers, Amy J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Castiglioni, Alessandra; Hettmer, Simone; Lynes, Matthew D.; Rao, Tata Nageswara; Tchessalova, Daria; Tseng, Yu-Hua; Wagers, Amy J.] Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. [Castiglioni, Alessandra] Univ Vita Salute San Raffaele, I-20132 Milan, Italy. [Hettmer, Simone] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hettmer, Simone] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Sinha, Indranil] Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. [Lee, Bernard T.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02215 USA. RP Wagers, AJ (reprint author), Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Cambridge, MA 02138 USA. EM amy_wagers@harvard.edu RI Lee, Bernard/K-1106-2016 OI Lee, Bernard/0000-0002-5533-3166 FU Boston Claude D. Pepper Center [NIH 5P30AG031679]; P.A.L.S. Bermuda/St. Baldrick's; Burroughs-Welcome Fund, Harvard Stem Cell Institute; Beckman Foundation; Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant [SU2C-AACR-IRG1111] FX We thank Perrin Larton and her staff at Advanced Bioscience Resources (ABR, Alameda, CA) as well as the staff at the National Development and Research Institutes (NDRI, Philadelphia, PA). We thank A. Wakabayashi, G. Buruzula, and J. LaVecchio at Joslin's HSCI/DRC Flow Cytometry Core (NIH P30DK036836), Katelyn Hughes at Joslin's DRC Genomics Core (NIH P30DK036836), the Biopolymers Facility Service at Harvard Medical School for BioAnalyzer evaluation of RNA, and C. Vernochet for assistance with adipogenic and osteogenic differentiation assays. This work was funded in part by a pilot grant from the Boston Claude D. Pepper Center (NIH 5P30AG031679 to S.H.) and grants from P.A.L.S. Bermuda/St. Baldrick's (to S.H.); by grants from the Burroughs-Welcome Fund, Harvard Stem Cell Institute, and Beckman Foundation; and by a Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant (SU2C-AACR-IRG1111) (to A.J.W.). A.C. conducted this study as partial fulfillment of her PhD in Molecular Medicine, Program in Preventive and Predictive Medicine, San Raffaele University, Milan, Italy. A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies. NR 40 TC 15 Z9 16 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD JAN 14 PY 2014 VL 2 IS 1 BP 92 EP 106 DI 10.1016/j.stemcr.2013.12.006 PG 15 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AI1XA UT WOS:000336647300010 PM 24678452 ER PT J AU Barocas, JA Brennan, MB Hull, SJ Stokes, S Fangman, JJ Westergaard, RP AF Barocas, Joshua A. Brennan, Meghan B. Hull, Shawnika J. Stokes, Scott Fangman, John J. Westergaard, Ryan P. TI Barriers and facilitators of hepatitis C screening among people who inject drugs: a multi-city, mixed-methods study SO HARM REDUCTION JOURNAL LA English DT Article DE Hepatitis C; Screening; Injection drug use; Stigma; Health care access ID VIRUS-INFECTION; UNITED-STATES; USERS; CARE; PERCEPTIONS; ANTIBODY; BEHAVIOR; IMPACT AB Background: People who inject drugs (PWID) are at high risk of contracting and transmitting and hepatitis C virus (HCV). While accurate screening tests and effective treatment are increasingly available, prior research indicates that many PWID are unaware of their HCV status. Methods: We examined characteristics associated with HCV screening among 553 PWID utilizing a free, multi-site syringe exchange program (SEP) in 7 cities throughout Wisconsin. All participants completed an 88-item, computerized survey assessing past experiences with HCV testing, HCV transmission risk behaviors, and drug use patterns. A subset of 362 clients responded to a series of open-ended questions eliciting their perceptions of barriers and facilitators to screening for HCV. Transcripts of these responses were analyzed qualitatively using thematic analysis. Results: Most respondents (88%) reported receiving a HCV test in the past, and most of these (74%) were tested during the preceding 12 months. Despite the availability of free HCV screening at the SEP, fewer than 20% of respondents had ever received a test at a syringe exchange site. Clients were more likely to receive HCV screening in the past year if they had a primary care provider, higher educational attainment, lived in a large metropolitan area, and a prior history of opioid overdose. Themes identified through qualitative analysis suggested important roles of access to medical care and prevention services, and nonjudgmental providers. Conclusions: Our results suggest that drug-injecting individuals who reside in non-urban settings, who have poor access to primary care, or who have less education may encounter significant barriers to routine HCV screening. Expanded access to primary health care and prevention services, especially in non-urban areas, could address an unmet need for individuals at high risk for HCV. C1 [Barocas, Joshua A.; Brennan, Meghan B.; Westergaard, Ryan P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 USA. [Brennan, Meghan B.] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Brennan, Meghan B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Hull, Shawnika J.] Univ Wisconsin, Sch Journalism & Mass Commun, Madison, WI 53706 USA. [Stokes, Scott; Fangman, John J.] AIDS Resource Ctr Wisconsin, Milwaukee, WI 53208 USA. [Fangman, John J.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Westergaard, Ryan P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA. RP Barocas, JA (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, 1685 Highland Ave,UWMFCB 5th Floor, Madison, WI 53705 USA. EM jbarocas@medicine.wisc.edu FU NCATS NIH HHS [UL1TR000427, UL1 TR000427]; NIDA NIH HHS [K23 DA032306, K23DA032306] NR 31 TC 14 Z9 14 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7517 J9 HARM REDUCT J JI Harm Reduct. J. PD JAN 14 PY 2014 VL 11 AR 1 DI 10.1186/1477-7517-11-1 PG 8 WC Substance Abuse SC Substance Abuse GA 295JZ UT WOS:000330113700001 PM 24422784 ER PT J AU Lyons, JL Coleman, ME Engstrom, JW Mateen, FJ AF Lyons, Jennifer L. Coleman, Mary E. Engstrom, John W. Mateen, Farrah J. TI International electives in neurology training A survey of US and Canadian program directors SO NEUROLOGY LA English DT Article ID GLOBAL HEALTH; MEDICAL-STUDENTS; RESIDENCY PROGRAMS; ISSUES NEUROLOGY; EDUCATION; OPPORTUNITIES; EXPERIENCE; SURGERY; RISKS AB Objective:To ascertain the current status of global health training and humanitarian relief opportunities in US and Canadian postgraduate neurology programs.Background:There is a growing interest among North American trainees to pursue medical electives in low- and middle-income countries. Such training opportunities provide many educational and humanitarian benefits but also pose several challenges related to organization, human resources, funding, and trainee and patient safety. The current support and engagement of neurology postgraduate training programs for trainees to pursue international rotations is unknown.Methods:A survey was distributed to all program directors in the United States and Canada (December 2012-February 2013) through the American Academy of Neurology to assess the training opportunities, institutional partnerships, and support available for international neurology electives.Results:Approximately half of responding programs (53%) allow residents to pursue global health-related electives, and 11% reported that at least 1 trainee participated in humanitarian relief during training (survey response rate 61%, 143/234 program directors). Canadian programs were more likely to allow residents to pursue international electives than US programs (10/11, 91% vs 65/129, 50%, p = 0.023). The number of trainees participating in international electives was low: 0%-9% of residents (55% of programs) and 10%-19% of residents (21% of programs). Lack of funding was the most commonly cited reason for residents not participating in global health electives. If funding was available, 93% of program directors stated there would be time for residents to participate. Most program directors (75%) were interested in further information on global health electives.Conclusions:In spite of high perceived interest, only half of US neurology training programs include international electives, mostly due to a reported lack of funding. By contrast, the majority of Canadian programs that responded allow international electives, likely due to clearer guidelines from the Royal College of Physicians and Surgeons of Canada compared to the Accreditation Council of Graduate Medical Education. However, the number of both Canadian and US neurology trainees venturing abroad remains a minority. Most program directors are interested in learning more information related to global health electives for neurology residents. C1 [Lyons, Jennifer L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Coleman, Mary E.] Amer Acad Neurol, Minneapolis, MN USA. [Engstrom, John W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM fmateen@partners.org FU NIMH NIH HHS [R25 MH080663] NR 30 TC 9 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 14 PY 2014 VL 82 IS 2 BP 119 EP 125 DI 10.1212/WNL.0000000000000019 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 292RO UT WOS:000329920100009 PM 24319037 ER PT J AU Wang, HF Zang, CZ Taing, L Arnett, KL Wong, YJ Pear, WS Blacklow, SC Liu, XS Aster, JC AF Wang, Hongfang Zang, Chongzhi Taing, Len Arnett, Kelly L. Wong, Yinling Joey Pear, Warren S. Blacklow, Stephen C. Liu, X. Shirley Aster, Jon C. TI NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene regulation; Notch signaling ID SUPER-ENHANCERS; LYMPHOBLASTIC-LEUKEMIA; TRANSCRIPTION FACTORS; CELL IDENTITY; ACTIVATION; DOMAINS; MUTATIONS; DISEASE; BINDING; GENOME AB The main oncogenic driver in T-lymphoblastic leukemia is NOTCH1, which activates genes by forming chromatin-associated Notch transcription complexes. Gamma-secretase-inhibitor treatment prevents NOTCH1 nuclear localization, but most genes with NOTCH1-binding sites are insensitive to gamma-secretase inhibitors. Here, we demonstrate that fewer than 10% of NOTCH1-binding sites show dynamic changes in NOTCH1 occupancy when T-lymphoblastic leukemia cells are toggled between the Notch-on and -off states with gamma-secretase inhibiters. Dynamic NOTCH1 sites are functional, being highly associated with Notch target genes, are located mainly in distal enhancers, and frequently overlap with RUNX1 binding. In line with the latter association, we show that expression of IL7R, a gene with key roles in normal T-cell development and in T-lymphoblastic leukemia, is coordinately regulated by Runx factors and dynamic NOTCH1 binding to distal enhancers. Like IL7R, most Notch target genes and associated dynamic NOTCH1-binding sites cooccupy chromatin domains defined by constitutive binding of CCCTC binding factor, which appears to restrict the regulatory potential of dynamic NOTCH1 sites. More remarkably, the majority of dynamic NOTCH1 sites lie in superenhancers, distal elements with exceptionally broad and high levels of H3K27ac. Changes in Notch occupancy produces dynamic alterations in H3K27ac levels across the entire breadth of superenhancers and in the promoters of Notch target genes. These findings link regulation of superenhancer function to NOTCH1, a master regulatory factor and potent oncoprotein in the context of immature T cells, and delineate a generally applicable roadmap for identifying functional Notch sites in cellular genomes. C1 [Wang, Hongfang; Wong, Yinling Joey; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Zang, Chongzhi; Taing, Len; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Arnett, Kelly L.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Pear, Warren S.] Univ Penn, Perelman Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. RP Aster, JC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM xsliu.dfci@gmail.com; jaster@rics.bwh.harvard.edu RI Zang, Chongzhi/D-1445-2011; OI Arnett, Kelly/0000-0001-5117-3647 FU National Institutes of Health (NIH) [T32HL007627]; Leukemia and Lymphoma Society; NIH [P01 CA119070, R01 GM099409] FX H.W. is supported by a National Institutes of Health (NIH) training grant (T32HL007627). C.Z. is supported by a fellowship from the Leukemia and Lymphoma Society. W.S.P., S.C.B., X.S.L., and J.C.A. are supported by NIH Grant P01 CA119070, and X.S.L. is supported by NIH Grant R01 GM099409. NR 36 TC 46 Z9 47 U1 4 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 14 PY 2014 VL 111 IS 2 BP 705 EP 710 DI 10.1073/pnas.1315023111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 288LW UT WOS:000329614500040 PM 24374627 ER PT J AU McCabe, JM Kennedy, KF Eisenhauer, AC Waldman, HM Mort, EA Pomerantsev, E Resnic, FS Yeh, RW AF McCabe, James M. Kennedy, Kevin F. Eisenhauer, Andrew C. Waldman, Howard M. Mort, Elizabeth A. Pomerantsev, Eugene Resnic, Frederic S. Yeh, Robert W. TI Reporting Trends and Outcomes in ST-Segment-Elevation Myocardial Infarction National Hospital Quality Assessment Programs SO CIRCULATION LA English DT Article DE Centers for Medicare & Medicaid Services (U; S; ); Medicare; myocardial infarction; percutaneous coronary intervention; public policy; quality indicators; health care ID TO-BALLOON TIME; PERCUTANEOUS CORONARY INTERVENTION; CARDIOVASCULAR DATA REGISTRY; ASSOCIATION TASK-FORCE; DOOR-OUT TIME; AMERICAN-COLLEGE; MORTALITY; ANGIOPLASTY; PERFORMANCE; MANAGEMENT AB Background For patients who undergo primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction, the door-to-balloon time is an important performance measure reported to the Centers for Medicare & Medicaid Services (CMS) and tied to hospital quality assessment and reimbursement. We sought to assess the use and impact of exclusion criteria associated with the CMS measure of door-to-balloon time in primary PCI. Methods and Results All primary PCI-eligible patients at 3 Massachusetts hospitals (Brigham and Women's, Massachusetts General, and North Shore Medical Center) were evaluated for CMS reporting status. Rates of CMS reporting exclusion were the primary end points of interest. Key secondary end points were between-group differences in patient characteristics, door-to-balloon times, and 1-year mortality rates. From 2005 to 2011, 26% (408) of the 1548 primary PCI cases were excluded from CMS reporting. This percentage increased over the study period from 13.9% in 2005 to 36.7% in the first 3 quarters of 2011 (P<0.001). The most frequent cause of exclusion was for a diagnostic dilemma such as a nondiagnostic initial ECG, accounting for 31.2% of excluded patients. Although 95% of CMS-reported cases met door-to-balloon time goals in 2011, this was true of only 61% of CMS-excluded cases and consequently 82.6% of all primary PCI cases performed that year. The 1-year mortality for CMS-excluded patients was double that of CMS-included patients (13.5% versus 6.6%; P<0.001). Conclusions More than a quarter of patients who underwent primary PCI were excluded from hospital quality reports collected by CMS, and this percentage has grown substantially over time. These findings may have significant implications for our understanding of process improvement in primary PCI and mechanisms for reimbursement through Medicare. C1 [McCabe, James M.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Kennedy, Kevin F.] St Lukes Mid Amer Heart Inst, Div Cardiol, Kansas City, MO USA. [Eisenhauer, Andrew C.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Waldman, Howard M.] North Shore Med Ctr, Div Cardiol, Salem, MA USA. [Mort, Elizabeth A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pomerantsev, Eugene; Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Resnic, Frederic S.] Tufts Med Sch, Lahey Clin, Div Cardiovasc Med, Burlington, MA USA. RP McCabe, JM (reprint author), Univ Washington, Div Cardiol, 1959 NE Pacific St,Box 356422, Seattle, WA 98195 USA. EM mccabe@aya.yale.edu FU Partners Long-term Outcomes Registry; American Heart Association FX Funding for this project was provided via the Partners Long-term Outcomes Registry and a grant from the American Heart Association. Neither funding source participated in the design, conduct, analysis, or interpretation of the data. NR 27 TC 14 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 14 PY 2014 VL 129 IS 2 BP 194 EP 202 DI 10.1161/CIRCULATIONAHA.113.006165 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 287IO UT WOS:000329535600005 PM 24249721 ER PT J AU Koren, MJ Giugliano, RP Raal, FJ Sullivan, D Bolognese, M Langslet, G Civeira, F Somaratne, R Nelson, P Liu, T Scott, R Wasserman, SM Sabatine, MS AF Koren, Michael J. Giugliano, Robert P. Raal, Frederick J. Sullivan, David Bolognese, Michael Langslet, Gisle Civeira, Fernando Somaratne, Ransi Nelson, Patric Liu, Thomas Scott, Rob Wasserman, Scott M. Sabatine, Marc S. TI Efficacy and Safety of Longer-Term Administration of Evolocumab (AMG 145) in Patients With Hypercholesterolemia 52-Week Results From the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) Randomized Trial SO CIRCULATION LA English DT Article DE cholesterol; LDL; hypercholesterolemia; randomized controlled trial; serine proteases ID LOW-DENSITY-LIPOPROTEIN; SUBTILISIN/KEXIN TYPE 9; INTENSIVE STATIN THERAPY; LAPLACE-TIMI 57; MONOCLONAL-ANTIBODY; CHOLESTEROL LEVELS; DOUBLE-BLIND; FAMILIAL HYPERCHOLESTEROLEMIA; SERINE-PROTEASE; HDL CHOLESTEROL AB Background Evolocumab (AMG 145), a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein cholesterol (LDL-C) in phase 2 studies of 12 weeks' duration. The longer-term efficacy and safety of PCSK9 inhibition remain undefined. Methods and Results Of 1359 randomized and dosed patients in the 4 evolocumab phase 2 parent studies, 1104 (81%) elected to enroll into the Open-Label Study of Long-term Evaluation Against LDL-C (OSLER) study. Regardless of their treatment assignment in the parent study, patients were randomized 2:1 to receive either open-label subcutaneous evolocumab 420 mg every 4 weeks with standard of care (SOC) (evolocumab+SOC, n=736) or SOC alone (n=368). Ninety-two percent of patients in the evolocumab+SOC group and 89% of patients in the SOC group completed 52 weeks of follow-up. Patients who first received evolocumab in OSLER experienced a mean 52.3% [SE, 1.8%] reduction in LDL-C at week 52 (P<0.0001). Patients who received 1 of 6 dosing regimens of evolocumab in the parent studies and received evolocumab+SOC in OSLER had persistent LDL-C reductions (mean reduction, 50.4% [SE, 0.8%] at the end of the parent study versus 52.1% [SE, 1.0%] at 52 weeks; P=0.31). In patients who discontinued evolocumab on entry into OSLER, LDL-C levels returned to near baseline levels. Adverse events and serious adverse events occurred in 81.4% and 7.1% of the evolocumab+SOC group patients and 73.1% and 6.3% of the SOC group patients, respectively. Conclusion Evolocumab dosed every 4 weeks demonstrated continued efficacy and encouraging safety and tolerability over 1 year of treatment in the largest and longest evaluation of a PCSK9 inhibitor in hypercholesterolemic patients to date. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT01439880. C1 [Koren, Michael J.] Jacksonville Ctr Clin Res, Jacksonville, FL 32216 USA. [Giugliano, Robert P.; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Giugliano, Robert P.; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. [Raal, Frederick J.] Univ Witwatersrand, Dept Med, Carbohydrate & Lipid Metab Res Unit, Div Endocrinol & Metab,Fac Hlth Sci, ZA-2001 Johannesburg, South Africa. [Sullivan, David] Royal Prince Alfred Hosp, Dept Clin Biochem, Camperdown, NSW 2050, Australia. [Bolognese, Michael] Bethesda Hlth Res Ctr, Bethesda, MD USA. [Langslet, Gisle] Oslo Univ Hosp, Lipid Clin, Oslo, Norway. [Civeira, Fernando] Hosp Univ Miguel Servet, Zaragoza, Spain. [Somaratne, Ransi; Liu, Thomas; Scott, Rob; Wasserman, Scott M.] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Koren, MJ (reprint author), Jacksonville Ctr Clin Res, 4085 Univ Blvd S,Ste 1, Jacksonville, FL 32216 USA. EM mkoren@encoredocs.com OI Scott, Robert/0000-0001-8266-1061 FU Amgen Inc.; Pfizer; Regeneron; Roche; Sanofi FX This trial was funded by Amgen Inc. The Jacksonville Center for Clinical Research also received research grants for studying anti-PCSK9 therapy from Pfizer, Regeneron, Roche, and Sanofi. NR 26 TC 98 Z9 107 U1 1 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 14 PY 2014 VL 129 IS 2 BP 234 EP 243 DI 10.1161/CIRCULATIONAHA.113.007012 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 287IO UT WOS:000329535600020 PM 24255061 ER PT J AU Hawkins, BM Fitzgerald-McKeon, LM Yeh, RW AF Hawkins, Beau M. Fitzgerald-McKeon, Lisa M. Yeh, Robert W. TI High-Risk Percutaneous Coronary Intervention in the Era of Public Reporting Clinical and Ethical Considerations in the Care of an Elderly Patient With Critical Left Main Disease and Shock SO CIRCULATION LA English DT Article DE coronary stenosis; ethics; shock; cardiogenic ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR DATA REGISTRY; SURROGATE DECISION-MAKERS; QUALITY-OF-CARE; CARDIOGENIC-SHOCK; ST-ELEVATION; EARLY REVASCULARIZATION; MEDICAL FUTILITY; ARTERY STENOSIS; LEAD AVR C1 [Hawkins, Beau M.] Univ Oklahoma, Hlth Sci Ctr, Cardiovasc Sect, Oklahoma City, OK USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Fitzgerald-McKeon, Lisa M.] Amo & Doceo Liberi Ctr, East Walpole, MA USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 8-843, Boston, MA 02114 USA. EM ryeh@partners.org FU National Heart, Lung, and Blood Institute [1K23HL118138]; American Heart Association [12CRP9010016]; Harvard Clinical Research Institute; Hassenfeld Scholars Program FX Dr Yeh receives funding from the National Heart, Lung, and Blood Institute (1K23HL118138), the American Heart Association (12CRP9010016), the Harvard Clinical Research Institute, and the Hassenfeld Scholars Program. The other authors report no conflicts. NR 36 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 14 PY 2014 VL 129 IS 2 BP 258 EP 265 DI 10.1161/CIRCULATIONAHA.113.004604 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 287IO UT WOS:000329535600004 PM 24421361 ER PT J AU Li, JZ Gallien, S Ribaudo, H Heisey, A Bangsberg, DR Kuritzkes, DR AF Li, Jonathan Z. Gallien, Sebastien Ribaudo, Heather Heisey, Andrea Bangsberg, David R. Kuritzkes, Daniel R. TI Incomplete adherence to antiretroviral therapy is associated with higher levels of residual HIV-1 viremia SO AIDS LA English DT Article DE HIV reservoir; medication adherence; residual viremia ID VIRAL LOAD; RALTEGRAVIR INTENSIFICATION; DRUG-RESISTANCE; SAN-FRANCISCO; LESS-THAN-50 COPIES/ML; INFECTED INDIVIDUALS; INDIGENT POPULATION; REPLICATION; SUPPRESSION; NONADHERENCE AB Objectives:To evaluate the relationship between incomplete antiretroviral therapy (ART) adherence and levels of residual HIV-1 viremia. Design:Medication adherence and residual viremia less than 50copies/ml were quantified in participants of a cohort of homeless and marginally housed individuals with HIV/AIDS. Methods:Participants had at least 6 months of virologic suppression of less than 50copies/ml and were in the adherence monitoring cohort with monthly unannounced pill counts. Residual viremia was measured by the single-copy assay. Results:The median average ART adherence over the prior 1 and 2 months were 94% [interquartile range (IQR) 79-100%] and 93% (IQR 82-98%), respectively. Average ART adherence over the past 2 months was significantly associated with levels of residual HIV viremia (Spearman r=-0.25, P=0.04). One-third of participants with 100% ART adherence over the past 2 months had detectable residual viremia. On multivariate regression analysis, ART adherence over the past 2 months, but not duration of virologic suppression, CD4(+) T-cell count or ART regimen, was significantly associated with levels of residual HIV viremia. Detectable residual viremia was associated with virologic failure (>50copies/ml) on univariate Cox proportional hazard analysis (hazard ratio 2.08, P=0.02). However, on multivariate analysis, only ART adherence was associated with risk of virologic failure. Conclusion:Incomplete ART adherence is associated with higher levels of residual HIV-1 viremia, but detectable residual viremia can be present despite 100% measured ART adherence. (c) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Li, Jonathan Z.; Gallien, Sebastien; Heisey, Andrea; Kuritzkes, Daniel R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Gallien, Sebastien] Hop St Louis, Paris, France. [Ribaudo, Heather] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Li, JZ (reprint author), Brigham & Womens Hosp, Div Infect Dis, 65 Landsdowne St,Rm 435, Cambridge, MA 02139 USA. EM jli22@partners.org RI Gallien, Sebastien/F-9930-2015 OI Gallien, Sebastien/0000-0002-8033-0936 FU NIH (Statistical and Data Management Center of the AIDS Clinical Trials Group) [U01 AI068634]; NIH (Harvard University CFAR) [P30 AI060354]; NIH [U01 AI 068636]; ACTG [UM1 AI-068636] FX J.Z.L. is the recipient of the Virology Fellows Research Training Program grant from Bristol-Myers Squibb. H.R. is supported in part by grants from the NIH (Statistical and Data Management Center of the AIDS Clinical Trials Group U01 AI068634 and Harvard University CFAR P30 AI060354). D.R.K. is supported in part by grants from the NIH (U01 AI 068636) and an ACTG Virology Specialty Laboratory subcontract from the ACTG (UM1 AI-068636). NR 34 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 14 PY 2014 VL 28 IS 2 BP 181 EP 186 DI 10.1097/QAD.0000000000000123 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 282QZ UT WOS:000329188800004 PM 24361679 ER PT J AU Siedner, MJ Musinguzi, N Tsai, AC Muzoora, C Kembabazi, A Weiser, SD Bennett, J Hunt, PW Martin, JN Haberer, JE Bangsberg, DR AF Siedner, Mark J. Musinguzi, Nicholas Tsai, Alexander C. Muzoora, Conrad Kembabazi, Annet Weiser, Sheri D. Bennett, John Hunt, Peter W. Martin, Jeffrey N. Haberer, Jessica E. Bangsberg, David R. TI Treatment as long-term prevention: sustained reduction in HIV sexual transmission risk with use of antiretroviral therapy in rural Uganda SO AIDS LA English DT Article DE antiretroviral therapy; HIV/AIDS; sub-Saharan Africa; treatment as prevention; Uganda ID BEHAVIOR; STIGMA; AFRICA AB Objectives: Suppressive antiretroviral therapy (ART) substantially decreases HIV transmission in clinical research settings. We sought to measure the frequency and correlates of periods of transmission risk among individuals taking ART during multiple years of observation in rural, southwestern Uganda. Design: Observational cohort study. Methods: We collected sexual behavior and viral load data in a Ugandan cohort of people living with HIV/AIDS from the time of ART initiation. We defined each 90-day visit as a potential transmission period if HIV-1 RNA was more than 400copies/ml and the participant reported sexual transmission risk behavior, defined as unprotected sexual contact with at least 1 HIV-uninfected partners or partners of unknown serostatus in the prior 90 days. Results: We evaluated data from 463 individuals on ART over a median 3.5 years of observation and 5293 total study visits. During that time, over half (259, 56%) had detectable viremia or reported sexual transmission risk behavior at least once. However, only 23 (5%) had both simultaneously, at 28 (<1%) of all visits. Transmission sexual behavior was reported at 6% of visits with detectable viremia. In multivariable regression modeling, correlates of transmission risk periods included younger age, lower CD4(+) cell count, low household asset ownership and increased internalized stigma. Conclusion: Although detectable viremia and/or sexual transmission risk behavior occurred in over half of individuals, ART reduced periods of HIV transmission risk by over 90% during up to 6 years of observation time. These findings provide further support for provision of ART, along with interventions to promote long-term adherence, to reduce HIV transmission in HIV-endemic settings. (c) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Siedner, Mark J.; Tsai, Alexander C.; Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Musinguzi, Nicholas; Muzoora, Conrad; Kembabazi, Annet] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Weiser, Sheri D.; Bennett, John; Hunt, Peter W.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bangsberg, David R.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. RP Siedner, MJ (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. EM msiedner@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU US National Institutes of Health (NIH) [R01MH054907, P30AI27763]; Mark and Lisa Schwartz Family Foundation; Sullivan Family Foundation; Bacca Foundation; [K23MH087228]; [K23MH096620]; [K23MH079713]; [K24MH087227]; [K23MH099916] FX This work was supported by US National Institutes of Health (NIH) R01MH054907 and P30AI27763. The authors also acknowledge the following additional sources of support: K23MH087228 (Haberer); K23MH096620 (Tsai); K23MH079713 (Weiser); K24MH087227 (Bangsberg); and K23MH099916 (Siedner). Additional study funding was provided by the Mark and Lisa Schwartz Family Foundation, the Sullivan Family Foundation, and the Bacca Foundation. NR 20 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 14 PY 2014 VL 28 IS 2 BP 267 EP 271 DI 10.1097/QAD.0000000000000136 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 282QZ UT WOS:000329188800014 PM 24361683 ER PT J AU Wang, XF Roberts, CWM AF Wang, Xiaofeng Roberts, Charles W. M. TI CARMA: CARM1 Methylation of SWI/SNF in Breast Cancer SO CANCER CELL LA English DT Editorial Material C1 [Wang, Xiaofeng; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wang, Xiaofeng; Roberts, Charles W. M.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Wang, Xiaofeng; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu FU NCI NIH HHS [R01 CA113794, R01 CA172152, U01 CA105423] NR 10 TC 4 Z9 4 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD JAN 13 PY 2014 VL 25 IS 1 BP 3 EP 4 DI 10.1016/j.ccr.2013.12.017 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AA0XE UT WOS:000330819900002 PM 24434203 ER PT J AU Lohr, JG Stojanov, P Carter, SL Cruz-Gordillo, P Lawrence, MS Auclair, D Sougnez, C Knoechel, B Gould, J Saksena, G Cibulskis, K McKenna, A Chapman, MA Straussman, R Levy, J Perkins, LM Keats, JJ Schumacher, SE Rosenberg, M Getz, G Golub, TR AF Lohr, Jens G. Stojanov, Petar Carter, Scott L. Cruz-Gordillo, Peter Lawrence, Michael S. Auclair, Daniel Sougnez, Carrie Knoechel, Birgit Gould, Joshua Saksena, Gordon Cibulskis, Kristian McKenna, Aaron Chapman, Michael A. Straussman, Ravid Levy, Joan Perkins, Louise M. Keats, Jonathan J. Schumacher, Steven E. Rosenberg, Mara Getz, Gad Golub, Todd R. CA Multiple Myeloma Res Consortium TI Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy SO CANCER CELL LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; KAPPA-B PATHWAY; BREAST CANCERS; CELL LYMPHOMA; C-MYC; MUTATIONS; EVOLUTION; BRAF; ABNORMALITIES; MELANOMA AB We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g., KRAS, NRAS, and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of nonmutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions. C1 [Lohr, Jens G.; Stojanov, Petar; Carter, Scott L.; Cruz-Gordillo, Peter; Lawrence, Michael S.; Auclair, Daniel; Sougnez, Carrie; Knoechel, Birgit; Gould, Joshua; Saksena, Gordon; Cibulskis, Kristian; McKenna, Aaron; Straussman, Ravid; Schumacher, Steven E.; Rosenberg, Mara; Getz, Gad; Golub, Todd R.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02412 USA. [Lohr, Jens G.; Stojanov, Petar; Knoechel, Birgit; Schumacher, Steven E.; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Knoechel, Birgit] Boston Childrens Hosp, Boston, MA 02115 USA. [Chapman, Michael A.] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England. [Levy, Joan; Perkins, Louise M.] Multiple Myeloma Res Fdn, Norwalk, CT 06581 USA. [Keats, Jonathan J.] Translat Genom Res Inst TGen, Phoenix, AZ 85004 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Getz, Gad] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Golub, TR (reprint author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02412 USA. EM golub@broadinstitute.org FU Multiple Myeloma Research Foundation; NIH [5P50CA100707-09]; Conquer Cancer Foundation FX This project was funded by a grant from the Multiple Myeloma Research Foundation. This work was also supported by NIH grant 5P50CA100707-09 (DF/HCC SPORE in Multiple Myeloma) and a Conquer Cancer Foundation Young Investigator Award (J.G.L.). We are grateful to members of the Broad Institute's Genomics Platform, without whom this work would not have been possible, and to Jadwiga Grabarek and the members of the Golub lab for helpful discussions and critical review of the manuscript. NR 50 TC 190 Z9 195 U1 3 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD JAN 13 PY 2014 VL 25 IS 1 BP 91 EP 101 DI 10.1016/j.ccr.2013.12.015 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AA0XE UT WOS:000330819900012 PM 24434212 ER PT J AU Makela, KT Matilainen, M Pulkkinen, P Fenstad, AM Havelin, L Engesaeter, L Furnes, O Pedersen, AB Overgaard, S Karrholm, J Malchau, H Garellick, G Ranstam, J Eskelinen, A AF Makela, Keijo T. Matilainen, Markus Pulkkinen, Pekka Fenstad, Anne M. Havelin, Leif Engesaeter, Lars Furnes, Ove Pedersen, Alma B. Overgaard, Soren Karrholm, Johan Malchau, Henrik Garellick, Goran Ranstam, Jonas Eskelinen, Antti TI Failure rate of cemented and uncemented total hip replacements: register study of combined Nordic database of four nations SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID NORWEGIAN ARTHROPLASTY REGISTER; CONTROLLED-TRIALS; FOLLOW-UP; OSTEOARTHRITIS; ASSOCIATION; COMPONENTS; REVISIONS AB Objective To assess the failure rate of cemented, uncemented, hybrid, and reverse hybrid total hip replacements in patients aged 55 years or older. Design Register study. Setting Nordic Arthroplasty Register Association database (combined data from Sweden, Norway, Denmark, and Finland). Participants 347 899 total hip replacements performed during 1995-2011. Main outcome measures Probability of implant survival (Kaplan-Meier analysis) along with implant survival with revision for any reason as endpoint (Cox multiple regression) adjusted for age, sex, and diagnosis in age groups 55-64, 65-74, and 75 years or older. Results The proportion of total hip replacements using uncemented implants increased rapidly towards the end of the study period. The 10 year survival of cemented implants in patients aged 65 to 74 and 75 or older (93.8%, 95% confidence interval 93.6% to 94.0% and 95.9%, 95.8% to 96.1%, respectively) was higher than that of uncemented (92.9%, 92.3% to 93.4% and 93.0%, 91.8% to 94.0%), hybrid (91.6%, 90.9% to 92.2% and 93.9%, 93.1% to 94.5%), and reverse hybrid (90.7%, 87.3% to 93.2% and 93.2%, 90.7% to 95.1%) implants. The survival of cemented (92.2%, 91.8% to 92.5%) and uncemented (91.8%, 91.3% to 92.2%) implants in patients aged 55 to 64 was similar. During the first six months the risk of revision with cemented implants was lower than with all other types of fixation in all age groups. Conclusion The survival of cemented implants for total hip replacement was higher than that of uncemented implants in patients aged 65 years or older. The increased use of uncemented implants in this age group is not supported by these data. However, because our dataset includes only basic information common to all national registers there is potential for residual confounding. C1 [Makela, Keijo T.] Turku Univ Hosp, Dept Orthopaed & Traumatol, FI-20100 Turku, Finland. [Matilainen, Markus] Turku Univ, Dept Biostat, Turku, Finland. [Pulkkinen, Pekka] Univ Helsinki, Hjelt Inst, Helsinki, Finland. [Fenstad, Anne M.; Havelin, Leif; Engesaeter, Lars; Furnes, Ove] Haukeland Hosp, Dept Orthopaed Surg, N-5021 Bergen, Norway. [Havelin, Leif; Engesaeter, Lars; Furnes, Ove] Univ Bergen, Dept Clin Med, Bergen, Norway. [Pedersen, Alma B.] Aarhus Univ Hosp, Competence Ctr Clin Epidemiol & Biostat, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. [Overgaard, Soren] Odense Univ Hosp, Traumatol & Clin Inst, Dept Orthopaed Surg, DK-5000 Odense, Denmark. [Overgaard, Soren] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. [Karrholm, Johan; Malchau, Henrik; Garellick, Goran] Univ Gothenburg, Dept Orthopaed, Inst Surg Sci, Sahlgrenska Univ Hosp, Molndal, Sweden. [Malchau, Henrik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA. [Ranstam, Jonas] Skane Univ Hosp, Swedish Natl Competence Ctr Musculoskeletal Disor, Lund, Sweden. [Eskelinen, Antti] Coxa Hosp Joint Replacement, Tampere, Finland. RP Makela, KT (reprint author), Turku Univ Hosp, Dept Orthopaed & Traumatol, Rauhankatu 24 D 32, FI-20100 Turku, Finland. EM keijo.makela@fimnet.fi RI Eskelinen, Antti/E-6433-2015; OI Eskelinen, Antti/0000-0003-0302-0253; Ranstam, Jonas/0000-0002-8287-7273 FU Turku University Hospital; Orion-Farmos Research Foundation FX This study was funded by a research grant from Turku University Hospital and a grant from the Orion-Farmos Research Foundation. These are non-profit organisations and with no role in the study. The researchers are totally independent of the funders. NR 30 TC 31 Z9 32 U1 0 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JAN 13 PY 2014 VL 348 AR f7592 DI 10.1136/bmj.f7592 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 293MK UT WOS:000329975600002 PM 24418635 ER PT J AU Li, CG Lee, PS Sun, Y Gu, XX Zhang, E Guo, YN Wu, CL Auricchio, N Priolo, C Li, J Csibi, A Parkhitko, A Morrison, T Planaguma, A Kazani, S Israel, E Xu, KF Henske, EP Blenis, J Levy, BD Kwiatkowski, D Yu, JJ AF Li, Chenggang Lee, Po-Shun Sun, Yang Gu, Xiaoxiao Zhang, Erik Guo, Yanan Wu, Chin-Lee Auricchio, Neil Priolo, Carmen Li, Jing Csibi, Alfredo Parkhitko, Andrey Morrison, Tasha Planaguma, Anna Kazani, Shamsah Israel, Elliot Xu, Kai-Feng Henske, Elizabeth Petri Blenis, John Levy, Bruce D. Kwiatkowski, David Yu, Jane J. TI Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; MUTATIONAL ANALYSIS; SIGNALING PATHWAYS; DISEASE; CANCER; GENE; CYCLOOXYGENASE-2; PROGRESSION; INHIBITION AB Lymphangioleiomyomatosis (LAM) is a progressive neoplastic disorder that leads to lung destruction and respiratory failure primarily in women. LAM is typically caused by tuberous sclerosis complex 2 (TSC2) mutations resulting in mTORC1 activation in proliferative smooth muscle-like cells in the lung. The female predominance of LAM suggests that estradiol contributes to disease development. Metabolomic profiling identified an estradiol-enhanced prostaglandin biosynthesis signature in Tsc2-deficient (TSC-) cells, both in vitro and in vivo. Estradiol increased the expression of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in prostaglandin biosynthesis, which was also increased at baseline in TSC-deficient cells and was not affected by rapamycin treatment. However, both Torin 1 treatment and Rictor knockdown led to reduced COX-2 expression and phospho-Akt-S473. Prostaglandin production was also increased in TSC-deficient cells. In preclinical models, both Celecoxib and aspirin reduced tumor development. LAM patients had significantly higher serum prostaglandin levels than healthy women. 15-epi-lipoxin-A4 was identified in exhaled breath condensate from LAM subjects and was increased by aspirin treatment, indicative of functional COX-2 expression in the LAM airway. In vitro, 15-epi-lipoxin-A4 reduced the proliferation of LAM patient-derived cells in a dose-dependent manner. Targeting COX-2 and prostaglandin pathways may have therapeutic value in LAM and TSC-related diseases, and possibly in other conditions associated with mTOR hyperactivation. C1 [Li, Chenggang; Sun, Yang; Zhang, Erik; Priolo, Carmen; Parkhitko, Andrey; Morrison, Tasha; Planaguma, Anna; Kazani, Shamsah; Israel, Elliot; Henske, Elizabeth Petri; Levy, Bruce D.; Yu, Jane J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, Po-Shun; Guo, Yanan; Auricchio, Neil; Kwiatkowski, David] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Gu, Xiaoxiao; Li, Jing; Csibi, Alfredo; Blenis, John] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Csibi, Alfredo] Infin Pharmaceut Inc, Cambridge, MA 02139 USA. [Xu, Kai-Feng] Peking Union Med Coll, Beijing 100730, Peoples R China. RP Yu, JJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. EM dkwiatkowski@rics.bwh.harvard.edu; jyu13@partners.org RI Sun, Yang/B-2495-2016 OI Sun, Yang/0000-0002-1463-689X FU LAM Foundation; Adler Foundation; LAM Treatment Alliance; National Institutes of Health [GM51405]; National Heart Lung and Blood Institute [HL68669, HL118760]; National Cancer Institute [1P01CA120964, HL098216]; Department of Defense Exploratory Idea Development Award [W81XWH-12-1-0442]; Biomedical Research Institute-BWH Microgrants FX A. Csibi and X. Gu are LAM Foundation postdoctoral fellows. J. Li is a Tuberous Sclerosis Alliance postdoctoral fellow. J. Blenis is a LAM Foundation established investigator. This study is supported by The LAM Foundation, The Adler Foundation, The LAM Treatment Alliance (to E.P. Henske)., National Institutes of Health Grant GM51405 (to J. Blenis), the National Heart Lung and Blood Institute grants HL68669 (to B.D. Levy) and HL118760 (to E.P. Henske), the National Cancer Institute grants 1P01CA120964 (to D. Kwiatkowski) and HL098216 (to J.J. Yu), the Department of Defense Exploratory Idea Development Award (W81XWH-12-1-0442 to J.J. Yu), and Biomedical Research Institute-BWH Microgrants to C. Li and J.J. Yu. NR 45 TC 23 Z9 24 U1 1 U2 18 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD JAN 13 PY 2014 VL 211 IS 1 BP 15 EP 28 DI 10.1084/jem.20131080 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 290YA UT WOS:000329793300003 PM 24395886 ER PT J AU Park, SM Deering, RP Lu, Y Tivnan, P Lianoglou, S Al-Shahrour, F Ebert, BL Hacohen, N Leslie, C Daley, GQ Lengner, CJ Kharas, MG AF Park, Sun-Mi Deering, Raquel P. Lu, Yuheng Tivnan, Patrick Lianoglou, Steve Al-Shahrour, Fatima Ebert, Benjamin L. Hacohen, Nir Leslie, Christina Daley, George Q. Lengner, Christopher J. Kharas, Michael G. TI Musashi-2 controls cell fate, lineage bias, and TGF-beta signaling in HSCs SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MESSENGER-RNA TRANSLATION; BONE-MARROW; IN-VIVO; MYELOID-LEUKEMIA; DIFFERENTIAL ACTIVATION; DETERMINANT MUSASHI; EXPRESSION PROFILES; GENE-EXPRESSION; SELF-RENEWAL AB Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance and engraftment caused by a loss of quiescence and increased commitment divisions. Contrary to previous studies, we found that these phenotypes were independent of Numb. Global transcriptome profiling and RNA target analysis uncovered Msi2 interactions at multiple nodes within pathways that govern RNA translation, stem cell function, and TGF-beta signaling. Msi2-null HSCs are insensitive to TGF-beta-mediated expansion and have decreased signaling output, resulting in a loss of myeloid-restricted HSCs and myeloid reconstitution. Thus, Msi2 is an important regulator of the HSC translatome and balances HSC homeostasis and lineage bias. C1 [Park, Sun-Mi; Tivnan, Patrick; Kharas, Michael G.] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. [Park, Sun-Mi; Tivnan, Patrick; Kharas, Michael G.] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY 10065 USA. [Lu, Yuheng; Lianoglou, Steve; Leslie, Christina] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10065 USA. [Deering, Raquel P.; Ebert, Benjamin L.; Hacohen, Nir] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Al-Shahrour, Fatima] Spanish Natl Canc Res Ctr, Clin Res Programme, Translat Bioinformat Unit, E-28029 Madrid, Spain. [Ebert, Benjamin L.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02215 USA. [Lengner, Christopher J.] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. [Lengner, Christopher J.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Lengner, Christopher J.] Univ Penn, Perelman Sch Med, Inst Regenerat Med, Philadelphia, PA 19104 USA. [Daley, George Q.] Howard Hughes Med Inst, Childrens Hosp Boston, Hematol Stem Cell Program, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. RP Kharas, MG (reprint author), Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. EM Kharasm@mskcc.org FU US National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award; Tri-Institutional Starr Stem Cell Fellowship; NIH; Louis V. Gerstner Young Investigator Award; American Society of Hematology Junior Scholar Award; Tri-Institutional Starr Foundation; Howard Hughes Medical Institute; National Cancer Institute (NIH) [R01]; W.W. Smith Charitable Trust FX M.G. Kharas was supported by the US National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award. The Tri-Institutional Starr Stem Cell Fellowship supports S.-M. Park. This work was also supported by grants from the NIH (M.G. Kharas), the Louis V. Gerstner Young Investigator Award, American Society of Hematology Junior Scholar Award, the Tri-Institutional Starr Foundation, and the Howard Hughes Medical Institute (to G.Q. Daley). C.J. Lengner was supported by an R01 from the National Cancer Institute (NIH) and a fellowship from the W.W. Smith Charitable Trust. NR 48 TC 35 Z9 36 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD JAN 13 PY 2014 VL 211 IS 1 BP 71 EP 87 DI 10.1084/jem.20130736 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 290YA UT WOS:000329793300007 PM 24395885 ER PT J AU Gandhi, L Bahleda, R Tolaney, SM Kwak, EL Cleary, JM Pandya, SS Hollebecque, A Abbas, R Ananthakrishnan, R Berkenblit, A Krygowski, M Liang, YL Turnbull, KW Shapiro, GI Soria, JC AF Gandhi, Leena Bahleda, Rastislav Tolaney, Sara M. Kwak, Eunice L. Cleary, James M. Pandya, Shuchi S. Hollebecque, Antoine Abbas, Richat Ananthakrishnan, Revathi Berkenblit, Anna Krygowski, Mizue Liang, Yali Turnbull, Kathleen W. Shapiro, Geoffrey I. Soria, Jean-Charles TI Phase I Study of Neratinib in Combination With Temsirolimus in Patients With Human Epidermal Growth Factor Receptor 2-Dependent and Other Solid Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; METASTATIC BREAST-CANCER; HER2 STATUS; THERAPY; EXPRESSION; MUTATIONS; HKI-272; EGFR; TRASTUZUMAB AB Purpose Human epidermal growth factor (HER) -mediated signaling is critical in many cancers, including subsets of breast and lung cancer. HER family members signal via the phosphatidylinositide 3-kinase (PI3K) -AKT/protein kinase B-mammalian target of rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple contributors to tumor growth and invasion. On the basis of preclinical data suggesting synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we conducted a phase I combination study of neratinib, a small-molecule irreversible pan-HER tyrosine kinase inhibitor, and temsirolimus, an mTOR inhibitor, in patients with advanced solid tumors. Patients and Methods This study enrolled patients to dosing combinations of neratinib and temsirolimus. The primary objective was to estimate the toxicity contour of the combination and establish recommended phase II doses. Results Sixty patients were treated on 12 of 16 possible dosing combinations. Diarrhea was the most common drug-related (93%) and dose-limiting toxicity (DLT), constituting four of 10 DLTs. Dose-limiting grade 3 metabolic abnormalities were also observed. Other frequent drug-related toxicities included nausea, stomatitis (both 53%), and anemia (48%). Two maximum-tolerated dose combinations were identified: 200 mg of neratinib/25 mg of temsirolimus and 160 mg of neratinib/50 mg of temsirolimus. Responses were noted in patients with HER2-amplified breast cancer resistant to trastuzumab, HER2-mutant non-small-cell lung cancer, and tumor types without identified mutations in the HER-PI3K-mTOR pathway. Conclusion The combination of neratinib and temsirolimus was tolerable and demonstrated antitumor activity in multiple tumor types, warranting further evaluation. C1 [Gandhi, Leena; Tolaney, Sara M.; Cleary, James M.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Kwak, Eunice L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pandya, Shuchi S.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Berkenblit, Anna; Krygowski, Mizue] Aveo Pharmaceut, Cambridge, MA USA. [Ananthakrishnan, Revathi; Turnbull, Kathleen W.] Inventiv Hlth, Cambridge, MA USA. [Bahleda, Rastislav; Hollebecque, Antoine; Soria, Jean-Charles] Insitut Gussav Roussy, Villejuif, France. [Abbas, Richat; Liang, Yali] Pfizer, Collegeville, PA USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Early Drug Dev Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM geoffrey_shapiro@dfci.harvard.edu OI Gandhi, Leena/0000-0002-2398-9179 FU Wyeth Research FX Sponsored by Wyeth Research, which was acquired by Pfizer in October 2009. Sponsorship was transferred to Puma Biotechnology on April 10, 2012. NR 37 TC 62 Z9 64 U1 0 U2 14 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 JAN 10 PY 2014 VL 32 IS 2 BP 68 EP + DI 10.1200/JCO.2012.47.2787 PG 12 WC Oncology SC Oncology GA 297CU UT WOS:000330233700002 PM 24323026 ER PT J AU Michaelson, MD Oudard, S Ou, YC Sengelov, L Saad, F Houede, N Ostler, P Stenzl, A Daugaard, G Jones, R Laestadius, F Ullen, A Bahl, A Castellano, D Gschwend, J Maurina, T Maneval, EC Wang, SL Lechuga, MJ Paolini, J Chen, I AF Michaelson, M. Dror Oudard, Stephane Ou, Yen-Chuan Sengelov, Lisa Saad, Fred Houede, Nadine Ostler, Peter Stenzl, Arnulf Daugaard, Gedske Jones, Robert Laestadius, Fredrik Ullen, Anders Bahl, Amit Castellano, Daniel Gschwend, Juergen Maurina, Tristan Maneval, Edna Chow Wang, Shaw-Ling Lechuga, Maria Jose Paolini, Jolanda Chen, Isan TI Randomized, Placebo-Controlled, Phase III Trial of Sunitinib Plus Prednisone Versus Prednisone Alone in Progressive, Metastatic, Castration-Resistant Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; CLINICAL-TRIALS; FACTOR-RECEPTOR; IN-VIVO; INCREASED SURVIVAL; PLASMA-LEVELS; DOUBLE-BLIND; DOCETAXEL; SU11248 AB Purpose We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned. Results Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%). Conclusion The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational. C1 [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Oudard, Stephane] Univ Paris 05, George Pompidou European Hosp, Paris, France. [Houede, Nadine] Inst Bergonie, Bordeaux, France. [Maurina, Tristan] Hop Jean Minjoz, CHU Besancon, F-25030 Besancon, France. [Ou, Yen-Chuan] Taichung Vet Gen Hosp, Taichung, Taiwan. [Sengelov, Lisa] Herlev Hosp, DK-2730 Herlev, Denmark. [Daugaard, Gedske] Rigshosp, DK-2100 Copenhagen, Denmark. [Saad, Fred] Univ Montreal, Montreal, PQ, Canada. [Ostler, Peter] Mt Vernon Hosp, Northwood HA6 2RN, Middx, England. [Jones, Robert] Beatson West Scotland Canc, Glasgow, Lanark, Scotland. [Bahl, Amit] Bristol Haematol & Oncol Ctr, Bristol, Avon, England. [Stenzl, Arnulf] Univ Tubingen, Sch Med, Tubingen, Germany. [Gschwend, Juergen] Tech Univ Munich, D-80290 Munich, Germany. [Laestadius, Fredrik; Ullen, Anders] Karolinska Univ Hosp, Stockholm, Sweden. [Castellano, Daniel] Univ Hosp 12 Octubre, Res Inst I 12, Madrid, Spain. [Maneval, Edna Chow; Wang, Shaw-Ling; Chen, Isan] Pfizer Oncol, La Jolla, CA USA. [Lechuga, Maria Jose; Paolini, Jolanda] Pfizer Oncol, Milan, Italy. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, Claire & John Bertucci Ctr Genitourinary Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM dmichaelson1@partners.org OI Daugaard, Gedske/0000-0002-9618-9180; Michaelson, Dror/0000-0001-9249-6338 FU Pfizer Inc. FX We thank all of the participating patients and their families, as well as the global network of investigators, research nurses, study coordinators, and operations staff. The study was sponsored by Pfizer Inc. Medical writing support was provided by Molly Heitz and Jean Scott at ACUMED (Tytherington, United Kingdom) and was funded by Pfizer Inc. NR 47 TC 64 Z9 65 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2014 VL 32 IS 2 BP 76 EP + DI 10.1200/JCO.2012.48.5268 PG 8 WC Oncology SC Oncology GA 297CU UT WOS:000330233700003 PM 24323035 ER PT J AU Traeger, L Cannon, S Keating, NL Pirl, WF Lathan, C Martin, MY He, YL Park, ER AF Traeger, Lara Cannon, Sheila Keating, Nancy L. Pirl, William F. Lathan, Christopher Martin, Michelle Y. He, Yulei Park, Elyse R. TI Race by Sex Differences in Depression Symptoms and Psychosocial Service Use Among Non-Hispanic Black and White Patients With Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; AFRICAN-AMERICANS; TREATMENT PREFERENCES; UNITED-STATES; CARE; ASSOCIATIONS; RELIGIOSITY; PERSPECTIVE; DISPARITIES; PREVALENCE AB Purpose This study examined race by sex differences in depression symptoms and psychosocial service use (pastors, social workers, mental health workers, support groups) among patients with lung cancer. Patients and Methods The multiregional Cancer Care Outcomes Research and Surveillance study surveyed black and white adults with stages I to III lung cancer (n = 1,043) about depression symptoms, interest in help for mood, and psychosocial service use. Multivariable logistic regression was used to evaluate race/sex differences in depression symptoms (modified Center for Epidemiologic Studies Depression Scale 6) and psychosocial service use, independent of demographic, clinical, psychosocial, and behavioral covariates. Results A total of 18.2% screened positive for depression symptoms. This proportion was highest among black men (24.7%), followed by white women (20.6%), black women (15.8%), and white men (15.0%). In adjusted analyses, white women showed greater risk for depression symptoms relative to black women (P = .01) and white men (P = .002), with no other differences among groups. Black patients were less likely than white patients to receive desired help for mood from their doctors (P = .02), regardless of sex. Among all patients, black women were most likely to have contact with pastoral care and social work. Conclusion Race and sex interacted to predict risk of depression symptoms. Covariates accounted for elevated risk among black men. White women showed greater risk than black women and white men, independent of covariates. Black patients may experience greater barriers to receiving help for mood from their doctors. Race by sex differences in contact with psychosocial services highlight potential differences in the extent to which services are available, acceptable, and/or sought by patients. C1 [Traeger, Lara; Pirl, William F.; Park, Elyse R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Traeger, Lara; Keating, Nancy L.; Pirl, William F.; He, Yulei; Park, Elyse R.] Harvard Univ, Sch Med, Boston, MA USA. [Cannon, Sheila] Univ Massachusetts, Boston, MA 02125 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lathan, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, Michelle Y.] Univ Alabama Birmingham, Birmingham, AL USA. RP Traeger, L (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,Suite 701, Boston, MA 02114 USA. EM ltraeger@partners.org FU National Cancer Institute [U01 CA093344]; Primary Data Collection and Research Centers [U01-CA093332, U01-CA093324, U01-CA093348, U01-CA093329, U01-CA093339, U01-CA093326, CRS-02-164, 1U54-CA156732-01]; American Cancer Society [PF PCSM 120414] FX Supported by National Cancer Institute grants to CanCORS Consortium Statistical Coordinating Center (Grant No. U01 CA093344) and Primary Data Collection and Research Centers (Grants No. U01-CA093332, U01-CA093324, U01-CA093348, U01-CA093329, U01-CA093339, U01-CA093326, CRS-02-164), and to E.R.P. and S.C. (Grant No. 1U54-CA156732-01). Additional support provided by an American Cancer Society grant to L.T. (Grant No. PF PCSM 120414). NR 32 TC 6 Z9 6 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2014 VL 32 IS 2 BP 107 EP 113 DI 10.1200/JCO.2012.46.6466 PG 7 WC Oncology SC Oncology GA 297CU UT WOS:000330233700007 PM 24323033 ER PT J AU Miranda, RN Aladily, TN Prince, HM Kanagal-Shamanna, R de Jong, D Fayad, LE Amin, MB Haideri, N Bhagat, G Brooks, GS Shifrin, DA O'Malley, DP Cheah, CY Bacchi, CE Gualco, G Li, SY Keech, JA Hochberg, EP Carty, MJ Hanson, SE Mustafa, E Sanchez, S Manning, JT Xu-Monette, ZY Miranda, AR Fox, P Bassett, RL Castillo, JJ Beltran, BE de Boer, JP Chakhachiro, Z Ye, DJ Clark, D Young, KH Medeiros, LJ AF Miranda, Roberto N. Aladily, Tariq N. Prince, H. Miles Kanagal-Shamanna, Rashmi de Jong, Daphne Fayad, Luis E. Amin, Mitual B. Haideri, Nisreen Bhagat, Govind Brooks, Glen S. Shifrin, David A. O'Malley, Dennis P. Cheah, Chan Y. Bacchi, Carlos E. Gualco, Gabriela Li, Shiyong Keech, John A., Jr. Hochberg, Ephram P. Carty, Matthew J. Hanson, Summer E. Mustafa, Eid Sanchez, Steven Manning, John T., Jr. Xu-Monette, Zijun Y. Miranda, Alonso R. Fox, Patricia Bassett, Roland L. Castillo, Jorge J. Beltran, Brady E. de Boer, Jan Paul Chakhachiro, Zaher Ye, Dongjiu Clark, Douglas Young, Ken H. Medeiros, L. Jeffrey TI Breast Implant-Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OF-THE-LITERATURE; CAPSULE; RECONSTRUCTION AB Purpose Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants. C1 [Miranda, Roberto N.; Kanagal-Shamanna, Rashmi; Fayad, Luis E.; Hanson, Summer E.; Manning, John T., Jr.; Xu-Monette, Zijun Y.; Fox, Patricia; Bassett, Roland L.; Young, Ken H.; Medeiros, L. Jeffrey] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Miranda, Alonso R.] Univ Houston, Houston, TX USA. [Mustafa, Eid] Plast & Reconstruct Surg, Wichita Falls, TX USA. [Sanchez, Steven] Pathol Associates Tyler, Tyler, TX USA. [Amin, Mitual B.] Oakland Univ, William Beaumont Sch Med, Royal Oak, MI USA. [Haideri, Nisreen] St Lukes Canc Inst, Kansas City, MO USA. [Bhagat, Govind] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Bhagat, Govind] Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Brooks, Glen S.] Tufts Univ, Longmeadow, MA USA. [Hochberg, Ephram P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carty, Matthew J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shifrin, David A.] Advocate Med Grp Plast Surg, Oak Lawn, IL USA. [O'Malley, Dennis P.] Clarient Labs GE Healthcare, Aliso Viejo, CA USA. [Li, Shiyong] Emory Univ Hosp, Atlanta, GA 30322 USA. [Keech, John A., Jr.] MultiCare Hlth Syst, MultiCare Reg Canc Ctr, Tacoma, WA USA. [Castillo, Jorge J.] Brown Univ, Miriam Hosp, Warren Alpert Med Sch, Providence, RI USA. [Ye, Dongjiu] Bioreference Labs, Elmwood Pk, NJ USA. [Clark, Douglas] New Mexico Canc Ctr, Albuquerque, NM USA. [Aladily, Tariq N.] Univ Jordan, Amman, Jordan. [Prince, H. Miles; Cheah, Chan Y.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Prince, H. Miles; Cheah, Chan Y.] Univ Melbourne, Melbourne, Vic, Australia. [de Jong, Daphne] Vrije Univ, Med Ctr, Amsterdam, Netherlands. [de Boer, Jan Paul] Netherlands Canc Inst, Amsterdam, Netherlands. [Bacchi, Carlos E.; Gualco, Gabriela] Consultoria Patol, Sao Paulo, Brazil. [Beltran, Brady E.] Edgardo Rebagliati Martins Hosp, Lima, Peru. [Chakhachiro, Zaher] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. RP Miranda, RN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Unit 72, Houston, TX 77030 USA. EM roberto.miranda@mdanderson.org RI Aladily, Tariq/C-5385-2015; OI Aladily, Tariq/0000-0001-8683-2374; Miranda, Roberto/0000-0002-8467-5464; Kanagal-Shamanna, Rashmi/0000-0001-7829-5249; Bhagat, Govind/0000-0001-6250-048X; Cheah, Chan Yoon/0000-0001-7988-1565; Beltran, Brady/0000-0003-4469-3817; Castillo, Jorge/0000-0001-9490-7532 FU Cancer Center Support Grant from the National Cancer Institute [P30 CA016672] FX Supported in part by Cancer Center Support Grant No. P30 CA016672 from the National Cancer Institute (data analyses). NR 30 TC 61 Z9 64 U1 1 U2 6 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 JAN 10 PY 2014 VL 32 IS 2 BP 114 EP 120 DI 10.1200/JCO.2013.52.7911 PG 7 WC Oncology SC Oncology GA 297CU UT WOS:000330233700008 PM 24323027 ER PT J AU Kim, Y Hammerman, PS Kim, J Yoon, JA Lee, Y Sun, JM Wilkerson, MD Pedamallu, CS Cibulskis, K Yoo, YK Lawrence, MS Stojanov, P Carter, SL McKenna, A Stewart, C Sivachenko, AY Oh, IJ Kim, HK Choi, YS Kim, K Shim, YM Kim, KS Song, SY Na, KJ Choi, YL Hayes, DN Kim, J Cho, S Kim, YC Ahn, JS Ahn, MJ Getz, G Meyerson, M Park, K AF Kim, Youngwook Hammerman, Peter S. Kim, Jaegil Yoon, Ji-ae Lee, Yoomi Sun, Jong-Mu Wilkerson, Matthew D. Pedamallu, Chandra Sekhar Cibulskis, Kristian Yoo, Yeong Kyung Lawrence, Michael S. Stojanov, Petar Carter, Scott L. McKenna, Aaron Stewart, Chip Sivachenko, Andrey Y. Oh, In-Jae Kim, Hong Kwan Choi, Yong Soo Kim, Kwhanmien Shim, Young Mog Kim, Kyu-Sik Song, Sang-Yun Na, Kook-Joo Choi, Yoon-La Hayes, D. Neil Kim, Jhingook Cho, Sukki Kim, Young-Chul Ahn, Jin Seok Ahn, Myung-Ju Getz, Gad Meyerson, Matthew Park, Keunchil TI Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; HUMAN CANCERS; GENE FUSIONS; MUTATIONS; GEFITINIB; ADENOCARCINOMA; EGFR; IDENTIFICATION; AMPLIFICATION; GLIOBLASTOMA AB Purpose Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients. Patients and Methods We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated. Results This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC. Conclusion These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs. C1 [Kim, Youngwook; Yoon, Ji-ae; Lee, Yoomi; Yoo, Yeong Kyung; Park, Keunchil] Samsung Biomed Res Inst, Samsung Med Ctr, Seoul, South Korea. [Sun, Jong-Mu; Kim, Hong Kwan; Choi, Yong Soo; Kim, Kwhanmien; Shim, Young Mog; Choi, Yoon-La; Kim, Jhingook; Ahn, Jin Seok; Ahn, Myung-Ju; Park, Keunchil] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul 135710, South Korea. [Cho, Sukki] Seoul Natl Univ, Coll Med, Bundang Hosp, Seoul, South Korea. [Oh, In-Jae; Kim, Kyu-Sik; Song, Sang-Yun; Na, Kook-Joo; Kim, Young-Chul] Chonnam Natl Univ, Hwasun Hosp, Jeonnam, South Korea. [Hammerman, Peter S.; Kim, Jaegil; Pedamallu, Chandra Sekhar; Cibulskis, Kristian; Lawrence, Michael S.; Stojanov, Petar; Carter, Scott L.; McKenna, Aaron; Stewart, Chip; Sivachenko, Andrey Y.; Getz, Gad; Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MA USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Boston, MA USA. [Hammerman, Peter S.; Pedamallu, Chandra Sekhar] Dana Farber Canc Inst, Boston, MA 02115 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Wilkerson, Matthew D.; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Park, K (reprint author), Sungkyunkwan Univ, Sch Med, Div Hematol Oncol, Dept Med,Samsung Med Ctr, 50 Irwon Dong, Seoul 135710, South Korea. EM kpark@skku.edu RI sun, jm/O-5938-2014 FU National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea [A111218-GM08]; Stephen and Alice Cutler Foundation; [NCI K08 CA163677] FX Supported by Grant No. A111218-GM08 from the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea; by Korea Biobank Network (provided tissue samples; distribution 2012-0006); by Grant No. NCI K08 CA163677 (P.S.H.); and by the Stephen and Alice Cutler Foundation. NR 36 TC 64 Z9 68 U1 2 U2 23 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 JAN 10 PY 2014 VL 32 IS 2 BP 121 EP + DI 10.1200/JCO.2013.50.8556 PG 9 WC Oncology SC Oncology GA 297CU UT WOS:000330233700009 PM 24323028 ER PT J AU Partridge, AH Gelber, S Gelber, R AF Partridge, Ann H. Gelber, Shari Gelber, Richard TI Recurrence of Breast Cancer in Elderly Women Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Partridge, Ann H.; Gelber, Shari; Gelber, Richard] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 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 JAN 10 PY 2014 VL 32 IS 2 BP 161 EP 161 DI 10.1200/JCO.2013.53.2705 PG 1 WC Oncology SC Oncology GA 297CU UT WOS:000330233700012 PM 24323031 ER PT J AU Xie, YJ Stewart, SM Lam, TH Viswanath, K Chan, SS AF Xie, Yao Jie Stewart, Sunita M. Lam, Tai Hing Viswanath, Kasisomayajula Chan, Sophia S. TI Television Viewing Time in Hong Kong Adult Population: Associations with Body Mass Index and Obesity SO PLOS ONE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; PUBLIC-HEALTH; SCREEN-TIME; RISK; CHILDREN; BEHAVIOR; WOMEN; MEN AB Background: Obesity is increasing dramatically in the Asia-Pacific region particularly China. The population of Hong Kong was exposed to modernization far earlier than the rest of China, reflecting conditions that are likely to be replicated as other Chinese cities undergo rapid change. This study examined the relationship between television viewing and obesity in a Hong Kong sample. Information about the relationship between a key sedentary behavior, TV viewing, and obesity, and its moderation by demographic characteristics may identify sectors of the population at highest risk for excess weight. Methods: Data were from Hong Kong Family and Health Information Trends Survey (2009-2010), a population-based survey on the public's use of media for health information and family communication by telephone interviews with 3,016 Hong Kong adults (age >= 18 years). TV viewing time, body mass index (BMI), physical activity and other lifestyle variables were analyzed. Results: Viewing time was longer in women, increased with age but decreased with education level and vigorous physical activity (all P<0.01). Longer TV viewing time was significantly associated with higher BMI (Coefficients B = 0.17, 95% CI: 0.11, 0.24) after adjusting for age, gender, employment status, marital status, education level, smoking activity and vigorous physical activity. This association was stronger in women than men (Coefficients B: 0.19 versus 0.15) and strongest in those aged 18 to 34 years (Coefficients B = 0.35). Furthermore, an hour increase in daily TV viewing was associated with 10% greater odds of being obese. Conclusions: A significant socioeconomic gradient in television viewing time was observed. TV viewing time positively associated with BMI and obesity. The TV viewing - BMI associations were strongest in women and young adults, suggesting vulnerable groups to target for obesity prevention by decreasing TV viewing. C1 [Xie, Yao Jie; Lam, Tai Hing] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. [Stewart, Sunita M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res,Dept Soc & Behav Sci, Boston, MA 02115 USA. [Chan, Sophia S.] Univ Hong Kong, Sch Nursing, Hong Kong, Hong Kong, Peoples R China. RP Lam, TH (reprint author), Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. EM hrmrlth@hku.hk RI Xie, Yao Jie/K-7001-2014 OI Xie, Yao Jie/0000-0001-9289-4985 FU Hong Kong Jockey Club Charities Trust FX This study was a part of the project "FAMILY: A Jockey Club Initiative for a Harmonious Society," which was funded by The Hong Kong Jockey Club Charities Trust. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 9 Z9 9 U1 3 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 10 PY 2014 VL 9 IS 1 AR e85440 DI 10.1371/journal.pone.0085440 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291YG UT WOS:000329868200050 PM 24427309 ER PT J AU Arokiaraj, MC Palacios, IF AF Arokiaraj, Mark C. Palacios, Igor F. TI Finite Element Modeling of A Novel Self-Expanding Endovascular Stent Method in Treatment of Aortic Aneurysms SO SCIENTIFIC REPORTS LA English DT Article ID WALL STRESS; ENDOTHELIAL-CELLS; OPEN REPAIR; RUPTURE; IMPACT; RISK AB A novel large self-expanding endovascular stent was designed with strut thickness of 70 mu m x 70 mu m width. The method was developed and investigated to identify a novel simpler technique in aortic aneurysm therapy. Stage 1 analysis was performed after deploying it in a virtual aneurysm model of 6 cm wide x 6 cm long fusiform hyper-elastic anisotropic design. At cell width of 9 mm, there was no buckling or migration of the stent at 180 Hg. Radial force of the stents was estimated after parametric variations. In stage 2 analysis, a prototype 300 mu m x 150 mu m stent with a cell width of 9 mm was chosen, and it was evaluated similarly after embedding in the aortic wall, and also with a tissue overgrowth of 1 mm over the stent. The 300/150 mm stent reduced the peak wall stress by 70% in the aneurysm and 50% reduction in compliance after embedding. Stage 3 analysis was performed to study the efficacy of stents with struts (thickness/width) 70/70, 180/100 and 300/150 mm after embedding and tissue overgrowth. The adjacent wall stresses were very minimal in stents with 180/100 and 70/70 mm struts after embedding. There is potential for a novel stent method in aortic aneurysm therapy. C1 [Arokiaraj, Mark C.] Pondicherry Inst Med Sci, Kalapet, Pondicherry, India. [Palacios, Igor F.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Arokiaraj, MC (reprint author), Pondicherry Inst Med Sci, Kalathumettupathai St, Kalapet, Pondicherry, India. EM christomark@gmail.com NR 35 TC 3 Z9 3 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 10 PY 2014 VL 4 AR 3630 DI 10.1038/srep03630 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291PQ UT WOS:000329841400010 PM 24406869 ER PT J AU Shirozu, K Tokuda, K Marutani, E Lefer, D Wang, R Ichinose, F AF Shirozu, Kazuhiro Tokuda, Kentaro Marutani, Eizo Lefer, David Wang, Rui Ichinose, Fumito TI Cystathionine gamma-Lyase Deficiency Protects Mice from Galactosamine/Lipopolysaccharide-Induced Acute Liver Failure SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID ACUTE HEPATIC-FAILURE; HYDROGEN-SULFIDE; ANIMAL-MODELS; RESCUES MICE; MITOCHONDRIAL; ACTIVATION; INFLAMMATION; METABOLISM; ENDOTOXIN; STRESS AB Aims: Acute liver failure (ALF) is a fatal syndrome attributed to massive hepatocyte death. Hydrogen sulfide (H2S) has been reported to exert cytoprotective or cytotoxic effects. Here, we examined the role of cystathionine -lyase (CSE, an enzyme produces H2S) in ALF induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS). Results: Wild-type (WT) mice exhibited high mortality rate, prominent liver injury, and increased plasma alanine aminotransferase levels after GalN/LPS challenge. Congenital deficiency or chemical inhibition of CSE by DL-propargylglycine attenuated GalN/LPS-induced liver injury. CSE deficiency markedly improved survival rate and attenuated GalN/LPS-induced upregulation of inflammatory cytokines and activation of caspase 3 and poly (ADP-ribose) polymerase (PARP) in the liver. CSE deficiency protected primary hepatocytes from GalN/tumor necrosis factor- (TNF-)-induced cell death without affecting LPS-induced TNF- production from primary peritoneal macrophages. Beneficial effects of CSE deficiency were associated with markedly elevated homocysteine and thiosulfate levels, upregulation of NF-E2 p45-related factor 2 (Nrf2) and antioxidant proteins, activation of Akt-dependent anti-apoptotic signaling, and inhibition of GalN/LPS-induced JNK phosphorylation in the liver. Finally, administration of sodium thiosulfate (STS) attenuated GalN/LPS-induced liver injury via activation of Akt- and Nrf2-dependent signaling and inhibition of GalN/LPS-induced JNK phosphorylation in WT mice. Innovation: These results suggest that inhibition of CSE or administration of STS prevents acute inflammatory liver failure by augmenting thiosulfate levels and upregulating antioxidant and anti-apoptotic defense in the liver. Conclusion: Congenital deficiency or chemical inhibition of CSE increases thiosulfate levels in the liver and prevents ALF at least in part by augmentation of antioxidant and anti-apoptotic mechanisms. Antioxid. Redox Signal. 20, 204-216. C1 [Shirozu, Kazuhiro; Tokuda, Kentaro; Marutani, Eizo; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Lefer, David] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Wang, Rui] Lakehead Univ, Dept Biol, Thunder Bay, ON P7B 5E1, Canada. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Suite 4315, Charlestown, MA 02129 USA. EM fichinose@partners.org FU National Institutes of Health [HL101930] FX This work was supported by National Institutes of Health grant HL101930 to F. Ichinose. NR 35 TC 25 Z9 26 U1 1 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN 10 PY 2014 VL 20 IS 2 BP 204 EP 216 DI 10.1089/ars.2013.5354 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 284VR UT WOS:000329349800002 PM 23758073 ER PT J AU Gao, A Van Dyke, TE AF Gao, Anqi Van Dyke, Thomas E. TI Role of suppressors of cytokine signaling 3 in bone inflammatory responses SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE SOCS3; bone; inflammation ID KAPPA-B LIGAND; ADJUVANT-INDUCED ARTHRITIS; JANUS TYROSINE KINASE; OSTEOCLAST FORMATION; RECEPTOR ACTIVATOR; GROWTH-FACTOR; T-CELLS; TRANSCRIPTIONAL ACTIVATION; RHEUMATOID-ARTHRITIS; STAT3 ACTIVATION AB Suppressor of cytokine signaling 3 (SOCS3) is a potent regulator of cytokine signaling in macrophages and T cells. In recent studies, evidence has been provided for SOCS3 activation in all major bone cells including osteoclasts, chondrocytes, synoviocytes, and osteoblasts. The investigation of SOCS3 function in bone remodeling systems implicates SOCS3 as a key signaling molecule in bone cell-mediated inflammatory responses. Both pro- and anti-inflammatory functions of SOCS3 have been demonstrated in different types of bone cells. This review provides an overview of the important role of SOCS3 in inflammatory responses of various bone cells and in bone inflammatory disorders such as periodontal disease and arthritis. Understanding the roles of SOCS3 in inflammatory diseases of bone and joints such as arthritis, osteomyelitis, and periodontal diseases is critical to revealing insights into signaling pathways that can be manipulated in potential therapeutic approaches. C1 [Gao, Anqi; Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Appl Oral Sci, 245 First St,17th Floor, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org OI Van Dyke, Thomas/0000-0003-0568-124X NR 46 TC 3 Z9 3 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD JAN 10 PY 2014 VL 4 AR 506 DI 10.3389/fimmu.2013.00506 PG 7 WC Immunology SC Immunology GA CH4VS UT WOS:000354032000001 PM 24454312 ER PT J AU Borrero, S Zite, N Potter, JE Trussell, J AF Borrero, Sonya Zite, Nikki Potter, Joseph E. Trussell, James TI Medicaid Policy on Sterilization - Anachronistic or Still Relevant? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID FORM C1 [Borrero, Sonya] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Borrero, Sonya] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Zite, Nikki] Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, Knoxville, TN USA. [Potter, Joseph E.] Univ Texas Austin, Populat Res Ctr, Austin, TX 78712 USA. [Trussell, James] Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA. [Trussell, James] Hull York Med Sch, Kingston Upon Hull, N Humberside, England. RP Borrero, S (reprint author), Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. OI Potter, Joseph/0000-0002-8960-813X FU NICHD NIH HHS [P2C HD047879, R24 HD042849] NR 4 TC 10 Z9 10 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 2014 VL 370 IS 2 BP 102 EP 104 DI 10.1056/NEJMp1313325 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AH4TA UT WOS:000336119800004 PM 24401047 ER PT J AU Koven, S AF Koven, Suzanne TI Mom at Bedside, Appears Calm SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Koven, Suzanne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koven, Suzanne] Harvard Univ, Sch Med, Boston, MA USA. RP Koven, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 2014 VL 370 IS 2 BP 104 EP 105 DI 10.1056/NEJMp1312171 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AH4TA UT WOS:000336119800005 PM 24401048 ER PT J AU Blanchard, MS Romero, JM Hoang, MP AF Blanchard, Melvin S. Romero, Javier M. Hoang, Mai P. TI Case 1-2014: A 32-Year-Old Man with Loss of Vision and a Rash SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VITAMIN-A-DEFICIENCY; XEROPHTHALMIA; SCURVY; KERATOMALACIA C1 [Blanchard, Melvin S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63130 USA. [Romero, Javier M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Romero, Javier M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hoang, Mai P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blanchard, MS (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63130 USA. FU Lundbeck; Synark FX Dr. Romero reports receiving payment for board membership at Lundbeck and consulting fees from Lundbeck and Synark. No other potential conflict of interest relevant to this article was reported. NR 17 TC 2 Z9 2 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 2014 VL 370 IS 2 BP 159 EP 166 DI 10.1056/NEJMcpc1214217 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AH4TA UT WOS:000336119800012 PM 24401054 ER PT J AU Lamas, D AF Lamas, Daniela TI Chronic Critical Illness SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PROLONGED MECHANICAL VENTILATION; OUTCOMES C1 [Lamas, Daniela] Brigham & Womens Hosp, Beth Israel Deaconess Med Ctr, Dept Pulm, Boston, MA 02115 USA. [Lamas, Daniela] Brigham & Womens Hosp, Beth Israel Deaconess Med Ctr, Dept Crit Care Med, Boston, MA 02115 USA. [Lamas, Daniela] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lamas, D (reprint author), Brigham & Womens Hosp, Beth Israel Deaconess Med Ctr, Dept Pulm, 75 Francis St, Boston, MA 02115 USA. NR 7 TC 13 Z9 14 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 2014 VL 370 IS 2 BP 175 EP 177 DI 10.1056/NEJMms1310675 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AH4TA UT WOS:000336119800016 PM 24401058 ER PT J AU Wylie, BJ Coull, BA Hamer, DH Singh, MP Jack, D Yeboah-Antwi, K Sabin, L Singh, N MacLeod, WB AF Wylie, Blair J. Coull, Brent A. Hamer, Davidson H. Singh, Mrigendra P. Jack, Darby Yeboah-Antwi, Kojo Sabin, Lora Singh, Neeru MacLeod, William B. TI Impact of biomass fuels on pregnancy outcomes in central East India SO ENVIRONMENTAL HEALTH LA English DT Article DE Indoor air pollution; Household air pollution; Birth weight; Stillbirth; Preterm birth; Preterm delivery; Pregnancy outcome; Biofuel; Biomass; India ID LOW-BIRTH-WEIGHT; ENVIRONMENTAL TOBACCO-SMOKE; MIDDLE-INCOME COUNTRIES; AMBIENT AIR-POLLUTION; OF-THE-LITERATURE; RISK-FACTORS; PROPENSITY SCORE; GESTATIONAL-AGE; RURAL GUATEMALA; BALLARD SCORE AB Background: Smoke from biomass burning has been linked to reduced birth weight; association with other birth outcomes is poorly understood. Our objective was to evaluate effects of exposure to biomass smoke on birth weight, preterm birth and stillbirth. Methods: Information on household cooking fuel was available for secondary analysis from two cohorts of pregnant women enrolled at delivery in India (n = 1744). Birth weight was measured and the modified Ballard performed to assess gestational age. Linear and logistic regression models were used to explore associations between fuel and birth outcomes. Effect sizes were adjusted in multivariate models for socio-demographic characteristics using propensity score techniques and for medical/obstetric covariates. Results: Compared to women who use gas (n = 265), women cooking with wood (n = 1306) delivered infants that were on average 112 grams lighter (95% CI -170.1, -54.6) and more likely to be preterm (OR 3.11, 95% CI 2.12, 4.59). Stillbirths were also more common in the wood group (4% versus 0%, p < 0.001). In adjusted models, the association between wood use and birth weight was no longer significant (14 g reduction; 95% CI -93, 66); however, the increased odds for preterm birth persisted (aOR 2.29; 95% CI 1.24, 4.21). Wood fuel use did not increase the risk of delivering either a low birth weight or small for gestational age infant. Conclusions: The association between wood fuel use and reduced birth weight was insignificant in multivariate models using propensity score techniques to account for socio-demographic differences. In contrast, we demonstrated a persistent adverse impact of wood fuel use on preterm delivery. If prematurity is confirmed as a consequence of antenatal exposure to household air pollution, perinatal morbidity and mortality from household air pollution may be higher than previously appreciated. C1 [Wylie, Blair J.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Wylie, Blair J.] Harvard Univ, Sch Med, Boston, MA USA. [Wylie, Blair J.; Hamer, Davidson H.; Yeboah-Antwi, Kojo; Sabin, Lora; MacLeod, William B.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02215 USA. [Wylie, Blair J.; Hamer, Davidson H.; MacLeod, William B.] Boston Univ, Sch Publ Hlth, Dept Int Hlth, Boston, MA 02215 USA. [Wylie, Blair J.; Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hamer, Davidson H.] Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. [Hamer, Davidson H.] Zambia Ctr Appl Hlth Res & Dev, Lusaka, Zambia. [Singh, Mrigendra P.] Natl Inst Malaria Res Field Stn, Jabalpur, Madhya Pradesh, India. [Jack, Darby] Columbia Univ, Dept Environm Hlth, Mailman Sch Publ Hlth, New York, NY USA. [Singh, Neeru] Indian Council Med Res, Reg Med Res Ctr Tribals, Jabalpur, Madhya Pradesh, India. RP Wylie, BJ (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Maternal Fetal Med, 55 Fruit St, Boston, MA 02114 USA. EM bwylie@partners.org FU United States Agency for International Development (USAID) [GHS-A-00-03-00020-00]; Child and Family Applied Research project at Boston University, Boston; Indo-U. S. Collaborative Network; Indian Council for Medical Research (ICMR); National Institute of Child Health and Development [1 R03 HD52167-01]; National Institute of Environmental Health Sciences [NIH K23 ES021471]; National Institutes of Health [NIH ES 000002] FX We would like to thank Dr. MK Das, the study nurses, Mobassir Hussain, Amrit Alok, Meghna Desai, and V Udhayakumar for their efforts on behalf of the study. We acknowledge the kind administrative and logistical support of the Chief Medical Officers at the participating facilities, the Jharkhand and Chhattisgarh State health officials, and the Indian Council of Medical Research. The United States Agency for International Development (USAID)/ India mission provided funding for this study to the Child and Family Applied Research project at Boston University, Boston, MA by means of the USAID cooperative agreement (GHS-A-00-03-00020-00). This work was also supported by the Indo-U. S. Collaborative Network with funding from the Indian Council for Medical Research (ICMR) and the National Institute of Child Health and Development (1 R03 HD52167-01). BJW was supported by the National Institute of Environmental Health Sciences (NIH K23 ES021471). BC was supported by the National Institutes of Health (NIH ES 000002). The Jharkhand results were presented at the 29th Annual meeting of the Society for Maternal-Fetal Medicine in 2009. NR 40 TC 9 Z9 9 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD JAN 9 PY 2014 VL 13 AR 1 DI 10.1186/1476-069X-13-1 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AF2JE UT WOS:000334537600001 PM 24405644 ER PT J AU Gautam, V D'Avanzo, C Hebisch, M Kovacs, DM Kim, DY AF Gautam, Vivek D'Avanzo, Carla Hebisch, Matthias Kovacs, Dora M. Kim, Doo Yeon TI BACE1 activity regulates cell surface contactin-2 levels SO MOLECULAR NEURODEGENERATION LA English DT Article ID AMYLOID PRECURSOR PROTEIN; BETA-SECRETASE ENZYME; OLFACTORY SENSORY NEURONS; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; NERVOUS-SYSTEM; AXON GUIDANCE; IN-VIVO; TAG-1; MOLECULE AB Background: Although BACE1 is a major therapeutic target for Alzheimer's disease (AD), potential side effects of BACE1 inhibition are not well characterized. BACE1 cleaves over 60 putative substrates, however the majority of these cleavages have not been characterized. Here we investigated BACE1-mediated cleavage of human contactin-2, a GPI-anchored cell adhesion molecule. Results: Our initial protein sequence analysis showed that contactin-2 harbors a strong putative BACE1 cleavage site close to its GPI membrane linker domain. When we overexpressed BACE1 in CHO cells stably transfected with human contactin-2, we found increased release of soluble contactin-2 in the conditioned media. Conversely, pharmacological inhibition of BACE1 in CHO cells expressing human contactin-2 and mouse primary neurons decreased soluble contactin-2 secretion. The BACE1 cleavage site mutation 1008MM/AA dramatically impaired soluble contactin-2 release. We then asked whether contactin-2 release induced by BACE1 expression would concomitantly decrease cell surface levels of contactin-2. Using immunofluorescence and surface-biotinylation assays, we showed that BACE1 activity tightly regulates contactin-2 surface levels in CHO cells as well as in mouse primary neurons. Finally, contactin-2 levels were decreased in Alzheimer's disease brain samples correlating inversely with elevated BACE1 levels in the same samples. Conclusion: Our results clearly demonstrate that mouse and human contactin-2 are physiological substrates for BACE1. BACE1-mediated contactin-2 cleavage tightly regulates the surface expression of contactin-2 in neuronal cells. Given the role of contactin-2 in cell adhesion, neurite outgrowth and axon guidance, our data suggest that BACE1 may play an important role in these physiological processes by regulating contactin-2 surface levels. C1 [Gautam, Vivek; D'Avanzo, Carla; Hebisch, Matthias; Kovacs, Dora M.; Kim, Doo Yeon] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit MassGeneral Inst Neurodege, Charlestown, MA 02129 USA. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit MassGeneral Inst Neurodege, Charlestown, MA 02129 USA. EM dora_kovacs@hms.harvard.edu; dkim@helix.mgh.harvard.edu FU NIA FX We would like to thank Dr. Yong Shen (Roskamp Institute, Sarasota, FL) for providing AD and control age-matched brain samples. We also would like to thank Ms. Carmilla Peach, Carolyn C. Sachse and Mr. Manuel T. Gersbacher (Massachusetts General Hospital, Boston, MA) for technical help in this study. This work is supported by grants from the NIA to DMK and DYK. NR 42 TC 12 Z9 13 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD JAN 9 PY 2014 VL 9 AR 4 DI 10.1186/1750-1326-9-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AB1JO UT WOS:000331547700001 PM 24405708 ER PT J AU Langenau, DM AF Langenau, David M. TI Pten regulates zebrafish hematopoiesis SO BLOOD LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR; STEM-CELLS C1 [Langenau, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Langenau, DM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 9 PY 2014 VL 123 IS 2 BP 149 EP 150 DI 10.1182/blood-2013-11-536136 PG 2 WC Hematology SC Hematology GA 290HL UT WOS:000329745400001 PM 24408201 ER PT J AU Meynard, D Babitt, JL Lin, HY AF Meynard, Delphine Babitt, Jodie L. Lin, Herbert Y. TI The liver: conductor of systemic iron balance SO BLOOD LA English DT Review ID REGULATES HEPCIDIN EXPRESSION; ANTIMICROBIAL PEPTIDE HEPCIDIN; PROTEASE MATRIPTASE-2 TMPRSS6; GENOME-WIDE ASSOCIATION; TRANSFERRIN RECEPTOR 2; HEREDITARY HEMOCHROMATOSIS; DEFICIENCY ANEMIA; JUVENILE HEMOCHROMATOSIS; SOLUBLE HEMOJUVELIN; MOUSE-LIVER AB Iron is a micronutrient essential for almost all organisms: bacteria, plants, and animals. It is a metal that exists in multiple redox states, including the divalent ferrous (Fe2+) and the trivalent ferric (Fe3+) species. The multiple oxidation states of iron make it excellent for electron transfer, allowing iron to be selected during evolution as a cofactor for many proteins involved in central cellular processes including oxygen transport, mitochondrial respiration, and DNA synthesis. However, the redox cycling of ferrous and ferric iron in the presence of H2O2, which is physiologically present in the cells, also leads to the production of free radicals (Fenton reaction) that can attack and damage lipids, proteins, DNA, and other cellular components. To meet the physiological needs of the body, but to prevent cellular damage by iron, the amount of iron in the body must be tightly regulated. Here we review how the liver is the central conductor of systemic iron balance and show that this central role is related to the secretion of a peptide hormone hepcidin by hepatocytes. We then review how the liver receives and integrates the many signals that report the body's iron needs to orchestrate hepcidin production and maintain systemic iron homeostasis. C1 [Meynard, Delphine; Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Program Membrane Biol,Ctr Syst Biol,P, Boston, MA USA. RP Lin, HY (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,CPZN 8216, Boston, MA 02114 USA. EM lin.herbert@mgh.harvard.edu RI meynard, delphine/B-4236-2014 FU National Institutes of Health [R01 DK087727]; Massachusetts General Hospital; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK069533, R01 DK071837] FX This study was supported by in part by National Institutes of Health grant R01 DK087727, a Howard Goodman Fellowship from the Massachusetts General Hospital (J.L.B.); and National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases grants R01 DK069533 and R01 DK071837 (H.Y.L.). NR 117 TC 48 Z9 50 U1 10 U2 31 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 9 PY 2014 VL 123 IS 2 BP 168 EP 176 DI 10.1182/blood-2013-06-427757 PG 9 WC Hematology SC Hematology GA 290HL UT WOS:000329745400011 PM 24200681 ER PT J AU Fiorentino, M Levine, MM Sztein, MB Fasano, A AF Fiorentino, Maria Levine, Myron M. Sztein, Marcelo B. Fasano, Alessio TI Effect of Wild-Type Shigella Species and Attenuated Shigella Vaccine Candidates on Small Intestinal Barrier Function, Antigen Trafficking, and Cytokine Release SO PLOS ONE LA English DT Article ID TIGHT JUNCTION; EPITHELIAL-CELLS; OCCLUDIN PHOSPHORYLATION; RHESUS-MONKEYS; HUMAN-COLON; DYSENTERIAE TYPE-1; FLEXNERI INFECTION; TRAVELERS DIARRHEA; DIVERSE SEROTYPES; ESCHERICHIA-COLI AB Bacterial dysentery due to Shigella species is a major cause of morbidity and mortality worldwide. The pathogenesis of Shigella is based on the bacteria's ability to invade and replicate within the colonic epithelium, resulting in severe intestinal inflammatory response and epithelial destruction. Although the mechanisms of pathogenesis of Shigella in the colon have been extensively studied, little is known on the effect of wild-type Shigella on the small intestine and the role of the host response in the development of the disease. Moreover, to the best of our knowledge no studies have described the effects of apically administered Shigella flexneri 2a and S. dysenteriae 1 vaccine strains on human small intestinal enterocytes. The aim of this study was to assess the coordinated functional and immunological human epithelial responses evoked by strains of Shigella and candidate vaccines on small intestinal enterocytes. To model the interactions of Shigella with the intestinal mucosa, we apically exposed monolayers of human intestinal Caco2 cells to increasing bacterial inocula. We monitored changes in paracellular permeability, examined the organization of tight-junctions and the pro-inflammatory response of epithelial cells. Shigella infection of Caco2 monolayers caused severe mucosal damage, apparent as a drastic increase in paracellular permeability and disruption of tight junctions at the cell-cell boundary. Secretion of pro-inflammatory IL-8 was independent of epithelial barrier dysfunction. Shigella vaccine strains elicited a pro-inflammatory response without affecting the intestinal barrier integrity. Our data show that wild-type Shigella infection causes a severe alteration of the barrier function of a small intestinal cell monolayer (a proxy for mucosa) and might contribute (along with enterotoxins) to the induction of watery diarrhea. Diarrhea may be a mechanism by which the host attempts to eliminate harmful bacteria and transport them from the small to the large intestine where they invade colonocytes inducing a strong inflammatory response. C1 [Fiorentino, Maria; Fasano, Alessio] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA. [Levine, Myron M.; Sztein, Marcelo B.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Levine, Myron M.; Sztein, Marcelo B.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. [Levine, Myron M.; Sztein, Marcelo B.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. RP Fasano, A (reprint author), Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA. EM afasano@mgh.harvard.edu OI Fiorentino, Maria R/0000-0001-5318-7313 FU NIAID, NIH, DHHS [U19 AI082655] FX These studies were funded by NIAID, NIH, DHHS grant U19 AI082655 (Cooperative Center for Translational Research in Human Immunology and Biodefense; CCHI) to M. B. S and A. F. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 6 Z9 6 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 9 PY 2014 VL 9 IS 1 AR e85211 DI 10.1371/journal.pone.0085211 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291XP UT WOS:000329866300055 PM 24416363 ER PT J AU Pretorius, E Bester, J Vermeulen, N Lipinski, B Gericke, GS Kell, DB AF Pretorius, Etheresia Bester, Janette Vermeulen, Natasha Lipinski, Boguslaw Gericke, George S. Kell, Douglas B. TI Profound Morphological Changes in the Erythrocytes and Fibrin Networks of Patients with Hemochromatosis or with Hyperferritinemia, and Their Normalization by Iron Chelators and Other Agents SO PLOS ONE LA English DT Article ID SICKLE-CELL-DISEASE; RED-BLOOD-CELL; HFE HEREDITARY HEMOCHROMATOSIS; SCANNING-ELECTRON-MICROSCOPY; SERUM FERRITIN; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; PARKINSONS-DISEASE; IDIOPATHIC HEMOCHROMATOSIS; ASYMPTOMATIC SUBJECTS AB It is well-known that individuals with increased iron levels are more prone to thrombotic diseases, mainly due to the presence of unliganded iron, and thereby the increased production of hydroxyl radicals. It is also known that erythrocytes (RBCs) may play an important role during thrombotic events. Therefore the purpose of the current study was to assess whether RBCs had an altered morphology in individuals with hereditary hemochromatosis (HH), as well as some who displayed hyperferritinemia (HF). Using scanning electron microscopy, we also assessed means by which the RBC and fibrin morphology might be normalized. An important objective was to test the hypothesis that the altered RBC morphology was due to the presence of excess unliganded iron by removing it through chelation. Very striking differences were observed, in that the erythrocytes from HH and HF individuals were distorted and had a much greater axial ratio compared to that accompanying the discoid appearance seen in the normal samples. The response to thrombin, and the appearance of a platelet-rich plasma smear, were also markedly different. These differences could largely be reversed by the iron chelator desferal and to some degree by the iron chelator clioquinol, or by the free radical trapping agents salicylate or selenite (that may themselves also be iron chelators). These findings are consistent with the view that the aberrant morphology of the HH and HF erythrocytes is caused, at least in part, by unliganded ('free') iron, whether derived directly via raised ferritin levels or otherwise, and that lowering it or affecting the consequences of its action may be of therapeutic benefit. The findings also bear on the question of the extent to which accepting blood donations from HH individuals may be desirable or otherwise. C1 [Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha] Univ Pretoria, Dept Physiol, Arcadia, South Africa. [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Gericke, George S.] AMPATH Natl Reference Lab, Centurion, South Africa. [Kell, Douglas B.] Univ Manchester, Sch Chem, Manchester M13 9PL, Lancs, England. [Kell, Douglas B.] Univ Manchester, Manchester Inst Biotechnol, Manchester M13 9PL, Lancs, England. RP Pretorius, E (reprint author), Univ Pretoria, Dept Physiol, Arcadia, South Africa. EM resia.pretorius@up.ac.za OI Pretorius, Etheresia/0000-0002-9108-2384; Kell, Douglas/0000-0001-5838-7963 FU National Research Foundation of South Africa (NRF) FX Funding body: The National Research Foundation of South Africa (NRF): E Pretorius. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 154 TC 19 Z9 19 U1 3 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 9 PY 2014 VL 9 IS 1 AR e85271 DI 10.1371/journal.pone.0085271 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291XP UT WOS:000329866300062 PM 24416376 ER EF